Back to resultsTo Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetics of a Single Dose Regimen of Ferroquine and Artefenomel in Adults and Children With Uncomplicated Plasmodium Falciparum Malaria (FALCI)
Primary Purpose
Plasmodium Falciparum Infection
Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Ferroquine SSR97193
Artefenomel
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Plasmodium Falciparum Infection
Eligibility Criteria
Inclusion criteria:
Male or female participant aged greater than (>) 6 months old and <70 years old:
- Cohort 1 = 14 years < age <70 years and body weight greater than or equal to (>=) 35 kilogram (kg).
- Cohort 2 = 5 years < age less than or equal to (<=) 14 years.
- Cohort 3 = 2 years < age <=5 years.
- Cohort 4 = 6 months < age <=2 years.
Body weight >=5 kg and <=90 kg.
Presence of mono-infection by Plasmodium falciparum with:
- Fever, as defined by axillary temperature >=37.5 degrees Celsius (°C) or oral/rectal/tympanic temperature >=38°C, or history of fever in the previous 24 hours (history of fever must be documented) and,
- Microscopically (blood smear) confirmed parasite infection, ranging from 1000 to 100 000 asexual parasites/microliter of blood.
Informed consent form signed by the participant or by the legally acceptable representative of the minor participant.
Exclusion criteria:
Presence of severe malaria.
Anti-malarial treatment:
- With piperaquine-based compound, mefloquine, naphthoquine or sulphadoxine/pyrimethamine (SP) within the previous 6 weeks (after their inhibition of new infections had fallen below 50%).
- With amodiaquine or chloroquine within the previous 4 weeks.
- With quinine, halofantrine, lumefantrine-based compounds and any other anti-malarial treatment or antibiotics with antimalarial activity (including cotrimoxazole, tetracyclines, quinolones and fluoroquinolones, and azithromycin) within the past 14 days.
- With any herbal products or traditional medicines, within the past 7 days.
Known history or evidence of clinically significant disorders.
Previous treatment within 5 times the half-life or within the last 14 days, whichever the longest which are: P-glycoprotein substrates, Cytochrome P450 (CYP) 2D6 main substrates and/or strong CYP2C or CYP3A inhibitors and/or moderate inhibitors but inhibiting both CYP2C and CYP3A and/or CYP inducers.
Mixed plasmodium infection.
Severe vomiting.
Severe malnutrition.
Laboratory parameters with clinically significant abnormalities and/or reaching critical values. For Liver Function Test. Aspartate aminotransferase (>2 [upper limit of normal] ULN), or alanine aminotransferase (>2 ULN) or total bilirubin >1.5 ULN.
Presence of Hepatitis A Immunoglobulin M, Hepatitis B surface antigen or Hepatitis C antibody.
Had received an investigational drug within the past 4 weeks.
Previous participation in any malaria vaccine study or received malaria vaccine in any other circumstance.
Measles and yellow fever vaccine injection within the last 15 days and or planned for the 28 days after randomization.
Female participant of child bearing potential not willing to use an effective contraceptive(s) method(s) for the duration of the study.
Positive serum or urine beta-human chorionic gonadotropin pregnancy test at study screening for female participants of childbearing potential.
Breastfeeding women.
Male participant having a partner of child bearing potential not willing to use an effective method of birth control during the study treatment period.
Splenectomized participants or presence of surgical scar on left hypochondrium. Participant unable to drink.
Known history of hypersensitivity, allergic or anaphylactoid reactions to ferroquine or other amino-quinolines or to OZ439 or OZ277 or to any of the excipients.
Family history of sudden death or of congenital prolongation of the Corrected QT (QTc) interval or known congenital prolongation of the QTc interval or any clinical condition known to prolong the QTc interval e.g., participants with a history of symptomatic cardiac arrhythmias or with clinically relevant bradycardia.
QTc using Fridericia's formula >450 millisecond at screening or pre-dose.
Hypokalemia (<3.5 millimoles per liter [mmol/L]), hypocalcemia (<2.0 mmol/L) or hypomagnesemia (<0.5 mmol/L) at screening or pre-dose.
Any treatment known to induce a lengthening of QT interval.
The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Sites / Locations
- Investigational Site Number 204001
- Investigational Site Number 854002
- Investigational Site Number 854003
- Investigational Site Number 854001
- Investigational Site Number 266002
- Investigational Site Number 266001
- Investigational Site Number 404003
- Investigational Site Number 404002
- Investigational Site Number 508001
- Investigational Site Number 800002
- Investigational Site Number 704003
- Investigational Site Number 704004
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg)
Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg)
Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg)
Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg)
Arm Description
On Day 0, based on the body weight (BW), participants received orally a single dose of ferroquine (FQ) capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of artefenomel (OZ439) (maximum dose up to 800 milligrams [mg]) oral suspension as follows: BW greater than or equal to (>=) 35 kilograms (kg): FQ 400 mg + OZ439 800 mg; BW >=24 kg to less than (<) 35 kg: FQ 300 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 200 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 150 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 100 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 75 mg + OZ439 150 mg.
On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 600 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 450 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 300 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 225 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 150 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 115 mg + OZ439 150 mg.
On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 900 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 675 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 450 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 335 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 225 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 170 mg + OZ439 150 mg.
On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 1200 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 900 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 600 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 450 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 300 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 225 mg + OZ439 150 mg.
Outcomes
Primary Outcome Measures
Percentage of Participants With Polymerase Chain Reaction (PCR)-Adjusted Adequate Clinical and Parasitological Response (ACPR) at Day 28: African <=5 Years Per Protocol Population at Day 28 (PP28)
ACPR: negative parasitemia at Day 28, irrespective of axillary temperature(AT), in participants not meeting any criteria of early therapy failure (ETF):Danger signs (DS)/severe malaria (SM) at Day 1, 2 or 3 in presence of parasitemia; or Day 2 parasite count >Day 0 irrespective of AT; or parasitemia at Day 3 with AT >=37.5 degree Celsius (°C); or parasite count on Day 3>=25 percent (%) on Day 0, or late clinical failure(LCF):DS/ SM in presence of parasitemia between Day 4 and 28; or presence of parasitemia and AT>=37.5°C between Day 4 and 28, or late parasitological failure (LPF):presence of parasitemia between Day 7 and 28 and AT<37.5°C or having rescue therapy for malaria. PCR-adjusted ACPR applied to recrudescence (appearance of asexual parasites after clearance of initial infection with genotype identical to that present at Baseline), excluding participants with re-infection. In data table, "overall number of participants analyzed"=participants evaluable for this outcome measure.
Secondary Outcome Measures
Percentage of Participants With Polymerase Chain Reaction-adjusted Adequate Clinical and Parasitological Response at Day 28: African >5 Years Per Protocol Population at Day 28 (A5PP28)
ACPR: negative parasitemia at Day 28, irrespective of AT, in participants not meeting any criteria of ETF: DS or SM at Day 1, 2 or 3 in presence of parasitemia; or Day 2 parasite count > Day 0 irrespective of AT; or parasitemia at Day 3 with AT >=37.5°C; or parasite count on Day 3 >=25% on Day 0, or LCF: DS/ SM in presence of parasitemia between Day 4 and 28; or presence of parasitemia and AT >=37.5°C between Day 4 and 28, or LPF: presence of parasitemia between Day 7 and 28 and AT <37.5°C or having rescue therapy for malaria. PCR-adjusted ACPR was applied to recrudescence (appearance of asexual parasites after clearance of initial infection with a genotype identical to that of parasites present at Baseline), excluding participants with re-infection. Here, in the data table, "overall number of participants analyzed"=participants evaluable for this outcome measure.
Percentage of Participants With Polymerase Chain Reaction-adjusted Adequate Clinical and Parasitological Response at Day 28: Asian PP Population at Day 28 (APP28)
ACPR: negative parasitemia at Day 28, irrespective of AT, in participants not meeting any criteria of ETF: DS or SM at Day 1, 2 or 3 in presence of parasitemia; or Day 2 parasite count > Day 0 irrespective of AT; or parasitemia at Day 3 with AT >=37.5°C; or parasite count on Day 3 >=25% on Day 0, or LCF: DS/ SM in presence of parasitemia between Day 4 and 28; or presence of parasitemia and AT >=37.5°C between Day 4 and 28, or LPF: presence of parasitemia between Day 7 and 28 and AT <37.5°C or having rescue therapy for malaria. PCR-adjusted ACPR was applied to recrudescence (appearance of asexual parasites after clearance of initial infection with a genotype identical to that of parasites present at Baseline), excluding participants with re-infection. Here, in the data table, "overall number of participants analyzed"=participants evaluable for this outcome measure.
Percentage of Participants With Polymerase Chain Reaction-adjusted Adequate Clinical and Parasitological Response at Day 42: African <=5 Years PP Population at Day 42 (PP42)
ACPR: negative parasitemia at Day 42, irrespective of AT, in participants not meeting any criteria of ETF: DS or SM at Day 1, 2 or 3 in presence of parasitemia; or Day 2 parasite count > Day 0 irrespective of AT; or parasitemia at Day 3 with AT >=37.5°C; or parasite count on Day 3 >=25% on Day 0, or LCF: DS/ SM in presence of parasitemia between Day 4 and 42; or presence of parasitemia and AT >=37.5°C between Day 4 and 42, or LPF: presence of parasitemia between Day 7 and 42 and AT <37.5°C or having rescue therapy for malaria. PCR-adjusted ACPR was applied to recrudescence (appearance of asexual parasites after clearance of initial infection with a genotype identical to that of parasites present at Baseline), excluding participants with re-infection. Here, in the data table, "overall number of participants analyzed"=participants evaluable for this outcome measure.
Percentage of Participants With Polymerase Chain Reaction-adjusted Adequate Clinical and Parasitological Response at Day 63: African <=5 Years PP Population at Day 63 (PP63)
ACPR: negative parasitemia at Day 63, irrespective of AT, in participants not meeting any criteria of ETF: DS or SM at Day 1, 2 or 3 in presence of parasitemia; or Day 2 parasite count > Day 0 irrespective of AT; or parasitemia at Day 3 with AT >=37.5°C; or parasite count on Day 3 >=25% on Day 0, or LCF: DS/ SM in presence of parasitemia between Day 4 and 63; or presence of parasitemia and AT >=37.5°C between Day 4 and 63, or LPF: presence of parasitemia between Day 7 and 63 and AT <37.5°C or having rescue therapy for malaria. PCR-adjusted ACPR was applied to recrudescence (appearance of asexual parasites after clearance of initial infection with a genotype identical to that of parasites present at Baseline), excluding participants with re-infection. Here, in the data table, "overall number of participants analyzed"=participants evaluable for this outcome measure.
Percentage of Participants With Crude Adequate Clinical and Parasitological Response at Day 28: African <=5 Years PP28 Population
ACPR was defined as negative parasitemia at Day 28, irrespective of AT, in participants not meeting any criteria of ETF: DS or SM at Day 1, 2 or 3 in presence of parasitemia; or Day 2 parasite count > Day 0 irrespective of AT; or parasitemia at Day 3 with AT >=37.5°C; or parasite count on Day 3 >=25% on Day 0, or LCF: DS/ SM in presence of parasitemia between Day 4 and 28; or presence of parasitemia and AT >=37.5°C between Day 4 and 28 or, LPF: presence of parasitemia between Day 7 and 28 and AT <37.5°C or having rescue therapy for malaria. PCR-adjusted ACPR applied to recrudescence (appearance of asexual parasites after clearance of initial infection with a genotype identical to that of parasites present at Baseline), excluding participants with re-infection, whereas crude ACPR does not distinguish re-infection (new clone of parasite) or recrudescence.
Percentage of Participants With Crude Adequate Clinical and Parasitological Response at Day 42: African <=5 Years PP42 Population
ACPR was defined as negative parasitemia at Day 42, irrespective of AT, in participants not meeting any criteria of ETF: DS or SM at Day 1, 2 or 3 in presence of parasitemia; or Day 2 parasite count > Day 0 irrespective of AT; or parasitemia at Day 3 with AT >=37.5°C; or parasite count on Day 3 >=25% on Day 0, or LCF: DS/ SM in presence of parasitemia between Day 4 and 42; or presence of parasitemia and AT >=37.5°C between Day 4 and 42 or, LPF: presence of parasitemia between Day 7 and 42 and AT <37.5°C or having rescue therapy for malaria PCR-adjusted ACPR applied to recrudescence (appearance of asexual parasites after clearance of initial infection with a genotype identical to that of parasites present at Baseline), excluding participants with re-infection, whereas crude ACPR did not distinguish re-infection (new clone of parasite) or recrudescence.
Percentage of Participants With Crude Adequate Clinical and Parasitological Response at Day 63: African <=5 Years PP63 Population
Crude ACPR was defined as negative parasitemia at Day 63, irrespective of AT, in participants not meeting any criteria of ETF: DS or SM at Day 1, 2 or 3 in presence of parasitemia; or Day 2 parasite count > Day 0 irrespective of AT; or parasitemia at Day 3 with AT >=37.5°C; or parasite count on Day 3 >=25% on Day 0, or LCF: DS/ SM in presence of parasitemia between Day 4 and 63; or presence of parasitemia and AT >=37.5°C between Day 4 and 63 or, LPF: presence of parasitemia between Day 7 and 63 and AT <37.5°C or having rescue therapy for malaria. PCR-adjusted ACPR applied to recrudescence (appearance of asexual parasites after clearance of initial infection with a genotype identical to that of parasites present at Baseline), excluding participants with re-infection, whereas crude ACPR did not distinguish re-infection (new clone of parasite) or recrudescence.
Time to Re-emergence
Time to re-emergence (in days) was defined as the time to appearance of asexual parasites after clearance of initial infection irrespective of genotype. Participants with no event were censored at the time of study completion, premature study discontinuation, including switch to established anti-malarial treatment or start of any other treatment with anti-malarial activity, whichever was earliest. Re-emergence was confirmed by microscopy (positive blood smear). Kaplan-Maier method was used for estimation. Here, "overall number of participants analyzed"=participants who were included in the analysis of below reported results which consisted of both, who had the event, plus those who were censored.
Time to Recrudescence
Time to recrudescence (in days) was defined as the time to appearance of asexual parasites after clearance of initial infection with a genotype identical to that of parasites present at Baseline. Recrudescence was confirmed by PCR analysis. Kaplan-Maier method was used for estimation.
Time to Re-infection
Time to re-infection (in days) was defined as the time to appearance of asexual parasites after clearance of initial infection with a genotype that differs from that of parasites present at Baseline. Re-infection was confirmed by PCR analysis. Kaplan-Maier method was used for estimation.
Parasite Clearance Time (PCT): African <=5 Years PP Population
PCT was defined as the time (in hours) from the start of study drug administration until the time of first negative blood film (no asexual parasites). This first negative film was confirmed by a second negative film which was taken >=6 to <=12 hours of the first film. Kaplan-Meier method was used for the estimation. Here, in the data table "overall number of participants analyzed"=participants who were included in the analysis of below reported results which consisted of both, who had the event, plus those who were censored.
Parasite Clearance Time: African >5 Years PP Population
PCT was defined as the time (in hours) from the start of study drug administration until the time of first negative blood film (no asexual parasites). This first negative film was confirmed by a second negative film which was taken >=6 to <=12 hours of the first film. Kaplan-Meier method was used for the estimation. Here, "overall number of participants analyzed"=participants who were included in the analysis of below reported results which consisted of both, who had the event, plus those who were censored.
Parasite Clearance Time: Asian PP Population
PCT was defined as the time (in hours) from the start of study drug administration until the time of first negative blood film (no asexual parasites). This first negative film was confirmed by a second negative film which was taken >=6 to <=12 hours of the first film. Kaplan-Meier method was used for the estimation. Here, "overall number of participants analyzed"=participants who were included in the analysis of below reported results which consisted of both, who had the event, plus those who were censored.
Fever Clearance Time (FCT): African <=5 Years PP Population
FCT was defined as the time (in hours) from start of study drug administration to the first assessment of adjusted body temperature <37.5°C, confirmed by second assessment, taken within >=6 to <=12 hours of the first assessment. Only participants with fever (adjusted body temperature >=37.5°C present at Baseline) and did not receive paracetamol on day of study drug administration until 96 hours after study drug administration were included in FCT analysis. Participants with no event were censored at the time of study completion, premature study discontinuation, including switch to established anti-malarial treatment or start of any other treatment with anti-malarial activity, whichever was earliest. Kaplan-Meier method was used for the estimation.
Fever Clearance Time: African >5 Years PP Population
FCT was defined as the time (in hours) from start of study drug administration to the first assessment of adjusted body temperature <37.5°C, confirmed by second assessment, taken within >=6 to <=12 hours of the first. Only participants with fever (adjusted body temperature >=37.5°C present at Baseline) and did not receive paracetamol on day of study drug administration until 96 hours after study drug administration were included in FCT analysis. Participants with no event were censored at the time of study completion, premature study discontinuation, including switch to established anti-malarial treatment or start of any other treatment with anti-malarial activity, whichever was earliest. Kaplan-Meier method was used for the estimation.
Fever Clearance Time: Asian PP Population
FCT was defined as the time (in hours) from start of study drug administration to the first assessment of adjusted body temperature <37.5°C, confirmed by second assessment, taken within >=6 to <=12 hours of the first. Only participants with fever (adjusted body temperature >=37.5°C present at Baseline) and did not receive paracetamol on day of study drug administration until 96 hours after study drug administration were included in FCT analysis. Participants with no event were censored at the time of study completion, premature study discontinuation, including switch to established anti-malarial treatment or start of any other treatment with anti-malarial activity, whichever was earliest. Kaplan-Meier method was used for the estimation. Here, "overall number of participants analyzed"=participants who were included in the analysis of below reported results which consisted of both, who had the event, plus those who were censored.
Parasite Reduction Ratio (PRRlog10) at 24 Hours and 48 Hours: African <=5 Years PP Population
The PRR was calculated as the slope of the linear portion of the regression fit of logarithm parasitemia (per milliliter) versus time (in hours). The PRR24 and PRR48 was the drop-in log units over 24 and 48 hours, respectively.
Parasite Reduction Ratio at 24 Hours and 48 Hours: African >5 Years PP Population
The PRR was calculated as the slope of the linear portion of the regression fit of logarithm parasitemia (per milliliter) versus time (in hours). The PRR24 and PRR48 was the drop-in log units over 24 and 48 hours, respectively.
Parasite Reduction Ratio at 24 Hours and 48 Hours: Asian PP Population
The PRR was calculated as the slope of the linear portion of the regression fit of logarithm parasitemia (per milliliter) versus time (in hours). The PRR24 and PRR48 was the drop-in log units over 24 and 48 hours, respectively.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Event of Special Interest (AESI)
An AE was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily had to have a causal relationship with the treatment. SAEs were any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. TEAEs were defined as AEs that developed or worsened or became serious during on-treatment phase that was defined as the time from the start of the first dose of double-blind drug administration up to the Day 63. AE of special interest (AESI) was an AE (serious or non-serious) of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring and immediate notification by the Investigator to the Sponsor was required.
Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) of Artefenomel
Cmax is the maximum observed plasma concentration of artefenomel.
Pharmacokinetics: Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Artefenomel
Area under the plasma concentration versus time curve from time zero to infinity.
Pharmacokinetics (PK): Apparent Total Clearance of Artefenomel From Plasma After Oral Administration
Clearance is defined as a quantitative measure of the rate at which a drug substance is removed from the body.
Pharmacokinetics: Apparent Volume of Distribution at Steady State After Non-intravenous Administration (Vss/F) of Artefenomel
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.
Pharmacokinetics: Maximum Observed Plasma Concentration of Ferroquine (Cmax)
Cmax is the maximum observed plasma concentration of Ferroquine.
Pharmacokinetics: Area Under the Curve From Time 0 to Day 28 (AUC0-day28) of Ferroquine
Area under the plasma concentration versus time curve from time 0 to Day 28 (i.e. 672 hours).
Pharmacokinetics: Apparent Total Clearance of Ferroquine From Plasma After Oral Administration
Clearance is defined as a quantitative measure of the rate at which a drug substance is removed from the body.
Pharmacokinetics: Apparent Volume of Distribution at Steady State After Non-intravenous Administration of Ferroquine
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.
Pharmacokinetics: Blood/Plasma Ratio for Ferroquine and Its Active Metabolite SSR97213
Full Information
NCT ID
NCT02497612
First Posted
July 8, 2015
Last Updated
March 15, 2022
Sponsor
Sanofi
Collaborators
Medicines for Malaria Venture
1. Study Identification
Unique Protocol Identification Number
NCT02497612
Brief Title
To Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetics of a Single Dose Regimen of Ferroquine and Artefenomel in Adults and Children With Uncomplicated Plasmodium Falciparum Malaria
Acronym
FALCI
Official Title
A Randomized, Double-blind, Phase IIb Study to Investigate the Efficacy, Safety, Tolerability and Pharmacokinetics of a Single Dose Regimen of Ferroquine (FQ) With Artefenomel (OZ439) in Adults and Children With Uncomplicated Plasmodium Falciparum Malaria
Study Type
Interventional
2. Study Status
Record Verification Date
March 2022
Overall Recruitment Status
Terminated
Why Stopped
All treatment arms met the futility criteria for efficacy during the pre-planned interim analysis, therefore the study was stopped.
Study Start Date
July 25, 2015 (Actual)
Primary Completion Date
September 23, 2019 (Actual)
Study Completion Date
September 23, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sanofi
Collaborators
Medicines for Malaria Venture
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Primary Objective:
To determine whether a single dose combination of OZ439 (Artefenomel)/FQ (Ferroquine) was an efficacious treatment for uncomplicated Plasmodium falciparum malaria in adults and children.
Secondary Objectives:
To evaluate the efficacy of OZ439/FQ:
To determine the incidence of recrudescence and re-infection.
To determine the time to relief of fever and parasite clearance.
To evaluate the safety and tolerability of OZ439/FQ in adults and children.
To characterize the pharmacokinetics of OZ439 in plasma, FQ and its active metabolite SSR97213 in blood.
To determine the blood/plasma ratio for FQ and SSR97213 in some participants at limited time points in selected sites.
Detailed Description
Total duration was 63 days for each participant.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Plasmodium Falciparum Infection
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
377 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Ferroquine (up to 400 mg) + Artefenomel (up to 800 mg)
Arm Type
Experimental
Arm Description
On Day 0, based on the body weight (BW), participants received orally a single dose of ferroquine (FQ) capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of artefenomel (OZ439) (maximum dose up to 800 milligrams [mg]) oral suspension as follows: BW greater than or equal to (>=) 35 kilograms (kg): FQ 400 mg + OZ439 800 mg; BW >=24 kg to less than (<) 35 kg: FQ 300 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 200 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 150 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 100 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 75 mg + OZ439 150 mg.
Arm Title
Ferroquine (up to 600 mg) + Artefenomel (up to 800 mg)
Arm Type
Experimental
Arm Description
On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 600 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 450 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 300 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 225 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 150 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 115 mg + OZ439 150 mg.
Arm Title
Ferroquine (up to 900 mg) + Artefenomel (up to 800 mg)
Arm Type
Experimental
Arm Description
On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 900 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 675 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 450 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 335 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 225 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 170 mg + OZ439 150 mg.
Arm Title
Ferroquine (up to 1200 mg) + Artefenomel (up to 800 mg)
Arm Type
Experimental
Arm Description
On Day 0, based on the BW, participants received orally a single dose of FQ capsules or oral suspension (along with matching placebo, as applicable to maintain blinding) and a single dose of OZ439 (maximum dose up to 800 mg) oral suspension as follows: BW >= 35 kg: FQ 1200 mg + OZ439 800 mg; BW >=24 kg to <35 kg: FQ 900 mg + OZ439 600 mg; BW >=15 kg to <24 kg: FQ 600 mg + OZ439 400 mg; BW >=10 kg to <15 kg: FQ 450 mg + OZ439 300 mg; BW >=7 kg to <10 kg: FQ 300 mg + OZ439 200 mg; >=5 kg to <7kg: FQ 225 mg + OZ439 150 mg.
Intervention Type
Drug
Intervention Name(s)
Ferroquine SSR97193
Intervention Description
Pharmaceutical form:Capsules Route of administration: oral
Intervention Type
Drug
Intervention Name(s)
Artefenomel
Intervention Description
Pharmaceutical form:Granules for suspension Route of administration: oral
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Capsules. Placebo capsules were used to keep the same number of capsules in each weight band while keeping the ferroquine dose blinded. No participant received placebo only.
Primary Outcome Measure Information:
Title
Percentage of Participants With Polymerase Chain Reaction (PCR)-Adjusted Adequate Clinical and Parasitological Response (ACPR) at Day 28: African <=5 Years Per Protocol Population at Day 28 (PP28)
Description
ACPR: negative parasitemia at Day 28, irrespective of axillary temperature(AT), in participants not meeting any criteria of early therapy failure (ETF):Danger signs (DS)/severe malaria (SM) at Day 1, 2 or 3 in presence of parasitemia; or Day 2 parasite count >Day 0 irrespective of AT; or parasitemia at Day 3 with AT >=37.5 degree Celsius (°C); or parasite count on Day 3>=25 percent (%) on Day 0, or late clinical failure(LCF):DS/ SM in presence of parasitemia between Day 4 and 28; or presence of parasitemia and AT>=37.5°C between Day 4 and 28, or late parasitological failure (LPF):presence of parasitemia between Day 7 and 28 and AT<37.5°C or having rescue therapy for malaria. PCR-adjusted ACPR applied to recrudescence (appearance of asexual parasites after clearance of initial infection with genotype identical to that present at Baseline), excluding participants with re-infection. In data table, "overall number of participants analyzed"=participants evaluable for this outcome measure.
Time Frame
Day 28
Secondary Outcome Measure Information:
Title
Percentage of Participants With Polymerase Chain Reaction-adjusted Adequate Clinical and Parasitological Response at Day 28: African >5 Years Per Protocol Population at Day 28 (A5PP28)
Description
ACPR: negative parasitemia at Day 28, irrespective of AT, in participants not meeting any criteria of ETF: DS or SM at Day 1, 2 or 3 in presence of parasitemia; or Day 2 parasite count > Day 0 irrespective of AT; or parasitemia at Day 3 with AT >=37.5°C; or parasite count on Day 3 >=25% on Day 0, or LCF: DS/ SM in presence of parasitemia between Day 4 and 28; or presence of parasitemia and AT >=37.5°C between Day 4 and 28, or LPF: presence of parasitemia between Day 7 and 28 and AT <37.5°C or having rescue therapy for malaria. PCR-adjusted ACPR was applied to recrudescence (appearance of asexual parasites after clearance of initial infection with a genotype identical to that of parasites present at Baseline), excluding participants with re-infection. Here, in the data table, "overall number of participants analyzed"=participants evaluable for this outcome measure.
Time Frame
Day 28
Title
Percentage of Participants With Polymerase Chain Reaction-adjusted Adequate Clinical and Parasitological Response at Day 28: Asian PP Population at Day 28 (APP28)
Description
ACPR: negative parasitemia at Day 28, irrespective of AT, in participants not meeting any criteria of ETF: DS or SM at Day 1, 2 or 3 in presence of parasitemia; or Day 2 parasite count > Day 0 irrespective of AT; or parasitemia at Day 3 with AT >=37.5°C; or parasite count on Day 3 >=25% on Day 0, or LCF: DS/ SM in presence of parasitemia between Day 4 and 28; or presence of parasitemia and AT >=37.5°C between Day 4 and 28, or LPF: presence of parasitemia between Day 7 and 28 and AT <37.5°C or having rescue therapy for malaria. PCR-adjusted ACPR was applied to recrudescence (appearance of asexual parasites after clearance of initial infection with a genotype identical to that of parasites present at Baseline), excluding participants with re-infection. Here, in the data table, "overall number of participants analyzed"=participants evaluable for this outcome measure.
Time Frame
Day 28
Title
Percentage of Participants With Polymerase Chain Reaction-adjusted Adequate Clinical and Parasitological Response at Day 42: African <=5 Years PP Population at Day 42 (PP42)
Description
ACPR: negative parasitemia at Day 42, irrespective of AT, in participants not meeting any criteria of ETF: DS or SM at Day 1, 2 or 3 in presence of parasitemia; or Day 2 parasite count > Day 0 irrespective of AT; or parasitemia at Day 3 with AT >=37.5°C; or parasite count on Day 3 >=25% on Day 0, or LCF: DS/ SM in presence of parasitemia between Day 4 and 42; or presence of parasitemia and AT >=37.5°C between Day 4 and 42, or LPF: presence of parasitemia between Day 7 and 42 and AT <37.5°C or having rescue therapy for malaria. PCR-adjusted ACPR was applied to recrudescence (appearance of asexual parasites after clearance of initial infection with a genotype identical to that of parasites present at Baseline), excluding participants with re-infection. Here, in the data table, "overall number of participants analyzed"=participants evaluable for this outcome measure.
Time Frame
Day 42
Title
Percentage of Participants With Polymerase Chain Reaction-adjusted Adequate Clinical and Parasitological Response at Day 63: African <=5 Years PP Population at Day 63 (PP63)
Description
ACPR: negative parasitemia at Day 63, irrespective of AT, in participants not meeting any criteria of ETF: DS or SM at Day 1, 2 or 3 in presence of parasitemia; or Day 2 parasite count > Day 0 irrespective of AT; or parasitemia at Day 3 with AT >=37.5°C; or parasite count on Day 3 >=25% on Day 0, or LCF: DS/ SM in presence of parasitemia between Day 4 and 63; or presence of parasitemia and AT >=37.5°C between Day 4 and 63, or LPF: presence of parasitemia between Day 7 and 63 and AT <37.5°C or having rescue therapy for malaria. PCR-adjusted ACPR was applied to recrudescence (appearance of asexual parasites after clearance of initial infection with a genotype identical to that of parasites present at Baseline), excluding participants with re-infection. Here, in the data table, "overall number of participants analyzed"=participants evaluable for this outcome measure.
Time Frame
Day 63
Title
Percentage of Participants With Crude Adequate Clinical and Parasitological Response at Day 28: African <=5 Years PP28 Population
Description
ACPR was defined as negative parasitemia at Day 28, irrespective of AT, in participants not meeting any criteria of ETF: DS or SM at Day 1, 2 or 3 in presence of parasitemia; or Day 2 parasite count > Day 0 irrespective of AT; or parasitemia at Day 3 with AT >=37.5°C; or parasite count on Day 3 >=25% on Day 0, or LCF: DS/ SM in presence of parasitemia between Day 4 and 28; or presence of parasitemia and AT >=37.5°C between Day 4 and 28 or, LPF: presence of parasitemia between Day 7 and 28 and AT <37.5°C or having rescue therapy for malaria. PCR-adjusted ACPR applied to recrudescence (appearance of asexual parasites after clearance of initial infection with a genotype identical to that of parasites present at Baseline), excluding participants with re-infection, whereas crude ACPR does not distinguish re-infection (new clone of parasite) or recrudescence.
Time Frame
Day 28
Title
Percentage of Participants With Crude Adequate Clinical and Parasitological Response at Day 42: African <=5 Years PP42 Population
Description
ACPR was defined as negative parasitemia at Day 42, irrespective of AT, in participants not meeting any criteria of ETF: DS or SM at Day 1, 2 or 3 in presence of parasitemia; or Day 2 parasite count > Day 0 irrespective of AT; or parasitemia at Day 3 with AT >=37.5°C; or parasite count on Day 3 >=25% on Day 0, or LCF: DS/ SM in presence of parasitemia between Day 4 and 42; or presence of parasitemia and AT >=37.5°C between Day 4 and 42 or, LPF: presence of parasitemia between Day 7 and 42 and AT <37.5°C or having rescue therapy for malaria PCR-adjusted ACPR applied to recrudescence (appearance of asexual parasites after clearance of initial infection with a genotype identical to that of parasites present at Baseline), excluding participants with re-infection, whereas crude ACPR did not distinguish re-infection (new clone of parasite) or recrudescence.
Time Frame
Day 42
Title
Percentage of Participants With Crude Adequate Clinical and Parasitological Response at Day 63: African <=5 Years PP63 Population
Description
Crude ACPR was defined as negative parasitemia at Day 63, irrespective of AT, in participants not meeting any criteria of ETF: DS or SM at Day 1, 2 or 3 in presence of parasitemia; or Day 2 parasite count > Day 0 irrespective of AT; or parasitemia at Day 3 with AT >=37.5°C; or parasite count on Day 3 >=25% on Day 0, or LCF: DS/ SM in presence of parasitemia between Day 4 and 63; or presence of parasitemia and AT >=37.5°C between Day 4 and 63 or, LPF: presence of parasitemia between Day 7 and 63 and AT <37.5°C or having rescue therapy for malaria. PCR-adjusted ACPR applied to recrudescence (appearance of asexual parasites after clearance of initial infection with a genotype identical to that of parasites present at Baseline), excluding participants with re-infection, whereas crude ACPR did not distinguish re-infection (new clone of parasite) or recrudescence.
Time Frame
Day 63
Title
Time to Re-emergence
Description
Time to re-emergence (in days) was defined as the time to appearance of asexual parasites after clearance of initial infection irrespective of genotype. Participants with no event were censored at the time of study completion, premature study discontinuation, including switch to established anti-malarial treatment or start of any other treatment with anti-malarial activity, whichever was earliest. Re-emergence was confirmed by microscopy (positive blood smear). Kaplan-Maier method was used for estimation. Here, "overall number of participants analyzed"=participants who were included in the analysis of below reported results which consisted of both, who had the event, plus those who were censored.
Time Frame
Up to Day 63
Title
Time to Recrudescence
Description
Time to recrudescence (in days) was defined as the time to appearance of asexual parasites after clearance of initial infection with a genotype identical to that of parasites present at Baseline. Recrudescence was confirmed by PCR analysis. Kaplan-Maier method was used for estimation.
Time Frame
Up to Day 63
Title
Time to Re-infection
Description
Time to re-infection (in days) was defined as the time to appearance of asexual parasites after clearance of initial infection with a genotype that differs from that of parasites present at Baseline. Re-infection was confirmed by PCR analysis. Kaplan-Maier method was used for estimation.
Time Frame
Up to Day 63
Title
Parasite Clearance Time (PCT): African <=5 Years PP Population
Description
PCT was defined as the time (in hours) from the start of study drug administration until the time of first negative blood film (no asexual parasites). This first negative film was confirmed by a second negative film which was taken >=6 to <=12 hours of the first film. Kaplan-Meier method was used for the estimation. Here, in the data table "overall number of participants analyzed"=participants who were included in the analysis of below reported results which consisted of both, who had the event, plus those who were censored.
Time Frame
From the start of study drug administration up to the time of the first negative film (up to Day 63)
Title
Parasite Clearance Time: African >5 Years PP Population
Description
PCT was defined as the time (in hours) from the start of study drug administration until the time of first negative blood film (no asexual parasites). This first negative film was confirmed by a second negative film which was taken >=6 to <=12 hours of the first film. Kaplan-Meier method was used for the estimation. Here, "overall number of participants analyzed"=participants who were included in the analysis of below reported results which consisted of both, who had the event, plus those who were censored.
Time Frame
From the start of study drug administration up to the time of the first negative film (up to Day 63)
Title
Parasite Clearance Time: Asian PP Population
Description
PCT was defined as the time (in hours) from the start of study drug administration until the time of first negative blood film (no asexual parasites). This first negative film was confirmed by a second negative film which was taken >=6 to <=12 hours of the first film. Kaplan-Meier method was used for the estimation. Here, "overall number of participants analyzed"=participants who were included in the analysis of below reported results which consisted of both, who had the event, plus those who were censored.
Time Frame
From the start of study drug administration up to the time of the first negative film (up to Day 63)
Title
Fever Clearance Time (FCT): African <=5 Years PP Population
Description
FCT was defined as the time (in hours) from start of study drug administration to the first assessment of adjusted body temperature <37.5°C, confirmed by second assessment, taken within >=6 to <=12 hours of the first assessment. Only participants with fever (adjusted body temperature >=37.5°C present at Baseline) and did not receive paracetamol on day of study drug administration until 96 hours after study drug administration were included in FCT analysis. Participants with no event were censored at the time of study completion, premature study discontinuation, including switch to established anti-malarial treatment or start of any other treatment with anti-malarial activity, whichever was earliest. Kaplan-Meier method was used for the estimation.
Time Frame
From the start of study drug administration up to the time of the first temperature measurement <37.5°C (up to Day 63)
Title
Fever Clearance Time: African >5 Years PP Population
Description
FCT was defined as the time (in hours) from start of study drug administration to the first assessment of adjusted body temperature <37.5°C, confirmed by second assessment, taken within >=6 to <=12 hours of the first. Only participants with fever (adjusted body temperature >=37.5°C present at Baseline) and did not receive paracetamol on day of study drug administration until 96 hours after study drug administration were included in FCT analysis. Participants with no event were censored at the time of study completion, premature study discontinuation, including switch to established anti-malarial treatment or start of any other treatment with anti-malarial activity, whichever was earliest. Kaplan-Meier method was used for the estimation.
Time Frame
From the start of study drug administration up to the time of the first temperature measurement <37.5°C (up to Day 63)
Title
Fever Clearance Time: Asian PP Population
Description
FCT was defined as the time (in hours) from start of study drug administration to the first assessment of adjusted body temperature <37.5°C, confirmed by second assessment, taken within >=6 to <=12 hours of the first. Only participants with fever (adjusted body temperature >=37.5°C present at Baseline) and did not receive paracetamol on day of study drug administration until 96 hours after study drug administration were included in FCT analysis. Participants with no event were censored at the time of study completion, premature study discontinuation, including switch to established anti-malarial treatment or start of any other treatment with anti-malarial activity, whichever was earliest. Kaplan-Meier method was used for the estimation. Here, "overall number of participants analyzed"=participants who were included in the analysis of below reported results which consisted of both, who had the event, plus those who were censored.
Time Frame
From the start of study drug administration up to the time of the first temperature measurement <37.5°C (up to Day 63)
Title
Parasite Reduction Ratio (PRRlog10) at 24 Hours and 48 Hours: African <=5 Years PP Population
Description
The PRR was calculated as the slope of the linear portion of the regression fit of logarithm parasitemia (per milliliter) versus time (in hours). The PRR24 and PRR48 was the drop-in log units over 24 and 48 hours, respectively.
Time Frame
24 and 48 hours post dose
Title
Parasite Reduction Ratio at 24 Hours and 48 Hours: African >5 Years PP Population
Description
The PRR was calculated as the slope of the linear portion of the regression fit of logarithm parasitemia (per milliliter) versus time (in hours). The PRR24 and PRR48 was the drop-in log units over 24 and 48 hours, respectively.
Time Frame
24 and 48 hours post dose
Title
Parasite Reduction Ratio at 24 Hours and 48 Hours: Asian PP Population
Description
The PRR was calculated as the slope of the linear portion of the regression fit of logarithm parasitemia (per milliliter) versus time (in hours). The PRR24 and PRR48 was the drop-in log units over 24 and 48 hours, respectively.
Time Frame
24 and 48 hours post dose
Title
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Event of Special Interest (AESI)
Description
An AE was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily had to have a causal relationship with the treatment. SAEs were any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. TEAEs were defined as AEs that developed or worsened or became serious during on-treatment phase that was defined as the time from the start of the first dose of double-blind drug administration up to the Day 63. AE of special interest (AESI) was an AE (serious or non-serious) of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring and immediate notification by the Investigator to the Sponsor was required.
Time Frame
From Baseline up to Day 63
Title
Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) of Artefenomel
Description
Cmax is the maximum observed plasma concentration of artefenomel.
Time Frame
2, 4, 6, 12, 24, 48, 72 and 672 hours post dose
Title
Pharmacokinetics: Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Artefenomel
Description
Area under the plasma concentration versus time curve from time zero to infinity.
Time Frame
2, 4, 6, 12, 24, 48, 72 and 672 hours post dose
Title
Pharmacokinetics (PK): Apparent Total Clearance of Artefenomel From Plasma After Oral Administration
Description
Clearance is defined as a quantitative measure of the rate at which a drug substance is removed from the body.
Time Frame
2, 4, 6, 12, 24, 48, 72 and 672 hours post dose
Title
Pharmacokinetics: Apparent Volume of Distribution at Steady State After Non-intravenous Administration (Vss/F) of Artefenomel
Description
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.
Time Frame
2, 4, 6, 12, 24, 48, 72 and 672 hours post dose
Title
Pharmacokinetics: Maximum Observed Plasma Concentration of Ferroquine (Cmax)
Description
Cmax is the maximum observed plasma concentration of Ferroquine.
Time Frame
2, 4, 6, 12, 24, 48, 72 and 672 hours post dose
Title
Pharmacokinetics: Area Under the Curve From Time 0 to Day 28 (AUC0-day28) of Ferroquine
Description
Area under the plasma concentration versus time curve from time 0 to Day 28 (i.e. 672 hours).
Time Frame
2, 4, 6, 8, 12, 24, 48, 168, 336 and 672 hours postdose
Title
Pharmacokinetics: Apparent Total Clearance of Ferroquine From Plasma After Oral Administration
Description
Clearance is defined as a quantitative measure of the rate at which a drug substance is removed from the body.
Time Frame
2, 4, 6, 12, 24, 48, 72 and 672 hours post dose
Title
Pharmacokinetics: Apparent Volume of Distribution at Steady State After Non-intravenous Administration of Ferroquine
Description
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.
Time Frame
2, 4, 6, 12, 24, 48, 72 and 672 hours post dose
Title
Pharmacokinetics: Blood/Plasma Ratio for Ferroquine and Its Active Metabolite SSR97213
Time Frame
2, 4, 6, 12, 24, 48, 72 and 672 hours post dose
10. Eligibility
Sex
All
Minimum Age & Unit of Time
6 Months
Maximum Age & Unit of Time
69 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria:
Male or female participant aged greater than (>) 6 months old and <70 years old:
Cohort 1 = 14 years < age <70 years and body weight greater than or equal to (>=) 35 kilogram (kg).
Cohort 2 = 5 years < age less than or equal to (<=) 14 years.
Cohort 3 = 2 years < age <=5 years.
Cohort 4 = 6 months < age <=2 years.
Body weight >=5 kg and <=90 kg.
Presence of mono-infection by Plasmodium falciparum with:
Fever, as defined by axillary temperature >=37.5 degrees Celsius (°C) or oral/rectal/tympanic temperature >=38°C, or history of fever in the previous 24 hours (history of fever must be documented) and,
Microscopically (blood smear) confirmed parasite infection, ranging from 1000 to 100 000 asexual parasites/microliter of blood.
Informed consent form signed by the participant or by the legally acceptable representative of the minor participant.
Exclusion criteria:
Presence of severe malaria.
Anti-malarial treatment:
With piperaquine-based compound, mefloquine, naphthoquine or sulphadoxine/pyrimethamine (SP) within the previous 6 weeks (after their inhibition of new infections had fallen below 50%).
With amodiaquine or chloroquine within the previous 4 weeks.
With quinine, halofantrine, lumefantrine-based compounds and any other anti-malarial treatment or antibiotics with antimalarial activity (including cotrimoxazole, tetracyclines, quinolones and fluoroquinolones, and azithromycin) within the past 14 days.
With any herbal products or traditional medicines, within the past 7 days.
Known history or evidence of clinically significant disorders.
Previous treatment within 5 times the half-life or within the last 14 days, whichever the longest which are: P-glycoprotein substrates, Cytochrome P450 (CYP) 2D6 main substrates and/or strong CYP2C or CYP3A inhibitors and/or moderate inhibitors but inhibiting both CYP2C and CYP3A and/or CYP inducers.
Mixed plasmodium infection.
Severe vomiting.
Severe malnutrition.
Laboratory parameters with clinically significant abnormalities and/or reaching critical values. For Liver Function Test. Aspartate aminotransferase (>2 [upper limit of normal] ULN), or alanine aminotransferase (>2 ULN) or total bilirubin >1.5 ULN.
Presence of Hepatitis A Immunoglobulin M, Hepatitis B surface antigen or Hepatitis C antibody.
Had received an investigational drug within the past 4 weeks.
Previous participation in any malaria vaccine study or received malaria vaccine in any other circumstance.
Measles and yellow fever vaccine injection within the last 15 days and or planned for the 28 days after randomization.
Female participant of child bearing potential not willing to use an effective contraceptive(s) method(s) for the duration of the study.
Positive serum or urine beta-human chorionic gonadotropin pregnancy test at study screening for female participants of childbearing potential.
Breastfeeding women.
Male participant having a partner of child bearing potential not willing to use an effective method of birth control during the study treatment period.
Splenectomized participants or presence of surgical scar on left hypochondrium. Participant unable to drink.
Known history of hypersensitivity, allergic or anaphylactoid reactions to ferroquine or other amino-quinolines or to OZ439 or OZ277 or to any of the excipients.
Family history of sudden death or of congenital prolongation of the Corrected QT (QTc) interval or known congenital prolongation of the QTc interval or any clinical condition known to prolong the QTc interval e.g., participants with a history of symptomatic cardiac arrhythmias or with clinically relevant bradycardia.
QTc using Fridericia's formula >450 millisecond at screening or pre-dose.
Hypokalemia (<3.5 millimoles per liter [mmol/L]), hypocalcemia (<2.0 mmol/L) or hypomagnesemia (<0.5 mmol/L) at screening or pre-dose.
Any treatment known to induce a lengthening of QT interval.
The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Sciences & Operations
Organizational Affiliation
Sanofi
Official's Role
Study Director
Facility Information:
Facility Name
Investigational Site Number 204001
City
Cotonou
Country
Benin
Facility Name
Investigational Site Number 854002
City
Comoé
Country
Burkina Faso
Facility Name
Investigational Site Number 854003
City
Niangoloko
Country
Burkina Faso
Facility Name
Investigational Site Number 854001
City
Ouagadougou
Country
Burkina Faso
Facility Name
Investigational Site Number 266002
City
Lambaréné
Country
Gabon
Facility Name
Investigational Site Number 266001
City
Libreville
Country
Gabon
Facility Name
Investigational Site Number 404003
City
Kisumu
Country
Kenya
Facility Name
Investigational Site Number 404002
City
Siaya
Country
Kenya
Facility Name
Investigational Site Number 508001
City
Chokwé
Country
Mozambique
Facility Name
Investigational Site Number 800002
City
Tororo
Country
Uganda
Facility Name
Investigational Site Number 704003
City
Binh Phuoc
Country
Vietnam
Facility Name
Investigational Site Number 704004
City
Gia Lai
Country
Vietnam
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
Citations:
PubMed Identifier
34011358
Citation
Adoke Y, Zoleko-Manego R, Ouoba S, Tiono AB, Kaguthi G, Bonzela JE, Duong TT, Nahum A, Bouyou-Akotet M, Ogutu B, Ouedraogo A, Macintyre F, Jessel A, Laurijssens B, Cherkaoui-Rbati MH, Cantalloube C, Marrast AC, Bejuit R, White D, Wells TNC, Wartha F, Leroy D, Kibuuka A, Mombo-Ngoma G, Ouattara D, Mugenya I, Phuc BQ, Bohissou F, Mawili-Mboumba DP, Olewe F, Soulama I, Tinto H; FALCI Study Group. A randomized, double-blind, phase 2b study to investigate the efficacy, safety, tolerability and pharmacokinetics of a single-dose regimen of ferroquine with artefenomel in adults and children with uncomplicated Plasmodium falciparum malaria. Malar J. 2021 May 19;20(1):222. doi: 10.1186/s12936-021-03749-4.
Results Reference
derived
Learn more about this trial
To Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetics of a Single Dose Regimen of Ferroquine and Artefenomel in Adults and Children With Uncomplicated Plasmodium Falciparum Malaria
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