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L9LS MAb in Malian Adults

Primary Purpose

Plasmodium Falciparum Infection, Malaria

Status
Recruiting
Phase
Phase 2
Locations
Mali
Study Type
Interventional
Intervention
L9LS (VRC-MALMAB0114-00-AB)
Normal Saline
Sponsored by
National Institute of Allergy and Infectious Diseases (NIAID)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Plasmodium Falciparum Infection

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: Females aged ≥18 and ≤49 years and weighing ≥ 45.0 and ≤ 90.0 kg. Males aged ≥18 and ≤55 years and weighing ≥ 50.0 and ≤ 100.0 kg. Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process. In good general health and without clinically significant medical history. Able to provide informed consent. Willing to have blood samples and data stored for future research. Resides in or near Kalifabougou, Faladje, or Torodo, Mali, and available for the duration of the study. Females of childbearing potential must be willing to use reliable contraception from 21 days prior to study day 0 through the final study visit as described below. Reliable methods of birth control include 1 of the following: confirmed pharmacologic contraceptives via parenteral delivery or intrauterine or implantable device. Nonchildbearing women will be required to report date of last menstrual period, history of surgical sterility (i.e., tubal ligation, hysterectomy) or premature ovarian insufficiency, and will have urine or serum pregnancy tests performed per protocol. Exclusion Criteria: Pregnancy, as determined by a positive urine or serum beta-human choriogonadotropin (β hCG) test (if female). Currently breastfeeding. Behavioral, cognitive, or psychiatric disease that in the opinion of the investigator affects the ability of the subject to understand and comply with the study protocol. Study comprehension examination score of <80% correct or per investigator discretion. Hemoglobin, white blood cell, absolute neutrophil, or platelet count outside the local laboratory-defined limits of normal. (Subjects may be included at the investigator's discretion for "not clinically significant" values.) Alanine transaminase (ALT) or creatinine (Cr) level above the local laboratory-defined upper limit of normal. (Subjects may be included at the investigator's discretion for "not clinically significant" values.) Infected with human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV). Known or documented sickle cell disease by history. (Note: Known sickle cell trait is NOT exclusionary.) Clinically significant abnormal electrocardiogram (ECG; QTc >460 or other significant abnormal findings, including unexplained tachycardia or bradycardia). Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, endocrine, rheumatologic, autoimmune, hematological, oncologic, or renal disease by history, physical examination, and/or laboratory studies including urinalysis. Receipt of any investigational product within the past 30 days. Participation or planned participation in an interventional trial with an investigational product until the last required protocol visit. [Note: Past, current, or planned participation in observational studies is NOT exclusionary; participation in the placebo arm of the Mali adult CIS43LS MAb trial (ClinicalTrials.gov Identifier: NCT04329104) is NOT exclusionary.] Medical, occupational, or family problems as a result of alcohol or illicit drug use during the past 12 months. History of a severe allergic reaction or anaphylaxis. Severe asthma (defined as asthma that is unstable or required emergent care, urgent care, hospitalization, or intubation during the past 2 years, or that has required the use of oral or parenteral corticosteroids at any time during the past 2 years). Pre-existing autoimmune or antibody-mediated diseases including but not limited to: systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, Sjögren's syndrome, or autoimmune thrombocytopenia. Salivary gland disorder diagnosed by a doctor (e.g., parotitis, sialadenitis, sialolithiasis, salivary gland tumors). Known immunodeficiency syndrome. Known asplenia or functional asplenia. Use of chronic (≥14 days) oral or IV corticosteroids (excluding topical or nasal) at immunosuppressive doses (i.e., prednisone >10 mg/day) or immunosuppressive drugs within 30 days of day 0. Receipt of a live vaccine within the past 4 weeks or a killed vaccine within the past 2 weeks prior to study agent administration. Receipt of immunoglobulins and/or blood products within the past 6 months. Previous receipt of an investigational malaria vaccine or monoclonal antibody in the last 5 years. Known allergies or contraindication against artemether lumefantrine. Other condition(s) that, in the opinion of the investigator, would jeopardize the safety or rights of a subject participating in the trial, interfere with the evaluation of the study objectives, or render the subject unable to comply with the protocol.

Sites / Locations

  • Faladje MRTC Clinic
  • Kalifabougou MRTC ClinicRecruiting
  • Torodo MRTC Clinic

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Arm 1: 900 mg of L9LS SC

Arm 2: Placebo (normal saline) SC

Arm Description

Participants will receive 900 mg of L9LS SC.

Participants will receive placebo of Normal Saline for comparison.

Outcomes

Primary Outcome Measures

Incidence of local and systemic AEs occurring within 7 days after the administration of study agent.
Severity of local and systemic AEs occurring within 7 days after the administration of study agent.
Occurrence of Pf blood-stage infection
Detected by microscopic examination of thick blood smear for 24 weeks after administration of study agent.

Secondary Outcome Measures

Pf blood-stage infection as detected by RT-PCR for 24 weeks after administration of study agent.
Measurement of L9LS in sera of recipients.

Full Information

First Posted
March 31, 2023
Last Updated
May 31, 2023
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
National Institutes of Health (NIH), Vaccine Research Center (VRC), Malaria Research and Training Center (MRTC), Faculté de Médecine Pharmacie d'Odontostomatologie (FMOS/FAPH), University of Sciences, Techniques, & Technologies of Bamako (USTTB), University of Washington, Harvard T.H. Chan School of Public Health (HSPH), Indiana University School of Medicine, Indiana University
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1. Study Identification

Unique Protocol Identification Number
NCT05816330
Brief Title
L9LS MAb in Malian Adults
Official Title
Safety and Efficacy of L9LS, a Human Monoclonal Antibody Against Plasmodium Falciparum, in a Randomized, Double-Blind, Placebo-Controlled Trial of Adults in Mali
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 25, 2023 (Actual)
Primary Completion Date
March 2024 (Anticipated)
Study Completion Date
March 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
National Institutes of Health (NIH), Vaccine Research Center (VRC), Malaria Research and Training Center (MRTC), Faculté de Médecine Pharmacie d'Odontostomatologie (FMOS/FAPH), University of Sciences, Techniques, & Technologies of Bamako (USTTB), University of Washington, Harvard T.H. Chan School of Public Health (HSPH), Indiana University School of Medicine, Indiana University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to evaluate the safety and tolerability of a one time SC administration of L9LS in healthy adults in Mali, as well as its protective efficacy against naturally occurring Plasmodium falciparum (Pf) infection over a 6-month malaria season. A secondary objective is to determine if SC administration of L9LS at 900 mg (compared to placebo) mediates protection against naturally occurring Pf infection in healthy Malian adult females stratified by weight during a single malaria season.
Detailed Description
A phase 2 trial evaluating the safety and tolerability of a one time subcutaneous (SC) administration of L9LS, as well its protective efficacy against naturally occurring Pf infection over a 6-month malaria season. The primary study hypotheses is that L9LS will be safe and protective against malaria infection. As a secondary objective, the efficacy of L9LS within three body weight strata among female participants will each be compared to placebo. Before study agent administration, all subjects will be given artemether lumefantrine to clear any preexisting Pf blood stage infection. The study is a randomized, double-blind, placebo-controlled, sex-stratified (2:1 female to male ratio) and weight-stratified trial (N=288 total) with 2 treatment arms: L9LS 900 mg SC (n=216) and placebo (n=72) to assess safety and protective efficacy of L9LS compared to placebo. Subjects will receive the study agent and be followed at study visits 1, 3, 7, 14, 21, and 28 days later, and once every 2 weeks thereafter through 24 weeks. Primary study assessments include physical examination and blood collection for identification of Pf infection and other research laboratory evaluations.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Plasmodium Falciparum Infection, Malaria

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Sequential Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
288 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm 1: 900 mg of L9LS SC
Arm Type
Experimental
Arm Description
Participants will receive 900 mg of L9LS SC.
Arm Title
Arm 2: Placebo (normal saline) SC
Arm Type
Placebo Comparator
Arm Description
Participants will receive placebo of Normal Saline for comparison.
Intervention Type
Biological
Intervention Name(s)
L9LS (VRC-MALMAB0114-00-AB)
Intervention Description
Administered one time via subcutaneous route.
Intervention Type
Other
Intervention Name(s)
Normal Saline
Intervention Description
Administered one time via subcutaneous route.
Primary Outcome Measure Information:
Title
Incidence of local and systemic AEs occurring within 7 days after the administration of study agent.
Time Frame
Measured through Day 7
Title
Severity of local and systemic AEs occurring within 7 days after the administration of study agent.
Time Frame
Measured through Day 7
Title
Occurrence of Pf blood-stage infection
Description
Detected by microscopic examination of thick blood smear for 24 weeks after administration of study agent.
Time Frame
Measured through Week 24
Secondary Outcome Measure Information:
Title
Pf blood-stage infection as detected by RT-PCR for 24 weeks after administration of study agent.
Time Frame
Measured through week 24
Title
Measurement of L9LS in sera of recipients.
Time Frame
Measure through week 24

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Females aged ≥18 and ≤49 years and weighing ≥ 45.0 and ≤ 90.0 kg. Males aged ≥18 and ≤55 years and weighing ≥ 50.0 and ≤ 100.0 kg. Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process. In good general health and without clinically significant medical history. Able to provide informed consent. Willing to have blood samples and data stored for future research. Resides in or near Kalifabougou, Faladje, or Torodo, Mali, and available for the duration of the study. Females of childbearing potential must be willing to use reliable contraception from 21 days prior to study day 0 through the final study visit as described below. Reliable methods of birth control include 1 of the following: confirmed pharmacologic contraceptives via parenteral delivery or intrauterine or implantable device. Nonchildbearing women will be required to report date of last menstrual period, history of surgical sterility (i.e., tubal ligation, hysterectomy) or premature ovarian insufficiency, and will have urine or serum pregnancy tests performed per protocol. Exclusion Criteria: Pregnancy, as determined by a positive urine or serum beta-human choriogonadotropin (β hCG) test (if female). Currently breastfeeding. Behavioral, cognitive, or psychiatric disease that in the opinion of the investigator affects the ability of the subject to understand and comply with the study protocol. Study comprehension examination score of <80% correct or per investigator discretion. Hemoglobin, white blood cell, absolute neutrophil, or platelet count outside the local laboratory-defined limits of normal. (Subjects may be included at the investigator's discretion for "not clinically significant" values.) Alanine transaminase (ALT) or creatinine (Cr) level above the local laboratory-defined upper limit of normal. (Subjects may be included at the investigator's discretion for "not clinically significant" values.) Infected with human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV). Known or documented sickle cell disease by history. (Note: Known sickle cell trait is NOT exclusionary.) Clinically significant abnormal electrocardiogram (ECG; QTc >460 or other significant abnormal findings, including unexplained tachycardia or bradycardia). Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, endocrine, rheumatologic, autoimmune, hematological, oncologic, or renal disease by history, physical examination, and/or laboratory studies including urinalysis. Receipt of any investigational product within the past 30 days. Participation or planned participation in an interventional trial with an investigational product until the last required protocol visit. [Note: Past, current, or planned participation in observational studies is NOT exclusionary; participation in the placebo arm of the Mali adult CIS43LS MAb trial (ClinicalTrials.gov Identifier: NCT04329104) is NOT exclusionary.] Medical, occupational, or family problems as a result of alcohol or illicit drug use during the past 12 months. History of a severe allergic reaction or anaphylaxis. Severe asthma (defined as asthma that is unstable or required emergent care, urgent care, hospitalization, or intubation during the past 2 years, or that has required the use of oral or parenteral corticosteroids at any time during the past 2 years). Pre-existing autoimmune or antibody-mediated diseases including but not limited to: systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, Sjögren's syndrome, or autoimmune thrombocytopenia. Salivary gland disorder diagnosed by a doctor (e.g., parotitis, sialadenitis, sialolithiasis, salivary gland tumors). Known immunodeficiency syndrome. Known asplenia or functional asplenia. Use of chronic (≥14 days) oral or IV corticosteroids (excluding topical or nasal) at immunosuppressive doses (i.e., prednisone >10 mg/day) or immunosuppressive drugs within 30 days of day 0. Receipt of a live vaccine within the past 4 weeks or a killed vaccine within the past 2 weeks prior to study agent administration. Receipt of immunoglobulins and/or blood products within the past 6 months. Previous receipt of an investigational malaria vaccine or monoclonal antibody in the last 5 years. Known allergies or contraindication against artemether lumefantrine. Other condition(s) that, in the opinion of the investigator, would jeopardize the safety or rights of a subject participating in the trial, interfere with the evaluation of the study objectives, or render the subject unable to comply with the protocol.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Kassoum Kayentao, MD, MPH, PhD
Phone
+223 7646 0173
Email
kayentao@icermali.org
First Name & Middle Initial & Last Name or Official Title & Degree
Boubacar Traore, PharmD, PhD
Phone
+223 2022 8109
Email
bouba.traore@mrtcbko.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kassoum Kayentao, MD, MPH, PhD
Organizational Affiliation
Faculté de Médecine Pharmacie d'Odontostomatologie (FMPOS)
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Peter Crompton, MD, MPH
Organizational Affiliation
National Institutes of Health (NIH)
Official's Role
Principal Investigator
Facility Information:
Facility Name
Faladje MRTC Clinic
City
Faladje
State/Province
Région De Koulikoro
Country
Mali
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kassoum Kayentao, MD, MPH, PhD
Phone
+223 7646 0173
Email
kayentao@icermali.org
Facility Name
Kalifabougou MRTC Clinic
City
Kalifabougou
State/Province
Région De Koulikoro
Country
Mali
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kassoum Kayentao, MD, MPH, PhD
Phone
+223 7646 0173
Email
kayentao@icermali.org
Facility Name
Torodo MRTC Clinic
City
Torodo
State/Province
Région De Koulikoro
Country
Mali
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kassoum Kayentao, MD, MPH, PhD
Phone
+223 7646 0173
Email
kayentao@icermali.org

12. IPD Sharing Statement

Plan to Share IPD
No

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L9LS MAb in Malian Adults

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