Back to resultsInterLeukin-7 to Improve Clinical Outcomes in Lymphopenic pAtients With COVID-19 Infection (Brazil Cohort) (ILIAD-7-BRA)
Primary Purpose
COVID-19, Lymphocytopenia
Status
Terminated
Phase
Phase 2
Locations
Brazil
Study Type
Interventional
Intervention
Interleukin-7
PLACEBO
Sponsored by
About this trial
This is an interventional treatment trial for COVID-19
Eligibility Criteria
Inclusion Criteria:
- A written, signed informed consent, or emergency oral consent, by the patient or the patient's legally authorized representative, and the anticipated ability for participant to be re-consented in the future for ongoing Study participation
- Men and women aged ≥ 25 - 80 (included) years of age
- Hospitalized patients with two absolute lymphocyte count (ALC) ≤ 1000 cells/mm3, at two time points at least 24 hours apart, following HOSPITALIZATION:
- Hospitalized patients with moderate to severe hypoxemia requiring oxygen therapy at >4L per minute nasal cannula or greater to keep saturations >90%, non-invasive positive pressure ventilation (e.g., BIPAP), or patients intubated / ventilated for respiratory failure
- Confirmed infection with COVID-19 by any acceptable test available / utilized at each site
- Willingness and ability to practice contraception regardless of the gender of the patient during 5 months after last drug exposure
- Private insurance or government / institution financial support (through CMS or other)
Exclusion Criteria:
- Pregnancy or breast feeding
- ALT and/or AST > 5 x ULN
- Known, active auto-immune disease;
- Ongoing cancer treatment with chemotherapy / immunotherapy or any cancer therapy within last 3 months and/or ongoing
- Patients with past history of Solid Organ transplant
- Active tuberculosis, uncontrolled active HBV or HCV infection, HIV with positive viral load
- Hospitalized patients with refractory hypoxia, defined as inability to maintain saturation >85% with maximal available therapy for >6 hours
- Patients receiving any agent with immune suppressive effects, other than steroids at dosages less than 300 mg/day equivalent hydrocortisone and/or anti-IL-6R treatments like Tocilizumab or Sarilumab or anti-IL-1 treatment like Anakinra which should preferably be minimized
- Patients with baseline Rockwood Clinical Frailty Scale ≥ 6 at Hospital admission
- Patients showing an increase of the NEWS2 score by more than 6 points during the screening/ baseline period (48 to 72 hrs prior to first administration)
- Patients under guardianship
Sites / Locations
- Hospital de Clinicas de Porto Alegre
- Hospital Sao Jose
- Upeclin-Unesp
- Hospital Das Clinicas de Ribeirao Preto
- Universidade Federal de Sao Paolo
- Hospital Edmundo Vasconcelos
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
CYT107
PLACEBO
Arm Description
IM administration of CYT107 / Interleukin-7
IM administration of Saline at the same volume
Outcomes
Primary Outcome Measures
Change of the absolute lymphocyte count (ALC) of lymphopenic (ALC≤1000/mm3) COVID-19 infected participants out to approximately 30 days following initial Study drug administration or Hospital discharge (HD), whichever occurs first
A statistically significant increase of the absolute lymphocyte count (ALC) from randomization to day 30 or Hospital Discharge
Secondary Outcome Measures
To obtain "clinical improvement" as defined by an improvement in a 11-points WHO score for Clinical Assessment, through day 30 or HD.
to determine if CYT107 will improve the clinical status of hospitalized COVID-19 patients as measured by the 11 points WHO clinical score
a significant change of SARS-CoV-2 viral load through day 30 or HD
The decrease of SARS-CoV-2 viral load from measurements at baseline and days of treatment dose 4 and dose 5, Day 21 and Day 30 or HD (whichever occurs first)
frequency of secondary infections through day 45 compared to placebo arm
Incidence of secondary infections based on pre-specified criteria as adjudicated by the Secondary Infections Committee (SIC) through Day 45
length of hospitalization compared to placebo arm
Number of days of hospitalization during index hospitalization (defined as time from initial Study drug treatment through HD)
Length of stay in ICU compared to placebo arm
Number of days in ICU during index hospitalization
number of readmissions to ICU compared to placebo arm
Readmissions to ICU through Day 45
organ support free days compared to placebo arm
Organ support free days (OSFDs) during index hospitalization (This includes ventilator assistance free days)
Frequency of re-hospitalization through day 45 compared to placebo arm
Number of readmissions to the hospital through Day 45
All-cause mortality through day 45 compared to placebo arm
All-cause mortality through Day 45
CD4+ and CD8+ T cell counts compared to placebo arm
Absolute numbers of CD4+ and CD8+ T-cell counts at time points indicated on the Schedule of Activities (SoA)through Day 30 or HD
level of other known biomarkers of inflammation: Ferritin compared to placebo
Track and evaluate other known biomarkers of inflammation, Ferritin, from baseline to day 30
Level of other known biomarkers of inflammation: C reactive protein level (CRP) compared to placebo arm
Level of other known biomarkers of inflammation: CRP compared to placebo arm
Level of other known biomarkers of inflammation: D-dimer compared to placebo arm
Track and evaluate other known biomarkers of inflammation, D-dimer from baseline to day 30
Physiological status through National Early Warning Score (NEWS2) evaluation compared to Placebo arm
Evaluate chnage of the NEWS2 score value. Score form 0 to 4: NO Risk Score of 7 or more: High risk
Full Information
NCT ID
NCT04927169
First Posted
June 14, 2021
Last Updated
March 30, 2022
Sponsor
Revimmune
Collaborators
ReSolution Latin America S.A.
1. Study Identification
Unique Protocol Identification Number
NCT04927169
Brief Title
InterLeukin-7 to Improve Clinical Outcomes in Lymphopenic pAtients With COVID-19 Infection (Brazil Cohort)
Acronym
ILIAD-7-BRA
Official Title
Recombinant Human InterLeukin-7 (CYT107) to Improve Clinical Outcomes in Lymphopenic PAtients With COVID-19 Infection - "ILIAD 7 Trial" Brazil Cohort
Study Type
Interventional
2. Study Status
Record Verification Date
March 2022
Overall Recruitment Status
Terminated
Why Stopped
POOR ACCRUAL
Study Start Date
March 1, 2021 (Actual)
Primary Completion Date
December 31, 2021 (Actual)
Study Completion Date
March 30, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Revimmune
Collaborators
ReSolution Latin America S.A.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Comparison of the effects of CYT107 vs Placebo administered by intra-muscular route (IM) at 10μg/kg twice a week for three weeks on immune reconstitution of lymphopenic COVID-19 patients
Detailed Description
Approximately forty-eight (48) participants will be randomized 1:1 to receive
(a) Intramuscular (IM) administration of CYT107 at 10 μg/kg followed, after 72hrs of observation, by 10 μg/kg twice a week for 3 weeks (maximum 7administrations adjusted to patient's length of stay in the hospital) or (b)Intramuscular (IM) placebo (normal saline) at the same frequency. The aim of the study is to test the ability of CYT107 to produce an immune reconstitution of these patients and observe possible association with a clinical improvement.
This cohort excludes oncology patients on treatment
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID-19, Lymphocytopenia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
randomized controlled of treatment vs placebo
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Unblinded Pharmacist will prepare blinded syringes of colorless drug or placebo
Allocation
Randomized
Enrollment
4 (Actual)
8. Arms, Groups, and Interventions
Arm Title
CYT107
Arm Type
Experimental
Arm Description
IM administration of CYT107 / Interleukin-7
Arm Title
PLACEBO
Arm Type
Placebo Comparator
Arm Description
IM administration of Saline at the same volume
Intervention Type
Drug
Intervention Name(s)
Interleukin-7
Other Intervention Name(s)
CYT107
Intervention Description
IM administration at 10μg/kg twice a week for three weeks and up to 7 administrations according to Hospital length of stay
Intervention Type
Drug
Intervention Name(s)
PLACEBO
Other Intervention Name(s)
SALINE
Intervention Description
IM administration of a volume of saline identical to 10μg/kg CYT107, twice a week for three weeks and up to 7 administrations according to Hospital length of stay
Primary Outcome Measure Information:
Title
Change of the absolute lymphocyte count (ALC) of lymphopenic (ALC≤1000/mm3) COVID-19 infected participants out to approximately 30 days following initial Study drug administration or Hospital discharge (HD), whichever occurs first
Description
A statistically significant increase of the absolute lymphocyte count (ALC) from randomization to day 30 or Hospital Discharge
Time Frame
one month
Secondary Outcome Measure Information:
Title
To obtain "clinical improvement" as defined by an improvement in a 11-points WHO score for Clinical Assessment, through day 30 or HD.
Description
to determine if CYT107 will improve the clinical status of hospitalized COVID-19 patients as measured by the 11 points WHO clinical score
Time Frame
one month
Title
a significant change of SARS-CoV-2 viral load through day 30 or HD
Description
The decrease of SARS-CoV-2 viral load from measurements at baseline and days of treatment dose 4 and dose 5, Day 21 and Day 30 or HD (whichever occurs first)
Time Frame
one month
Title
frequency of secondary infections through day 45 compared to placebo arm
Description
Incidence of secondary infections based on pre-specified criteria as adjudicated by the Secondary Infections Committee (SIC) through Day 45
Time Frame
45 days
Title
length of hospitalization compared to placebo arm
Description
Number of days of hospitalization during index hospitalization (defined as time from initial Study drug treatment through HD)
Time Frame
45 days
Title
Length of stay in ICU compared to placebo arm
Description
Number of days in ICU during index hospitalization
Time Frame
45 days
Title
number of readmissions to ICU compared to placebo arm
Description
Readmissions to ICU through Day 45
Time Frame
45 days
Title
organ support free days compared to placebo arm
Description
Organ support free days (OSFDs) during index hospitalization (This includes ventilator assistance free days)
Time Frame
45 days
Title
Frequency of re-hospitalization through day 45 compared to placebo arm
Description
Number of readmissions to the hospital through Day 45
Time Frame
45 days
Title
All-cause mortality through day 45 compared to placebo arm
Description
All-cause mortality through Day 45
Time Frame
45 days
Title
CD4+ and CD8+ T cell counts compared to placebo arm
Description
Absolute numbers of CD4+ and CD8+ T-cell counts at time points indicated on the Schedule of Activities (SoA)through Day 30 or HD
Time Frame
30 days
Title
level of other known biomarkers of inflammation: Ferritin compared to placebo
Description
Track and evaluate other known biomarkers of inflammation, Ferritin, from baseline to day 30
Time Frame
30 days
Title
Level of other known biomarkers of inflammation: C reactive protein level (CRP) compared to placebo arm
Description
Level of other known biomarkers of inflammation: CRP compared to placebo arm
Time Frame
30 days
Title
Level of other known biomarkers of inflammation: D-dimer compared to placebo arm
Description
Track and evaluate other known biomarkers of inflammation, D-dimer from baseline to day 30
Time Frame
30 days
Title
Physiological status through National Early Warning Score (NEWS2) evaluation compared to Placebo arm
Description
Evaluate chnage of the NEWS2 score value. Score form 0 to 4: NO Risk Score of 7 or more: High risk
Time Frame
30 days
Other Pre-specified Outcome Measures:
Title
Safety assessment through incidence and scoring of grade 3-4 adverse events
Description
Incidence and scoring of all grade 3-4 adverse events through Day 45 (using CTCAE Version 5.0) to assess safety
Time Frame
45 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
25 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
A written, signed informed consent, or emergency oral consent, by the patient or the patient's legally authorized representative, and the anticipated ability for participant to be re-consented in the future for ongoing Study participation
Men and women aged ≥ 25 - 80 (included) years of age
Hospitalized patients with two absolute lymphocyte count (ALC) ≤ 1000 cells/mm3, at two time points at least 24 hours apart, following HOSPITALIZATION:
Hospitalized patients with moderate to severe hypoxemia requiring oxygen therapy at >4L per minute nasal cannula or greater to keep saturations >90%, non-invasive positive pressure ventilation (e.g., BIPAP), or patients intubated / ventilated for respiratory failure
Confirmed infection with COVID-19 by any acceptable test available / utilized at each site
Willingness and ability to practice contraception regardless of the gender of the patient during 5 months after last drug exposure
Private insurance or government / institution financial support (through CMS or other)
Exclusion Criteria:
Pregnancy or breast feeding
ALT and/or AST > 5 x ULN
Known, active auto-immune disease;
Ongoing cancer treatment with chemotherapy / immunotherapy or any cancer therapy within last 3 months and/or ongoing
Patients with past history of Solid Organ transplant
Active tuberculosis, uncontrolled active HBV or HCV infection, HIV with positive viral load
Hospitalized patients with refractory hypoxia, defined as inability to maintain saturation >85% with maximal available therapy for >6 hours
Patients receiving any agent with immune suppressive effects, other than steroids at dosages less than 300 mg/day equivalent hydrocortisone and/or anti-IL-6R treatments like Tocilizumab or Sarilumab or anti-IL-1 treatment like Anakinra which should preferably be minimized
Patients with baseline Rockwood Clinical Frailty Scale ≥ 6 at Hospital admission
Patients showing an increase of the NEWS2 score by more than 6 points during the screening/ baseline period (48 to 72 hrs prior to first administration)
Patients under guardianship
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Reinaldo SALOMAO, MD
Organizational Affiliation
Escola Paulista de Medicina Universidade Federal de São Paulo
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hospital de Clinicas de Porto Alegre
City
Porto Alegre
State/Province
RIO Grande DO SUL
ZIP/Postal Code
90035
Country
Brazil
Facility Name
Hospital Sao Jose
City
São José
State/Province
Santa Catarina
ZIP/Postal Code
88103
Country
Brazil
Facility Name
Upeclin-Unesp
City
Botucatu
State/Province
SAO Paolo
ZIP/Postal Code
18618
Country
Brazil
Facility Name
Hospital Das Clinicas de Ribeirao Preto
City
Monte Alegre
State/Province
SAO Paolo
ZIP/Postal Code
14051
Country
Brazil
Facility Name
Universidade Federal de Sao Paolo
City
São Paulo
State/Province
SAO Paolo
ZIP/Postal Code
04021
Country
Brazil
Facility Name
Hospital Edmundo Vasconcelos
City
Vila Clementino
State/Province
SAO Paolo
ZIP/Postal Code
04038
Country
Brazil
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
Publication
Citations:
PubMed Identifier
32171076
Citation
Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X, Guan L, Wei Y, Li H, Wu X, Xu J, Tu S, Zhang Y, Chen H, Cao B. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020 Mar 28;395(10229):1054-1062. doi: 10.1016/S0140-6736(20)30566-3. Epub 2020 Mar 11. Erratum In: Lancet. 2020 Mar 28;395(10229):1038. Lancet. 2020 Mar 28;395(10229):1038.
Results Reference
result
PubMed Identifier
32031570
Citation
Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, Wang B, Xiang H, Cheng Z, Xiong Y, Zhao Y, Li Y, Wang X, Peng Z. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA. 2020 Mar 17;323(11):1061-1069. doi: 10.1001/jama.2020.1585. Erratum In: JAMA. 2021 Mar 16;325(11):1113.
Results Reference
result
PubMed Identifier
29515037
Citation
Francois B, Jeannet R, Daix T, Walton AH, Shotwell MS, Unsinger J, Monneret G, Rimmele T, Blood T, Morre M, Gregoire A, Mayo GA, Blood J, Durum SK, Sherwood ER, Hotchkiss RS. Interleukin-7 restores lymphocytes in septic shock: the IRIS-7 randomized clinical trial. JCI Insight. 2018 Mar 8;3(5):e98960. doi: 10.1172/jci.insight.98960.
Results Reference
result
PubMed Identifier
18946659
Citation
Venet F, Chung CS, Kherouf H, Geeraert A, Malcus C, Poitevin F, Bohe J, Lepape A, Ayala A, Monneret G. Increased circulating regulatory T cells (CD4(+)CD25 (+)CD127 (-)) contribute to lymphocyte anergy in septic shock patients. Intensive Care Med. 2009 Apr;35(4):678-86. doi: 10.1007/s00134-008-1337-8. Epub 2008 Oct 23.
Results Reference
result
Learn more about this trial
InterLeukin-7 to Improve Clinical Outcomes in Lymphopenic pAtients With COVID-19 Infection (Brazil Cohort)
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