search
Back to results

InterLeukin-7 to Improve Clinical Outcomes in Lymphopenic pAtients With COVID-19 Infection FR BL Cohort (ILIAD-7-FR)

Primary Purpose

COVID-19, Lymphocytopenia

Status
Terminated
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
Interleukin-7
Placebo
Sponsored by
Revimmune
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for COVID-19

Eligibility Criteria

25 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 one absolute lymphocyte count (ALC) ≤ 1000 cells/mm3, collected at baseline or no more than 72h before baseline
  • 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) for respiratory failure
  • Confirmed infection with COVID-19 by any acceptable test available/ utilized at each site
  • Patient with medical insurance or government support

Exclusion Criteria:

  • Pregnancy or breast feeding;
  • Refusal or inability to practice contraception regardless of the gender of the patient;
  • 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.

  • Patients whose respiratory condition is showing significant deterioration as indicated by:

    • 8a requirement for an increase in inspired oxygen concentrations of 20% or more over the past 24 hours to maintain SpO2 at greater than or equal to 88%
    • 8b or need for invasive mechanical ventilation
  • 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 with chronic kidney dialysis
  • Patients with a SOFA score ≥ 9 at baseline
  • Patients with a BMI > 40
  • Patients receiving any agent with immune suppressive effects,such as anti-IL6 treatments like Tocilizumab or Sarilumab which should preferably be minimized
  • Presence of any of the following abnormal laboratory values at screening: absolute neutrophil count (ANC) < 1.5x109/L, Platelets < 50,000 per mm3
  • Patients with uncontrolled pre-existing severe major organ dysfunction (cardiac, liver or renal failure)
  • Vaccination with live attenuated vaccines in the month preceding the inclusion
  • Use of chronic oral corticosteroids ≥ 10mg prednisone equivalent a day for a non-COVID-19 related condition
  • Patients with baseline Rockwood Clinical Frailty Scale ≥ 6.
  • Patients with known hypersensitivity to natural or recombinant Interleukin-7 or to any of the excipients
  • Patients under guardianship

Sites / Locations

  • University Hospital of Limoges
  • Hôpital Edouard Herriot
  • hopital Edouard Herriot
  • Chr Orleans La Source
  • hopital COCHIN
  • Chru Tours

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

CYT107

Saline

Arm Description

Intra-muscular administration of CYT107 twice a week for a total of 5 administrations

Intramuscular (IM) administration of saline at the same volume and same time for a total of 5 administrations

Outcomes

Primary Outcome Measures

Improvement 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 11 steps WHO clinical improvement score
a significant decline 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 tp 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 timepoints indicated on the Schedule of Activities (SoA) through Day 30 or HD
level of other known biomarkers of inflammation: Ferritin compared to placebo arm
Track and evaluate other known biomarkers of inflammation, Ferritin, from baseline to day 30
Level of other known biomarkers of inflammation: CRP compared to placebo arm
Track and evaluate other known biomarkers of inflammation, CRP from baseline to day 30
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 NEWS2 evaluation compared to Placebo arm
Evaluate improvement of the NEWS2 score value. Score form 0 to 4: NO Risk Score of 7 or more: High risk

Full Information

First Posted
May 27, 2020
Last Updated
March 30, 2022
Sponsor
Revimmune
Collaborators
University Hospital, Limoges, Amarex Clinical Research
search

1. Study Identification

Unique Protocol Identification Number
NCT04407689
Brief Title
InterLeukin-7 to Improve Clinical Outcomes in Lymphopenic pAtients With COVID-19 Infection FR BL Cohort
Acronym
ILIAD-7-FR
Official Title
A Multicenter, Randomized, Double-blinded Placebo-controlled Study of Recombinant Interleukin-7 (CYT107) for Immune Restoration of Hospitalized Lymphopenic Patients With Coronavirus COVID-19 Infection in France and Belgium
Study Type
Interventional

2. Study Status

Record Verification Date
March 2022
Overall Recruitment Status
Terminated
Why Stopped
poor accrual
Study Start Date
June 8, 2020 (Actual)
Primary Completion Date
March 30, 2022 (Actual)
Study Completion Date
March 30, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Revimmune
Collaborators
University Hospital, Limoges, Amarex Clinical Research

4. Oversight

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

5. Study Description

Brief Summary
Comparison of the effects of CYT107 vs Placebo administered IM at 10μg/ kg twice a week for two 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 3 μg/kg followed, after 48hrs of observation, by 10 μg/kg twice a week for 2 weeks or (b) Intramuscular (IM) placebo (normal saline) at the same frequency. An interim safety review took place after the first 12 patients. Since the CYT107 was well tolerated, the test dose (3 μg/kg) ceased and the initial dose became the same as the rest of the doses (10 μg/kg). So, the remaining patients will be randomized to receive 5 administrations of (a) CYT107 at 10 μg/kg every 3 to 4 days for 2 weeks 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

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
Double blind
Allocation
Randomized
Enrollment
34 (Actual)

8. Arms, Groups, and Interventions

Arm Title
CYT107
Arm Type
Experimental
Arm Description
Intra-muscular administration of CYT107 twice a week for a total of 5 administrations
Arm Title
Saline
Arm Type
Placebo Comparator
Arm Description
Intramuscular (IM) administration of saline at the same volume and same time for a total of 5 administrations
Intervention Type
Drug
Intervention Name(s)
Interleukin-7
Other Intervention Name(s)
CYT107
Intervention Description
Intramuscular (IM) administration of CYT107 at 3 μg/ kg followed, after 48hrs of observation, by 10 μg/kg twice a week for 2 weeks or
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Saline
Intervention Description
Intramuscular (IM) placebo (normal saline) at the same frequency
Primary Outcome Measure Information:
Title
Improvement 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
1 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 11 steps WHO clinical improvement score
Time Frame
1 month
Title
a significant decline 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
1 month or HD (whichever occurs first)
Title
frequency of secondary infections through day 45 compared tp 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 timepoints 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 arm
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: CRP compared to placebo arm
Description
Track and evaluate other known biomarkers of inflammation, CRP from baseline to day 30
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 NEWS2 evaluation compared to Placebo arm
Description
Evaluate improvement 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 severity)
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 one absolute lymphocyte count (ALC) ≤ 1000 cells/mm3, collected at baseline or no more than 72h before baseline 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) for respiratory failure Confirmed infection with COVID-19 by any acceptable test available/ utilized at each site Patient with medical insurance or government support Exclusion Criteria: Pregnancy or breast feeding; Refusal or inability to practice contraception regardless of the gender of the patient; 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. Patients whose respiratory condition is showing significant deterioration as indicated by: 8a requirement for an increase in inspired oxygen concentrations of 20% or more over the past 24 hours to maintain SpO2 at greater than or equal to 88% 8b or need for invasive mechanical ventilation 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 with chronic kidney dialysis Patients with a SOFA score ≥ 9 at baseline Patients with a BMI > 40 Patients receiving any agent with immune suppressive effects,such as anti-IL6 treatments like Tocilizumab or Sarilumab which should preferably be minimized Presence of any of the following abnormal laboratory values at screening: absolute neutrophil count (ANC) < 1.5x109/L, Platelets < 50,000 per mm3 Patients with uncontrolled pre-existing severe major organ dysfunction (cardiac, liver or renal failure) Vaccination with live attenuated vaccines in the month preceding the inclusion Use of chronic oral corticosteroids ≥ 10mg prednisone equivalent a day for a non-COVID-19 related condition Patients with baseline Rockwood Clinical Frailty Scale ≥ 6. Patients with known hypersensitivity to natural or recombinant Interleukin-7 or to any of the excipients Patients under guardianship
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bruno François, MD
Organizational Affiliation
University Hospital, Limoges
Official's Role
Study Chair
Facility Information:
Facility Name
University Hospital of Limoges
City
Limoges
ZIP/Postal Code
87042
Country
France
Facility Name
Hôpital Edouard Herriot
City
Lyon
ZIP/Postal Code
69003
Country
France
Facility Name
hopital Edouard Herriot
City
Lyon
ZIP/Postal Code
69437
Country
France
Facility Name
Chr Orleans La Source
City
Orléans
ZIP/Postal Code
45067
Country
France
Facility Name
hopital COCHIN
City
Paris
ZIP/Postal Code
75014
Country
France
Facility Name
Chru Tours
City
Tours
ZIP/Postal Code
37000
Country
France

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
publication
Citations:
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
background
PubMed Identifier
23053510
Citation
Venet F, Foray AP, Villars-Mechin A, Malcus C, Poitevin-Later F, Lepape A, Monneret G. IL-7 restores lymphocyte functions in septic patients. J Immunol. 2012 Nov 15;189(10):5073-81. doi: 10.4049/jimmunol.1202062. Epub 2012 Oct 10.
Results Reference
background
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

Learn more about this trial

InterLeukin-7 to Improve Clinical Outcomes in Lymphopenic pAtients With COVID-19 Infection FR BL Cohort

We'll reach out to this number within 24 hrs