InterLeukin-7 to Improve Clinical Outcomes in Lymphopenic pAtients With COVID-19 Infection ( ILIAD-7-US-I ) (ILIAD-7-US-I)

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. US Infectious Cohort

Comparison of the effects of CYT107 vs Placebo administered IM at 10μg/kg twice a week for three weeks on immune reconstitution of lymphopenic COVID-19 patients

Study Overview

• Status: Terminated
• Conditions: COVID-19; Lymphocytopenia
• Intervention / Treatment: Drug: CYT107; Drug: Placebo

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

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32608
      • University of Florida College of Medicine
  • Missouri
    • Saint Louis, Missouri, United States, 63131
      • Missouri Baptist Medical Center
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Rutgers Health
  • New York
    • Stony Brook, New York, United States, 11794
      • Stony Brook Medicine
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Lerner College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 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
2. Men and women aged ≥ 25 - 80 (included) years of age
3. Hospitalized patients with two absolute lymphocyte count (ALC) ≤ 1000 cells/mm3, at two time points at least 24 hours apart, following HOSPITALIZATION:
4. 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
5. Confirmed infection with COVID-19 by any acceptable test available / utilized at each site
6. Willingness and ability to practice contraception regardless of the gender of the patient during 5 month after last drug exposure
7. Private insurance or government / institution financial support (through CMS or other)

Exclusion Criteria:

1. Pregnancy or breast feeding
2. ALT and/or AST > 5 x ULN
3. Known, active auto-immune disease;
4. Ongoing cancer treatment with chemotherapy / immunotherapy or any cancer therapy within last 3 months and/or ongoing
5. Patients with past history of Solid Organ transplant
6. Active tuberculosis, uncontrolled active HBV or HCV infection, HIV with positive viral load
7. Hospitalized patients with refractory hypoxia, defined as inability to maintain saturation >85% with maximal available therapy for >6 hours
8. 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
9. Patients with baseline Rockwood Clinical Frailty Scale ≥ 6 at Hospital admission
10. 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)
11. Patients under guardianship

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: CYT107 Treatment; Intramuscular (IM) administration of CYT107 twice a week for 3 weeks	Drug: CYT107; IM administration at 10μg/kg twice a week for three weeks and up to 7 administrations according to Hospital length of stay; Other Names: Interleukin-7
PLACEBO_COMPARATOR: Placebo; Intramuscular (IM) administration of Saline twice a week for 3 weeks	Drug: Placebo; IM administration at 10μg/kg twice a week for three weeks and up to 7 administrations according to Hospital length of stay; Other Names: Saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	one month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	one month
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	45 days
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)	45 days
number of readmissions to ICU compared to placebo arm	Readmissions to ICU through Day 45	45 days
organ support free days compared to placebo arm	Organ support free days (OSFDs) during index hospitalization (This includes ventilator assistance free days)	45 days
Frequency of re-hospitalization through day 45 compared to placebo arm	Number of readmissions to the hospital through Day 45	45 days
All-cause mortality through day 45 compared to placebo arm	All-cause mortality through Day 45	45 days
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	30 days
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	30 days
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)	one month
Length of stay in ICU compared to placebo arm	Number of days in ICU during index hospitalization	45 days
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	30 days
level of other known biomarkers of inflammation: Ferritin compared to placebo a	Track and evaluate other known biomarkers of inflammation, Ferritin, from baseline to day 30	30 days
Level of other known biomarkers of inflammation: CRP compared to placebo arm	Level of other known biomarkers of inflammation: CRP compared to placebo arm	30 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety assessment through incidence and scoring of grade 3-4 adverse events	Incidence and scoring of all grade 3-4 adverse events through Day 45 (using CTCAE Version 5.0) to assess safety	45 days

Collaborators and Investigators

• Sponsor: Revimmune
• Collaborators: Washington University School of Medicine; Amarex Clinical Research
• Investigators: Principal Investigator: Richard Hotchkiss, MD PhD, Washington University School of Medicine

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 15, 2020
• Primary Completion (ACTUAL): March 30, 2022
• Study Completion (ACTUAL): March 30, 2022

Study Registration Dates

• First Submitted: June 19, 2020
• First Submitted That Met QC Criteria: June 19, 2020
• First Posted (ACTUAL): June 22, 2020

Study Record Updates

• Last Update Posted (ACTUAL): April 8, 2022
• Last Update Submitted That Met QC Criteria: March 30, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Hematologic Diseases; Leukopenia; Leukocyte Disorders; COVID-19; Lymphopenia
• Other Study ID Numbers: ILIAD-7 COVID US INFECTIOUS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Publication

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No