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

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 Oncology 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 7 administrations 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 is dedicated to oncology patients

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

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. Patient receiving active or recent chemotherapy or immunotherapy (within 6 months) for cancer (and/or)
3. Patients who have received hematopoietic stem cell transplantation (for a diagnosis other than lymphoma) within the past 1 year (and/or)
4. Patients who received CAR-T cell therapy within the past 1 year (but not within last 30 days- see also exclusion criteria number 6 & 7) (and/or)
5. Patients receiving hormonal therapy for cancer (and/or)
6. Patients who have undergone surgery or radiotherapy for cancer within the past 6 months
7. Patients with newly diagnosed (biopsy proven) malignancy who have not yet received cancer treatment but get COVID pneumonia in the interim (Incl. Criteria 11)
8. Men and women aged ≥ 25 - 80 (included) years of age

9. Hospitalized patients with one absolute lymphocyte count (ALC) ≤ 1000 cells/mm3, collected at baseline or no more than 72h before baseline .

   From this time point the investigator may choose to further postpone the commencement of IL-7 (CYT107) treatment according to patient's clinical status.

10. 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
11. Confirmed infection with COVID-19 by any acceptable test available/utilized at each site
12. Willingness and ability to practice contraception regardless of the gender of the patient during 5 months after last drug exposure

Exclusion Criteria:

1. Pregnancy or breast feeding;
2. ALT and/or AST > 5 x ULN
3. Known, active auto-immune disease;
4. Patients with a history of lymphoid malignancy
5. Patients with any malignancy that is present at time of enrollment where treating physician expects life expectancy due to the underlying malignancy to be less than 6 months
6. Patients who received CAR-T cell therapy within the past 30 days or with unresolved cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS)
7. Patients with unresolved grade > 2 toxicities from prior chemotherapy, immunotherapy, or CAR-T cell therapy
8. Patients with past history of Solid Organ transplant.
9. Active tuberculosis, uncontrolled active HBV or HCV infection, HIV with positive viral load.
10. Hospitalized patients with refractory hypoxia, defined as inability to maintain saturation >85% with maximal available therapy for >6 hours
11. Patients with a mechanical ventilation support ≥ 7 days
12. Patients with chronic kidney dialysis
13. Patients with a SOFA score ≥ 9 at baseline
14. Patients with a BMI > 40
15. 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)
16. Patients with hospital admission Rockwood Clinical Frailty Scale ≥ 6. (assessed as patient or proxy 4-week recall of chronic health and frailty status prior to COVID infection)

11. Patients under guardianship

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• 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: Saline control; Intramuscular (IM) placebo (normal saline) at the same frequency	Drug: Placebo; Same number, volume and frequency of IM administration of saline; 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 HospitalDischarge	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
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)	1 month 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	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
length of stay in ICU compared to placebo arm	Number of days in ICU during index hospitalization	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
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 arm	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	Track and evaluate other known biomarkers of inflammation, CRP from baseline to day 30	30 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

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: M.D. Anderson Cancer Center; Memorial Sloan Kettering Cancer Center; Cancer Research Institute, New York City; Amarex Clinical Research
• Investigators: Principal Investigator: Marcel van den Brink, MD, PhD, Memorial Sloan Kettering Cancer Center; Principal Investigator: Steve Pastores, MD, Memorial Sloan Kettering Cancer Center

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): December 20, 2020
• Primary Completion (Actual): June 30, 2022
• Study Completion (Actual): June 30, 2022

Study Registration Dates

• First Submitted: June 9, 2020
• First Submitted That Met QC Criteria: June 9, 2020
• First Posted (Actual): June 11, 2020

Study Record Updates

• Last Update Posted (Actual): April 11, 2024
• Last Update Submitted That Met QC Criteria: April 10, 2024
• Last Verified: April 1, 2024

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; Cytopenia; COVID-19; Lymphopenia
• Other Study ID Numbers: ILIAD-7 COVID US ONCO

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