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

COVID-19 Clinical Trial

— ILIAD-7-US-I  

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. US Infectious Cohort

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04442178
• Other study ID #: ILIAD-7 COVID US INFECTIOUS
• Status: Terminated
• Phase: Phase 2
• Start date: September 15, 2020
• Est. completion date: March 30, 2022

Study information

• Verified date: March 2022
• Source: Revimmune
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 26
• Est. completion date: March 30, 2022
• Est. primary completion date: March 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 25 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• COVID-19
• Lymphocytopenia
• Lymphopenia

Intervention

Drug:
• CYT107
IM administration at 10µg/kg twice a week for three weeks and up to 7 administrations according to Hospital length of stay
• Placebo
IM administration at 10µg/kg twice a week for three weeks and up to 7 administrations according to Hospital length of stay

Locations

Country	Name	City	State
United States	Cleveland Clinic Lerner College of Medicine	Cleveland	Ohio
United States	University of Florida College of Medicine	Gainesville	Florida
United States	Rutgers Health	New Brunswick	New Jersey
United States	Missouri Baptist Medical Center	Saint Louis	Missouri
United States	Stony Brook Medicine	Stony Brook	New York

Sponsors (3)

Lead Sponsor	Collaborator
Revimmune	Amarex Clinical Research, Washington University School of Medicine

Country where clinical trial is conducted

United States, 

References & Publications (4)

Francois B, Jeannet R, Daix T, Walton AH, Shotwell MS, Unsinger J, Monneret G, Rimmelé 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 clinic — View Citation

Venet F, Foray AP, Villars-Méchin 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. — View 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):106 — View 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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Length of stay in ICU compared to placebo arm	Number of days in ICU during index hospitalization	45 days
Secondary	number of readmissions to ICU compared to placebo arm	Readmissions to ICU through Day 45	45 days
Secondary	organ support free days compared to placebo arm	Organ support free days (OSFDs) during index hospitalization (This includes ventilator assistance free days)	45 days
Secondary	Frequency of re-hospitalization through day 45 compared to placebo arm	Number of readmissions to the hospital through Day 45	45 days
Secondary	All-cause mortality through day 45 compared to placebo arm	All-cause mortality through Day 45	45 days
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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