InterLeukin-7 (CYT107) to Improve Clinical Outcomes in Lymphopenic pAtients With COVID-19 Infection UK Cohort

COVID-19 Clinical Trial

— ILIAD-7-UK  

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 UK

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04379076
• Other study ID #: CLI107 COVID UK (ILIAD-7-UK)
• Status: Terminated
• Phase: Phase 2
• Start date: May 14, 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 two 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 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 will take place after the first 12 patients. If the CYT107 is well tolerated, the test dose (3 μg/kg) will cease and that initial dose will become 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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 35
• Est. completion date: March 30, 2022
• Est. primary completion date: February 28, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 25 Years to 80 Years

Eligibility

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 >2L 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
• Private insurance or government support (through NHS or other)

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:

• requirement for a persistent and sustained increase in inspired oxygen concentrations of 20% or more over the past 24 hours to maintain SpO2 at greater than or equal to 88% (this 20 % limit does not apply to O2 delivered by nasal canula)
• or need for invasive mechanical ventilation
• Patients with chronic kidney dialysis
• 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 a SOFA score = 9 at baseline
• Patients with a BMI > 40
• Patients with baseline Rockwood Clinical Frailty Scale = 6.(assessed as patient or proxy 4-week recall of chronic health and frailty status prior to COVID infection)
• Patients under guardianship

Related Conditions & MeSH terms

• COVID-19
• Lymphocytopenia
• Lymphopenia

Intervention

Drug:
• Interleukin-7
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
• Placebos
Intramuscular (IM) placebo (normal saline) at the same frequency

Locations

Country	Name	City	State
United Kingdom	Sandwell Birmingham Hospital	Birmingham
United Kingdom	Sandwell Birmingham Hospital	Birmingham
United Kingdom	Bradford Institute for Health Research	Bradford
United Kingdom	ST JAMES's UNIVERSITY HOSPITAL	Leeds
United Kingdom	Guy's and St Thomas' NHS Foundation Trust	London
United Kingdom	King'S College Hospital	London
United Kingdom	Medway Maritime Hospital	London
United Kingdom	North Manchester General Hospital	Manchester
United Kingdom	Wythenshawe Hospital/ Manchester Royal Infirmary	Manchester
United Kingdom	Royal Victoria Infirmary and Freeman Hospital	Newcastle
United Kingdom	Royal Preston Hospital	Preston
United Kingdom	Sunderland Royal Hospital	Sunderland
United Kingdom	Watford General Hospital	Watford

Sponsors (2)

Lead Sponsor	Collaborator
Revimmune	Amarex Clinical Research

Country where clinical trial is conducted

United Kingdom, 

References & Publications (6)

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 clinical trial. JCI Insight. 2018 Mar 8;3(5). pii: 98960. doi: 10.1172/jci.insight.98960. — View Citation

Hotchkiss RS, Monneret G, Payen D. Immunosuppression in sepsis: a novel understanding of the disorder and a new therapeutic approach. Lancet Infect Dis. 2013 Mar;13(3):260-8. doi: 10.1016/S1473-3099(13)70001-X. Review. — View Citation

Manzanilla-Sevilla R, González-Iñiguez R, Casanova-Alvarez N, Martínez-Alcalá F. Tubal sterilization and ovarian perfusion: selective arteriography in vivo and in vitro. Int J Gynaecol Obstet. 1978-1979;16(2):137-43. — 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):1061-1069. doi: 10.1001/jama.2020.1585. Erratum in: JAMA. 2021 Mar 16;325(11):1113. — 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 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Safety assessment	Incidence and scoring of all grade 3-4 adverse events through Day 45 (using CTCAE Version 5.0 to assess severity)	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), whicheve	A statistically significant increase of the absolute lymphocyte count (ALC) from randomization to day 30 or Hospital Discharge	1 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 WHO score	1 month
Secondary	determine if CYT107 will lead to 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	To compare the effect of CYT107 versus placebo on the frequency of secondary infections through day 45	Incidence of secondary infections based on pre-specified criteria as adjudicated by the Secondary Infections Committee (SIC) through Day 45	45 days
Secondary	To compare the effect of CYT107 versus placebo on the length of hospitalization	Number of days of hospitalization during index hospitalization (defined as time from initial Study drug treatment through HD)	45 days
Secondary	To compare the effect of CYT107 versus placebo on the length of stay in ICU	Number of days in ICU during index hospitalization	45 days
Secondary	To compare the effect of CYT107 versus placebo on readmissions to ICU	Readmissions to ICU through Day 45	45 days
Secondary	To compare the effect of CYT107 versus placebo on organ support free days	Organ support free days (OSFDs) during index hospitalization (This includes ventilator assistance free days.)	45 days
Secondary	To compare the effect of CYT107 versus placebo on the frequency of re-hospitalization through day 45	Number of readmissions to the hospital through Day 45	45 days
Secondary	To assess the impact of CYT107 on all-cause mortality through day 45	All-cause mortality through Day 45	45 days
Secondary	To determine the effect of CYT107 on CD4+ and CD8+ T cell counts	Absolute numbers of CD4+ and CD8+ T-cell counts at timepoints indicated on the Schedule of Activities (SoA) through Day 30 or HD	30 days
Secondary	To track and evaluate other known biomarkers of inflammation: Ferritin	Track and evaluate other known biomarkers of inflammation, Ferritin, from baseline to day 30	30 days
Secondary	To track and evaluate other known biomarkers of inflammation: CRP	Track and evaluate other known biomarkers of inflammation, CRP from baseline to day 30	30 days
Secondary	To track and evaluate other known biomarkers of inflammation: D-dimer	Track and evaluate other known biomarkers of inflammation, D-dimer from baseline to day 30	30 days
Secondary	Evaluation of physiological status through NEWS2 score	Evaluate improvement of the NEWS2 score value	30 days