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

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

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.

Study Overview

• Status: Terminated
• Conditions: COVID-19; Lymphocytopenia
• Intervention / Treatment: Drug: Interleukin-7; Drug: Placebos

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 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

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • Birmingham, United Kingdom, B18 7QH
    • Sandwell Birmingham Hospital
  • Birmingham, United Kingdom
    • Sandwell Birmingham Hospital
  • Bradford, United Kingdom, BD9 6RJ
    • Bradford Institute for Health Research
  • Leeds, United Kingdom, LS9 7TF
    • St James's University Hospital
  • London, United Kingdom, SE5 9RS
    • King's College Hospital
  • London, United Kingdom, ME7 5NY
    • Medway Maritime Hospital
  • London, United Kingdom, SE1 9RS
    • Guy's and St Thomas' NHS Foundation Trust
  • Manchester, United Kingdom, M8 5RB
    • North Manchester General Hospital
  • Manchester, United Kingdom, M23 9LT
    • Wythenshawe Hospital/ Manchester Royal Infirmary
  • Newcastle, United Kingdom, NE1 4LP
    • Royal Victoria Infirmary and Freeman Hospital
  • Preston, United Kingdom
    • Royal Preston Hospital
  • Sunderland, United Kingdom
    • Sunderland Royal Hospital
  • Watford, United Kingdom, WD18 0HB
    • Watford General Hospital

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:

• 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

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; Intra-muscular administration of CYT107 twice a week for a total of 5 administrations	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; Other Names: CYT107
PLACEBO_COMPARATOR: Saline; Intramuscular (IM) administration of saline at the same volume and same time for a total of 5 administrations	Drug: Placebos; Intramuscular (IM) placebo (normal saline) at the same frequency; 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), whicheve	A statistically significant increase of the absolute lymphocyte count (ALC) from randomization to day 30 or Hospital Discharge	1 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 WHO score	1 month
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
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
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
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
To compare the effect of CYT107 versus placebo on readmissions to ICU	Readmissions to ICU through Day 45	45 days
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
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
To assess the impact of CYT107 on all-cause mortality through day 45	All-cause mortality through Day 45	45 days
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
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
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
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
Evaluation of physiological status through NEWS2 score	Evaluate improvement of the NEWS2 score value	30 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Revimmune
• Collaborators: Amarex Clinical Research
• Investigators: Principal Investigator: Manu Shankar-Hari, MD PhD, Guy's and St Thomas' NHS Foundation Trust

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.
• Manzanilla-Sevilla R, Gonzalez-Iniguez R, Casanova-Alvarez N, Martinez-Alcala F. Tubal sterilization and ovarian perfusion: selective arteriography in vivo and in vitro. Int J Gynaecol Obstet. 1978-1979;16(2):137-43. doi: 10.1002/j.1879-3479.1978.tb00414.x.
• 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.
• 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.
• 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): May 14, 2020
• Primary Completion (ACTUAL): February 28, 2022
• Study Completion (ACTUAL): March 30, 2022

Study Registration Dates

• First Submitted: May 5, 2020
• First Submitted That Met QC Criteria: May 5, 2020
• First Posted (ACTUAL): May 7, 2020

Study Record Updates

• Last Update Posted (ACTUAL): April 7, 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: CLI107 COVID UK (ILIAD-7-UK)

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: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No