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

NCT04379076 | Terminated Phase 2 DMC

• 1 other identifier: CLI107 COVID UK (ILIAD-7-UK)
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 13

Brief 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.

Conditions

COVID-19; Lymphocytopenia

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (14)

• To obtain "clinical improvement" as defined by an improvement in a 11-points WHO score for Clinical Assessment, through day 30 or HD.

  1 month

• determine if CYT107 will lead to a significant decline of SARS-CoV-2 viral load through day 30 or HD

  one month

• To compare the effect of CYT107 versus placebo on the frequency of secondary infections through day 45

  45 days

• To compare the effect of CYT107 versus placebo on the length of hospitalization

  45 days

• To compare the effect of CYT107 versus placebo on the length of stay in ICU

  45 days

Other Outcomes (1)

• Safety assessment

  45 days

Study Arms (2)

CYT107

EXPERIMENTAL

Intra-muscular administration of CYT107 twice a week for a total of 5 administrations

Drug: Interleukin-7

Saline

PLACEBO COMPARATOR

Intramuscular (IM) administration of saline at the same volume and same time for a total of 5 administrations

Drug: Placebos

Interventions

Interleukin-7 DRUG

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

Also known as: CYT107

CYT107

Placebos DRUG

Intramuscular (IM) placebo (normal saline) at the same frequency

Also known as: Saline

Saline

Eligibility Criteria

• Age: 25 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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)

Sponsors & Collaborators

• Revimmune: lead
• Amarex Clinical Research: collaborator

Study Sites (13)

Sandwell Birmingham Hospital

Birmingham, B18 7QH, United Kingdom

Location

Sandwell Birmingham Hospital

Birmingham, United Kingdom

Location

Bradford Institute for Health Research

Bradford, BD9 6RJ, United Kingdom

Location

ST JAMES's UNIVERSITY HOSPITAL

Leeds, LS9 7TF, United Kingdom

Location

Medway Maritime Hospital

London, ME7 5NY, United Kingdom

Location

Guy's and St Thomas' NHS Foundation Trust

London, SE1 9RS, United Kingdom

Location

King'S College Hospital

London, SE5 9RS, United Kingdom

Location

Wythenshawe Hospital/ Manchester Royal Infirmary

Manchester, M23 9LT, United Kingdom

Location

North Manchester General Hospital

Manchester, M8 5RB, United Kingdom

Location

Royal Victoria Infirmary and Freeman Hospital

Newcastle, NE1 4LP, United Kingdom

Location

Royal Preston Hospital

Preston, United Kingdom

Location

Sunderland Royal Hospital

Sunderland, United Kingdom

Location

Watford General Hospital

Watford, WD18 0HB, United Kingdom

Location

Related Publications (7)

• 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.

  PMID: 32109 BACKGROUND

• 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.

  PMID: 32171076 BACKGROUND

• 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.

  PMID: 32031570 BACKGROUND

• 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.

  PMID: 29515037 BACKGROUND

• 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.

  PMID: 23427891 BACKGROUND

• 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.

  PMID: 23053510 BACKGROUND

• Shankar-Hari M, Francois B, Remy KE, Gutierrez C, Pastores S, Daix T, Jeannet R, Blood J, Walton AH, Salomao R, Auzinger G, Striker D, Martin RS, Anand NJ, Bosanquet J, Blood T, Brakenridge S, Moldawer LL, Vachharajani V, Yee C, Dal-Pizzol F, Morre M, Berbille F, van den Brink M, Hotchkiss R. A randomized, double-blind, placebo-controlled trial of IL-7 in critically ill patients with COVID-19. JCI Insight. 2025 Feb 4;10(6):e189150. doi: 10.1172/jci.insight.189150.

  PMID: 39903535 DERIVED

MeSH Terms

Conditions

COVID-19; Lymphopenia

Interventions

Interleukin-7; Sodium Chloride

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Leukopenia; Cytopenia; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukocyte Disorders; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Manu Shankar-Hari, MD PhD

  Guy's and St Thomas' NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: randomized controlled of treatment vs placebo

Study Record Dates

• First Submitted: May 5, 2020
• First Posted: May 7, 2020
• Study Start: May 14, 2020
• Primary Completion: February 28, 2022
• Study Completion: March 30, 2022
• Last Updated: April 7, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

GB (13)