InterLeukin-7 (CYT107) to Improve Clinical Outcomes in Lymphopenic pAtients With COVID-19 Infection UK Cohort
- Registration Number
- NCT04379076
- Lead Sponsor
- Revimmune
- 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.
- 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
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 35
- 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)
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Saline Placebos Intramuscular (IM) administration of saline at the same volume and same time for a total of 5 administrations CYT107 Interleukin-7 Intra-muscular administration of CYT107 twice a week for a total of 5 administrations
- Primary Outcome Measures
Name Time Method 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 1 month A statistically significant increase of the absolute lymphocyte count (ALC) from randomization to day 30 or Hospital Discharge
- Secondary Outcome Measures
Name Time Method To track and evaluate other known biomarkers of inflammation: CRP 30 days Track and evaluate other known biomarkers of inflammation, CRP from baseline to day 30
To compare the effect of CYT107 versus placebo on the length of hospitalization 45 days Number of days of hospitalization during index hospitalization (defined as time from initial Study drug treatment through HD)
To assess the impact of CYT107 on all-cause mortality through day 45 45 days All-cause mortality through Day 45
To compare the effect of CYT107 versus placebo on the frequency of secondary infections through day 45 45 days Incidence of secondary infections based on pre-specified criteria as adjudicated by the Secondary Infections Committee (SIC) through Day 45
To compare the effect of CYT107 versus placebo on the length of stay in ICU 45 days Number of days in ICU during index hospitalization
To compare the effect of CYT107 versus placebo on readmissions to ICU 45 days Readmissions to ICU through Day 45
To track and evaluate other known biomarkers of inflammation: Ferritin 30 days Track and evaluate other known biomarkers of inflammation, Ferritin, from baseline to day 30
determine if CYT107 will lead to a significant decline of SARS-CoV-2 viral load through day 30 or HD one month 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)
To compare the effect of CYT107 versus placebo on the frequency of re-hospitalization through day 45 45 days Number of readmissions to the hospital through Day 45
To determine the effect of CYT107 on CD4+ and CD8+ T cell counts 30 days Absolute numbers of CD4+ and CD8+ T-cell counts at timepoints indicated on the Schedule of Activities (SoA) through Day 30 or HD
To track and evaluate other known biomarkers of inflammation: D-dimer 30 days Track and evaluate other known biomarkers of inflammation, D-dimer from baseline to day 30
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 to determine if CYT107 will improve the clinical status of hospitalized COVID-19 patients as measured by WHO score
To compare the effect of CYT107 versus placebo on organ support free days 45 days Organ support free days (OSFDs) during index hospitalization (This includes ventilator assistance free days.)
Evaluation of physiological status through NEWS2 score 30 days Evaluate improvement of the NEWS2 score value
Trial Locations
- Locations (12)
Sandwell Birmingham Hospital
🇬🇧Birmingham, United Kingdom
ST JAMES's UNIVERSITY HOSPITAL
🇬🇧Leeds, United Kingdom
Medway Maritime Hospital
🇬🇧London, United Kingdom
King'S College Hospital
🇬🇧London, United Kingdom
Wythenshawe Hospital/ Manchester Royal Infirmary
🇬🇧Manchester, United Kingdom
North Manchester General Hospital
🇬🇧Manchester, United Kingdom
Royal Victoria Infirmary and Freeman Hospital
🇬🇧Newcastle, United Kingdom
Sunderland Royal Hospital
🇬🇧Sunderland, United Kingdom
Royal Preston Hospital
🇬🇧Preston, United Kingdom
Watford General Hospital
🇬🇧Watford, United Kingdom
Bradford Institute for Health Research
🇬🇧Bradford, United Kingdom
Guy's and St Thomas' NHS Foundation Trust
🇬🇧London, United Kingdom