Clinical trial NCT04407689: InterLeukin-7 to Improve Clinical Outcomes in Lymphopenic pAtients With COVID-19 Infection FR BL Cohort
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 France and Belgium
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: COVID-19
Lymphocytopenia
Lead sponsor: Revimmune
Sponsor class: INDUSTRY
Collaborators: name: University Hospital, Limoges
name: Amarex Clinical Research
First posted: 2020-05-29
Enrollment: 34
Sex: ALL
Minimum age (years): 25
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: randomized controlled of treatment vs placebo
Primary purpose: TREATMENT

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 took place after the first 12 patients. Since the CYT107 was well tolerated, the test dose (3 μg/kg) ceased and the initial dose became 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

Eligibility criteria: 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 \>4L per minute nasal cannula or greater to keep saturations \>90%, non-invasive positive pressure ventilation (e.g., BIPAP) for respiratory failure
* Confirmed infection with COVID-19 by any acceptable test available/ utilized at each site
* Patient with medical insurance or government support

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:

  * 8a requirement for an increase in inspired oxygen concentrations of 20% or more over the past 24 hours to maintain SpO2 at greater than or equal to 88%
  * 8b or need for invasive mechanical ventilation
* 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 chronic kidney dialysis
* Patients with a SOFA score ≥ 9 at baseline
* Patients with a BMI \> 40
* Patients receiving any agent with immune suppressive effects,such as anti-IL6 treatments like Tocilizumab or Sarilumab which should preferably be minimized
* Presence of any of the following abnormal laboratory values at screening: absolute neutrophil count (ANC) \< 1.5x109/L, Platelets \< 50,000 per mm3
* Patients with uncontrolled pre-existing severe major organ dysfunction (cardiac, liver or renal failure)
* Vaccination with live attenuated vaccines in the month preceding the inclusion
* Use of chronic oral corticosteroids ≥ 10mg prednisone equivalent a day for a non-COVID-19 related condition
* Patients with baseline Rockwood Clinical Frailty Scale ≥ 6.
* Patients with known hypersensitivity to natural or recombinant Interleukin-7 or to any of the excipients
* Patients under guardianship

Primary outcomes:
measure: 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
timeFrame: 1 month
Secondary outcomes:
measure: To obtain "clinical improvement" as defined by an improvement in a 11-points WHO score for Clinical Assessment, through day 30 or HD.
timeFrame: 1 month
measure: a significant decline of SARS-CoV-2 viral load through day 30 or HD
timeFrame: 1 month or HD (whichever occurs first)
measure: frequency of secondary infections through day 45 compared tp placebo arm
timeFrame: 45 days
measure: length of hospitalization compared to placebo arm
timeFrame: 45 days
measure: length of stay in ICU compared to placebo arm
timeFrame: 45 days
measure: number of readmissions to ICU compared to placebo arm
timeFrame: 45 days
measure: organ support free days compared to placebo arm
timeFrame: 45 days
measure: Frequency of re-hospitalization through day 45 compared to placebo arm
timeFrame: 45 days
measure: All-cause mortality through day 45 compared to placebo arm
timeFrame: 45 days
measure: CD4+ and CD8+ T cell counts compared to placebo arm
timeFrame: 30 days
measure: level of other known biomarkers of inflammation: Ferritin compared to placebo arm
timeFrame: 30 days
measure: Level of other known biomarkers of inflammation: CRP compared to placebo arm
timeFrame: 30 days
measure: Level of other known biomarkers of inflammation: D-dimer compared to placebo arm
timeFrame: 30 days
measure: Physiological status through NEWS2 evaluation compared to Placebo arm
timeFrame: 30 days
Other outcomes:
measure: Safety assessment through incidence and scoring of grade 3-4 adverse events
timeFrame: 45 days
Locations:
city: Limoges
country: France
facility: University Hospital of Limoges
city: Lyon
country: France
facility: Hôpital Edouard Herriot
city: Lyon
country: France
facility: hopital Edouard Herriot
city: Orléans
country: France
facility: Chr Orleans La Source
city: Paris
country: France
facility: hopital COCHIN
city: Tours
country: France
facility: Chru Tours
Study officials:
affiliation: University Hospital, Limoges
name: Bruno François, MD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
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.
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.