Clinical trial NCT04927169: InterLeukin-7 to Improve Clinical Outcomes in Lymphopenic pAtients With COVID-19 Infection (Brazil Cohort)
Official title: Recombinant Human InterLeukin-7 (CYT107) to Improve Clinical Outcomes in Lymphopenic PAtients With COVID-19 Infection - "ILIAD 7 Trial" Brazil Cohort
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: COVID-19
Lymphocytopenia
Lead sponsor: Revimmune
Sponsor class: INDUSTRY
Collaborators: name: Resolution Latin America
First posted: 2021-06-15
Enrollment: 4
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 by intra-muscular route (IM) at 10μg/kg twice a week for three 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 10 μg/kg followed, after 72hrs of observation, by 10 μg/kg twice a week for 3 weeks (maximum 7administrations adjusted to patient's length of stay in the hospital) 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.

This cohort excludes oncology patients on treatment

Eligibility criteria: Inclusion Criteria:

1. 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
2. Men and women aged ≥ 25 - 80 (included) years of age
3. Hospitalized patients with two absolute lymphocyte count (ALC) ≤ 1000 cells/mm3, at two time points at least 24 hours apart, following HOSPITALIZATION:
4. 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), or patients intubated / ventilated for respiratory failure
5. Confirmed infection with COVID-19 by any acceptable test available / utilized at each site
6. Willingness and ability to practice contraception regardless of the gender of the patient during 5 months after last drug exposure
7. Private insurance or government / institution financial support (through CMS or other)

Exclusion Criteria:

1. Pregnancy or breast feeding
2. ALT and/or AST \> 5 x ULN
3. Known, active auto-immune disease;
4. Ongoing cancer treatment with chemotherapy / immunotherapy or any cancer therapy within last 3 months and/or ongoing
5. Patients with past history of Solid Organ transplant
6. Active tuberculosis, uncontrolled active HBV or HCV infection, HIV with positive viral load
7. Hospitalized patients with refractory hypoxia, defined as inability to maintain saturation \>85% with maximal available therapy for \>6 hours
8. Patients receiving any agent with immune suppressive effects, other than steroids at dosages less than 300 mg/day equivalent hydrocortisone and/or anti-IL-6R treatments like Tocilizumab or Sarilumab or anti-IL-1 treatment like Anakinra which should preferably be minimized
9. Patients with baseline Rockwood Clinical Frailty Scale ≥ 6 at Hospital admission
10. 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)
11. Patients under guardianship

Primary outcomes:
measure: Change 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: one 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: one month
measure: a significant change of SARS-CoV-2 viral load through day 30 or HD
timeFrame: one month
measure: frequency of secondary infections through day 45 compared to 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
timeFrame: 30 days
measure: Level of other known biomarkers of inflammation: C reactive protein level (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 National Early Warning Score (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: Porto Alegre
country: Brazil
facility: Hospital de Clinicas de Porto Alegre
state: RIO Grande DO SUL
city: São José
country: Brazil
facility: Hospital Sao Jose
state: Santa Catarina
city: Botucatu
country: Brazil
facility: Upeclin-Unesp
state: SAO Paolo
city: Monte Alegre
country: Brazil
facility: Hospital Das Clinicas de Ribeirao Preto
state: SAO Paolo
city: São Paulo
country: Brazil
facility: Universidade Federal de Sao Paolo
state: SAO Paolo
city: Vila Clementino
country: Brazil
facility: Hospital Edmundo Vasconcelos
state: SAO Paolo
Study officials:
affiliation: Escola Paulista de Medicina Universidade Federal de São Paulo
name: Reinaldo SALOMAO, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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, Chung CS, Kherouf H, Geeraert A, Malcus C, Poitevin F, Bohe J, Lepape A, Ayala A, Monneret G. Increased circulating regulatory T cells (CD4(+)CD25 (+)CD127 (-)) contribute to lymphocyte anergy in septic shock patients. Intensive Care Med. 2009 Apr;35(4):678-86. doi: 10.1007/s00134-008-1337-8. Epub 2008 Oct 23.