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

Phase 2
Terminated
Conditions
COVID-19
Lymphocytopenia
Interventions
Drug: PLACEBO
Registration Number
NCT04927169
Lead Sponsor
Revimmune
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

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
4
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
CYT107Interleukin-7IM administration of CYT107 / Interleukin-7
PLACEBOPLACEBOIM administration of Saline at the same volume
Primary Outcome Measures
NameTimeMethod
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 firstone month

A statistically significant increase of the absolute lymphocyte count (ALC) from randomization to day 30 or Hospital Discharge

Secondary Outcome Measures
NameTimeMethod
To obtain "clinical improvement" as defined by an improvement in a 11-points WHO score for Clinical Assessment, through day 30 or HD.one month

to determine if CYT107 will improve the clinical status of hospitalized COVID-19 patients as measured by the 11 points WHO clinical score

a significant change of SARS-CoV-2 viral load through day 30 or HDone 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)

frequency of secondary infections through day 45 compared to placebo arm45 days

Incidence of secondary infections based on pre-specified criteria as adjudicated by the Secondary Infections Committee (SIC) through Day 45

length of hospitalization compared to placebo arm45 days

Number of days of hospitalization during index hospitalization (defined as time from initial Study drug treatment through HD)

All-cause mortality through day 45 compared to placebo arm45 days

All-cause mortality through Day 45

Length of stay in ICU compared to placebo arm45 days

Number of days in ICU during index hospitalization

number of readmissions to ICU compared to placebo arm45 days

Readmissions to ICU through Day 45

organ support free days compared to placebo arm45 days

Organ support free days (OSFDs) during index hospitalization (This includes ventilator assistance free days)

level of other known biomarkers of inflammation: Ferritin compared to placebo30 days

Track and evaluate other known biomarkers of inflammation, Ferritin, from baseline to day 30

Level of other known biomarkers of inflammation: C reactive protein level (CRP) compared to placebo arm30 days

Level of other known biomarkers of inflammation: CRP compared to placebo arm

Level of other known biomarkers of inflammation: D-dimer compared to placebo arm30 days

Track and evaluate other known biomarkers of inflammation, D-dimer from baseline to day 30

Physiological status through National Early Warning Score (NEWS2) evaluation compared to Placebo arm30 days

Evaluate chnage of the NEWS2 score value. Score form 0 to 4: NO Risk Score of 7 or more: High risk

Frequency of re-hospitalization through day 45 compared to placebo arm45 days

Number of readmissions to the hospital through Day 45

CD4+ and CD8+ T cell counts compared to placebo arm30 days

Absolute numbers of CD4+ and CD8+ T-cell counts at time points indicated on the Schedule of Activities (SoA)through Day 30 or HD

Trial Locations

Locations (6)

Hospital Edmundo Vasconcelos

🇧🇷

Vila Clementino, SAO Paolo, Brazil

Universidade Federal de Sao Paolo

🇧🇷

São Paulo, SAO Paolo, Brazil

Upeclin-Unesp

🇧🇷

Botucatu, SAO Paolo, Brazil

Hospital de Clinicas de Porto Alegre

🇧🇷

Porto Alegre, RIO Grande DO SUL, Brazil

Hospital Das Clinicas de Ribeirao Preto

🇧🇷

Monte Alegre, SAO Paolo, Brazil

Hospital Sao Jose

🇧🇷

São José, Santa Catarina, Brazil

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