InterLeukin-7 to Improve Clinical Outcomes in Lymphopenic Patients With COVID-19 Infection ( ILIAD-7-US-O )

COVID-19 Clinical Trial

— ILIAD-7-US-O  

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. US Oncology Cohort

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04426201
• Other study ID #: ILIAD-7 COVID US ONCO
• Status: Terminated
• Phase: Phase 2
• Start date: December 20, 2020
• Est. completion date: June 30, 2022

Study information

• Verified date: April 2024
• Source: Revimmune
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Comparison of the effects of CYT107 vs Placebo administered IM at 10μg/kg twice a week for three weeks on immune reconstitution of lymphopenic COVID-19 patients

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 7 administrations 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 is dedicated to oncology patients

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 10
• Est. completion date: June 30, 2022
• Est. primary completion date: June 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 25 Years to 80 Years

Eligibility

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. Patient receiving active or recent chemotherapy or immunotherapy (within 6 months) for cancer (and/or)

3. Patients who have received hematopoietic stem cell transplantation (for a diagnosis other than lymphoma) within the past 1 year (and/or)

4. Patients who received CAR-T cell therapy within the past 1 year (but not within last 30 days- see also exclusion criteria number 6 & 7) (and/or)

5. Patients receiving hormonal therapy for cancer (and/or)

6. Patients who have undergone surgery or radiotherapy for cancer within the past 6 months

7. Patients with newly diagnosed (biopsy proven) malignancy who have not yet received cancer treatment but get COVID pneumonia in the interim (Incl. Criteria 11)

8. Men and women aged = 25 - 80 (included) years of age

9. Hospitalized patients with one absolute lymphocyte count (ALC) = 1000 cells/mm3, collected at baseline or no more than 72h before baseline .

From this time point the investigator may choose to further postpone the commencement of IL-7 (CYT107) treatment according to patient's clinical status.

10. 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

11. Confirmed infection with COVID-19 by any acceptable test available/utilized at each site

12. Willingness and ability to practice contraception regardless of the gender of the patient during 5 months after last drug exposure

Exclusion Criteria:

1. Pregnancy or breast feeding;

2. ALT and/or AST > 5 x ULN

3. Known, active auto-immune disease;

4. Patients with a history of lymphoid malignancy

5. Patients with any malignancy that is present at time of enrollment where treating physician expects life expectancy due to the underlying malignancy to be less than 6 months

6. Patients who received CAR-T cell therapy within the past 30 days or with unresolved cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS)

7. Patients with unresolved grade > 2 toxicities from prior chemotherapy, immunotherapy, or CAR-T cell therapy

8. Patients with past history of Solid Organ transplant.

9. Active tuberculosis, uncontrolled active HBV or HCV infection, HIV with positive viral load.

10. Hospitalized patients with refractory hypoxia, defined as inability to maintain saturation >85% with maximal available therapy for >6 hours

11. Patients with a mechanical ventilation support = 7 days

12. Patients with chronic kidney dialysis

13. Patients with a SOFA score = 9 at baseline

14. Patients with a BMI > 40

15. 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)

16. Patients with hospital admission Rockwood Clinical Frailty Scale = 6. (assessed as patient or proxy 4-week recall of chronic health and frailty status prior to COVID infection)

11. Patients under guardianship

Related Conditions & MeSH terms

• COVID-19
• Lymphocytopenia
• Lymphopenia

Intervention

Drug:
• CYT107
IM administration at 10µg/kg twice a week for three weeks and up to 7 administrations according to Hospital length of stay
• Placebo
Same number, volume and frequency of IM administration of saline

Locations

Country	Name	City	State
United States	MD Anderson cancer center	Houston	Texas
United States	Memorial sloan kettering	New York	New York

Sponsors (5)

Lead Sponsor	Collaborator
Revimmune	Amarex Clinical Research, Cancer Research Institute, New York City, M.D. Anderson Cancer Center, Memorial Sloan Kettering Cancer Center

Country where clinical trial is conducted

United States, 

References & Publications (4)

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 clinic — View 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. — View 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):106 — View 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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Safety assessment through incidence and scoring of grade 3-4 adverse events	Incidence and scoring of all grade 3-4 adverse events through Day 45 (using CTCAE Version 5.0) to assess safety	45 days
Primary	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	A statistically significant increase of the absolute lymphocyte count (ALC) from randomization to day 30 or HospitalDischarge	one month
Secondary	To obtain "clinical improvement" as defined by an improvement in a 11-points WHO score for Clinical Assessment, through day 30 or HD.	to determine if CYT107 will improve the clinical status of hospitalized COVID-19 patients as measured by 11 steps WHO clinical improvement score	one month
Secondary	a significant decline of SARS-CoV-2 viral load through day 30 or HD	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)	1 month or HD (whichever occurs first)
Secondary	frequency of secondary infections through day 45 compared to placebo arm	Incidence of secondary infections based on pre-specified criteria as adjudicated by the Secondary Infections Committee (SIC) through Day 45	45 days
Secondary	length of hospitalization compared to placebo arm	Number of days of hospitalization during index hospitalization (defined as time from initial Study drug treatment through HD)	45 days
Secondary	length of stay in ICU compared to placebo arm	Number of days in ICU during index hospitalization	45 days
Secondary	number of readmissions to ICU compared to placebo arm	Readmissions to ICU through Day 45	45 days
Secondary	organ support free days compared to placebo arm	Organ support free days (OSFDs) during index hospitalization (This includes ventilator assistance free days)	45 days
Secondary	Frequency of re-hospitalization through day 45 compared to placebo arm	Number of readmissions to the hospital through Day 45	45 days
Secondary	All-cause mortality through day 45 compared to placebo arm	All-cause mortality through Day 45	45 days
Secondary	CD4+ and CD8+ T cell counts compared to placebo arm	Absolute numbers of CD4+ and CD8+ T-cell counts at time points indicated on the Schedule of Activities (SoA) through Day 30 or HD	30 days
Secondary	level of other known biomarkers of inflammation: Ferritin compared to placebo arm	Track and evaluate other known biomarkers of inflammation, Ferritin, from baseline to day 30	30 days
Secondary	Level of other known biomarkers of inflammation: CRP compared to placebo arm	Track and evaluate other known biomarkers of inflammation, CRP from baseline to day 30	30 days
Secondary	Level of other known biomarkers of inflammation: D-dimer compared to placebo arm	Track and evaluate other known biomarkers of inflammation, D-dimer from baseline to day 30	30 days
Secondary	Physiological status through NEWS2 evaluation compared to Placebo arm	Evaluate improvement of the NEWS2 score value. Score form 0 to 4: NO Risk Score of 7 or more: High risk	30 days