search
Back to results

InterLeukin-7 (CYT107) to Improve Clinical Outcomes in Lymphopenic pAtients With COVID-19 Infection UK Cohort (ILIAD-7-UK)

Primary Purpose

COVID-19, Lymphocytopenia

Status
Terminated
Phase
Phase 2
Locations
United Kingdom
Study Type
Interventional
Intervention
Interleukin-7
Placebos
Sponsored by
Revimmune
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for COVID-19

Eligibility Criteria

25 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 >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)

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:
  • 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

Sites / Locations

  • Sandwell Birmingham Hospital
  • Sandwell Birmingham Hospital
  • Bradford Institute for Health Research
  • ST JAMES's UNIVERSITY HOSPITAL
  • Medway Maritime Hospital
  • Guy's and St Thomas' NHS Foundation Trust
  • King'S College Hospital
  • Wythenshawe Hospital/ Manchester Royal Infirmary
  • North Manchester General Hospital
  • Royal Victoria Infirmary and Freeman Hospital
  • Royal Preston Hospital
  • Sunderland Royal Hospital
  • Watford General Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

CYT107

Saline

Arm Description

Intra-muscular administration of CYT107 twice a week for a total of 5 administrations

Intramuscular (IM) administration of saline at the same volume and same time for a total of 5 administrations

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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 WHO score
determine if CYT107 will lead to 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)
To compare the effect of CYT107 versus placebo on the frequency of secondary infections through day 45
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 hospitalization
Number of days of hospitalization during index hospitalization (defined as time from initial Study drug treatment through HD)
To compare the effect of CYT107 versus placebo on the length of stay in ICU
Number of days in ICU during index hospitalization
To compare the effect of CYT107 versus placebo on readmissions to ICU
Readmissions to ICU through Day 45
To compare the effect of CYT107 versus placebo on organ support free days
Organ support free days (OSFDs) during index hospitalization (This includes ventilator assistance free days.)
To compare the effect of CYT107 versus placebo on the frequency of re-hospitalization through day 45
Number of readmissions to the hospital through Day 45
To assess the impact of CYT107 on all-cause mortality through day 45
All-cause mortality through Day 45
To determine the effect of CYT107 on CD4+ and CD8+ T cell counts
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: Ferritin
Track and evaluate other known biomarkers of inflammation, Ferritin, from baseline to day 30
To track and evaluate other known biomarkers of inflammation: CRP
Track and evaluate other known biomarkers of inflammation, CRP from baseline to day 30
To track and evaluate other known biomarkers of inflammation: D-dimer
Track and evaluate other known biomarkers of inflammation, D-dimer from baseline to day 30
Evaluation of physiological status through NEWS2 score
Evaluate improvement of the NEWS2 score value

Full Information

First Posted
May 5, 2020
Last Updated
March 30, 2022
Sponsor
Revimmune
Collaborators
Amarex Clinical Research
search

1. Study Identification

Unique Protocol Identification Number
NCT04379076
Brief Title
InterLeukin-7 (CYT107) to Improve Clinical Outcomes in Lymphopenic pAtients With COVID-19 Infection UK Cohort
Acronym
ILIAD-7-UK
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 UK
Study Type
Interventional

2. Study Status

Record Verification Date
March 2022
Overall Recruitment Status
Terminated
Why Stopped
POOR ACCRUAL
Study Start Date
May 14, 2020 (Actual)
Primary Completion Date
February 28, 2022 (Actual)
Study Completion Date
March 30, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Revimmune
Collaborators
Amarex Clinical Research

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID-19, Lymphocytopenia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
randomized controlled of treatment vs placebo
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Double blind
Allocation
Randomized
Enrollment
35 (Actual)

8. Arms, Groups, and Interventions

Arm Title
CYT107
Arm Type
Experimental
Arm Description
Intra-muscular administration of CYT107 twice a week for a total of 5 administrations
Arm Title
Saline
Arm Type
Placebo Comparator
Arm Description
Intramuscular (IM) administration of saline at the same volume and same time for a total of 5 administrations
Intervention Type
Drug
Intervention Name(s)
Interleukin-7
Other Intervention Name(s)
CYT107
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Placebos
Other Intervention Name(s)
Saline
Intervention Description
Intramuscular (IM) placebo (normal saline) at the same frequency
Primary Outcome Measure Information:
Title
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
Description
A statistically significant increase of the absolute lymphocyte count (ALC) from randomization to day 30 or Hospital Discharge
Time Frame
1 month
Secondary Outcome Measure Information:
Title
To obtain "clinical improvement" as defined by an improvement in a 11-points WHO score for Clinical Assessment, through day 30 or HD.
Description
to determine if CYT107 will improve the clinical status of hospitalized COVID-19 patients as measured by WHO score
Time Frame
1 month
Title
determine if CYT107 will lead to a significant decline of SARS-CoV-2 viral load through day 30 or HD
Description
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)
Time Frame
one month
Title
To compare the effect of CYT107 versus placebo on the frequency of secondary infections through day 45
Description
Incidence of secondary infections based on pre-specified criteria as adjudicated by the Secondary Infections Committee (SIC) through Day 45
Time Frame
45 days
Title
To compare the effect of CYT107 versus placebo on the length of hospitalization
Description
Number of days of hospitalization during index hospitalization (defined as time from initial Study drug treatment through HD)
Time Frame
45 days
Title
To compare the effect of CYT107 versus placebo on the length of stay in ICU
Description
Number of days in ICU during index hospitalization
Time Frame
45 days
Title
To compare the effect of CYT107 versus placebo on readmissions to ICU
Description
Readmissions to ICU through Day 45
Time Frame
45 days
Title
To compare the effect of CYT107 versus placebo on organ support free days
Description
Organ support free days (OSFDs) during index hospitalization (This includes ventilator assistance free days.)
Time Frame
45 days
Title
To compare the effect of CYT107 versus placebo on the frequency of re-hospitalization through day 45
Description
Number of readmissions to the hospital through Day 45
Time Frame
45 days
Title
To assess the impact of CYT107 on all-cause mortality through day 45
Description
All-cause mortality through Day 45
Time Frame
45 days
Title
To determine the effect of CYT107 on CD4+ and CD8+ T cell counts
Description
Absolute numbers of CD4+ and CD8+ T-cell counts at timepoints indicated on the Schedule of Activities (SoA) through Day 30 or HD
Time Frame
30 days
Title
To track and evaluate other known biomarkers of inflammation: Ferritin
Description
Track and evaluate other known biomarkers of inflammation, Ferritin, from baseline to day 30
Time Frame
30 days
Title
To track and evaluate other known biomarkers of inflammation: CRP
Description
Track and evaluate other known biomarkers of inflammation, CRP from baseline to day 30
Time Frame
30 days
Title
To track and evaluate other known biomarkers of inflammation: D-dimer
Description
Track and evaluate other known biomarkers of inflammation, D-dimer from baseline to day 30
Time Frame
30 days
Title
Evaluation of physiological status through NEWS2 score
Description
Evaluate improvement of the NEWS2 score value
Time Frame
30 days
Other Pre-specified Outcome Measures:
Title
Safety assessment
Description
Incidence and scoring of all grade 3-4 adverse events through Day 45 (using CTCAE Version 5.0 to assess severity)
Time Frame
45 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
25 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
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 >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) 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: 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Manu Shankar-Hari, MD PhD
Organizational Affiliation
Guy's and St Thomas' NHS Foundation Trust
Official's Role
Principal Investigator
Facility Information:
Facility Name
Sandwell Birmingham Hospital
City
Birmingham
ZIP/Postal Code
B18 7QH
Country
United Kingdom
Facility Name
Sandwell Birmingham Hospital
City
Birmingham
Country
United Kingdom
Facility Name
Bradford Institute for Health Research
City
Bradford
ZIP/Postal Code
BD9 6RJ
Country
United Kingdom
Facility Name
ST JAMES's UNIVERSITY HOSPITAL
City
Leeds
ZIP/Postal Code
LS9 7TF
Country
United Kingdom
Facility Name
Medway Maritime Hospital
City
London
ZIP/Postal Code
ME7 5NY
Country
United Kingdom
Facility Name
Guy's and St Thomas' NHS Foundation Trust
City
London
ZIP/Postal Code
SE1 9RS
Country
United Kingdom
Facility Name
King'S College Hospital
City
London
ZIP/Postal Code
SE5 9RS
Country
United Kingdom
Facility Name
Wythenshawe Hospital/ Manchester Royal Infirmary
City
Manchester
ZIP/Postal Code
M23 9LT
Country
United Kingdom
Facility Name
North Manchester General Hospital
City
Manchester
ZIP/Postal Code
M8 5RB
Country
United Kingdom
Facility Name
Royal Victoria Infirmary and Freeman Hospital
City
Newcastle
ZIP/Postal Code
NE1 4LP
Country
United Kingdom
Facility Name
Royal Preston Hospital
City
Preston
Country
United Kingdom
Facility Name
Sunderland Royal Hospital
City
Sunderland
Country
United Kingdom
Facility Name
Watford General Hospital
City
Watford
ZIP/Postal Code
WD18 0HB
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
publication
Citations:
PubMed Identifier
32109
Citation
Manzanilla-Sevilla R, Gonzalez-Iniguez R, Casanova-Alvarez N, Martinez-Alcala F. Tubal sterilization and ovarian perfusion: selective arteriography in vivo and in vitro. Int J Gynaecol Obstet. 1978-1979;16(2):137-43. doi: 10.1002/j.1879-3479.1978.tb00414.x.
Results Reference
background
PubMed Identifier
32171076
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. Erratum In: Lancet. 2020 Mar 28;395(10229):1038. Lancet. 2020 Mar 28;395(10229):1038.
Results Reference
background
PubMed Identifier
32031570
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. Erratum In: JAMA. 2021 Mar 16;325(11):1113.
Results Reference
background
PubMed Identifier
29515037
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.
Results Reference
background
PubMed Identifier
23427891
Citation
Hotchkiss RS, Monneret G, Payen D. Immunosuppression in sepsis: a novel understanding of the disorder and a new therapeutic approach. Lancet Infect Dis. 2013 Mar;13(3):260-8. doi: 10.1016/S1473-3099(13)70001-X.
Results Reference
background
PubMed Identifier
23053510
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.
Results Reference
background

Learn more about this trial

InterLeukin-7 (CYT107) to Improve Clinical Outcomes in Lymphopenic pAtients With COVID-19 Infection UK Cohort

We'll reach out to this number within 24 hrs