Study of Adalimumab or Placebo in Patients With Mild to Moderate COVID-19 (COMBAAT) (COMBAAT)
Primary Purpose
Mild to Moderate COVID-19
Status
Withdrawn
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Adalimumab
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Mild to Moderate COVID-19
Eligibility Criteria
Inclusion Criteria:
- Subject (or their legally authorized representative) is willing and able to provide written informed consent prior to performing study procedures.
- Understands and agrees to comply with planned study procedures.
- Male or non-pregnant female adult ≥60 and ≤ 80years of age OR male or non-pregnant female adult ≥40 and ≤80 years, with one or more of the following risk factors (asthma, diabetes, hypertension, obesity [body mass index >30], cardiovascular disease).
- Has a laboratory-confirmed SARS-CoV-2 infection as determined by FDA-approved rapid diagnostic (e.g., polymerase chain reaction [PCR]) assay within the preceding 7 days (168 hours).
- Has at least 2 COVID-19 related symptoms on the 14-question COVID-19 questionnaire.
- Has peripheral capillary oxygen saturation (SpO2) >93% by pulse oximetry.
- C-reactive protein (CRP) >50 mg/L or lymphopenia (<1.5×109/L) or neutrophilia (>7.5×109/L).
- Agrees to the collection of blood and urine samples, nasal swabs , and non-invasive oxygen monitoring (via pulse oximeter) per protocol.
- Willing to receive 4 injections at separate sites on the thigh or abdomen.
- Women of childbearing potential must agree to either abstinence or use of at least one primary form of contraception (not including hormonal contraception) from the time of screening through Day 29 following randomization.
- Agrees to not participate in any other clinical trial (both pharmacologic and other types of interventions) through Day 29 following randomization
Exclusion Criteria:
- Received or contemplating any COVID-19 vaccine or participated in a COVID-19 vaccine trial.
- Subject is considered to be in their last few weeks of life prior to this acute illness.
- History of pulmonary alveolar proteinosis.
- History of hematopoietic stem cell transplant or solid organ transplant.
- Previous malignancy and lymphoproliferative disorders (within the last 5 years) with the exception of stable prostate cancer and basal cell carcinoma.
- Chronic obstructive pulmonary disease on long-term oxygen therapy - subjects with forced expiratory volume in 1 second known to be <50% will also be excluded.
- Demyelinating disease.
- Known history of hepatitis B, HIV, or untreated hepatitis C infection
- Severe hepatic impairment or known cirrhosis - Child-Pugh score B or higher.
- Acute kidney injury Stage 3
- Tuberculosis or other severe infections such as (non-COVID-19) sepsis, abscesses, fungal superinfection and opportunistic infections requiring treatment.
- Positive Quantiferon Gold test at screening
- Moderate or severe heart failure (New York Heart Association Class III/IV).
- Treatment with monoclonal antibodies targeting cytokines (e.g., TNF inhibitors [adalimumab, infliximab, etanercept, golimumab, certolizumab]; anti-IL-1 [e.g., anakinra, canakinumab]; anti-IL-6 or anti-IL-6r [e.g., tocilizumab, sarilumab, sitlukimab]; or T-cells [e.g., abatacept]) in past 90 days (5 half-lives of the drug), or contemplating treatment with any of these agents during the trial period.
- Treatment with monoclonal antibodies targeting B-cells (e.g., rituximab, and including any targeting multiple cell lines including B-cells) in the 3 months prior to screening.
- Received GM-CSF agents (e.g., sargramostim) within 2 months prior to screening.
- Treatment with other immunosuppressants in the 4 weeks prior to screening and in the judgment of the Investigator, the risk of immunosuppression with adalimumab is larger than the risk of COVID-19.
- Treatment with small molecule tyrosine kinase inhibitors (e.g., baricitinib, ibrutinib, acalabrutinib, imatinib, gefitinib), in the 4 weeks prior to screening.
- Received or contemplating receipt of any live vaccine or any investigational vaccine in the 4 weeks prior to screening.
- Current participation or previous participation in any other clinical trial within 30 days prior to randomization.
- Subjects with known hypersensitivity to adalimumab or excipients of adalimumab as stated in the label.
- Pregnant female
- Lactating female
- Women of childbearing potential who do not agree to either abstinence or use of at least one primary form of contraception (not including hormonal contraception) from the time of screening through Day 29 following randomization.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Adalimumab
Placebo
Arm Description
single dose of adalimumab(160 mg administered as 4×40 mg subcutaneous [SC] injections at separate sites on the thigh or abdomen
single dose of placebo (administered as 4×40 mg subcutaneous [SC] injections at separate sites on the thigh or abdomen
Outcomes
Primary Outcome Measures
Establish whether treatment with adalimumab is associated with a lower rate of progression to severe disease as defined by severe illness or critical illness, or death in outpatient subjects with COVID-19
Proportion of subjects with the following outcomes attributed to COVID-19 from time of first dose through Day 28 following randomization:
Death
Alive and hospitalized or requiring supplemental oxygen for ≥1 hour
Alive and not hospitalized or requiring supplemental oxygen for ≥1 hour
Assess the safety of adalimumab in subjects with COVID-19
Incidence of Grade 3 and Grade 4 clinical adverse events (AEs) from first dose through Day 28 following randomization
Secondary Outcome Measures
Assess the impact of treatment with adalimumab on clinical course of COVID-19 infection
Clinical status by 9-point WHO COVID 19 ordinal scale from first dose through Day 120 following randomization
Incidence of venous thromboembolism, CVA, myocardial infarction, and acute kidney injury C from first dose through Day 120 following randomization
Time to resolution of symptoms using 14 point COVID-19 Symptom Score from first dose through Day 120 following randomization
COVID-19 Clinical Assessment from first dose through Day 120 following randomization
Full Information
NCT ID
NCT04705844
First Posted
January 10, 2021
Last Updated
March 2, 2022
Sponsor
Ology Bioservices
Collaborators
Pharm-Olam, LLC, Chemical, Biological, Radiological, and Nuclear Medical
1. Study Identification
Unique Protocol Identification Number
NCT04705844
Brief Title
Study of Adalimumab or Placebo in Patients With Mild to Moderate COVID-19 (COMBAAT)
Acronym
COMBAAT
Official Title
Multi-Center, Randomized, Double-Blind, Placebo-Controlled Study of Adalimumab (Humira) or Placebo in Patients With Mild-Moderate COVID-19
Study Type
Interventional
2. Study Status
Record Verification Date
March 2022
Overall Recruitment Status
Withdrawn
Why Stopped
study withdrawn prior to screening subjects
Study Start Date
September 2021 (Anticipated)
Primary Completion Date
September 2022 (Anticipated)
Study Completion Date
September 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ology Bioservices
Collaborators
Pharm-Olam, LLC, Chemical, Biological, Radiological, and Nuclear Medical
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Clinical study of Humira (adalimumab) or placebo in subjects with mild-moderate COVID-19
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mild to Moderate COVID-19
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Subjects will be randomized to receive a single dose of adalimumab or placebo. Subjects will receive standard care of therapy (per study site written policies or guidelines) together with adalimumab or matching placebo.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Randomized, Double-Blind, Placebo-Controlled
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Adalimumab
Arm Type
Experimental
Arm Description
single dose of adalimumab(160 mg administered as 4×40 mg subcutaneous [SC] injections at separate sites on the thigh or abdomen
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
single dose of placebo (administered as 4×40 mg subcutaneous [SC] injections at separate sites on the thigh or abdomen
Intervention Type
Drug
Intervention Name(s)
Adalimumab
Other Intervention Name(s)
Humira
Intervention Description
adalimumab (160 mg administered as 4×40 mg subcutaneous [SC] injections at separate sites on the thigh or abdomen)
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
placebo (4 SC injections of equal volume administered at separate sites on the thigh or abdomen)
Primary Outcome Measure Information:
Title
Establish whether treatment with adalimumab is associated with a lower rate of progression to severe disease as defined by severe illness or critical illness, or death in outpatient subjects with COVID-19
Description
Proportion of subjects with the following outcomes attributed to COVID-19 from time of first dose through Day 28 following randomization:
Death
Alive and hospitalized or requiring supplemental oxygen for ≥1 hour
Alive and not hospitalized or requiring supplemental oxygen for ≥1 hour
Time Frame
28 Days
Title
Assess the safety of adalimumab in subjects with COVID-19
Description
Incidence of Grade 3 and Grade 4 clinical adverse events (AEs) from first dose through Day 28 following randomization
Time Frame
28 Days
Secondary Outcome Measure Information:
Title
Assess the impact of treatment with adalimumab on clinical course of COVID-19 infection
Description
Clinical status by 9-point WHO COVID 19 ordinal scale from first dose through Day 120 following randomization
Incidence of venous thromboembolism, CVA, myocardial infarction, and acute kidney injury C from first dose through Day 120 following randomization
Time to resolution of symptoms using 14 point COVID-19 Symptom Score from first dose through Day 120 following randomization
COVID-19 Clinical Assessment from first dose through Day 120 following randomization
Time Frame
120 Days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Subject (or their legally authorized representative) is willing and able to provide written informed consent prior to performing study procedures.
Understands and agrees to comply with planned study procedures.
Male or non-pregnant female adult ≥60 and ≤ 80years of age OR male or non-pregnant female adult ≥40 and ≤80 years, with one or more of the following risk factors (asthma, diabetes, hypertension, obesity [body mass index >30], cardiovascular disease).
Has a laboratory-confirmed SARS-CoV-2 infection as determined by FDA-approved rapid diagnostic (e.g., polymerase chain reaction [PCR]) assay within the preceding 7 days (168 hours).
Has at least 2 COVID-19 related symptoms on the 14-question COVID-19 questionnaire.
Has peripheral capillary oxygen saturation (SpO2) >93% by pulse oximetry.
C-reactive protein (CRP) >50 mg/L or lymphopenia (<1.5×109/L) or neutrophilia (>7.5×109/L).
Agrees to the collection of blood and urine samples, nasal swabs , and non-invasive oxygen monitoring (via pulse oximeter) per protocol.
Willing to receive 4 injections at separate sites on the thigh or abdomen.
Women of childbearing potential must agree to either abstinence or use of at least one primary form of contraception (not including hormonal contraception) from the time of screening through Day 29 following randomization.
Agrees to not participate in any other clinical trial (both pharmacologic and other types of interventions) through Day 29 following randomization
Exclusion Criteria:
Received or contemplating any COVID-19 vaccine or participated in a COVID-19 vaccine trial.
Subject is considered to be in their last few weeks of life prior to this acute illness.
History of pulmonary alveolar proteinosis.
History of hematopoietic stem cell transplant or solid organ transplant.
Previous malignancy and lymphoproliferative disorders (within the last 5 years) with the exception of stable prostate cancer and basal cell carcinoma.
Chronic obstructive pulmonary disease on long-term oxygen therapy - subjects with forced expiratory volume in 1 second known to be <50% will also be excluded.
Demyelinating disease.
Known history of hepatitis B, HIV, or untreated hepatitis C infection
Severe hepatic impairment or known cirrhosis - Child-Pugh score B or higher.
Acute kidney injury Stage 3
Tuberculosis or other severe infections such as (non-COVID-19) sepsis, abscesses, fungal superinfection and opportunistic infections requiring treatment.
Positive Quantiferon Gold test at screening
Moderate or severe heart failure (New York Heart Association Class III/IV).
Treatment with monoclonal antibodies targeting cytokines (e.g., TNF inhibitors [adalimumab, infliximab, etanercept, golimumab, certolizumab]; anti-IL-1 [e.g., anakinra, canakinumab]; anti-IL-6 or anti-IL-6r [e.g., tocilizumab, sarilumab, sitlukimab]; or T-cells [e.g., abatacept]) in past 90 days (5 half-lives of the drug), or contemplating treatment with any of these agents during the trial period.
Treatment with monoclonal antibodies targeting B-cells (e.g., rituximab, and including any targeting multiple cell lines including B-cells) in the 3 months prior to screening.
Received GM-CSF agents (e.g., sargramostim) within 2 months prior to screening.
Treatment with other immunosuppressants in the 4 weeks prior to screening and in the judgment of the Investigator, the risk of immunosuppression with adalimumab is larger than the risk of COVID-19.
Treatment with small molecule tyrosine kinase inhibitors (e.g., baricitinib, ibrutinib, acalabrutinib, imatinib, gefitinib), in the 4 weeks prior to screening.
Received or contemplating receipt of any live vaccine or any investigational vaccine in the 4 weeks prior to screening.
Current participation or previous participation in any other clinical trial within 30 days prior to randomization.
Subjects with known hypersensitivity to adalimumab or excipients of adalimumab as stated in the label.
Pregnant female
Lactating female
Women of childbearing potential who do not agree to either abstinence or use of at least one primary form of contraception (not including hormonal contraception) from the time of screening through Day 29 following randomization.
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Study of Adalimumab or Placebo in Patients With Mild to Moderate COVID-19 (COMBAAT)
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