Study of Adalimumab or Placebo in Patients With Mild to Moderate COVID-19 (COMBAAT) (COMBAAT)

• ClinicalTrials.gov Identifier: NCT04705844
• Recruitment Status: Withdrawn
• First Posted: January 12, 2021
• Last Update Posted: March 3, 2022
• Sponsor: Ology Bioservices
• Collaborators: Pharm-Olam, LLC; Chemical, Biological, Radiological, and Nuclear Medical
• Information provided by (Responsible Party): Ology Bioservices

Tracking Information

• First Submitted Date: January 10, 2021
• First Posted Date: January 12, 2021
• Last Update Posted Date: March 3, 2022
• Estimated Study Start Date: September 2021
• Estimated Primary Completion Date: September 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 10, 2021)

• 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 [ Time Frame: 28 Days ]
  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 [ Time Frame: 28 Days ]
  Incidence of Grade 3 and Grade 4 clinical adverse events (AEs) from first dose through Day 28 following randomization

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 10, 2021)

Assess the impact of treatment with adalimumab on clinical course of COVID-19 infection [ Time Frame: 120 Days ]

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of Adalimumab or Placebo in Patients With Mild to Moderate COVID-19 (COMBAAT)
• Official Title: Multi-Center, Randomized, Double-Blind, Placebo-Controlled Study of Adalimumab (Humira) or Placebo in Patients With Mild-Moderate COVID-19
• Brief Summary: Clinical study of Humira (adalimumab) or placebo in subjects with mild-moderate COVID-19
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention 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: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

Randomized, Double-Blind, Placebo-Controlled

Primary Purpose: Treatment

• Condition: Mild to Moderate COVID-19

Intervention

• Drug: Adalimumab
  adalimumab (160 mg administered as 4×40 mg subcutaneous [SC] injections at separate sites on the thigh or abdomen)
  Other Name: Humira
• Drug: Placebo
  placebo (4 SC injections of equal volume administered at separate sites on the thigh or abdomen)

Study Arms

• Experimental: Adalimumab
  single dose of adalimumab(160 mg administered as 4×40 mg subcutaneous [SC] injections at separate sites on the thigh or abdomen
  Intervention: Drug: Adalimumab
• Placebo Comparator: Placebo
  single dose of placebo (administered as 4×40 mg subcutaneous [SC] injections at separate sites on the thigh or abdomen
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Withdrawn
• Actual Enrollment (submitted: September 22, 2021): 0
• Original Estimated Enrollment (submitted: January 10, 2021): 1444
• Estimated Study Completion Date: September 2022
• Estimated Primary Completion Date: September 2022 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 40 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Not Provided

Administrative Information

• NCT Number: NCT04705844
• Other Study ID Numbers: A21-070
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Ology Bioservices
• Original Responsible Party: Same as current
• Current Study Sponsor: Ology Bioservices
• Original Study Sponsor: Same as current

Collaborators

• Pharm-Olam, LLC
• Chemical, Biological, Radiological, and Nuclear Medical

• Investigators: Not Provided
• PRS Account: Ology Bioservices
• Verification Date: March 2022