Clinical trial NCT04705844: 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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Mild to Moderate COVID-19
Lead sponsor: Resilience Government Services, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Pharm-Olam, LLC
name: Chemical, Biological, Radiological, and Nuclear Medical
First posted: 2021-01-12
Enrollment: 0
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

Brief summary: Clinical study of Humira (adalimumab) or placebo in subjects with mild-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.

Primary outcomes:
measure: 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
timeFrame: 28 Days
measure: Assess the safety of adalimumab in subjects with COVID-19
timeFrame: 28 Days
Secondary outcomes:
measure: Assess the impact of treatment with adalimumab on clinical course of COVID-19 infection
timeFrame: 120 Days
Other outcomes:
Locations:
Study officials:
References: