Immune Modulators for Treating COVID-19

  • STATUS
    Recruiting
  • End date
    Sep 23, 2022
  • participants needed
    2160
  • sponsor
    Daniel Benjamin
Updated on 23 September 2021
Investigator
Theresa Jasion
Primary Contact
Hospital Nacional Aezobispo Loayza (3.3 mi away) Contact
+85 other location

Summary

ACTIV-1 IM is a master protocol designed to evaluate multiple investigational agents for the treatment of moderately or severely ill patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The research objectives are to evaluate each agent with respect to speed of recovery, mortality, illness severity, and hospital resource utilization. Each agent will be evaluated as add-on therapy to the standard of care (SoC) in use at the local clinics, including remdesivir (provided). The SoC may change during the course of the study based on other research findings. Comparisons of the agents among themselves is not a research objective.

The study population corresponds to moderately and severely ill patients infected with the coronavirus disease 2019 (COVID-19) virus. Recruitment will target patients already hospitalized for treatment of COVID-19 infection as well as patients being treated for COVID-19 infection in Emergency Departments while waiting to be admitted to the hospital. Patients both in and out of the ICU are included in the study population.

Description

ACTIV-1 IM is a master protocol designed to evaluate immune modulators for the treatment of moderately or severely ill hospitalized patients infected with COVID-19. Trial participants will be assessed daily while hospitalized. If the participants are discharged from the hospital prior to Day 29, they will have follow-up study visits at Days 8, 11, 15, 22, and 29. For discharged participants, it is preferred that the Day 8, 11, 15, and 29 visits are in person to obtain safety laboratory tests and blood (serum/plasma) samples for secondary research as well as clinical outcome data. However, infection control or other restrictions may limit the ability of the participant to return to the clinic. In this case, these visits may be conducted by phone, and only clinical data will be obtained. The Day 22 visit does not have laboratory tests or collection of samples and is conducted by phone. The Day 60 assessment will be conducted by phone.

The effectiveness of each therapeutic agent as add-on therapy to SoC plus remdesivir (provided) will be evaluated based on the primary endpoint of time to recovery by Day 29. The sample size requirements are based on the ability to detect a moderate improvement in time to recovery (3-4 fewer days) for each agent. A total of 788 recoveries are required for each comparison to provide approximately 85% power to detect a recovery rate ratio of 1.25. Assuming 73% of participants achieve recovery in 28 days, consistent with the ACTT-1 results, the total sample size to evaluate 1, 2, and 3 agents in ACTIV-1 IM is approximately 1080, 1620, and 2160, respectively. Because each agent is being compared to SoC with no between-agent comparisons, no multiplicity adjustments for multiple agents are planned.

Details
Condition COVID19
Treatment Infliximab, Abatacept, Cenicriviroc, Remdesivir
Clinical Study IdentifierNCT04593940
SponsorDaniel Benjamin
Last Modified on23 September 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Admitted to a hospital or awaiting admission in the ED with symptoms suggestive of COVID-19
Subject (or legally authorized representative) provides informed consent prior to initiation of any study procedures
Subject (or legally authorized representative) understands and agrees to comply with planned study procedures
Male or non-pregnant female adults 18 years of age at time of enrollment
Has laboratory-confirmed (within 14 days prior to enrollment) SARS-CoV-2 infection as determined by PCR or other commercial or public health assay in any specimen
Ongoing illness of any duration, and at least one of the following
Radiographic infiltrates by imaging (chest x-ray, CT scan, etc.), OR
Blood oxygen saturation (SpO2) 94% on room air, OR
Requiring supplemental oxygen, OR
Requiring mechanical ventilation or ECMO
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 60
Agrees to not to participate in another interventional trial for the treatment of COVID-19 through Day 60
Exception 1: Participant may co-enroll in ACTIV-4 (ACTIV-4A and ACTIV-4C)
Exception 2: Participants in ACTIV-2 who have been hospitalized may be
enrolled in ACTIV-1 as long as ACTIV-2 study therapy has been discontinued
They will remain in ACTIV-2 follow-up
Exception 3: If participant is already participating in a COVID-19 vaccine
trial but develops COVID-19 disease that requires hospitalization, participant
are met

Exclusion Criteria

Estimated glomerular filtration rate (eGFR) <30 mL/min (including patients receiving hemodialysis or hemofiltration)
ALT or AST >10 times the upper limit of normal
Exception: Participants with an eGFR <30 mL/min may enroll as long as their
renal insufficiency has been stable without renal replacement therapy for 1
month and they are not current candidates for renal replacement therapy. These
participants will not receive remdesivir
\. Neutropenia (absolute neutrophil count <1000 cells/L) (<1.0 x 103/L or
<1.0 GI/L)
\. Lymphopenia (absolute lymphocyte count <200 cells/L) (<0.20 x 103/L or
<0.20 GI/L)
\. Pregnancy or breast feeding
\. Anticipated discharge from the hospital or transfer to another hospital
which is not a study site within 72 hours
\. Known allergy to any study medication
\. Received cytotoxic or biologictargeted immune-modulator treatments (such
as anti-interleukin-1 [IL-1], anti-IL-6 [tocilizumab or sarilumab], anti-
IL-17, or T-cell or B-cell targeted therapies ([e.g., rituximab), tyrosine
kinase], JAK inhibitors [including baricitinib,], TNF inhibitors, or
interferon) within 4 weeks or 5 half-lives prior to screening., whichever is
longer. Steroid dependency, defined as need for prednisone at a dose >10 mg
(or equivalent) for >1 month within 2 weeks of screening, is exclusionary
Note Exception 1: Dexamethasone (at a dose of 6 mg per day for up to 10 days)
is permitted for the treatment of COVID-19 in patients who are already
mechanically ventilated and in patients who require supplemental oxygen at
screening, but who are not mechanically ventilated in accordance with national
guidelines. Note Exception 2: Infusion of convalescent plasma given for
treatment of COVID-19 while on-study is also allowed
Exception 3: Monoclonal antibody therapy given for COVID-19 treatment at any
time prior to enrollment is also allowed
\. BasedKnown or suspected history of untreated tuberculosis (TB). TB
diagnosis may be suspected based on medical history and concomitant therapies
that would suggest TB infection, have suspected clinical diagnosis of current
active tuberculosis (TB) or, if. Participants are also excluded if they have
known, latent TB treated for less than 4 weeks with appropriate anti-
tuberculosis therapy per local guidelines (by history only, no screening
required)
\. Based on medical history and concomitant therapies that would suggest
infection,Known or suspected serious, active bacterial, fungal, or viral
(infection (excepting SARS-CoV-2 and including, but not limited to, active
HBV, HCV, or HIV/AIDS). with the latter defined as a CD4 count <200 or an
unsuppressed HIV viral load), or other infection (besides COVID-19) that in
the opinion of the investigator could constitute a risk when taking
investigational product
Note: Broad-spectrum empiric antibiotic usage does not exclude participation
\. Have received any live vaccine (that is,or live attenuated) within 3
months before screening, or intend to receive a live vaccine (or live
attenuated) during the study. Note Exception: Use of prior non-live
(inactivated) vaccinations is allowed for all participants, including any
vaccine for COVID-19
\. Severe hepatic impairment (defined as liver cirrhosis Child stage C)
\. CurrentKnown severe heart failure (New York Heart Association [NYHA] III-
IV).) or new-onset left-systolic or global cardiac dysfunction in the setting
of COVID-19
Exception: Right-sided heart dysfunction or pulmonary hypertension thought
related to COVID-19 is permitted
\. In the Investigator's judgment, the patient has any advanced organ
dysfunction that would not make participation appropriate
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