Phase 2 Completed N=201 Randomized Double-blind Treatment

ACTIV-5 / Big Effect Trial (BET-C) for the Treatment of COVID-19

COVID

Source: ClinicalTrials.gov NCT04988035 ↗

Enrolled (actual)

201

Serious AEs

27.7%

Results posted

Jun 2023

Primary outcomePrimary: Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 8 — 11; 15; 24; 28 Participants — p=0.090

Summary

This is a platform trial to conduct a series of randomized, double-blind, placebo-controlled trials using common assessments and endpoints in hospitalized adults diagnosed with COVID-19. BET is a proof-of-concept study with the intent of identifying promising treatments to enter a more definitive study. The study will be conducted in up to 70 domestic sites and 5 international sites. The study will compare different investigational therapeutic agents to a common control arm and determine which have relatively large effects. In order to maintain the double blind, each intervention will have a matched placebo. However, the control arm will be shared between interventions and may include participants receiving the matched placebo for a different intervention. The goal is not to determine clear statistical significance for an intervention, but rather to determine which products have clinical data suggestive of efficacy and should be moved quickly into larger studies. Estimates produced from BET will provide an improved basis for designing the larger trial, in terms of sample size and endpoint selection. Products with little indication of efficacy will be dropped on the basis of interim evaluations. In addition, some interventions may be discontinued on the basis of interim futility or efficacy analyses. One or more interventions may be started at any time. The number of interventions enrolling are programmatic decisions and will be based on the number of sites and the pace of enrollment. At the time of enrollment, subjects will be randomized to receive any one of the active arms they are eligible for or placebo. Approximately 200 (100 treatment and 100 shared placebo) subjects will be assigned to each arm entering the platform and a given site will generally have no more than 3 interventions at once. The BET-C stage will evaluate the combination of remdesivir with danicopan vs remdesivir with a placebo. Subjects will be assessed daily while hospitalized. Once subjects are discharged from the hospital, they will have a study visit at Days 8, 15, 22, 29, and 60 as an outpatient. The Day 8, Day 22 and Day 60 visits do not have laboratory tests or collection of samples and may be conducted by phone. All subjects will undergo a series of efficacy and safety laboratory assessments. Safety laboratory tests and blood (serum, plasma and RNA) research samples on Day 1 (prior to study product administration) and Days 3, 5, 8, and 11 while hospitalized. Blood research samples plus safety laboratory tests will be collected on Day 15 and 29 if the subject attends an in-person visit or is still hospitalized. However, if infection control considerations or other restrictions prevent the subject from returning to the clinic, Day 15 and 29 visits may be conducted by phone and only clinical data will be obtained. The primary objective is to evaluate the clinical efficacy of danicopan relative to the control arm in adults hospitalized with COVID-19 according to clinical status (8-point ordinal scale) at Day 8.

Outcome Measures

Outcome	Result	p-value
PRIMARY Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 8	11; 15; 24; 28; 1; 3	0.090
SECONDARY Proportion of Participants Not Meeting Criteria for One of Two Ordinal Scale Categories Through Day 29	0.79; 0.83	0.358
SECONDARY Time to Sustained Recovery	13.0; 7.0	0.014 sig
SECONDARY Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 15	22; 27; 37; 42; 0; 1	0.177
SECONDARY Number of Participants Meeting Criteria for Each of the 8 Ordinal Scale Categories on Day 29	33; 35; 34; 42; 0; 0	0.427
SECONDARY Change From Baseline in C-Reactive Protein (CRP)	-21.477; -48.165; -47.823; -46.581; -33.995; -73.535	—
SECONDARY Change From Baseline in Ferritin	-54.975; -154.437; 229.343; -364.747; -399.190; -400.668	—
SECONDARY Change From Baseline in D-dimer	194.0; -318.2; 233.3; 1006.2; 715.3; -2594.2	—
SECONDARY Change From Baseline in Fibrinogen	-96.062; -67.054; -121.644; -99.074; -100.419; -59.927	—
SECONDARY Change From Baseline in Alanine Aminotransferase (ALT)	1.2; 3.9; 23.7; 11.4; -9.6; -0.5	—
SECONDARY Change From Baseline in Aspartate Transaminase (AST)	-9.0; -5.8; -1.2; -8.2; -22.3; -16.7	—
SECONDARY Change From Baseline in Creatinine	-0.006; -0.035; 0.045; -0.031; 0.030; 0.428	—
SECONDARY Change From Baseline in International Normalized Ratio (INR)	-0.064; -0.005; -0.071; -0.037; 0.012; -0.129	—
SECONDARY Change From Baseline in Hemoglobin	-0.26; -0.16; -0.05; -0.27; -0.45; -0.24	—
SECONDARY Change From Baseline in Platelets Count	35.83; 53.84; 65.06; 87.31; 69.88; 120.49	—
SECONDARY Change From Baseline in Total Bilirubin	-0.425; 0.009; -0.494; 0.040; -0.715; 0.049	—
SECONDARY Change From Baseline in White Blood Cell (WBC) Count	2.041; 1.247; 3.276; 2.550; 5.625; 3.483	—
SECONDARY Change From Baseline in Neutrophils	0.2636; -0.2675; 3.7855; 1.5898; 4.2105; 0.1951	—
SECONDARY Change From Baseline in Eosinophils	-0.0055; 0.0047; 0.0073; 0.0559; 0.0750; 0.0569	—
SECONDARY Change From Baseline in Basophils	0.0000; 0.0111; 0.0027; 0.0119; 0.0100; 0.0340	—
SECONDARY Change From Baseline in Lymphocytes	0.2654; 0.1144; 0.4474; 0.3570; 0.5374; 0.0605	—
SECONDARY Change From Baseline in Monocytes	0.1490; 0.1991; 0.2622; 0.1637; 0.4576; 0.3227	—
SECONDARY Number of Participants Reporting Grade 3 ,4, or 5 Clinical and/or Laboratory Adverse Events (AEs)	43; 46	—
SECONDARY Number of Participants Reporting Serious Adverse Events (SAEs)	31; 23	—
SECONDARY Number of Participants Who Discontinued or Temporarily Suspended Study Treatment	9; 8	—
SECONDARY Duration of Hospitalization	9.5; 8.0; 10.0; 8.0	—
SECONDARY Duration of Intensive Care Unit (ICU) Stay	0.0; 0.0	—
SECONDARY Days of Invasive Mechanical Ventilation/Extracorporeal Membrane Oxygenation (ECMO) Use	0.0; 0.0	—
SECONDARY Days of New Mechanical Ventilation or Extracorporeal Membrane Oxygenation (ECMO) Use	0.0; 0.0	—
SECONDARY Days of New Non-invasive Ventilation/High Flow Oxygen Use	0.0; 0.0	—
SECONDARY Days of Non-invasive Ventilation/High Flow Oxygen Use	3.0; 3.0	—
SECONDARY Days of Supplemental Oxygen Use	19.5; 23.0	—
SECONDARY Number of Participants With New Invasive Mechanical Ventilation / Extracorporeal Membrane Oxygenation (ECMO) Use	16; 14	—
SECONDARY Number of Participants With New Non-invasive Ventilation/High Flow Oxygen Use	14; 18	—
SECONDARY Mean Change in Ordinal Scale	0.0; 0.0; -0.3; -0.5; -1.2; -1.7	—
SECONDARY Proportion of Participants Not Meeting Criteria for One of Two Ordinal Scale Categories at Day 29	0.78; 0.85	—
SECONDARY 14-day Participant Mortality	0.14; 0.08	—
SECONDARY 28-day Participant Mortality	0.18; 0.13	—
SECONDARY 59-day Participant Mortality	0.21; 0.14	—
SECONDARY Time to an Improvement of One Category From Baseline Using an Ordinal Scale	8.0; 6.0	0.109
SECONDARY Time to an Improvement of Two Categories From Baseline Using an Ordinal Scale	13.0; 10.0	0.036 sig
SECONDARY Time to Death	NA; NA	—

Eligibility Criteria

Inclusion Criteria

Admitted to a hospital with symptoms suggestive of COVID-19 and requires ongoing medical care.
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 adult >/=18 years of age at time of enrollment.
Illness of any duration and has laboratory-confirmed SARS-CoV-2 infection as determined by polymerase chain reaction (PCR) or other commercial or public health assay (e.g., Nucleic Acid Amplification Test [NAAT], antigen test) in any respiratory specimen or saliva 5 times the upper limit of normal.
Subjects with a low glomerular filtration rate (eGFR), specifically:
Subjects with an eGFR 15-30 mL/min are excluded unless in the opinion of the principal investigator (PI), the potential benefit of participation outweighs the potential risk of study participation.
All subjects with an eGFR <15 mL/min (including hemodialysis and hemofiltration) are excluded.
Pregnancy or breast feeding
Anticipated discharge from the hospital or transfer to another hospital which is not a study site within 72 hours of enrollment.
Allergy to any study medication.
Received five or more doses of remdesivir prior to screening.
Treatment with a complement inhibitor in the prior 8 weeks.*
Has active uncontrolled opportunistic infection, or uncontrolled cirrhosis.*
History of infection with N. meningitidis.*
Known history of hypersensitivity to danicopan or its excipients.*
Has a medical condition that could, in the judgment of the investigator, limit the interpretation and generalizability of trial results.
Positive test for influenza virus during the current illness (influenza testing is not required by protocol).
History of liver cirrhosis.*
Previous participation in an ACTIV-5/BET trial.
Refuses to refrain from breastfeeding from the time of screening through 30 days after the last dose of danicopan.*
Refuses to receive prophylactic antibiotics against meningococcal infections if the subject has not been vaccinated in the 3 years prior to Study Day 1.

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT04988035). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.