Study of Multiple Candidate Agents for the Treatment of COVID-19 in Hospitalized Patients

NCT04590586 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: COV-01
• Study Type: interventional
• Target: 515
• Locations: 8 countries
• Sites: 59

Brief Summary

The primary objective of this study is to evaluate the time to confirmed clinical recovery in participants hospitalized with COVID-19. Candidate agents will be evaluated frequently for efficacy and safety, with candidate agents being added to and/or removed from the study on an ongoing basis, depending on the results of their evaluation.

Conditions

COVID-19

Keywords

SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2

Outcome Measures

Primary Outcomes (3)

• Lanadelumab Sub-protocol: Time to Confirmed Clinical Recovery Without Rehospitalization Through Day 29

  Confirmed clinical recovery means the participant is fit for discharge from hospital, defined by achieving a score of 6 (hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care), 7 (not hospitalized, limitation on activities and/or requiring home oxygen), or 8 (not hospitalized, no limitations on activities) on the clinical severity status 8-point ordinal scale, without being re-hospitalized prior to Day 29. The Kaplan-Meier estimate of the time to confirmed clinical recovery through Day 29, without re-hospitalization through Day 29, was calculated from Study Day 1 to the earliest date on which the participant had a score of 6, 7, or 8 up to Day 29. Participants who never reached a score of 6, 7, or 8 on the clinical severity status 8-point ordinal scale before or on Day 29 were censored at Day 29. Participants who discontinued from the study before or on Day 29 were censored at time of discontinuation from study.

  Day 1 (the day of the first dose of study drug for randomized participants who received at least one dose of study drug or the day of randomization for randomized participants who did not receive any study drug) to Day 29

• Apremilast Sub-protocol: Time to Confirmed Clinical Recovery Without Rehospitalization Through Day 29

  Confirmed clinical recovery means the participant is fit for discharge from hospital, defined by achieving a score of 6 (hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care), 7 (not hospitalized, limitation on activities and/or requiring home oxygen), or 8 (not hospitalized, no limitations on activities) on the clinical severity status 8-point ordinal scale, without being re-hospitalized prior to Day 29. The Kaplan-Meier estimate of the time to confirmed clinical recovery through Day 29, without re-hospitalization through Day 29, was calculated from Study Day 1 to the earliest date on which the participant had a score of 6, 7, or 8 up to Day 29. Participants who never reached a score of 6, 7, or 8 on the clinical severity status 8-point ordinal scale before or on Day 29 were censored at Day 29. Participants who discontinued from the study before or on Day 29 were censored at time of discontinuation from study.

  Day 1 (the day of the first dose of study drug for randomized participants who received at least one dose of study drug or the day of randomization for randomized participants who did not receive any study drug) to Day 29

• Zilucoplan Sub-protocol: Time to Confirmed Clinical Recovery Without Rehospitalization Through Day 29

  Confirmed clinical recovery means the participant is fit for discharge from hospital, defined by achieving a score of 6 (hospitalized, not requiring supplemental oxygen, no longer requires ongoing medical care), 7 (not hospitalized, limitation on activities and/or requiring home oxygen), or 8 (not hospitalized, no limitations on activities) on the clinical severity status 8-point ordinal scale, without being re-hospitalized prior to Day 29. The Kaplan-Meier estimate of the time to confirmed clinical recovery through Day 29, without re-hospitalization through Day 29, was calculated from Study Day 1 to the earliest date on which the participant had a score of 6, 7, or 8 up to Day 29. Participants who never reached a score of 6, 7, or 8 on the clinical severity status 8-point ordinal scale before or on Day 29 were censored at Day 29. Participants who discontinued from the study before or on Day 29 were censored at time of discontinuation from study.

  Day 1 (the day of the first dose of study drug for randomized participants who received at least one dose of study drug or the day of randomization for randomized participants who did not receive any study drug) to Day 29

Secondary Outcomes (30)

• Lanadelumab Sub-protocol: Percentage of Participants Who Achieved Oxygen-Free Recovery at Day 29

  Day 29

• Lanadelumab Sub-protocol: Percentage of Participants With a ≥ 2-point Improvement From Baseline or Fit for Discharge on the Clinical Severity Status 8-Point Ordinal Scale at Day 29

  Baseline (Day 1) and Day 29

• Lanadelumab Sub-protocol: Percentage of Participants Who Died Before or on Day 29

  Day 1 to Day 29

• Lanadelumab Sub-protocol: Clinical Severity Status 8-Point Ordinal Scale Score at Days 8, 15, and 29

  Day 8, Day 15, and Day 29

• Lanadelumab Sub-protocol: Worst Post-Baseline Score on Clinical Severity Status 8-point Ordinal Scale From Baseline to Day 29

  Day 2 to Day 29

Study Arms (6)

Apremilast + Standard of Care

EXPERIMENTAL

Participants will be randomized to receive 30 mg apremilast orally twice a day (BID) in addition to standard of care treatment for 14 days or until hospital discharge, death, or discontinuation of investigational product, whichever occurred first.

Drug: Standard of care; Drug: Apremilast

Apremilast Placebo + Standard of Care

PLACEBO COMPARATOR

Participants will be randomized to receive matching placebo to apremilast orally twice a day in addition to standard of care treatment for 14 days or until hospital discharge, death, or discontinuation of investigational product, whichever occurred first.

Drug: Standard of care; Drug: Apremilast placebo

Lanadelumab + Standard of Care

EXPERIMENTAL

Participants will be randomized to receive lanadelumab 300 mg by intravenous infusion on Day 1, and a second dose administered on Day 4 in addition to standard of care.

Drug: Standard of care; Drug: Lanadelumab

Lanadelumab Placebo + Standard of Care

PLACEBO COMPARATOR

Participants will be randomized to receive placebo to lanadelumab by intravenous infusion on Day 1, and a second dose administered on Day 4 in addition to standard of care.

Drug: Standard of care; Drug: Lanadelumab placebo

Zilucoplan + Standard of Care

EXPERIMENTAL

Participants will be randomized to receive 32.4 mg zilucoplan by subcutaneous injection every day for 14 days, or until discharge if discharge was before 14 days of treatment in addition to standard of care.

Drug: Standard of care; Drug: Zilucoplan

Zilucoplan Placebo + Standard of Care

PLACEBO COMPARATOR

Participants will be randomized to receive placebo to zilucoplan by subcutaneous injection every day for 14 days, or until discharge if discharge was before 14 days of treatment in addition to standard of care.

Drug: Standard of care; Drug: Zilucoplan placebo

Interventions

Standard of care DRUG

Standard of care (SoC) treatment for COVID-19 infection in line with institutional practice. The SoC may change as new information becomes available about treating COVID-19.

Apremilast + Standard of Care; Apremilast Placebo + Standard of Care; Lanadelumab + Standard of Care; Lanadelumab Placebo + Standard of Care; Zilucoplan + Standard of Care; Zilucoplan Placebo + Standard of Care

Apremilast DRUG

Apremilast administered orally as a tablet.

Also known as: Otezla

Apremilast + Standard of Care

Apremilast placebo DRUG

Matching apremilast placebo administered orally as a tablet.

Apremilast Placebo + Standard of Care

Lanadelumab DRUG

Lanadelumab administered as an intravenous (IV) infusion.

Also known as: TAKHZYRO™, TAK-743

Lanadelumab + Standard of Care

Lanadelumab placebo DRUG

Matching lanadelumab placebo (normal saline) administered as an intravenous (IV) infusion.

Lanadelumab Placebo + Standard of Care

Zilucoplan DRUG

Zilucoplan administered as a subcutaneous (sc) injection in the abdomen, thigh, or upper arm.

Zilucoplan + Standard of Care

Zilucoplan placebo DRUG

Matching zilucoplan placebo administered as a subcutaneous (sc) injection in the abdomen, thigh, or upper arm.

Zilucoplan Placebo + Standard of Care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults (≥18 years of age) with active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection confirmed by laboratory tests and/or point of care tests (eg, commercial or public health assay, which is approved for emergency use). If no diagnostic test results are available that have been obtained during the previous 72 hours, then a test should be performed as part of the screening assessment.
• A score of Grade 2 (hospitalized, on invasive mechanical ventilation or ECMO), Grade 3 (hospitalized, on noninvasive ventilation or high-flow oxygen devices), Grade 4 (hospitalized, requiring supplemental oxygen), or Grade 5 (hospitalized, not requiring supplemental oxygen, requiring ongoing medical care \[COVID-19 related or otherwise\]), as defined by an 8 point ordinal scale.
• Male participants:
• A male participant must agree to use contraception during the treatment period and for at least 6 weeks after the last dose of study treatment and refrain from donating sperm during this period.
• Female participants:
• A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions applies:
• Not a woman of childbearing potential (WOCBP). OR
• A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 6 weeks after the last dose of study treatment.
• Ability to provide informed consent signed by the study participant or legally authorized representative.
• Ability and willingness to participate in telephone/telemedicine follow-up visits if needed.
• Zilucoplan only: Antibiotic prophylaxis: all participants must be willing to take antibiotic prophylaxis concomitantly, starting with the first dose of zilucoplan or placebo.

You may not qualify if:

• Participant has any condition for which, in the opinion of the Investigator, participation would not be in the best interest of the participant (eg, compromise their well-being) or that could prevent, limit, or confound the protocol-specified assessments (eg, participants unable to swallow study medication tablets).
• Stage 4 severe chronic kidney disease or requiring dialysis.
• Screening 12-lead electrocardiogram (ECG) with a measurable QTc interval according to Fridericia correction (QTcF) ≥ 500 ms.
• Anticipated transfer to another hospital that is not a study center within 72 hours.
• Participants who are currently pregnant or who are not willing to discontinue breastfeeding.
• Participants participating in another clinical study of an investigational medicinal product or other unapproved (or investigational) treatment for COVID-19.
• Active tuberculosis or a history of incompletely treated tuberculosis.
• Active, uncontrolled systemic bacterial or fungal infection(s).
• Apremilast only: Current treatment with apremilast, or another agent of similar mechanism of action, for any indication within 1 week prior to first dose of investigational product.
• Apremilast only: Concurrent use at screening or randomization of cytochrome P450 (CYP)3A inducers (eg, rifampin, phenobarbital, carbamazepine) within 1 week prior to first dose of investigational product.
• Apremilast only: Known hypersensitivity to apremilast or any excipients in formulation.
• Lanadelumab only: Known or suspected hypersensitivity to lanadelumab or any of its excipients.
• Lanadelumab only: Previous (within 3 months prior to baseline) or current use of immunomodulators (eg, methotrexate, azathioprine, 6-mercaptopurine, tumor necrosis factor \[TNF\] α inhibitor, Janus kinase \[JAK\] inhibitor, alpha-integrin inhibitor).
• Lanadelumab only: Known or suspected venous thromboembolism.
• Lanadelumab only: Previous (within 3 months \[or 5 half-lives, whichever is greater\] of screening) or current use of plasma kallikrein (pKal) inhibitor or bradykinin receptor blocker.

Sponsors & Collaborators

• Amgen: lead

Study Sites (59)

Pinnacle Research Group LLC

Anniston, Alabama, 36207, United States

Location

Good Samaritan Hospital

Bakersfield, California, 93309, United States

Location

Sharp Chula Vista Medical Center

Chula Vista, California, 91910, United States

Location

El Centro Regional Medical Center

El Centro, California, 92243, United States

Location

University of California Irvine Medical Center

Orange, California, 92868, United States

Location

Riverside Community Hospital

Riverside, California, 92501-4135, United States

Location

University of California Davis Health System

Sacramento, California, 95817, United States

Location

National Institute of Clinical Research

South El Monte, California, 91733, United States

Location

UF Health Shands Hospital

Gainesville, Florida, 32610, United States

Location

Memorial Hospital Jacksonville

Jacksonville, Florida, 32216, United States

Location

Grady Health System

Atlanta, Georgia, 30303, United States

Location

Great Lakes Clinical Trials

Chicago, Illinois, 60640, United States

Location

The University of Iowa

Iowa City, Iowa, 52242, United States

Location

Harper University Hospital

Detroit, Michigan, 48201-2018, United States

Location

Sinai Grace Hospital

Detroit, Michigan, 48235, United States

Location

Detroit Receiving Hospital

Royal Oak, Michigan, 48073, United States

Location

University of Tennessee Health Sciences Center

Memphis, Tennessee, 38103, United States

Location

Medical City Ft. Worth

Fort Worth, Texas, 76104, United States

Location

University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

Location

Texoma Medical Center

Sherman, Texas, 75090, United States

Location

MultiCare Health System Institute for Research and Innovation

Tacoma, Washington, 98405, United States

Location

Hospital San Juan de Dios

Ramos Mejía, Buenos Aires, 1704, Argentina

Location

Hospital General de Agudos Dr. J. M. Ramos Mejia

Ciudad Autonoma Buenos Aires, C1221ADC, Argentina

Location

Hospital General de Agudos Dr. Ignacio Pirovano

Ciudad Autonoma Buenos Aires, C1430BKC, Argentina

Location

Clinica Adventista Belgrano

Ciudad Autonoma Buenos Aires, C1430EGF, Argentina

Location

Hospital Italiano de Rosario

Rosario, 2000, Argentina

Location

Chronos Pesquisa Clinica

Brasília, Federal District, 72.145-450, Brazil

Location

HC-UFG - Hospital das Clínicas da Universidade Federal de Goiás

Goiânia, Goiás, 74605-020, Brazil

Location

Santa Casa de Misericórdia de Belo Horizonte

Belo Horizonte, Minas Gerais, 30150-221, Brazil

Location

Hospital de Clínicas de Porto Alegre

Porto Alegre, Rio Grande do Sul, 90035-903, Brazil

Location

UNESP - Faculdade de Medicina da Universidade Estadual Paulista - Campus Botucatu

Botucatu, São Paulo, 18618-970, Brazil

Location

Praxis Pesquisa Médica

Santo André, São Paulo, 09090-790, Brazil

Location

Hospital Base Osorno

Osorno, 5290000, Chile

Location

Hospital General de Tijuana

Tijuana, Baja California Norte, 22000, Mexico

Location

Hospital Civil de Guadalajara Dr. Juan I. Menchaca

Guadalajara, Jalisco, 44340, Mexico

Location

Universidad Autonoma de Nuevo Leon, Hospital Universitario Dr. Jose Eleuterio Gonzalez

Monterrey, Nuevo León, 64460, Mexico

Location

Hospital Civil de Culiacan

Culiacán, Sinaloa, 80030, Mexico

Location

TSBIH "Krasnoyarsk Interdistrict Clinical Hospital of Emergency Medical Care n.a. N.S. Karpovich

Krasnoyarsk, 660062, Russia

Location

SBIH of Moscow "Infectious Clinical Hospital # 1 of Department of Healthcare of Moscow"

Moscow, 125367, Russia

Location

SPb SBIH "Alexandrovskaya City Hospital"

Saint Petersburg, 193312, Russia

Location

St-George Hospital

Saint Petersburg, 194354, Russia

Location

SPb SBIH "Nikolaevskaya Hospital"

Saint Petersburg, 198510, Russia

Location

SPb SBIH "City Pokrovskaya Hospital"

Saint Petersburg, 199106, Russia

Location

SPb SBIH "City Hospital # 40 of Kurortnyi region"

Sestroretsk, 197706, Russia

Location

Nelson Mandela Academic Clinical Research Unit (NeMACRU)

Mthatha, Eastern Cape, 5100, South Africa

Location

Johese Clinical Research: Unitas

Centurion, Gauteng, 0157, South Africa

Location

MERC SiReN

Johannesburg, Gauteng, 2193, South Africa

Location

Drs Sarvan and Moodley

Durban, KwaZulu-Natal, 4320, South Africa

Location

Tread Research

Cape Town, Western Cape, 7500, South Africa

Location

Tiervlei Trial Centre

Cape Town, Western Cape, 7530, South Africa

Location

2 Military Hospital Internal Medicine

Cape Town, Western Cape, 7800, South Africa

Location

Dr JM Engelbrecht Trial Site

Somerset West, Western Cape, 7130, South Africa

Location

Clinical Projects Research SA (PTY) LTD

Worcester, Western Cape, 6850, South Africa

Location

Communal Noncommercial Profit "Clinical City Hospital 16 of Dnipro Regional Council"

Dnipro, 49069, Ukraine

Location

CNE of Kharkov RC Reg Cl Infectious Hospital

Kharkiv, 61096, Ukraine

Location

Communal Non-Commercial Medical Enterprise "O.T.Bohayevskyi Kremenchuk City Hospital #1"

Kremenchuk, 39623, Ukraine

Location

City Clinical infectious Hospital

Odesa, 65026, Ukraine

Location

Municipal Non-Profit Enterprise Central City Hospital Of Rivne City Council

Rivne, 33017, Ukraine

Location

CCH #1 Vinnytsia M.I.Pyrogov NMU Ch of Infectious Diseases

Vinnytsia, 21029, Ukraine

Location

Related Publications (1)

• Kreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, Neidhardt M, Piechotta V, Salomon S, Valk SJ, Monsef I, Schmaderer C, Wood EM, So-Osman C, Roberts DJ, McQuilten Z, Estcourt LJ, Skoetz N. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;9(9):CD013825. doi: 10.1002/14651858.CD013825.pub2.

  PMID: 34473343 DERIVED

MeSH Terms

Conditions

COVID-19

Interventions

Standard of Care; apremilast; lanadelumab; zilucoplan

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

medinfo@amgen.com

866-572-6436

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 14, 2020
• First Posted: October 19, 2020
• Study Start: November 24, 2020
• Primary Completion: August 3, 2021
• Study Completion: August 3, 2021
• Last Updated: June 29, 2022
• Results First Posted: June 29, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.

Locations

ME (4); AR (5); RU (7); CL (1); ZA (9); US (21); BR (6); UA (6)