Clinical Study to Compare Efficacy and Safety of Casirivimab and Imdevimab Combination, Remdesivir and Favipravir in Hospitalized COVID-19 Patients

NCT05502081 | Completed Phase 4 Results DMC FDA Drug

• 2 other identifiers: MS.21.11.173735039/11/21
• Study Type: interventional
• Target: 265
• Locations: 1 country
• Sites: 1

Brief Summary

Introduction: Corona Virus induced disease - 2019 (COVID-19) pandemic stimulates research works to find a solution to this crisis from starting 2020 year up to now. With ending of 2021 year, various advances in pharmacotherapy against COVID-19 have emerged. Regarding antiviral therapy, Casirivimab and imdevimab antibody combination is a type of new immunotherapy against COVID-19. Standard antiviral therapy against COVID-19 includes Remdesivir and Favipravir. Aim of Study:

1. 1.To compare the efficacy of antibodies cocktail (casirivimab and imdevimab), Remdesivir and Favipravir in reducing 28-day mortality in hospitalized patients with moderate, severe or critical COVID19
2. 2.To compare safety of antibodies cocktail (casirivimab and imdevimab), Remdesivir and Favipravir by monitoring hypersensitivity and infusion related reactions or other significant adverse effects
3. 3.Group A: REGN3048-3051(Antibodies cocktail (casirivimab and imdevimab))
4. 4.group B: Remdesivir
5. 5.group C: Favipravir

Conditions

COVID-19

Keywords

COVID-19; Casirivimab & Imdevimab; Remdesivir; Favipravir

Outcome Measures

Primary Outcomes (3)

• 28-days Mortality Rate

  Dead or alive

  28 days

• Number of Participants With Positive or Negative Polymerase Chain Reaction (PCR) Test Results at End of Hospital Visit

  positive or negative

  up to 60 days

• Number of Participants With Infusion Related Reactions, Hypersensitivity Reactions and Any Serious Adverse Events

  yes or no

  up to 60 days

Secondary Outcomes (61)

• Need for Invasive Mechanical Ventilation

  up to 60 days

• Oxygen Support Duration (Days)

  up to 60 days

• Time to Clinical Improvement (Defined as 2 Points Reduction in the WHO Disease Ordinal Progression Scale or Discharge, Whatever Happens First

  up to 60 days

• Duration of Hospitalization

  up to 60 days

• Sequential Organ Function Assessment (SOFA) Score on Day 3

  Day 3

Other Outcomes (8)

• Glasgow Coma Score (GCS) at Day 3

  day 3

• Arterial Oxygen Pressure / Fraction Inspired of Oxygen (PaO2/FiO2) at Day 3

  day 3

• Arterial Oxygen Pressure / Fraction Inspired of Oxygen (PaO2/FiO2) at Day 7

  day 7

Study Arms (3)

casirivimab and imdevimab

EXPERIMENTAL

casirivimab and imdevimab, vials 1.2 gm (1200 mg of combined antibodies) diluted in 250 ml 0.9% sodium chloride solution as single I.V infusion over 30-60 minutes.

Drug: Casirivimab and Imdevimab Drug Combination

Remdesivir

EXPERIMENTAL

Remdesivir, vials Day1 (loading dose): 200 mg (two 100mg vials) diluted in 500ml 0.9% sodium chloride solution infused I.V over 60 minutes Day 2-5 or Day 2-10 (maintenance dose): 100 mg (one 100mg vial) in 250 ml 0.9% sodium chloride solution infused I.V over 30 minutes

Drug: Remdesivir

Favipravir

EXPERIMENTAL

Favipravir, tablets Day 1 (loading dose): 1600 mg (8 tablets) or 1800 mg (9 tablets) orally or in Ryle tube / 12 hours Day 2-5 or day 2-10 (maintenance dose): 600 mg (3 tablets) or 800 mg (4 tablets) orally or in Ryle tube / 12 hours

Drug: Favipiravir

Interventions

Casirivimab and Imdevimab Drug Combination DRUG

antiviral Monoclonal Antibodies

Also known as: REGN-COV2

casirivimab and imdevimab

Remdesivir DRUG

antiviral drug

Also known as: Veklury

Remdesivir

Favipiravir DRUG

antiviral drug

Also known as: Avigan

Favipravir

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• age more than 12 years old.
• weight not less than 40 kg.
• Moderate, sever or critical COVID-19 disease as defined by WHO.

You may not qualify if:

• history of hypersensitivity or infusion related reactions after administration of monoclonal antibodies.
• prior use of standard antiviral therapy (remedsvir or favipravir).
• Current use of controversial antiviral therapy (hydroxychloroquine, ivermectin, nitazoxanide, oseltemavir, acyclovir, ribavirine, lopinvir/rotinvir, sofosfbuvir, decltasevir, semipirvir, azithromycin).
• patients expected to die within 48 hours.

Sponsors & Collaborators

• Mansoura University Hospital: lead

Study Sites (1)

El-gomhoria St

Al Mansurah, El-dkhalia, 050, Egypt

Location

Related Publications (14)

• Okonji EF, Okonji OC, Mukumbang FC, Van Wyk B. Understanding varying COVID-19 mortality rates reported in Africa compared to Europe, Americas and Asia. Trop Med Int Health. 2021 Jul;26(7):716-719. doi: 10.1111/tmi.13575. Epub 2021 May 1.

  PMID: 33733568 BACKGROUND

• COVID-19 Treatment Guidelines Panel. Coronavirus Disease 2019 (COVID-19) Treatment Guidelines [updated September 29, 2021. Available from: https://www.covid19treatmentguidelines.nih.gov.

  BACKGROUND

• Umakanthan S, Chattu VK, Ranade AV, Das D, Basavarajegowda A, Bukelo M. A rapid review of recent advances in diagnosis, treatment and vaccination for COVID-19. AIMS Public Health. 2021 Feb 1;8(1):137-153. doi: 10.3934/publichealth.2021011. eCollection 2021.

  PMID: 33575413 BACKGROUND

• Aleem A, Kothadia JP. Remdesivir. StatPearls. Treasure Island (FL): StatPearls Publishing Copyright © 2021, StatPearls Publishing LLC.; 2021

  BACKGROUND

• de Almeida SMV, Santos Soares JC, Dos Santos KL, Alves JEF, Ribeiro AG, Jacob ITT, da Silva Ferreira CJ, Dos Santos JC, de Oliveira JF, de Carvalho Junior LB, de Lima MDCA. COVID-19 therapy: What weapons do we bring into battle? Bioorg Med Chem. 2020 Dec 1;28(23):115757. doi: 10.1016/j.bmc.2020.115757. Epub 2020 Sep 10.

  PMID: 32992245 BACKGROUND

• Owji H, Negahdaripour M, Hajighahramani N. Immunotherapeutic approaches to curtail COVID-19. Int Immunopharmacol. 2020 Nov;88:106924. doi: 10.1016/j.intimp.2020.106924. Epub 2020 Aug 21.

  PMID: 32877828 BACKGROUND

• Baum A, Fulton BO, Wloga E, Copin R, Pascal KE, Russo V, Giordano S, Lanza K, Negron N, Ni M, Wei Y, Atwal GS, Murphy AJ, Stahl N, Yancopoulos GD, Kyratsous CA. Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies. Science. 2020 Aug 21;369(6506):1014-1018. doi: 10.1126/science.abd0831. Epub 2020 Jun 15.

  PMID: 32540904 BACKGROUND

• Hansen J, Baum A, Pascal KE, Russo V, Giordano S, Wloga E, Fulton BO, Yan Y, Koon K, Patel K, Chung KM, Hermann A, Ullman E, Cruz J, Rafique A, Huang T, Fairhurst J, Libertiny C, Malbec M, Lee WY, Welsh R, Farr G, Pennington S, Deshpande D, Cheng J, Watty A, Bouffard P, Babb R, Levenkova N, Chen C, Zhang B, Romero Hernandez A, Saotome K, Zhou Y, Franklin M, Sivapalasingam S, Lye DC, Weston S, Logue J, Haupt R, Frieman M, Chen G, Olson W, Murphy AJ, Stahl N, Yancopoulos GD, Kyratsous CA. Studies in humanized mice and convalescent humans yield a SARS-CoV-2 antibody cocktail. Science. 2020 Aug 21;369(6506):1010-1014. doi: 10.1126/science.abd0827. Epub 2020 Jun 15.

  PMID: 32540901 BACKGROUND

• Weinreich DM, Sivapalasingam S, Norton T, Ali S, Gao H, Bhore R, Musser BJ, Soo Y, Rofail D, Im J, Perry C, Pan C, Hosain R, Mahmood A, Davis JD, Turner KC, Hooper AT, Hamilton JD, Baum A, Kyratsous CA, Kim Y, Cook A, Kampman W, Kohli A, Sachdeva Y, Graber X, Kowal B, DiCioccio T, Stahl N, Lipsich L, Braunstein N, Herman G, Yancopoulos GD; Trial Investigators. REGN-COV2, a Neutralizing Antibody Cocktail, in Outpatients with Covid-19. N Engl J Med. 2021 Jan 21;384(3):238-251. doi: 10.1056/NEJMoa2035002. Epub 2020 Dec 17.

  PMID: 33332778 BACKGROUND

• FDA. EMERGENCY USE AUTHORIZATION (EUA) OF REGEN-COV (casirivimab and imdevimab): Food and Drug Adminsteration (FDA); 2021 [updated 16/9/2021. first:[FACT SHEET FOR HEALTH CARE PROVIDERS,]. Available from: https://www.fda.gov/media/145611/download

  BACKGROUND

• WHO COVID19 disease progression ordinal scale. February 18, 2020. [Available from: https://www.who.int/blueprint/priority-diseases/key-action/COVID-19_Treatment_Trial_Design_Master_Protocol_synopsis_Final_18022020.pdf

  BACKGROUND

• Placais L, Richier Q, Noel N, Lacombe K, Mariette X, Hermine O. Immune interventions in COVID-19: a matter of time? Mucosal Immunol. 2022 Feb;15(2):198-210. doi: 10.1038/s41385-021-00464-w. Epub 2021 Oct 28.

  PMID: 34711920 BACKGROUND

• Yang Z, Hu Q, Huang F, Xiong S, Sun Y. The prognostic value of the SOFA score in patients with COVID-19: A retrospective, observational study. Medicine (Baltimore). 2021 Aug 13;100(32):e26900. doi: 10.1097/MD.0000000000026900.

  PMID: 34397917 BACKGROUND

• Hegazy SK, Tharwat S, Hassan AH. Clinical study to compare the efficacy and safety of casirivimab & imdevimab, remdesivir, and favipravir in hospitalized COVID-19 patients. J Clin Virol Plus. 2023 Jun;3(2):100151. doi: 10.1016/j.jcvp.2023.100151. Epub 2023 May 10.

  PMID: 37220480 DERIVED

MeSH Terms

Conditions

COVID-19

Interventions

casirivimab and imdevimab drug combination; remdesivir; favipiravir

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

Limitations and Caveats

1. applicable only on hospitalized COVID-19 patients (not include outpatients), 2. non-randomization of antiviral drugs among included patients, 3. non-blinding of interventions to investigators

Results Point of Contact

• Title: Dr. Ahmed Hosny
• Organization: Mansoura University Hospital

ahmedony26@gmail.com

+2001554658010

Study Officials

• Shar K Hegazy, prof

  Tanta Unversity

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 10, 2022
• First Posted: August 16, 2022
• Study Start: September 2, 2022
• Primary Completion: December 28, 2022
• Study Completion: December 28, 2022
• Last Updated: July 25, 2023
• Results First Posted: February 21, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: After the end and publication of the study
• Access Criteria: all will be accessiable

Locations

EG (1)