A Phase 2/3 Study to Evaluate the Efficacy and Safety of CT-P59 in Patients With Mild to Moderate SARS-CoV-2 Infection

• ClinicalTrials.gov Identifier: NCT04602000
• Recruitment Status: Completed
• First Posted: October 26, 2020
• Results First Posted: July 20, 2022
• Last Update Posted: July 20, 2022
• Sponsor: Celltrion
• Information provided by (Responsible Party): Celltrion

Study Description

Brief Summary:

This was a Phase 2/3 study to assess the efficacy about therapeutic effect of CT-P59 to the mild to moderate SARS-CoV-2 infected patients and the safety during after study drug injection.

Condition or disease	Intervention/treatment	Phase
SARS-CoV-2 Infection	Biological: CT-P59; Biological: Placebo	Phase 2; Phase 3

Detailed Description:

CT-P59 is a human monoclonal antibody targeted against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein as a treatment for SARS-CoV-2 infection, which is manufactured by recombinant deoxyribonucleic acid technology in a Chinese hamster ovary mammalian cell line. This Phase 2/3, randomized, parallel-group, placebo-controlled, double-blind study was designed to evaluate the safety, tolerability, and therapeutic potential of CT-P59 in outpatients with mild to moderate SARS-CoV-2 infection, not requiring supplemental oxygen therapy.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 1642 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 2/3, Randomized, Parallel-group, Placebo-controlled, Double-Blind Study to Evaluate the Efficacy and Safety of CT-P59 in Combination With Standard of Care in Outpatients With SARS-CoV-2 Infection
• Actual Study Start Date: October 5, 2020
• Actual Primary Completion Date: May 21, 2021
• Actual Study Completion Date: October 20, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: CT-P59 40 mg/kg group (Part 1); CT-P59 (regdanvimab), 40 mg/kg by IV infusion once	Biological: CT-P59; CT-P59 (40 mg/kg) by IV infusion administered over 90 minutes, once (Part 1); Other Name: regdanvimab
Experimental: CT-P59 80 mg/kg group (Part 1); CT-P59 (regdanvimab), 80 mg/kg by IV infusion once	Biological: CT-P59; CT-P59 (80 mg/kg) by IV infusion administered over 90 minutes, once (Part 1); Other Name: regdanvimab
Placebo Comparator: Placebo group (Part 1); Placebo, matching in volume of CT-P59 80 mg/kg by IV infusion once	Biological: Placebo; Placebo (80 mg/kg) by IV infusion administered over 90 minutes, once (Part 1)
Experimental: CT-P59 40 mg/kg group (Part 2); CT-P59 (regdanvimab), 40 mg/kg by IV infusion once	Biological: CT-P59; CT-P59 (40 mg/kg) by IV infusion administered over 60 minutes, once (Part 2); Other Name: regdanvimab
Placebo Comparator: Placebo group (Part 2); Placebo, matching in volume of CT-P59 40 mg/kg by IV infusion once	Biological: Placebo; Placebo (40 mg/kg) by IV infusion administered over 60 minutes, once (Part 2)

Outcome Measures

Primary Outcome Measures :

1. Proportion of Patients With Clinical Symptom Requiring Hospitalization, Oxygen Therapy, or Experiencing Mortality Due to SARS-CoV-2 Infection (Part 1) [ Time Frame: Up to Day 28 ]
   To assess the clinically meaningful therapeutic efficacy of CT-P59 as determined by proportion of patients with clinical symptom requiring hospitalization, oxygen therapy, or experiencing mortality due to SARS-CoV-2 infection up to Day 28
2. Proportion of Patients With Negative Conversion in Nasopharyngeal Swab Specimen Based on RT-qPCR at Each Visit (Part 1) [ Time Frame: Up to Day 14 ]
   To assess the potential therapeutic efficacy of CT-P59 as determined by proportion of negative conversion in nasopharyngeal swab specimen based on RT-qPCR up to Day 14
3. Time to Negative Conversion in Nasopharyngeal Swab Specimen (Part 1) [ Time Frame: Up to Day 14 ]
   To evaluate the therapeutic efficacy of CT-P59 as determined by time to negative conversion by RT-qPCR up to Day 14
4. Time to Clinical Recovery (Part 1) [ Time Frame: Up to Day 14 ]

   To assess the potential therapeutic efficacy of CT-P59 as determined by time to clinical recovery up to Day 14.

   Clinical recovery was defined as all symptoms on the SARS-CoV-2 Infection Symptom Checklist 1 being recorded as 'absent' or 'mild' in intensity for at least 48 hours. SARS-CoV-2 Infection Symptom Checklist 1 consisted of 7 symptoms (feeling feverish, cough, shortness of breath or difficulty breathing, sore throat, body pain or muscle pain, fatigue, and headache) and the intensity of patient's self-aware for each SARS-CoV-2 infection symptom (absent [0], mild [1]. moderate [2], and severe [3]).

   To meet the clinical recovery, symptoms 'severe' or 'moderate' in intensity at baseline should be changed to 'mild' or 'absent', or symptoms 'mild' in intensity at baseline should be changed to 'absent', after the study drug administration. Symptoms "absent" in intensity at baseline should maintain as "absent" for at least 48 hours.

5. Proportion of Patients With Clinical Symptom Requiring Hospitalization, Oxygen Therapy, or Experiencing Mortality Due to SARS-CoV-2 Infection up to Day 28 in High-risk Patients (Part 2) [ Time Frame: Up to Day 28 ]
   To demonstrate the clinically meaningful therapeutic efficacy of CT-P59 as determined by proportion of patients with clinical symptom requiring hospitalization, oxygen therapy, or experiencing mortality due to SARS-CoV-2 infection up to Day 28 in high-risk patients

Secondary Outcome Measures :

1. Proportion of Patients With Clinical Symptom Requiring Hospitalization, Oxygen Therapy, or Experiencing Mortality Due to SARS-CoV-2 Infection up to Day 28 in All Randomized Patients (Part 2) [ Time Frame: Up to Day 28 ]
   To demonstrate the clinically meaningful therapeutic efficacy of CT-P59 as determined by proportion of patients with clinical symptom requiring hospitalization, oxygen therapy, or experiencing mortality due to SARS-CoV-2 infection up to Day 28 in all randomized patients
2. Time to Clinical Recovery up to Day 14 in High-risk Patients (Part 2) [ Time Frame: Up to Day 14 ]

   To assess the potential therapeutic efficacy of CT-P59 as determined by time to clinical recovery up to Day 14 in high-risk patients.

   Clinical recovery was defined as all symptoms on the SARS-CoV-2 Infection Symptom Checklist 1 being recorded as 'absent' or 'mild' in intensity for at least 48 hours. SARS-CoV-2 Infection Symptom Checklist 1 consisted of 7 symptoms (feeling feverish, cough, shortness of breath or difficulty breathing, sore throat, body pain or muscle pain, fatigue, and headache) and the intensity of patient's self-aware for each SARS-CoV-2 infection symptom (absent [0], mild [1]. moderate [2], and severe [3]).

   To meet the clinical recovery, symptoms 'severe' or 'moderate' in intensity at baseline should be changed to 'mild' or 'absent', or symptoms 'mild' in intensity at baseline should be changed to 'absent', after the study drug administration. Symptoms "absent" in intensity at baseline should maintain as "absent" for at least 48 hours.

3. Time to Clinical Recovery up to Day 14 in All Randomized Patients (Part 2) [ Time Frame: Up to Day 14 ]

   To assess the potential therapeutic efficacy of CT-P59 as determined by time to clinical recovery up to Day 14 in all randomized patients.

   Clinical recovery was defined as all symptoms on the SARS-CoV-2 Infection Symptom Checklist 1 being recorded as 'absent' or 'mild' in intensity for at least 48 hours. SARS-CoV-2 Infection Symptom Checklist 1 consisted of 7 symptoms (feeling feverish, cough, shortness of breath or difficulty breathing, sore throat, body pain or muscle pain, fatigue, and headache) and the intensity of patient's self-aware for each SARS-CoV-2 infection symptom (absent [0], mild [1]. moderate [2], and severe [3]).

   To meet the clinical recovery, symptoms 'severe' or 'moderate' in intensity at baseline should be changed to 'mild' or 'absent', or symptoms 'mild' in intensity at baseline should be changed to 'absent', after the study drug administration. Symptoms "absent" in intensity at baseline should maintain as "absent" for at least 48 hours.

4. Proportion of Patients With Hospital Admission Due to SARS-CoV-2 Infection (Part 1 and Part 2) [ Time Frame: Up to Day 28 ]
   To evaluate the additional efficacy of CT-P59
5. Proportion of Patients Requiring Supplemental Oxygen Due to SARS-CoV-2 Infection (Part 1 and Part 2) [ Time Frame: Up to Day 28 ]
   To evaluate the additional efficacy of CT-P59
6. Proportion of Patients With Mechanical Ventilation Use Due to SARS-CoV-2 Infection (Part 1 and Part 2) [ Time Frame: Up to Day 28 ]
   To evaluate the additional efficacy of CT-P59
7. Proportion of Patients Requiring Rescue Therapy Due to SARS-CoV-2 Infection (Part 1 and Part 2) [ Time Frame: Up to Day 28 ]
   To evaluate the additional efficacy of CT-P59
8. Proportion of Patients With Intensive Care Unit Transfer Due to SARS-CoV-2 Infection (Part 1 and Part 2) [ Time Frame: Up to Day 28 ]
   To evaluate the additional efficacy of CT-P59
9. Proportion of Patients With All-cause Mortality (Part 1 and Part 2) [ Time Frame: Up to Day 28 ]
   To evaluate the additional efficacy of CT-P59
10. Time to Negative Conversion in Nasopharyngeal Swab Specimen Based on RT-qPCR (Part 1 and Part 2) [ Time Frame: Up to Day 28 ]
    To evaluate the additional efficacy of CT-P59
11. Proportion of Patient With Negative Conversion in Nasopharyngeal Swab Specimen Based on RT-qPCR at Each Visit (Part 1 and Part 2) [ Time Frame: Days 3, 7, 10, 14, 21, and 28 ]
    To evaluate the additional efficacy of CT-P59
12. Time to Clinical Recovery (Part 1 and Part 2) [ Time Frame: Up to Day 28 ]

    To evaluate the additional efficacy of CT-P59. Clinical recovery was defined as all symptoms on the SARS-CoV-2 Infection Symptom Checklist 1 being recorded as 'absent' or 'mild' in intensity for at least 48 hours. SARS-CoV-2 Infection Symptom Checklist 1 consisted of 7 symptoms (feeling feverish, cough, shortness of breath or difficulty breathing, sore throat, body pain or muscle pain, fatigue, and headache) and the intensity of patient's self-aware for each SARS-CoV-2 infection symptom (absent [0], mild [1]. moderate [2], and severe [3]).

    To meet the clinical recovery, symptoms 'severe' or 'moderate' in intensity at baseline should be changed to 'mild' or 'absent', or symptoms 'mild' in intensity at baseline should be changed to 'absent', after the study drug administration. Symptoms "absent" in intensity at baseline should maintain as "absent" for at least 48 hours.

Other Outcome Measures:

1. [Virology] Viral Serology for SARS-CoV-2 Antibody [ Time Frame: Days 1, 7, 14, 28, and 56 ]
   To assess the serology of SARS-CoV-2 antibody. The proportions of patients positive with IgG or IgM were summarized.
2. [PK] Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-inf) (Part 1) [ Time Frame: Pre-dose, end of infusion, 1, 24, 48, 96, 144, 216, 312, 648, 1320, 2136 hours after start of infusion ]
   To assess the PK of CT-P59
3. [PK] Maximum Serum Concentration (Cmax) (Part 1) [ Time Frame: Pre-dose, end of infusion, 1, 24, 48, 96, 144, 216, 312, 648, 1320, 2136 hours after start of infusion ]
   To assess the PK of CT-P59
4. [PK] Terminal Half-life (t1/2) (Part 1) [ Time Frame: Pre-dose, end of infusion, 1, 24, 48, 96, 144, 216, 312, 648, 1320, 2136 hours after start of infusion ]
   To assess the PK of CT-P59

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

Patient had to meet all of the following criteria to be randomized in this study.

1. Patient was an adult male or female patient, aged 18 or above.
2. Patient was diagnosed with SARS-CoV-2 infection at Screening by using the sponsor-supplied rapid SARS-CoV-2 diagnostic test or RT-PCR (reverse transcription-polymerase chain reaction).

3. Patient with conditions meeting all of the following criteria:

   1. Oxygen saturation > 94% on room air.
   2. Not requiring supplemental oxygen.
4. Patient who had an onset of symptom no more than 7 days prior to the study drug administration.
5. Patient had 1 or more of the SARS-CoV-2 infection-associated symptoms within but no more than 7 days prior to the study drug administration.

Exclusion Criteria:

Patients meeting any of the following criteria were excluded from the study.

1. Patient had current severe condition meeting one of the following:

   1. Previous or current hospitalization or requirement of hospitalization for treatment of serious SARS-CoV-2 related conditions.
   2. Respiratory distress with respiratory rate ≥30 breaths/min.
   3. Required supplemental oxygen
   4. Experienced shock
   5. Complicated with other organs failure, and intensive care unit monitoring treatment is needed by investigator's discretion.

2. Patient had received or had a plan to receive any of the following prohibited medications or treatments:

   1. Drugs with actual or possible antiviral drugs and/or possible anti-SARS-CoV-2 activity including but not limited to remdesivir, chloroquine, hydroxychloroquine, dexamethasone (or alternative corticosteroids to dexamethasone), interferon beta-1b, ribavirin, and other immunomodulatory agents and human immunodeficiency virus protease inhibitors (lopinavir-ritonavir, etc.) for therapeutic purpose of SARS-CoV-2 infection prior to study drug administration
   2. Any SARS-CoV-2 human IV immunoglobulin, convalescent plasma for the treatment of SARS-CoV-2 infection prior to study drug administration
   3. Any other investigational device or medical product including but not limited to any monoclonal antibody (tocilizumab, sarilumab, etc.), fusion proteins or biologics for the treatment of SARS-CoV-2 infection prior to the study drug administration
   4. Use of medications that are contraindicated with SoC
   5. SARS-CoV-2 vaccine prior to the study drug administration

Contacts and Locations

Locations

Korea, Republic of

Chungnam National University Hospital

Daejeon, Jung-gu, Korea, Republic of, 35015

Sponsors and Collaborators

Celltrion

  Study Documents (Full-Text)

Documents provided by Celltrion:

Study Protocol  [PDF] April 30, 2021

Statistical Analysis Plan: Part 1  [PDF] July 22, 2021

Statistical Analysis Plan: Part 2  [PDF] December 16, 2021

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Kim JY, Sandulescu O, Preotescu LL, Rivera-Martinez NE, Dobryanska M, Birlutiu V, Miftode EG, Gaibu N, Caliman-Sturdza O, Florescu SA, Shi HJ, Streinu-Cercel A, Streinu-Cercel A, Lee SJ, Kim SH, Chang I, Bae YJ, Suh JH, Chung DR, Kim SJ, Kim MR, Lee SG, Park G, Eom JS. A Randomized Clinical Trial of Regdanvimab in High-Risk Patients With Mild-to-Moderate Coronavirus Disease 2019. Open Forum Infect Dis. 2022 Aug 8;9(8):ofac406. doi: 10.1093/ofid/ofac406. eCollection 2022 Aug. Erratum In: Open Forum Infect Dis. 2023 Apr 19;10(4):ofad196.

Hirsch C, Park YS, Piechotta V, Chai KL, Estcourt LJ, Monsef I, Salomon S, Wood EM, So-Osman C, McQuilten Z, Spinner CD, Malin JJ, Stegemann M, Skoetz N, Kreuzberger N. SARS-CoV-2-neutralising monoclonal antibodies to prevent COVID-19. Cochrane Database Syst Rev. 2022 Jun 17;6(6):CD014945. doi: 10.1002/14651858.CD014945.pub2.

Streinu-Cercel A, Sandulescu O, Preotescu LL, Kim JY, Kim YS, Cheon S, Jang YR, Lee SJ, Kim SH, Chang I, Suh JH, Lee SG, Kim MR, Chung DR, Kim HN, Streinu-Cercel A, Eom JS. Efficacy and Safety of Regdanvimab (CT-P59): A Phase 2/3 Randomized, Double-Blind, Placebo-Controlled Trial in Outpatients With Mild-to-Moderate Coronavirus Disease 2019. Open Forum Infect Dis. 2022 Feb 2;9(4):ofac053. doi: 10.1093/ofid/ofac053. eCollection 2022 Apr.

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.

• Responsible Party: Celltrion
• ClinicalTrials.gov Identifier: NCT04602000
• Other Study ID Numbers: CT-P59 3.2; 2020-003369-20 ( EudraCT Number )
• First Posted: October 26, 2020
• Results First Posted: July 20, 2022
• Last Update Posted: July 20, 2022
• Last Verified: June 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Infections; Communicable Diseases; COVID-19; Disease Attributes; Pathologic Processes; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases