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

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

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.

Study Overview

• Status: Completed
• Conditions: SARS-CoV-2 Infection
• Intervention / Treatment: Biological: CT-P59; Biological: CT-P59; Biological: CT-P59; Biological: Placebo; Biological: Placebo

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 Type: Interventional
• Enrollment (Actual): 1642
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Korea, Republic of
  • Jung-gu
    • Daejeon, Jung-gu, Korea, Republic of, 35015
      • Chungnam national university hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Patients With Clinical Symptom Requiring Hospitalization, Oxygen Therapy, or Experiencing Mortality Due to SARS-CoV-2 Infection (Part 1)	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	Up to Day 28
Proportion of Patients With Negative Conversion in Nasopharyngeal Swab Specimen Based on RT-qPCR at Each Visit (Part 1)	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	Up to Day 14
Time to Negative Conversion in Nasopharyngeal Swab Specimen (Part 1)	To evaluate the therapeutic efficacy of CT-P59 as determined by time to negative conversion by RT-qPCR up to Day 14	Up to Day 14
Time to Clinical Recovery (Part 1)	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.	Up to Day 14
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)	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	Up to Day 28

Secondary Outcome Measures

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

Other Outcome Measures

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

Collaborators and Investigators

• Sponsor: Celltrion

Publications and helpful links

General Publications

• 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.
• 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:CD014945. doi: 10.1002/14651858.CD014945.pub2. Review.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): October 5, 2020
• Primary Completion (Actual): May 21, 2021
• Study Completion (Actual): October 20, 2021

Study Registration Dates

• First Submitted: October 18, 2020
• First Submitted That Met QC Criteria: October 23, 2020
• First Posted (Actual): October 26, 2020

Study Record Updates

• Last Update Posted (Actual): July 20, 2022
• Last Update Submitted That Met QC Criteria: June 27, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Disease Attributes; COVID-19; Infections; Communicable Diseases
• Other Study ID Numbers: CT-P59 3.2; 2020-003369-20 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No