Clinical trial NCT04602000: A Phase 2/3 Study to Evaluate the Efficacy and Safety of CT-P59 in Patients With Mild to Moderate SARS-CoV-2 Infection
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: SARS-CoV-2 Infection
Lead sponsor: Celltrion
Sponsor class: INDUSTRY
First posted: 2020-10-26
Enrollment: 1642
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Proportion of Patients With Clinical Symptom Requiring Hospitalization, Oxygen Therapy, or Experiencing Mortality Due to SARS-CoV-2 Infection (Part 1)
timeFrame: Up to Day 28
measure: Proportion of Patients With Negative Conversion in Nasopharyngeal Swab Specimen Based on RT-qPCR at Each Visit (Part 1)
timeFrame: Up to Day 14
measure: Time to Negative Conversion in Nasopharyngeal Swab Specimen (Part 1)
timeFrame: Up to Day 14
measure: Time to Clinical Recovery (Part 1)
timeFrame: Up to Day 14
measure: 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)
timeFrame: Up to Day 28
Secondary outcomes:
measure: 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)
timeFrame: Up to Day 28
measure: Time to Clinical Recovery up to Day 14 in High-risk Patients (Part 2)
timeFrame: Up to Day 14
measure: Time to Clinical Recovery up to Day 14 in All Randomized Patients (Part 2)
timeFrame: Up to Day 14
measure: Proportion of Patients With Hospital Admission Due to SARS-CoV-2 Infection (Part 1 and Part 2)
timeFrame: Up to Day 28
measure: Proportion of Patients Requiring Supplemental Oxygen Due to SARS-CoV-2 Infection (Part 1 and Part 2)
timeFrame: Up to Day 28
measure: Proportion of Patients With Mechanical Ventilation Use Due to SARS-CoV-2 Infection (Part 1 and Part 2)
timeFrame: Up to Day 28
measure: Proportion of Patients Requiring Rescue Therapy Due to SARS-CoV-2 Infection (Part 1 and Part 2)
timeFrame: Up to Day 28
measure: Proportion of Patients With Intensive Care Unit Transfer Due to SARS-CoV-2 Infection (Part 1 and Part 2)
timeFrame: Up to Day 28
measure: Proportion of Patients With All-cause Mortality (Part 1 and Part 2)
timeFrame: Up to Day 28
measure: Time to Negative Conversion in Nasopharyngeal Swab Specimen Based on RT-qPCR (Part 1 and Part 2)
timeFrame: Up to Day 28
measure: Proportion of Patient With Negative Conversion in Nasopharyngeal Swab Specimen Based on RT-qPCR at Each Visit (Part 1 and Part 2)
timeFrame: Days 3, 7, 10, 14, 21, and 28
measure: Time to Clinical Recovery (Part 1 and Part 2)
timeFrame: Up to Day 28
Other outcomes:
measure: [Virology] Viral Serology for SARS-CoV-2 Antibody
timeFrame: Days 1, 7, 14, 28, and 56
measure: [PK] Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-inf) (Part 1)
timeFrame: Pre-dose, end of infusion, 1, 24, 48, 96, 144, 216, 312, 648, 1320, 2136 hours after start of infusion
measure: [PK] Maximum Serum Concentration (Cmax) (Part 1)
timeFrame: Pre-dose, end of infusion, 1, 24, 48, 96, 144, 216, 312, 648, 1320, 2136 hours after start of infusion
measure: [PK] Terminal Half-life (t1/2) (Part 1)
timeFrame: Pre-dose, end of infusion, 1, 24, 48, 96, 144, 216, 312, 648, 1320, 2136 hours after start of infusion
Locations:
city: Daejeon
country: Korea, Republic of
facility: Chungnam National University Hospital
state: Jung-gu
Study officials:
References:
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citation: 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.
citation: 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.
citation: 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.