A Safety, Tolerability, and Efficacy Study of IBI314 in Ambulatory Patients With COVID-19

Study Overview
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Brief Summary
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This is a dose-finding, inferentially seamless Phase 1/2 study evaluating the safety, tolerability and efficacy of IBI314 in Ambulatory Patients with COVID-19.

Detailed Description
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Phase 1 is a randomized, double-blind, placebo-controlled, single ascending dose study in up to 32 ambulatory adult patients with COVID-19. This phase of the study is designed to assess the safety, tolerability, PK, and PD of IBI314 administered as a single IV infusion. Phase 2 is a randomized, double-blind, placebo-controlled expansion study in approximately 208 ambulatory adult patients with COVID-19. This phase of the study is designed to assess the efficacy and safety of IBI314, administered by single IV infusion at dose levels that meet none of the termination criteria for dose escalation in Phase 1 of the study.

Official Title
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A Safety, Tolerability, and Efficacy Study of IBI314 in Ambulatory Patients With COVID-19

Conditions
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COVID-19

Intervention / Treatment
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* Biological: IBI314
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Main Inclusion Criteria: First onset of COVID-19 symptoms <7 days at randomization, symptoms such as fever and/or chills, fatigue, muscle or body aches, headache, new loss of taste or smell, sore throat, congestion or runny nose, nausea or vomiting, and diarrhea. Have a positive SARS-CoV-2 Reverse Transcription-Polymerase Chain Reaction (RT-PCR) test using an appropriate sample such as nasopharyngeal (NP), nasal, oropharyngeal, or saliva within 72 hours prior to randomization. A historical record of a positive result from a test conducted ≤72 hours prior to randomization is acceptable. Male or female patients ≥18 years of age at the time of signing informed consent. Agree to use an adequate method of contraception throughout the study period and for 90 days after the dose of study drug is administered. Women of childbearing potential (WOCBP) must have a negative urinary pregnancy test at screening. Main Exclusion Criteria: according to protocol v3.0, Note: Patients with mild-to-moderate disease who are placed in a facility where required by local guidelines can be enrolled. Have oxygen saturation (SpO2) ≤93 % on room air at sea level or a ratio of arterial oxygen partial pressure (PaO2 in millimeters of mercury) to fractional inspired oxygen (FiO2) <300, respiratory rate ≥30 per minute, heart rate ≥125 per minute. Have evidence of multi-organ dysfunction/failure. Systolic blood pressure <90 mmHg, diastolic blood pressure <60 mmHg, or requiring vasopressors. Require or anticipated impending need for endotracheal intubation and mechanical ventilation, oxygen delivered by high-flow nasal cannula noninvasive positive pressure ventilation, extracorporeal membrane oxygenation (ECMO).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IBI314<br>a cocktail of two SARS-CoV-2 S protein IgG1 antibodies, IBI314-A and IBI314-B, in a 1:1 [w/w] ratio | Biological: IBI314<br>* Low/medium/high dose, intravenously, once, on Day 1<br>|
| Placebo Comparator: Placebo<br> | Other: Placebo<br>* Placebo, intravenously, once, on Day 1<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of treatment related AEs | Any AEs and SAEs occurring during the study | 29 days after the last participant is randomized | 
| Virologic efficacy Evaluation | Time-weighted average change in viral shedding from baseline through Day 7 as measured by RT-qPCR in NP swab samples. | 7 days after the last participant is randomized | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| half-life (t1/2) | PK parameters to be evaluated for IBI314 including half-life (t1/2) will be determined when appropriate. Time to alleviation of symptoms (going to mild or absent); Proportion of patients admitted to a hospital and emergency room visit due to COVID-19 by Day 29; Proportion of patients with all-cause mortality by Day 29. | 29 days after the last participant is randomized | 
| clearance (CL) | PK parameters to be evaluated for IBI314 including clearance (CL) will be determined when appropriate. Change from baseline in viral shedding on Day 7, 11, 22; Time-weighted average change in viral shedding from baseline through D11 as measured by RT-qPCR in NP swab samples; Time-weighted average change in viral shedding from baseline through D22 as measured by RT-qPCR in NP swab samples. | 29 days after the last participant is randomized | 
| volume of distribution (V) | PK parameters to be evaluated for IBI314 including volume of distribution (V) will be determined when appropriate. | 29 days after the last participant is randomized | 
| The incidence of anti-IBI314 antibody (ADA) and neutralizing antibody (NAb) in serum before and after study drug administration | Each patient will be tested for anti-drug (IBI314) antibody (ADA), and ADA-positive serum samples will continue to be tested for neutralizing antibodies (NAb). | 29 days after the last participant is randomized | 
| Proportion of patients with at least one COVID-19 related medically attended visits by Day 29 | This is a clinical efficacy outcome measure. | 29 days after the last participant is randomized | 
| Time to alleviation of symptoms (going to mild or absent) | This is a clinical efficacy outcome measure. | 29 days after the last participant is randomized | 
| Proportion of patients admitted to a hospital and emergency room visit due to COVID-19 by Day 29 | This is a clinical efficacy outcome measure. | 29 days after the last participant is randomized | 
| Proportion of patients with all-cause mortality by Day 29 | This is a clinical efficacy outcome measure. | 29 days after the last participant is randomized | 
| Time to negative RT-qPCR in NP swab samples with no subsequent positive RT-qPCR | This is a virologic efficacy outcome measure. | 29 days after the last participant is randomized | 
| Change from baseline in viral shedding on Day 7, 11, 22 | This is a virologic efficacy outcome measure. | 29 days after the last participant is randomized | 
| Time-weighted average change in viral shedding from baseline through D11 as measured by RT-qPCR in NP swab samples | This is a virologic efficacy outcome measure. | 29 days after the last participant is randomized | 
| Time-weighted average change in viral shedding from baseline through D22 as measured by RT-qPCR in NP swab samples. | This is a virologic efficacy outcome measure. | 29 days after the last participant is randomized | 
| maximum concentration (Cmax) | PK parameters to be evaluated for IBI314 including maximum concentration (Cmax) will be determined when appropriate. | 29 days after the last participant is randomized | 
| area under the concentration-time curve (AUC) | PK parameters to be evaluated for IBI314 including area under the concentration-time curve (AUC) will be determined when appropriate. | 29 days after the last participant is randomized |