A Safety, Tolerability, and Efficacy Study of IBI314 in Patients With Mild to Moderate COVID-19

Study Overview
=================
Brief Summary
-----------------
This is a Phase 1/2 study evaluating the safety, tolerability and efficacy of IBI314.

Detailed Description
-----------------
Phase 1 is a randomized, double-blind, placebo-controlled, single ascending dose study in up to 24 health volunteers. This phase of the study is designed to assess the safety, tolerability and PK of IBI314 administered as a single IV infusion. Phase 2 is a randomized, double-blind, placebo-controlled expansion study in approximately 198 mild to moderate adult patients with COVID-19. This phase of the study is designed to assess the efficacy, safety, PK and PD of IBI314.

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

Conditions
-----------------
COVID-19

Intervention / Treatment
-----------------
* Biological: IBI314(low dose)
* Biological: IBI314(high dose)
* Biological: IBI314(medium dose)
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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 6 months 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: 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, mechanical ventilation, oxygen delivered by high-flow nasal cannula noninvasive positive pressure ventilation, extracorporeal membrane oxygenation (ECMO).

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IBI314<br>Low/medium/high dose, intravenously, once, on Day 1 | Biological: IBI314(low dose)<br>* intravenously, once, on Day 1<br>Biological: IBI314(high dose)<br>* intravenously, once, on Day 1<br>Biological: IBI314(medium dose)<br>* intravenously, once, on Day 1<br>|
| Placebo Comparator: Placebo<br>Placebo, intravenously, once, on Day 1 | Other: Placebo<br>* intravenously, once, on Day 1<br>|

What is the study measuring?
-----------------
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 |
| --- | --- | --- |
| 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 | 
| half-life (t1/2) | PK parameters to be evaluated for IBI314 including half-life (t1/2) will be determined when appropriate. | 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. | 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 | 
| 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 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. | 7, 11, 22 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. | 11 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. | 22 days after the last participant is randomized | 
| Proportion of patients demonstrating symptoms alleviation on D3, 7, 15, 22, 29 | This is a clinical efficacy outcome measure. | 3, 7, 15, 22, 29 days after the last participant is randomized | 
| Proportion of patients who become severe COVID-19 by Day 29 | This is a clinical efficacy outcome measure. | 29 days after the last participant is randomized | 
| Proportion of patients requiring mechanical ventilation by day 29 | This is a clinical efficacy outcome measure. | 29 days after the last participant is randomized |