A Phase 2/3 Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of ADG20 in the Treatment of Ambulatory Participants with Mild or Moderate COVID-19 (STAMP)

INTERVENTION: Product Code: ADG20 Pharmaceutical Form: Solution for injection CAS Number: 2516243‐50‐0 Current Sponsor code: ADG20 Other descriptive name: ADG20 Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 100‐ Pharmaceutical form of the placebo: Solution for injection Route of administration of the placebo: Intramuscular use CONDITION: COVID‐19 ; MedDRA version: 23.0 Level: LLT Classification code 10084382 Term: Coronavirus disease 2019 System Organ Class: 100000004862 Therapeutic area: Diseases [C] ‐ Virus Diseases [C02] PRIMARY OUTCOME: Main Objective: ‐ To evaluate the efficacy of ADG20 compared to placebo in the treatment of mild or moderate COVID 19 in participants at high risk of disease progression; ‐ To evaluate the safety and tolerability of ADG20 compared to placebo through Day 29 in participants with mild and moderate COVID‐19 and high risk of disease progression Primary end point(s): ‐ COVID‐19 related hospitalization or all‐cause death through Day 29; ‐ Assessment of safety through Day 29 based on:; o The incidence of TEAEs; o Incidence of solicited injection site reactions through Day 4; o Changes from baseline in clinical laboratory tests (ie, CBC with differential, serum chemistry, coagulation) ; o Changes from baseline in vital signs (body temperature, heart rate, respiration rate, and systolic and diastolic blood pressure); Secondary Objective: ‐ To evaluate the effect of ADG20 on the following clinical parameters in participants with mild or moderate COVID 19 and high risk of disease progression; o Severity of COVID‐19; o COVID‐19 related emergency room visits, COVID‐19 related hospitalizations, or all cause death; o COVID‐19 related medically attended visits; o Time to sustained recovery of COVID‐19 symptoms; o All cause mortality; ‐ To evaluate the effect of ADG20 on SARS‐CoV‐2 viral load and clearance in participants with mild or moderate COVID‐19 and high risk of disease progression; ‐ To evaluate the safety and tolerability of ADG20 compared to placebo through Month 14 in participants with mild or moderate COVID‐19 and high risk of disease progression; ‐ To evaluate the PK of ADG20 following IM administration ; ‐ To evaluate the immunogenicity (ADAs) to ADG20; ‐ To evaluate the emergence of resistance to ADG20; Timepoint(s) of evaluation of this end point: ‐ day 29; ‐ day 4 and day 29 SECONDARY OUTCOME: Secondary end point(s): o Severe/critical COVID‐19 or all‐cause death through Day 29; o COVID 19‐related emergency room visits, COVID‐19 related hospitalization, or all‐cause death through Day 29; o COVID‐19‐related medically attended visit (telemedicine, physician office, urgent care center, emergency room, hospitalization) or all‐cause death through Day 29; o Time to sustained recovery defined as sustained improvement or resolution of COVID 19 symptoms through Day 29; o All cause mortality through Day 29, Day 60, and Day 90 ; o Change from baseline in SARS‐CoV‐2 viral load (log10 copies/mL) to Day 7 (±1) assessed by RT qPCR from NP samples; o Viral load >5 (log10 copies/mL) on Day 7 (±1) based on nasopharyngeal sampling (Ph 3); o Duration of SARS‐CoV‐2 viral shedding from Day 1 through Day 29 assessed by RT‐qPCR from saliva samples; o Change from baseline in SARS‐CoV‐2 viral load (log10 copies/mL) to Days 3, 5, 7, 11, and 14 assessed by RT‐qPCR from saliva samples; o SARS‐CoV‐2 viral clearance (Days 5, 7, 11, 14, 21, and 29) assessed by RT‐qPCR from saliva samples (and NP samples for Day 7); o SARS‐CoV‐2 viral load AUC assessed by RT‐qPCR from saliva samples from baseline to Day 7, 11, 14, 21 and 29; ‐ Assessment of safety through Month 14 based on:; o The incidence of TEAEs; o Changes from baseline in clinical laboratory tests (ie, CBC with differential, serum chemistry, coagulation) ; o Changes from baseline in vital signs (body temperature, heart rate, respiration rate, and systolic and diastolic blood pressure); ‐ PK parameters of ADG20: As data permit, Cmax, Tmax, AUC 0‐last, AUC 0‐inf, CL, Vd, and T1/2. Additional PK parameters may be calculated as data permit; ‐ Incidence of ADAs against ADG20; ‐ Genotypic characterization of viral isolates for reduced susceptibility to ADG20, with phenotypic evaluation as appropriate; ; Exploratory; ‐ Effect of baseline SARS CoV 2 specific antibody response on select clinical outcomes; ‐ The level of viral load leading to the following adverse clinical outcomes:; • COVID‐19 related hospitalization or all‐cause death through Day 29; • COVID 19‐related emergency room visits, COVID‐19 related hospitalization, or all‐cause death through Day 29; • Severe/critical COVID‐19 or all‐cause death through Day 29; o Participants with symptomatic COVID‐19 among household contacts; o Participants with asymptomatic SARS‐CoV‐2 infection among household contacts; o COVID 19‐related mortality through Day 29; o Time to improvement of COVID‐19 symptoms through Day 29; o Time to sustained resolution of COVID 19 symptoms through Day 29; o Incidence of PASC at Day 60, Day 90, and Month 6; Timepoint(s) of evaluation of this end point: ‐ day 29; ‐ days 29, 60, 90; ‐ day 7; ‐ day 1, day 29; ‐ days 3, 5, 8, 11, 14; ‐ days 5, 7, 11, 14, 21, 29; ‐ day 7, 11, 14, 21, 29; ‐ month 14; ; Exploratory; ‐ day 29; ‐ day 60, 90, and month 6 INCLUSION CRITERIA: 1. Age: a. Ph 2: Is an adult aged 18 years and above b. Ph 3: Is an adult aged 18 years and above or is an adolescent aged 12‐17 years (inclusive) and weighing =40 kg at the time of screening 2. Has had SARS‐CoV‐2 positive antigen, RT‐PCR, or other locally approved molecular diagnostic assay obtained within 5 days prior to randomization 3. Has had initial onset of one or more of the following self‐reported COVID‐19‐related signs or symptoms within 5 days prior to randomization: (temperature =38°C, subjective fever, chills, cough, sore throat, congestion, shortness of breath or difficulty breathing with exertion worse than usual, muscle or body aches, fatigue, headache, loss of taste or smell, nausea or vomiting, diarrhea) 4. Has one or more of the following COVID‐19‐related signs or symptoms on the day of randomization (temperature =38°C, subjective fever, chills, cough, sore throat, congestion, shortness of breath or difficulty breathing