COVID-19
Conditions
Brief summary
This placebo controlled study is intended to generate safety and efficacy data in order to provide a treatment option for COVID-19 in patients with a high risk of disease progression based on age or co-morbid medical conditions.
Interventions
DRUGADG20
Single dose of ADG20
DRUGNormal saline
Single dose of normal saline
Sponsors
Invivyd, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
The investigator, participant and sponsor personnel involved in study intervention and study evaluation will be unaware of the intervention assignments. Investigators will remain blinded to each participant's assigned study treatment throughout the course of the study.
Intervention model description
Randomized, double-blind, placebo controlled
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Has had SARS-CoV-2 positive antigen, RT-PCR, or other locally approved molecular diagnostic assay obtained within 5 days prior to randomization * Has had symptoms consistent with COVID-19 with onset 5 days before randomization * Has one or more COVID-19-related signs or symptoms on the day of randomization * Phase 2: Is an adult aged 18 years and above * Phase 3: Is an adult aged 18 years and above or is an adolescent aged 12 to 17 years (inclusive) and weighing ≥40 kg at the time of screening
Exclusion criteria
* Is currently hospitalized or in the opinion of the investigator is anticipated to require hospitalization within 48 hours of randomization. * Has severe COVID-19 or is on supplemental oxygen * Has a history of a positive SARS-CoV-2 antibody serology test * Has participated, within the last 30 days, in a clinical study involving an investigational intervention * Has received a SARS-CoV-2 vaccine, monoclonal antibody, or plasma from a person who recovered from COVID-19 any time prior to participation in the study NOTE: Other protocol defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of COVID-19 Related Hospitalizations or All-cause Death | Through Day 29 | 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. Hospitalization is defined as ≥24 hours of acute care in a hospital or acute care facility (includes emergency rooms, intensive care units, acute care facilities created for COVID-19 pandemic hospitalization needs, or other acute care facilities). All-cause death is defined as death for any reason from Day 1 (postdose) through Day 29. |
| Incidence of Treatment-emergent Adverse Events | Through day 29 | Proportion of participants with at least one treatment emergent AE |
| Incidence of Solicited Injection Site Reactions | Through Day 4 | Proportion of participants with at least one solicited injection site reaction |
| Changes From Baseline in Clinical Laboratory Tests (ie, CBC With Differential, Serum Chemistry, Coagulation) | Through Day 29 | Proportion of participants with a potentially clinically significant change from baseline in post-baseline laboratory parameters - data presented for any analyte with \>/= 2% in any arm |
| Changes From Baseline in Vital Signs (Body Temperature, Heart Rate, Respiration Rate, and Systolic and Diastolic Blood Pressure) | Through Day 29 | Participants with Potentially Clinically Significant Changes (PCS) From Baseline in Vital Signs (Body Temperature, Heart Rate, Respiration Rate, and Systolic and Diastolic Blood Pressure) at Any Time Post-Baseline |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Sustained Resolution of COVID-19 Symptoms as Measured in the Daily COVID-19 Symptom Diary | Through Day 29 | Time to sustained resolution of COVID-19 symptoms through Day 29: Defined as time from the dose date to the first date when all of the defined symptoms are scored as absent with no symptom recurrence or new symptoms, except cough, fatigue, and headache which may be mild or absent, through Day 29. |
| Change From Baseline in SARS-CoV-2 Viral Load (log10 Copies/mL) to Day 7 (±1) | Day 7 (±1) | Assessed by RT qPCR From NP (Nasopharyngeal) Samples |
| Duration of SARS-CoV-2 Shedding Assessed by RT-qPCR From Saliva Samples | Through Day 29 | Duration of SARS-CoV-2 viral shedding is defined as time from the dose date to the first date the viral load is not detected, ie, below the limit of detection (LOD), and sustained through Day 29. Participants who do not have the defined event or who discontinue study prior to Day 29 are censored at the earlier date of the last viral load assessment or Day 30. Deaths occurring prior to Day 29 were censored at Day 30. |
| Viral Load >5 (log10 Copies/mL) Based on Nasopharyngeal Sampling at Day 7 | on Day 7 (+/- 1 Day) | Proportion of participants with Viral load \>5 (log10 copies/mL) on Day 7 assessed by RT-qPCR from NP sample. |
| 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) | Days 5, 7, 11, 14, 21, and 29 (saliva) | Proportions of SARS-CoV-2 viral clearance (Days 3, 5, 7, 11, 14, 21, and 29) assessed by RT-qPCR from saliva samples: In the mFAS-S, the cumulative proportion of participants with viral clearance (viral load not detected and sustained through Day 29) at Days 3, 5, 7, 11, 14, 21, and 29 will be assessed by RT-qPCR from saliva samples. Participants who have died or discontinued study prior to Day 29 are assumed to have no viral clearance. |
| Incidence of COVID-19 -Related Medically Attended Visits or All-cause Death | Through Day 29 | Proportion of participants with COVID-19-related medically attended visit (telemedicine, physician office, urgent care center, emergency room, hospitalization) or all-cause death through Day 29. In addition to events defined as the primary efficacy endpoint, this endpoint also includes any medically attended visits, in-person, or telemedicine, not specified in the protocol. These include unscheduled in-person or telemedicine visits conducted by the investigator for the purpose of evaluating worsening signs or symptoms attributed to COVID-19 or emergency room, urgent care center or physician office visits, or hospitalization for attention to worsening signs or symptoms attributed to COVID-19, in the opinion of the investigator. Incidence of COVID-19-related medically attended visits or all-cause death includes participants who met any event defined for this endpoint. Participants were counted only once even if multiple events were met in the time frame. |
| Incidence of Treatment Emergent Adverse Events | 14 months | An AE is defined as any untoward medical occurrence in a participant enrolled into this study regardless of its causal relationship to the study drug. AEs occurring from when the participant signed the ICF until the Month 14 (EOS) visit or discontinuation from study was recorded |
| Number of Participants With Potentially Clinically Significant (PCS) Changes From Baseline in Clinical Laboratory Test (PCS Defined Per Statistical Analysis Plan) | 14 Months | A PCS value is defined as any DAIDS grade 4 post-baseline or any increase of 2 or more DAIDS grades post-baseline, except for PCS low creatinine clearance, which is defined as any DAIDS Grade 4 post-baseline or any DAIDS grade shift from 0 to 3. Laboratory parameters not graded by DAIDs will be defined as PCS based on the criteria in the SAP (Appendix K.) |
| Number of Participants With Potentially Clinically Significant (PCS) Changes From Baseline in Vital Sign Parameters (PCS Defined Per Statistical Analysis Plan) | 14 Months | — |
| Incidence of ADA to ADG20 | 11 months | — |
| Genotypic Characterization of Viral Isolates for Reduced Susceptibility to ADG20 (G504 Mutations) | Through Day 29 | Post-baseline Treatment-emergent Variations at Amino Acid Positions Associated with Reduced Susceptibility to ADG20 (\>/= 15% Allele frequency); data limited to mutations observed. |
| SARS-CoV-2 Viral Load AUC Assessed by RT-qPCR From Saliva Samples | Baseline to Day 29 | The AUC from Day 1 through Day 29 was calculated according to the linear trapezoidal rule using the measured SARS-CoV-2 viral load above the lower limit of quantification. No AUC values will be calculated when Day 1 and/or Day 29 values are missing, or if there are more than 3 values missing in the profile. |
| Incidence of COVID-19 -Related Emergency Room Visits, COVID-19-related Hospitalization, or All Cause-death | Through Day 29 | Proportion of participants with any COVID 19-related emergency room visits, COVID-19-related hospitalization, or all cause death through Day 29. Defined as any stay in a hospital or acute care facility regardless of duration (includes emergency rooms, intensive care units, acute care facilities created for COVID-19 pandemic hospitalization needs, or other acute care facilities) for attention to worsening signs or symptoms attributed to COVID-19 in the opinion of the investigator or all cause death through Day 29. Incidence of COVID-19-related emergency room visits, COVID-19-related hospitalization, or all-cause death includes participants who met any event defined for this endpoint. Participants were counted only once even if multiple events were met in the time frame. |
| Incidence of Severe/Critical COVID-19 or All Cause Death | Through Day 29 | Proportion of participants with Severe/Critical COVID-19 or all-cause death through Day 29. All-cause death is defined as death for any reason (from Day 1postdose) through Day 29. Severity is based on the investigator's assessment of severity (eCRF COVID-19 Severity Assessment) per the protocol definitions. Incidence of Severe/Critical COVID-19 or all-cause death includes participants who met any event defined for this endpoint. Participants were counted only once even if multiple events were met in the time frame. |
| Time to Sustained Recovery Defined as Sustained Improvement or Resolution of COVID-19 Symptoms | Through Day 29 | Time to sustained recovery (improvement or resolution) of COVID-19 symptoms through Day 29: Defined as the time from the first dose date to the earliest date when sustained improvement or sustained resolution of COVID-19 symptoms is met (as detailed below) through Day 29. COVID-19 symptoms assessed include fever, chills, cough, sore throat, congestion, shortness of breath/difficulty breathing at rest, shortness of breath/difficulty breathing with exertion, muscle or body aches, fatigue, headache, nausea, vomiting, and diarrhea. Loss of taste/smell is excluded from this analysis. |
| Incidence of All-cause Mortality | Through Day 90 | Defined as death for any reason from Day 1 (postdose). In the overall survival analysis, participants who are alive or lost to follow-up at the time of analysis are censored at the date of last contact. |
Countries
Argentina, Brazil, Bulgaria, Germany, Greece, Hungary, Moldova, Poland, Romania, South Africa, Ukraine
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| ADG20 IM Participants will be dosed on Day 1 with ADG20 IM
ADG20: Single dose of ADG20 | 198 |
| Placebo IM Participants will be dosed on Day 1 with placebo IM
Normal saline: Single dose of normal saline | 201 |
| Total | 399 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 2 | 7 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Study terminated prematurely; participants active in the study discontinued from the trial. | 178 | 177 |
| Overall Study | Withdrawal by Subject | 9 | 7 |
Baseline characteristics
| Characteristic | ADG20 IM | Total | Placebo IM |
|---|---|---|---|
| Age, Categorical <=18 years | 1 Participants | 1 Participants | 0 Participants |
| Age, Categorical >=65 years | 47 Participants | 96 Participants | 49 Participants |
| Age, Categorical Between 18 and 65 years | 150 Participants | 302 Participants | 152 Participants |
| Age, Continuous | 55 years | 54 years | 53 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 2 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 198 Participants | 397 Participants | 199 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 14 Participants | 31 Participants | 17 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) White | 183 Participants | 364 Participants | 181 Participants |
| Region of Enrollment Brazil | 0 Participants | 2 Participants | 2 Participants |
| Region of Enrollment Bulgaria | 101 Participants | 201 Participants | 100 Participants |
| Region of Enrollment Germany | 1 Participants | 2 Participants | 1 Participants |
| Region of Enrollment Greece | 9 Participants | 20 Participants | 11 Participants |
| Region of Enrollment Poland | 13 Participants | 26 Participants | 13 Participants |
| Region of Enrollment Romania | 18 Participants | 36 Participants | 18 Participants |
| Region of Enrollment South Africa | 20 Participants | 40 Participants | 20 Participants |
| Region of Enrollment Ukraine | 36 Participants | 72 Participants | 36 Participants |
| Sex: Female, Male Female | 113 Participants | 217 Participants | 104 Participants |
| Sex: Female, Male Male | 85 Participants | 182 Participants | 97 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 192 | 7 / 200 |
| other Total, other adverse events | 23 / 192 | 16 / 200 |
| serious Total, serious adverse events | 18 / 192 | 36 / 200 |
Outcome results
Primary
Changes From Baseline in Clinical Laboratory Tests (ie, CBC With Differential, Serum Chemistry, Coagulation)
Proportion of participants with a potentially clinically significant change from baseline in post-baseline laboratory parameters - data presented for any analyte with \>/= 2% in any arm
Time frame: Through Day 29
Population: Safety Set: All participants who received any amount of study drug. Participants were analyzed based on the actual treatment (ADG20 versus Placebo) received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ADG20 IM | Changes From Baseline in Clinical Laboratory Tests (ie, CBC With Differential, Serum Chemistry, Coagulation) | Urea Nitrogen (mmol/L) - H | 26 Participants |
| ADG20 IM | Changes From Baseline in Clinical Laboratory Tests (ie, CBC With Differential, Serum Chemistry, Coagulation) | Lymphocytes (10^9/L) - L | 3 Participants |
| ADG20 IM | Changes From Baseline in Clinical Laboratory Tests (ie, CBC With Differential, Serum Chemistry, Coagulation) | Alanine Aminotransferase (U/L) - H | 6 Participants |
| ADG20 IM | Changes From Baseline in Clinical Laboratory Tests (ie, CBC With Differential, Serum Chemistry, Coagulation) | Albumin (g/L) - L | 0 Participants |
| ADG20 IM | Changes From Baseline in Clinical Laboratory Tests (ie, CBC With Differential, Serum Chemistry, Coagulation) | Creatinine (mcmol/L) - H | 26 Participants |
| ADG20 IM | Changes From Baseline in Clinical Laboratory Tests (ie, CBC With Differential, Serum Chemistry, Coagulation) | Creatinine Clearance, Estimated (mL/min/1.73m2) - L | 15 Participants |
| ADG20 IM | Changes From Baseline in Clinical Laboratory Tests (ie, CBC With Differential, Serum Chemistry, Coagulation) | Glucose (mmol/L) - H | 12 Participants |
| ADG20 IM | Changes From Baseline in Clinical Laboratory Tests (ie, CBC With Differential, Serum Chemistry, Coagulation) | Sodium (mmol/L) - L | 1 Participants |
| ADG20 IM | Changes From Baseline in Clinical Laboratory Tests (ie, CBC With Differential, Serum Chemistry, Coagulation) | Prothrombin Intl. Normalized Ratio - H | 5 Participants |
| Placebo IM | Changes From Baseline in Clinical Laboratory Tests (ie, CBC With Differential, Serum Chemistry, Coagulation) | Sodium (mmol/L) - L | 4 Participants |
| Placebo IM | Changes From Baseline in Clinical Laboratory Tests (ie, CBC With Differential, Serum Chemistry, Coagulation) | Creatinine Clearance, Estimated (mL/min/1.73m2) - L | 18 Participants |
| Placebo IM | Changes From Baseline in Clinical Laboratory Tests (ie, CBC With Differential, Serum Chemistry, Coagulation) | Lymphocytes (10^9/L) - L | 4 Participants |
| Placebo IM | Changes From Baseline in Clinical Laboratory Tests (ie, CBC With Differential, Serum Chemistry, Coagulation) | Urea Nitrogen (mmol/L) - H | 21 Participants |
| Placebo IM | Changes From Baseline in Clinical Laboratory Tests (ie, CBC With Differential, Serum Chemistry, Coagulation) | Alanine Aminotransferase (U/L) - H | 10 Participants |
| Placebo IM | Changes From Baseline in Clinical Laboratory Tests (ie, CBC With Differential, Serum Chemistry, Coagulation) | Glucose (mmol/L) - H | 16 Participants |
| Placebo IM | Changes From Baseline in Clinical Laboratory Tests (ie, CBC With Differential, Serum Chemistry, Coagulation) | Albumin (g/L) - L | 5 Participants |
| Placebo IM | Changes From Baseline in Clinical Laboratory Tests (ie, CBC With Differential, Serum Chemistry, Coagulation) | Prothrombin Intl. Normalized Ratio - H | 1 Participants |
| Placebo IM | Changes From Baseline in Clinical Laboratory Tests (ie, CBC With Differential, Serum Chemistry, Coagulation) | Creatinine (mcmol/L) - H | 23 Participants |
Primary
Changes From Baseline in Vital Signs (Body Temperature, Heart Rate, Respiration Rate, and Systolic and Diastolic Blood Pressure)
Participants with Potentially Clinically Significant Changes (PCS) From Baseline in Vital Signs (Body Temperature, Heart Rate, Respiration Rate, and Systolic and Diastolic Blood Pressure) at Any Time Post-Baseline
Time frame: Through Day 29
Population: Safety Set: All participants who received any amount of study drug. Participants were analyzed based on the actual treatment (ADG20 versus Placebo) received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ADG20 IM | Changes From Baseline in Vital Signs (Body Temperature, Heart Rate, Respiration Rate, and Systolic and Diastolic Blood Pressure) | Temp >=38 C or Increase >=1 C [c] | 5 Participants |
| ADG20 IM | Changes From Baseline in Vital Signs (Body Temperature, Heart Rate, Respiration Rate, and Systolic and Diastolic Blood Pressure) | SBP <=90 mmHg or Decrease >=20 mmHg | 17 Participants |
| ADG20 IM | Changes From Baseline in Vital Signs (Body Temperature, Heart Rate, Respiration Rate, and Systolic and Diastolic Blood Pressure) | SBP >=180 mmHg or Increase >=20 mmHg | 29 Participants |
| ADG20 IM | Changes From Baseline in Vital Signs (Body Temperature, Heart Rate, Respiration Rate, and Systolic and Diastolic Blood Pressure) | DBP <=50 mmHg or Decrease >=15 mmHg | 25 Participants |
| ADG20 IM | Changes From Baseline in Vital Signs (Body Temperature, Heart Rate, Respiration Rate, and Systolic and Diastolic Blood Pressure) | DBP >=105 mmHg or Increase >=15 mmHg | 24 Participants |
| ADG20 IM | Changes From Baseline in Vital Signs (Body Temperature, Heart Rate, Respiration Rate, and Systolic and Diastolic Blood Pressure) | HR <=50 bpm or Decrease >=15 bpm [a] | 78 Participants |
| ADG20 IM | Changes From Baseline in Vital Signs (Body Temperature, Heart Rate, Respiration Rate, and Systolic and Diastolic Blood Pressure) | HR >120 bpm or Increase >=15 bpm | 20 Participants |
| ADG20 IM | Changes From Baseline in Vital Signs (Body Temperature, Heart Rate, Respiration Rate, and Systolic and Diastolic Blood Pressure) | Temp <35 C or Decrease >=1 C [b] | 60 Participants |
| ADG20 IM | Changes From Baseline in Vital Signs (Body Temperature, Heart Rate, Respiration Rate, and Systolic and Diastolic Blood Pressure) | RR <=8 breaths/min or Decrease >=4 bpm | 20 Participants |
| ADG20 IM | Changes From Baseline in Vital Signs (Body Temperature, Heart Rate, Respiration Rate, and Systolic and Diastolic Blood Pressure) | RR >=30 breaths/min or Increase >=10 bpm [d] | 2 Participants |
| ADG20 IM | Changes From Baseline in Vital Signs (Body Temperature, Heart Rate, Respiration Rate, and Systolic and Diastolic Blood Pressure) | SpO2 <=93% or Decrease >=3% | 14 Participants |
| Placebo IM | Changes From Baseline in Vital Signs (Body Temperature, Heart Rate, Respiration Rate, and Systolic and Diastolic Blood Pressure) | RR <=8 breaths/min or Decrease >=4 bpm | 25 Participants |
| Placebo IM | Changes From Baseline in Vital Signs (Body Temperature, Heart Rate, Respiration Rate, and Systolic and Diastolic Blood Pressure) | HR >120 bpm or Increase >=15 bpm | 25 Participants |
| Placebo IM | Changes From Baseline in Vital Signs (Body Temperature, Heart Rate, Respiration Rate, and Systolic and Diastolic Blood Pressure) | SBP <=90 mmHg or Decrease >=20 mmHg | 23 Participants |
| Placebo IM | Changes From Baseline in Vital Signs (Body Temperature, Heart Rate, Respiration Rate, and Systolic and Diastolic Blood Pressure) | SpO2 <=93% or Decrease >=3% | 19 Participants |
| Placebo IM | Changes From Baseline in Vital Signs (Body Temperature, Heart Rate, Respiration Rate, and Systolic and Diastolic Blood Pressure) | SBP >=180 mmHg or Increase >=20 mmHg | 26 Participants |
| Placebo IM | Changes From Baseline in Vital Signs (Body Temperature, Heart Rate, Respiration Rate, and Systolic and Diastolic Blood Pressure) | Temp <35 C or Decrease >=1 C [b] | 56 Participants |
| Placebo IM | Changes From Baseline in Vital Signs (Body Temperature, Heart Rate, Respiration Rate, and Systolic and Diastolic Blood Pressure) | DBP <=50 mmHg or Decrease >=15 mmHg | 26 Participants |
| Placebo IM | Changes From Baseline in Vital Signs (Body Temperature, Heart Rate, Respiration Rate, and Systolic and Diastolic Blood Pressure) | Temp >=38 C or Increase >=1 C [c] | 17 Participants |
| Placebo IM | Changes From Baseline in Vital Signs (Body Temperature, Heart Rate, Respiration Rate, and Systolic and Diastolic Blood Pressure) | DBP >=105 mmHg or Increase >=15 mmHg | 31 Participants |
| Placebo IM | Changes From Baseline in Vital Signs (Body Temperature, Heart Rate, Respiration Rate, and Systolic and Diastolic Blood Pressure) | RR >=30 breaths/min or Increase >=10 bpm [d] | 2 Participants |
| Placebo IM | Changes From Baseline in Vital Signs (Body Temperature, Heart Rate, Respiration Rate, and Systolic and Diastolic Blood Pressure) | HR <=50 bpm or Decrease >=15 bpm [a] | 96 Participants |
Primary
Incidence of COVID-19 Related Hospitalizations or All-cause Death
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. Hospitalization is defined as ≥24 hours of acute care in a hospital or acute care facility (includes emergency rooms, intensive care units, acute care facilities created for COVID-19 pandemic hospitalization needs, or other acute care facilities). All-cause death is defined as death for any reason from Day 1 (postdose) through Day 29.
Time frame: Through Day 29
Population: Modified Full Analysis Set (mFAS-non-Omicron): All randomized participants with COVID-19 due to Whole Genome WGS)-confirmed or suspected non-Omicron SARS-CoV-2 variants.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ADG20 IM | Incidence of COVID-19 Related Hospitalizations or All-cause Death | 8 Participants |
| Placebo IM | Incidence of COVID-19 Related Hospitalizations or All-cause Death | 23 Participants |
Comparison: ADG20 vs Placebop-value: 0.004795% CI: [-14.71, -2.67]Regression, Logistic
Primary
Incidence of Solicited Injection Site Reactions
Proportion of participants with at least one solicited injection site reaction
Time frame: Through Day 4
Population: Safety Set: All participants who received any amount of study drug. Participants were analyzed based on the actual treatment (ADG20 versus Placebo) received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ADG20 IM | Incidence of Solicited Injection Site Reactions | 25 Participants |
| Placebo IM | Incidence of Solicited Injection Site Reactions | 19 Participants |
Primary
Incidence of Treatment-emergent Adverse Events
Proportion of participants with at least one treatment emergent AE
Time frame: Through day 29
Population: Safety Set: All participants who received any amount of study drug. Participants were analyzed based on the actual treatment (ADG20 versus Placebo) received. Participants with more than one AE were only counted once.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ADG20 IM | Incidence of Treatment-emergent Adverse Events | 47 Participants |
| Placebo IM | Incidence of Treatment-emergent Adverse Events | 62 Participants |
Secondary
Change From Baseline in SARS-CoV-2 Viral Load (log10 Copies/mL) to Day 7 (±1)
Assessed by RT qPCR From NP (Nasopharyngeal) Samples
Time frame: Day 7 (±1)
Population: Modified Full Analysis Set (mFAS-non-Omicron-NP): All randomized participants with COVID-19 due to Whole Genome Sequencing (WGS)-confirmed or suspected non-Omicron SARS-CoV-2 variants with a positive baseline NP sample.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| ADG20 IM | Change From Baseline in SARS-CoV-2 Viral Load (log10 Copies/mL) to Day 7 (±1) | -3.61 log10 copies/mL | Standard Error 0.238 |
| Placebo IM | Change From Baseline in SARS-CoV-2 Viral Load (log10 Copies/mL) to Day 7 (±1) | -3.44 log10 copies/mL | Standard Error 0.224 |
Comparison: ADG20 vs. Placebop-value: 0.497695% CI: [-0.66, 0.32]ANCOVA
Secondary
Duration of SARS-CoV-2 Shedding Assessed by RT-qPCR From Saliva Samples
Duration of SARS-CoV-2 viral shedding is defined as time from the dose date to the first date the viral load is not detected, ie, below the limit of detection (LOD), and sustained through Day 29. Participants who do not have the defined event or who discontinue study prior to Day 29 are censored at the earlier date of the last viral load assessment or Day 30. Deaths occurring prior to Day 29 were censored at Day 30.
Time frame: Through Day 29
Population: Modified Full Analysis Set (mFAS-non-Omicron-S): All randomized participants with COVID-19 due to Whole Genome Sequencing (WGS)-confirmed or suspected non-Omicron SARS-CoV-2 variants with a positive baseline saliva sample.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ADG20 IM | Duration of SARS-CoV-2 Shedding Assessed by RT-qPCR From Saliva Samples | 14 Days |
| Placebo IM | Duration of SARS-CoV-2 Shedding Assessed by RT-qPCR From Saliva Samples | 21 Days |
p-value: 0.723995% CI: [0.806, 1.364]Regression, Cox
Secondary
Genotypic Characterization of Viral Isolates for Reduced Susceptibility to ADG20 (G504 Mutations)
Post-baseline Treatment-emergent Variations at Amino Acid Positions Associated with Reduced Susceptibility to ADG20 (\>/= 15% Allele frequency); data limited to mutations observed.
Time frame: Through Day 29
Population: Participants with any mutation at a monitored position \>/= 15% allele frequency, in the population that had a qualifying (passed QC testing) baseline and post-baseline Whole Genome Sequencing sample.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ADG20 IM | Genotypic Characterization of Viral Isolates for Reduced Susceptibility to ADG20 (G504 Mutations) | 3 Participants |
| Placebo IM | Genotypic Characterization of Viral Isolates for Reduced Susceptibility to ADG20 (G504 Mutations) | 0 Participants |
Secondary
Incidence of ADA to ADG20
Time frame: 11 months
Population: All participants in the Safety Set who had a valid immunogenicity test result before the dose of study drug, and at least 1 valid result after the dose of study drug; analysis limited to participants who received ADG20 only.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ADG20 IM | Incidence of ADA to ADG20 | 12 Participants |
| Placebo IM | Incidence of ADA to ADG20 | 0 Participants |
Secondary
Incidence of All-cause Mortality
Defined as death for any reason from Day 1 (postdose). In the overall survival analysis, participants who are alive or lost to follow-up at the time of analysis are censored at the date of last contact.
Time frame: Through Day 90
Population: Modified Full Analysis Set (mFAS-non-Omicron): All randomized participants with COVID-19 due to Whole Genome Sequencing (WGS)-confirmed or suspected non-Omicron SARS-CoV-2 variants.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ADG20 IM | Incidence of All-cause Mortality | 1 Participants |
| Placebo IM | Incidence of All-cause Mortality | 7 Participants |
Comparison: ADG20 vs Placebop-value: 0.036195% CI: [0.016, 1.162]Regression, Cox
Secondary
Incidence of COVID-19 -Related Emergency Room Visits, COVID-19-related Hospitalization, or All Cause-death
Proportion of participants with any COVID 19-related emergency room visits, COVID-19-related hospitalization, or all cause death through Day 29. Defined as any stay in a hospital or acute care facility regardless of duration (includes emergency rooms, intensive care units, acute care facilities created for COVID-19 pandemic hospitalization needs, or other acute care facilities) for attention to worsening signs or symptoms attributed to COVID-19 in the opinion of the investigator or all cause death through Day 29. Incidence of COVID-19-related emergency room visits, COVID-19-related hospitalization, or all-cause death includes participants who met any event defined for this endpoint. Participants were counted only once even if multiple events were met in the time frame.
Time frame: Through Day 29
Population: Modified Full Analysis Set (mFAS-non-Omicron): All randomized participants with COVID-19 due to WGS-confirmed or suspected non-Omicron SARS-CoV-2 variants.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ADG20 IM | Incidence of COVID-19 -Related Emergency Room Visits, COVID-19-related Hospitalization, or All Cause-death | 8 Participants |
| Placebo IM | Incidence of COVID-19 -Related Emergency Room Visits, COVID-19-related Hospitalization, or All Cause-death | 23 Participants |
Comparison: ADG20 vs Placebop-value: 0.004795% CI: [-14.71, -2.67]Regression, Logistic
Secondary
Incidence of COVID-19 -Related Medically Attended Visits or All-cause Death
Proportion of participants with COVID-19-related medically attended visit (telemedicine, physician office, urgent care center, emergency room, hospitalization) or all-cause death through Day 29. In addition to events defined as the primary efficacy endpoint, this endpoint also includes any medically attended visits, in-person, or telemedicine, not specified in the protocol. These include unscheduled in-person or telemedicine visits conducted by the investigator for the purpose of evaluating worsening signs or symptoms attributed to COVID-19 or emergency room, urgent care center or physician office visits, or hospitalization for attention to worsening signs or symptoms attributed to COVID-19, in the opinion of the investigator. Incidence of COVID-19-related medically attended visits or all-cause death includes participants who met any event defined for this endpoint. Participants were counted only once even if multiple events were met in the time frame.
Time frame: Through Day 29
Population: Modified Full Analysis Set (mFAS-non-Omicron): All randomized participants with COVID-19 due to Whole Genome Sequencing (WGS)-confirmed or suspected non-Omicron SARS-CoV-2 variants.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ADG20 IM | Incidence of COVID-19 -Related Medically Attended Visits or All-cause Death | 9 Participants |
| Placebo IM | Incidence of COVID-19 -Related Medically Attended Visits or All-cause Death | 29 Participants |
Comparison: ADG20 vs Placebop-value: 0.000795% CI: [-17.86, -4.81]Regression, Logistic
Secondary
Incidence of Severe/Critical COVID-19 or All Cause Death
Proportion of participants with Severe/Critical COVID-19 or all-cause death through Day 29. All-cause death is defined as death for any reason (from Day 1postdose) through Day 29. Severity is based on the investigator's assessment of severity (eCRF COVID-19 Severity Assessment) per the protocol definitions. Incidence of Severe/Critical COVID-19 or all-cause death includes participants who met any event defined for this endpoint. Participants were counted only once even if multiple events were met in the time frame.
Time frame: Through Day 29
Population: Modified Full Analysis Set (mFAS-non-Omicron): All randomized participants with COVID-19 due to Whole Genome Sequencing (WGS)-confirmed or suspected non-Omicron SARS-CoV-2 variants.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ADG20 IM | Incidence of Severe/Critical COVID-19 or All Cause Death | 8 Participants |
| Placebo IM | Incidence of Severe/Critical COVID-19 or All Cause Death | 23 Participants |
Comparison: ADG20 vs Placebop-value: 0.000795% CI: [-17.86, -4.81]Regression, Logistic
Secondary
Incidence of Treatment Emergent Adverse Events
An AE is defined as any untoward medical occurrence in a participant enrolled into this study regardless of its causal relationship to the study drug. AEs occurring from when the participant signed the ICF until the Month 14 (EOS) visit or discontinuation from study was recorded
Time frame: 14 months
Population: Percent of participants who reported at least one TEAE.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ADG20 IM | Incidence of Treatment Emergent Adverse Events | 75 Participants |
| Placebo IM | Incidence of Treatment Emergent Adverse Events | 87 Participants |
Secondary
Number of Participants With Potentially Clinically Significant (PCS) Changes From Baseline in Clinical Laboratory Test (PCS Defined Per Statistical Analysis Plan)
A PCS value is defined as any DAIDS grade 4 post-baseline or any increase of 2 or more DAIDS grades post-baseline, except for PCS low creatinine clearance, which is defined as any DAIDS Grade 4 post-baseline or any DAIDS grade shift from 0 to 3. Laboratory parameters not graded by DAIDs will be defined as PCS based on the criteria in the SAP (Appendix K.)
Time frame: 14 Months
Population: Safety Set: All participants who received any amount of study drug. Participants were analyzed based on the actual treatment (ADG20 versus Placebo) received. Data presented for any analyte with \>/= 2% in any arm.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ADG20 IM | Number of Participants With Potentially Clinically Significant (PCS) Changes From Baseline in Clinical Laboratory Test (PCS Defined Per Statistical Analysis Plan) | Albumin (g/L) - L | 0 Participants |
| ADG20 IM | Number of Participants With Potentially Clinically Significant (PCS) Changes From Baseline in Clinical Laboratory Test (PCS Defined Per Statistical Analysis Plan) | Alanine Aminotransferase (U/L) - H | 6 Participants |
| ADG20 IM | Number of Participants With Potentially Clinically Significant (PCS) Changes From Baseline in Clinical Laboratory Test (PCS Defined Per Statistical Analysis Plan) | Sodium (mmol/L) - L | 1 Participants |
| ADG20 IM | Number of Participants With Potentially Clinically Significant (PCS) Changes From Baseline in Clinical Laboratory Test (PCS Defined Per Statistical Analysis Plan) | Creatinine (mcmol/L) - H | 26 Participants |
| ADG20 IM | Number of Participants With Potentially Clinically Significant (PCS) Changes From Baseline in Clinical Laboratory Test (PCS Defined Per Statistical Analysis Plan) | Urea Nitrogen (mmol/L) - H | 26 Participants |
| ADG20 IM | Number of Participants With Potentially Clinically Significant (PCS) Changes From Baseline in Clinical Laboratory Test (PCS Defined Per Statistical Analysis Plan) | Lymphocytes (10^9/L) - L | 3 Participants |
| ADG20 IM | Number of Participants With Potentially Clinically Significant (PCS) Changes From Baseline in Clinical Laboratory Test (PCS Defined Per Statistical Analysis Plan) | Prothrombin Intl. Normalized Ratio - H | 5 Participants |
| ADG20 IM | Number of Participants With Potentially Clinically Significant (PCS) Changes From Baseline in Clinical Laboratory Test (PCS Defined Per Statistical Analysis Plan) | Creatinine Clearance, Estimated (mL/min/1.73m2) - L | 15 Participants |
| ADG20 IM | Number of Participants With Potentially Clinically Significant (PCS) Changes From Baseline in Clinical Laboratory Test (PCS Defined Per Statistical Analysis Plan) | Prothrombin Time (sec) - H | 7 Participants |
| ADG20 IM | Number of Participants With Potentially Clinically Significant (PCS) Changes From Baseline in Clinical Laboratory Test (PCS Defined Per Statistical Analysis Plan) | Glucose (mmol/L) - H | 12 Participants |
| Placebo IM | Number of Participants With Potentially Clinically Significant (PCS) Changes From Baseline in Clinical Laboratory Test (PCS Defined Per Statistical Analysis Plan) | Prothrombin Time (sec) - H | 3 Participants |
| Placebo IM | Number of Participants With Potentially Clinically Significant (PCS) Changes From Baseline in Clinical Laboratory Test (PCS Defined Per Statistical Analysis Plan) | Lymphocytes (10^9/L) - L | 4 Participants |
| Placebo IM | Number of Participants With Potentially Clinically Significant (PCS) Changes From Baseline in Clinical Laboratory Test (PCS Defined Per Statistical Analysis Plan) | Alanine Aminotransferase (U/L) - H | 10 Participants |
| Placebo IM | Number of Participants With Potentially Clinically Significant (PCS) Changes From Baseline in Clinical Laboratory Test (PCS Defined Per Statistical Analysis Plan) | Albumin (g/L) - L | 5 Participants |
| Placebo IM | Number of Participants With Potentially Clinically Significant (PCS) Changes From Baseline in Clinical Laboratory Test (PCS Defined Per Statistical Analysis Plan) | Creatinine (mcmol/L) - H | 23 Participants |
| Placebo IM | Number of Participants With Potentially Clinically Significant (PCS) Changes From Baseline in Clinical Laboratory Test (PCS Defined Per Statistical Analysis Plan) | Creatinine Clearance, Estimated (mL/min/1.73m2) - L | 18 Participants |
| Placebo IM | Number of Participants With Potentially Clinically Significant (PCS) Changes From Baseline in Clinical Laboratory Test (PCS Defined Per Statistical Analysis Plan) | Glucose (mmol/L) - H | 16 Participants |
| Placebo IM | Number of Participants With Potentially Clinically Significant (PCS) Changes From Baseline in Clinical Laboratory Test (PCS Defined Per Statistical Analysis Plan) | Sodium (mmol/L) - L | 4 Participants |
| Placebo IM | Number of Participants With Potentially Clinically Significant (PCS) Changes From Baseline in Clinical Laboratory Test (PCS Defined Per Statistical Analysis Plan) | Urea Nitrogen (mmol/L) - H | 21 Participants |
| Placebo IM | Number of Participants With Potentially Clinically Significant (PCS) Changes From Baseline in Clinical Laboratory Test (PCS Defined Per Statistical Analysis Plan) | Prothrombin Intl. Normalized Ratio - H | 1 Participants |
Secondary
Number of Participants With Potentially Clinically Significant (PCS) Changes From Baseline in Vital Sign Parameters (PCS Defined Per Statistical Analysis Plan)
Time frame: 14 Months
Population: Safety Set: All participants who received any amount of study drug. Participants were analyzed based on the actual treatment (ADG20 versus Placebo) received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ADG20 IM | Number of Participants With Potentially Clinically Significant (PCS) Changes From Baseline in Vital Sign Parameters (PCS Defined Per Statistical Analysis Plan) | DBP >=105 mmHg or Increase >=15 mmHg | 24 participants |
| ADG20 IM | Number of Participants With Potentially Clinically Significant (PCS) Changes From Baseline in Vital Sign Parameters (PCS Defined Per Statistical Analysis Plan) | Temp <35 C or Decrease >=1 C [b] | 60 participants |
| ADG20 IM | Number of Participants With Potentially Clinically Significant (PCS) Changes From Baseline in Vital Sign Parameters (PCS Defined Per Statistical Analysis Plan) | DBP <=50 mmHg or Decrease >=15 mmHg | 25 participants |
| ADG20 IM | Number of Participants With Potentially Clinically Significant (PCS) Changes From Baseline in Vital Sign Parameters (PCS Defined Per Statistical Analysis Plan) | Temp >=38 C or Increase >=1 C [c] | 5 participants |
| ADG20 IM | Number of Participants With Potentially Clinically Significant (PCS) Changes From Baseline in Vital Sign Parameters (PCS Defined Per Statistical Analysis Plan) | HR <=50 bpm or Decrease >=15 bpm [a] | 78 participants |
| ADG20 IM | Number of Participants With Potentially Clinically Significant (PCS) Changes From Baseline in Vital Sign Parameters (PCS Defined Per Statistical Analysis Plan) | RR <=8 breaths/min or Decrease >=4 bpm | 20 participants |
| ADG20 IM | Number of Participants With Potentially Clinically Significant (PCS) Changes From Baseline in Vital Sign Parameters (PCS Defined Per Statistical Analysis Plan) | SBP >=180 mmHg or Increase >=20 mmHg | 29 participants |
| ADG20 IM | Number of Participants With Potentially Clinically Significant (PCS) Changes From Baseline in Vital Sign Parameters (PCS Defined Per Statistical Analysis Plan) | RR >=30 breaths/min or Increase >=10 bpm [d] | 2 participants |
| ADG20 IM | Number of Participants With Potentially Clinically Significant (PCS) Changes From Baseline in Vital Sign Parameters (PCS Defined Per Statistical Analysis Plan) | HR >120 bpm or Increase >=15 bpm | 20 participants |
| ADG20 IM | Number of Participants With Potentially Clinically Significant (PCS) Changes From Baseline in Vital Sign Parameters (PCS Defined Per Statistical Analysis Plan) | SpO2 <=93% or Decrease >=3% | 14 participants |
| ADG20 IM | Number of Participants With Potentially Clinically Significant (PCS) Changes From Baseline in Vital Sign Parameters (PCS Defined Per Statistical Analysis Plan) | SBP <=90 mmHg or Decrease >=20 mmHg | 17 participants |
| Placebo IM | Number of Participants With Potentially Clinically Significant (PCS) Changes From Baseline in Vital Sign Parameters (PCS Defined Per Statistical Analysis Plan) | SpO2 <=93% or Decrease >=3% | 19 participants |
| Placebo IM | Number of Participants With Potentially Clinically Significant (PCS) Changes From Baseline in Vital Sign Parameters (PCS Defined Per Statistical Analysis Plan) | SBP <=90 mmHg or Decrease >=20 mmHg | 23 participants |
| Placebo IM | Number of Participants With Potentially Clinically Significant (PCS) Changes From Baseline in Vital Sign Parameters (PCS Defined Per Statistical Analysis Plan) | SBP >=180 mmHg or Increase >=20 mmHg | 26 participants |
| Placebo IM | Number of Participants With Potentially Clinically Significant (PCS) Changes From Baseline in Vital Sign Parameters (PCS Defined Per Statistical Analysis Plan) | DBP <=50 mmHg or Decrease >=15 mmHg | 26 participants |
| Placebo IM | Number of Participants With Potentially Clinically Significant (PCS) Changes From Baseline in Vital Sign Parameters (PCS Defined Per Statistical Analysis Plan) | DBP >=105 mmHg or Increase >=15 mmHg | 31 participants |
| Placebo IM | Number of Participants With Potentially Clinically Significant (PCS) Changes From Baseline in Vital Sign Parameters (PCS Defined Per Statistical Analysis Plan) | HR <=50 bpm or Decrease >=15 bpm [a] | 96 participants |
| Placebo IM | Number of Participants With Potentially Clinically Significant (PCS) Changes From Baseline in Vital Sign Parameters (PCS Defined Per Statistical Analysis Plan) | HR >120 bpm or Increase >=15 bpm | 25 participants |
| Placebo IM | Number of Participants With Potentially Clinically Significant (PCS) Changes From Baseline in Vital Sign Parameters (PCS Defined Per Statistical Analysis Plan) | Temp <35 C or Decrease >=1 C [b] | 56 participants |
| Placebo IM | Number of Participants With Potentially Clinically Significant (PCS) Changes From Baseline in Vital Sign Parameters (PCS Defined Per Statistical Analysis Plan) | Temp >=38 C or Increase >=1 C [c] | 17 participants |
| Placebo IM | Number of Participants With Potentially Clinically Significant (PCS) Changes From Baseline in Vital Sign Parameters (PCS Defined Per Statistical Analysis Plan) | RR <=8 breaths/min or Decrease >=4 bpm | 25 participants |
| Placebo IM | Number of Participants With Potentially Clinically Significant (PCS) Changes From Baseline in Vital Sign Parameters (PCS Defined Per Statistical Analysis Plan) | RR >=30 breaths/min or Increase >=10 bpm [d] | 2 participants |
Secondary
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)
Proportions of SARS-CoV-2 viral clearance (Days 3, 5, 7, 11, 14, 21, and 29) assessed by RT-qPCR from saliva samples: In the mFAS-S, the cumulative proportion of participants with viral clearance (viral load not detected and sustained through Day 29) at Days 3, 5, 7, 11, 14, 21, and 29 will be assessed by RT-qPCR from saliva samples. Participants who have died or discontinued study prior to Day 29 are assumed to have no viral clearance.
Time frame: Days 5, 7, 11, 14, 21, and 29 (saliva)
Population: Modified Full Analysis Set (mFAS-non-Omicron-S): All randomized participants with COVID-19 due to Whole Genome Sequencing (WGS)-confirmed or suspected non-Omicron SARS-CoV-2 variants with a positive baseline saliva sample.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ADG20 IM | 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) | Participants with Day 5 Samples who achieved sustained viral clearance | 21 Participants |
| ADG20 IM | 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) | Participants with Day 7 Samples who achieved sustained viral clearance | 27 Participants |
| ADG20 IM | 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) | Participants with Day 11 Samples who achieved sustained viral clearance | 55 Participants |
| ADG20 IM | 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) | Participants with Day 14 Samples who achieved sustained viral clearance | 73 Participants |
| ADG20 IM | 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) | Participants with Day 21 Samples who achieved sustained viral clearance | 98 Participants |
| ADG20 IM | 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) | Participants with Day 29 Samples who achieved sustained viral clearance | 123 Participants |
| Placebo IM | 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) | Participants with Day 21 Samples who achieved sustained viral clearance | 83 Participants |
| Placebo IM | 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) | Participants with Day 5 Samples who achieved sustained viral clearance | 9 Participants |
| Placebo IM | 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) | Participants with Day 14 Samples who achieved sustained viral clearance | 62 Participants |
| Placebo IM | 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) | Participants with Day 7 Samples who achieved sustained viral clearance | 19 Participants |
| Placebo IM | 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) | Participants with Day 29 Samples who achieved sustained viral clearance | 116 Participants |
| Placebo IM | 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) | Participants with Day 11 Samples who achieved sustained viral clearance | 40 Participants |
p-value: 0.022795% CI: [1.15, 15.31]Regression, Logistic
Secondary
SARS-CoV-2 Viral Load AUC Assessed by RT-qPCR From Saliva Samples
The AUC from Day 1 through Day 29 was calculated according to the linear trapezoidal rule using the measured SARS-CoV-2 viral load above the lower limit of quantification. No AUC values will be calculated when Day 1 and/or Day 29 values are missing, or if there are more than 3 values missing in the profile.
Time frame: Baseline to Day 29
Population: Modified Full Analysis Set (mFAS-non-Omicron-S): All randomized participants with COVID-19 due to Whole Genome Sequencing (WGS)-confirmed or suspected non-Omicron SARS-CoV-2 variants with a positive baseline saliva sample.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ADG20 IM | SARS-CoV-2 Viral Load AUC Assessed by RT-qPCR From Saliva Samples | 49.96 log10 copies*day/mL | Standard Deviation 36.54 |
| Placebo IM | SARS-CoV-2 Viral Load AUC Assessed by RT-qPCR From Saliva Samples | 57.60 log10 copies*day/mL | Standard Deviation 37.52 |
p-value: 0.112495% CI: [-15.49, 1.64]ANCOVA
Secondary
Time to Sustained Recovery Defined as Sustained Improvement or Resolution of COVID-19 Symptoms
Time to sustained recovery (improvement or resolution) of COVID-19 symptoms through Day 29: Defined as the time from the first dose date to the earliest date when sustained improvement or sustained resolution of COVID-19 symptoms is met (as detailed below) through Day 29. COVID-19 symptoms assessed include fever, chills, cough, sore throat, congestion, shortness of breath/difficulty breathing at rest, shortness of breath/difficulty breathing with exertion, muscle or body aches, fatigue, headache, nausea, vomiting, and diarrhea. Loss of taste/smell is excluded from this analysis.
Time frame: Through Day 29
Population: Modified Full Analysis Set (mFAS-non-Omicron): All randomized participants with COVID-19 due to Whole Genome Sequencing (WGS)-confirmed or suspected non-Omicron SARS-CoV-2 variants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ADG20 IM | Time to Sustained Recovery Defined as Sustained Improvement or Resolution of COVID-19 Symptoms | 11 Days |
| Placebo IM | Time to Sustained Recovery Defined as Sustained Improvement or Resolution of COVID-19 Symptoms | 14 Days |
Comparison: ADG20 vs. Placebop-value: 0.093895% CI: [0.964, 1.586]Regression, Cox
Secondary
Time to Sustained Resolution of COVID-19 Symptoms as Measured in the Daily COVID-19 Symptom Diary
Time to sustained resolution of COVID-19 symptoms through Day 29: Defined as time from the dose date to the first date when all of the defined symptoms are scored as absent with no symptom recurrence or new symptoms, except cough, fatigue, and headache which may be mild or absent, through Day 29.
Time frame: Through Day 29
Population: Modified Full Analysis Set (mFAS-non-Omicron): All randomized participants with COVID-19 due to Whole Genome Sequencing (WGS)-confirmed or suspected non-Omicron SARS-CoV-2 variants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ADG20 IM | Time to Sustained Resolution of COVID-19 Symptoms as Measured in the Daily COVID-19 Symptom Diary | 13 Days |
| Placebo IM | Time to Sustained Resolution of COVID-19 Symptoms as Measured in the Daily COVID-19 Symptom Diary | 16 Days |
Comparison: ADG20 vs Placebop-value: 0.078195% CI: [0.974, 1.617]Regression, Cox
Secondary
Viral Load >5 (log10 Copies/mL) Based on Nasopharyngeal Sampling at Day 7
Proportion of participants with Viral load \>5 (log10 copies/mL) on Day 7 assessed by RT-qPCR from NP sample.
Time frame: on Day 7 (+/- 1 Day)
Population: Modified Full Analysis Set (mFAS-non-Omicron-NP): All randomized participants with COVID-19 due to Whole Genome Sequencing (WGS)-confirmed or suspected non-Omicron SARS-CoV-2 variants with a positive baseline NP sample.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ADG20 IM | Viral Load >5 (log10 Copies/mL) Based on Nasopharyngeal Sampling at Day 7 | 49 Participants |
| Placebo IM | Viral Load >5 (log10 Copies/mL) Based on Nasopharyngeal Sampling at Day 7 | 64 Participants |
p-value: 0.036495% CI: [-21.42, -0.7]Regression, Logistic