COVID-19
Conditions
Keywords
ensovibep, COVID-19 treatment, symptom reduction, viral load reduction,, EMPATHY, SARS-CoV-2, designed ankyrin repeat protein (DARPin®), angiotensin-converting enzyme 2 (ACE2)
Brief summary
The purpose of this study is to establish the antiviral efficacy of ensovibep against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in humans, identify the optimal dose, and demonstrate its clinical value for treating COVID-19 in adult ambulatory patients.
Detailed description
Primary objectives: Part A: The primary objective of this Part is to demonstrate superiority of ensovibep, compared to placebo, in reducing SARS-CoV-2 viral load through Day 8. Part B: The primary objective of this Part is to demonstrate superiority of ensovibep, compared to placebo, in reducing the occurrence of hospitalizations (≥ 24 hours of acute care) and/or emergency room visits related to COVID-19 or death from any cause up to Day 29. Secondary objectives: Part A: The secondary objectives of this Part are: * To assess the effect of ensovibep, compared to placebo, in reducing the occurrence of hospitalizations (≥ 24 hours of acute care) and/or emergency room visits related to COVID-19 or death from any cause up to Day 29 * To assess the effect of ensovibep, compared to placebo, in reducing COVID-19 symptoms through Day 29 * To evaluate safety and tolerability of ensovibep * To characterize the pharmacokinetics (PK) of ensovibep Part B: The secondary objectives of this Part are: * To assess the effect of ensovibep, compared to placebo, in reducing SARS-CoV-2 viral load through Day 8 * To assess the effect of ensovibep, compared to placebo, in reducing COVID-19 symptoms up to Day 29 * To evaluate the immunogenicity of ensovibep during the study and its clinical relevance (PK, efficacy and safety) * To evaluate safety and tolerability of ensovibep Although Amendment 2 was created, modifications for this amendment are not reflected as it was never approved or implemented in the US. The study was conducted under Global Protocol Amendment 1, the last active version of the protocol.
Interventions
DRUGensovibep
IV on day 1 only.
DRUGPlacebo
IV on day 1 only.
Sponsors
Novartis Pharmaceuticals
Molecular Partners AG
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
* Double Blind: two or more parties are unaware of the intervention assignment * Masked roles are: Subject, Caregiver, Investigator or Outcomes Assessor.
Intervention model description
* Parallel: participants are assigned to one of two or more groups in parallel for the duration of the study. * 4 Arms under Phase 2 and 2 Arms under Phase 3
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Part A Inclusion Criteria: 1. Men and women ≥ 18 years of age on the day of inclusion (no upper limit). 2. Presence of two or more of the following COVID-19 symptoms with an onset within 7 days of dosing: Feeling hot or feverish, cough, sore throat, low energy, or tiredness, headache, muscle or body aches, chills or shivering, and shortness of breath. 3. Positive test for SARS-CoV-2 in upper respiratory swab on the day of dosing (rapid antigen test). 4. Understand and agree to comply with the planned study procedures. 5. The patient or legally authorized representative give signed informed consent. Part A
Exclusion criteria
1. Requiring hospitalization at time of screening, or at time of study drug administration. 2. Oxygen saturation (SpO2) ≤ 93% on room air at sea level or ratio of arterial oxygen partial pressure (PaO2 in mmHg) to fractional inspired oxygen (FiO2) \< 300, respiratory rate ≥ 30 per minute, and heart rate ≥ 125 per minute. In India, patients with a respiratory rate ≥ 24 per minute or with an oxygen saturation ≤ 93% on room air (SpO2) are not eligible. 3. Known allergies to any of the components used in the formulation of the ensovibep or placebo. 4. Suspected or proven serious, active bacterial, fungal, viral, or other infection (besides SARS-CoV-2) that in the opinion of the investigator could constitute a risk when taking intervention. 5. Any serious concomitant systemic disease, condition, or disorder that, in the opinion of the investigator, should preclude participation in this study. 6. Any co-morbidity requiring surgery within 7 days of dosing, or that is considered life-threatening within 29 days of dosing. 7. Prior or concurrent use of any medication for treatment of COVID-19, including antiviral agents, convalescent serum, or anti-viral antibodies. Purely symptomatic therapies (e.g., over-the-counter \[OTC\] cough medications, acetaminophen, and nonsteroidal anti-inflammatory drugs \[NSAIDs\]) are permitted. Prior vaccination for COVID-19 is permitted. 8. Are concurrently enrolled or were enrolled within the last 30 days or within 5 half-lives (whichever is longer) in any other type of medical research judged not to be scientifically or medically compatible with this study. 9. Are pregnant or breast feeding. 10. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception at the time of dosing and for 11 weeks after dosing of study drug. Highly effective contraception methods include: 1. Total abstinence (when this is in line with the preferred and usual lifestyle of the patient). Periodic abstinence (i.e., calendar, ovulation, symptothermal, and postovulation methods) and withdrawal are not acceptable methods of contraception. 2. Female sterilization (have had bilateral surgical oophorectomy \[with or without hysterectomy\], total hysterectomy, or bilateral tubal ligation at least 6 weeks before taking study treatment). In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow-up hormone level assessment. 3. Male sterilization (at least 6 months prior to screening). The vasectomized male partner should be the sole partner for that patient. 4. Use of oral, injected, or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS) or other forms of hormonal contraception that have comparable efficacy (failure rate \< 1%), for example hormone vaginal ring or transdermal hormone contraception. In case of use of oral contraception, women should have been stable on the same pill for a minimum of 3 months before taking study treatment. If local regulations deviate from the contraception methods listed above to prevent pregnancy, local regulations apply and will be described in the informed consent form (ICF). 11. Patients in the USA who are at high risk of progression to severe COVID-19 illness or hospitalization must not be enrolled in Part A of this study as a placebo-controlled study may not be appropriate in this patient population due to the availability of anti-viral mAbs under EUA in the USA.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part A: Time-Weighted Change From Baseline in Log10 Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Viral Load Through Day 8 | Baseline (Day 1) and Days 3, 5 and 8 | The SARS-CoV-2 viral load was measured by means of a nasopharyngeal swab, followed by quantitative reverse transcription-polymerase chain reaction assay at a central laboratory. The multiple comparison procedure-modeling methodology was used. Time-weighted change from baseline was used as viral loads were measured at multiple time points. |
| Part B: Percentage of Participants With Hospitalizations and/or Emergency Room (ER) Visits Related to COVID-19 or Death From Any Cause | Up to Day 29 | Percentage of participants experiencing hospitalizations \[\>= 24 hour (h) of acute care\] and/or ER visits related to COVID-19 or death from any cause up to Day 29. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part A: Percentage of Participants With Hospitalizations and/or ER Visits Related to COVID-19 or Death From Any Cause | Up to Day 29 | Percentage of participants experiencing hospitalizations (\>= 24 h of acute care) and/or ER visits related to COVID-19 or death from any cause up to Day 29 were presented along with relative risk to placebo. |
| Part A: Time to Sustained Clinical Recovery | Up to Day 29 | Sustained clinical recovery was defined as follows; 1. All symptoms from the modified Food and Drug Administration (FDA) COVID-19 questionnaire scored as moderate or severe at baseline were subsequently scored as mild or absent, and 2. All symptoms from the modified FDA COVID-19 questionnaire scored as mild or absent at baseline were subsequently scored as absent, with no subsequent worsening, up to Day 29. |
| Part A: Observed Maximum Serum Concentration (Cmax) of Total and Free Ensovibep | Data was summarized from pre-dose and at 15 minutes and 90 minutes after end of study drug infusion on Day 1, and at Days 3, 8, 15, 29, 61 and 91 | Blood samples were collected to determine the Cmax of free ensovibep (ensovibep not bound to target) and total ensovibep (sum of ensovibep not bound to and bound to target) concentrations in serum. |
| Part A: Area Under the Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Total and Free Ensovibep | Data was summarized from pre-dose and at 15 minutes and 90 minutes after end of study drug infusion on Day 1, and at Days 3, 8, 15, 29, 61 and 91 | Blood samples were collected to determine the AUClast of free ensovibep (ensovibep not bound to target) and total ensovibep (sum of ensovibep not bound to and bound to target) concentrations in serum. |
| Part A: Area Under the Concentration-Time Curve From Time Zero to 48 Hours (AUC 0-48h) of Total and Free Ensovibep | Data was summarized from pre-dose and at 15 minutes and 90 minutes after end of study drug infusion on Day 1, and at Day 3 | Blood samples were collected to determine the AUC 0-48h of free ensovibep (ensovibep not bound to target) and total ensovibep (sum of ensovibep not bound to and bound to target) concentrations in serum. |
| Part A: Area Under the Concentration-Time Curve From Time Zero to 168 Hours (AUC 0-168h) of Total and Free Ensovibep | Data was summarized from pre-dose and at 15 minutes and 90 minutes after end of study drug infusion on Day 1, and at Days 3 and 8 | Blood samples were collected to determine the AUC 0-168h of free ensovibep (ensovibep not bound to target) and total ensovibep (sum of ensovibep not bound to and bound to target) concentrations in serum. |
| Part A: Area Under the Concentration-Time Curve From Time Zero to 336 Hours (AUC 0-336h) of Total and Free Ensovibep | Data was summarized from pre-dose and at 15 minutes and 90 minutes after end of study drug infusion on Day 1, and at Days 3, 8 and 15 | Blood samples were collected to determine the AUC 0-336h of free ensovibep (ensovibep not bound to target) and total ensovibep (sum of ensovibep not bound to and bound to target) concentrations in serum. |
| Part A: Area Under the Concentration-Time Curve From Time Zero to Infinity (AUCinfinity) of Total and Free Ensovibep | Data was summarized from pre-dose and at 15 minutes and 90 minutes after end of study drug infusion on Day 1, and at Days 3, 8, 15, 29, 61 and 91 | Blood samples were collected to determine the AUCinfinity of free ensovibep (ensovibep not bound to target) and total ensovibep (sum of ensovibep not bound to and bound to target) concentrations in serum. |
| Part A: Time to Reach the Maximum Concentration (Tmax) of Total and Free Ensovibep | Data was summarized from pre-dose and at 15 minutes and 90 minutes after end of study drug infusion on Day 1, and at Days 3, 8, 15, 29, 61 and 91 | Blood samples were collected to determine the Tmax of free ensovibep (ensovibep not bound to target) and total ensovibep (sum of ensovibep not bound to and bound to target) concentrations in serum. |
| Part A: Apparent Total Body Clearance (CL) of Total and Free Ensovibep | Data was summarized from pre-dose and at 15 minutes and 90 minutes after end of study drug infusion on Day 1, and at Days 3, 8, 15, 29, 61 and 91 | Blood samples were collected to determine the CL of free ensovibep (ensovibep not bound to target) and total ensovibep (sum of ensovibep not bound to and bound to target) concentrations in serum. |
| Part A: Terminal Elimination Rate Constant (Lambda z) of Total and Free Ensovibep | Data was summarized from pre-dose and at 15 minutes and 90 minutes after end of study drug infusion on Day 1, and at Days 3, 8, 15, 29, 61 and 91 | Blood samples were collected to determine the lambda z of free ensovibep (ensovibep not bound to target) and total ensovibep (sum of ensovibep not bound to and bound to target) concentrations in serum. |
| Part A: Terminal Elimination Half-Life (T1/2) of Total and Free Ensovibep | Data was summarized from pre-dose and at 15 minutes and 90 minutes after end of study drug infusion on Day 1, and at Days 3, 8, 15, 29, 61 and 91 | Blood samples were collected to determine the T1/2 of free ensovibep (ensovibep not bound to target) and total ensovibep (sum of ensovibep not bound to and bound to target) concentrations in serum. |
| Part A: Apparent Volume of Distribution (Vz) of Total and Free Ensovibep | Data was summarized from pre-dose and at 15 minutes and 90 minutes after end of study drug infusion on Day 1, and at Days 3, 8, 15, 29, 61 and 91 | Blood samples were collected to determine the Vz of free ensovibep (ensovibep not bound to target) and total ensovibep (sum of ensovibep not bound to and bound to target) concentrations in serum. |
| Part B: Change From Baseline in Log10 SARS-CoV-2 Viral Load Through Day 8 | Baseline (Day 1) and Days 3, 5 and 8 | The SARS-CoV-2 viral load was measured by means of a nasopharyngeal swab, followed by quantitative reverse transcription-polymerase chain reaction assay at a central laboratory. The multiple comparison procedure-modeling methodology was used. |
| Part B: Time to Sustained Clinical Recovery | Up to Day 29 | Sustained clinical recovery was defined as follows; 1. All symptoms from the modified FDA COVID-19 questionnaire scored as moderate or severe at baseline were subsequently scored as mild or absent, and 2. All symptoms from the modified FDA COVID-19 questionnaire scored as mild or absent at baseline were subsequently scored as absent, with no subsequent worsening, up to Day 29. |
| Part B: Percentage of Participants With Treatment-Emergent Anti-Drug Antibody (ADA) Response to Ensovibep | Pre-dose on Day 1 and Days 15, 29, 61 and 91 postdose of Ensovibep | Treatment-emergent ADA is defined as any participant with a 1. 2-fold (1 dilution) increase in titer than the minimum required dilution if no ADAs were detected at baseline (treatment-induced ADA); or, 2. 4-fold (2 dilutions) increase in titer compared with baseline if ADAs were detected at baseline (treatment-boosted ADA). |
Countries
Hungary, India, Netherlands, South Africa, United States
Participant flow
Recruitment details
This study consisted of 2 parts, Part A and Part B. The Part A was Phase II proof of efficacy study conducted in ambulatory adult participants with symptomatic coronavirus disease 2019 (COVID-19) at 45 centers across 5 countries (Hungary, India, Netherlands, South Africa, and USA) between 10 May 2021 and 27 Jan 2022. The Part B was to be a Phase III confirmatory study. Only Part A analysis is reported since Part B of the study was not initiated.
Pre-assignment details
The Part A of the study consisted of a screening period (up to 3 days) followed by study treatment on Day 1. Participants were randomized in 1:1:1:1 ratio, stratified by risk for COVID-19 disease progression, to receive 1 of 4 study treatments (Ensovibep 600 mg or Ensovibep 225 mg or Ensovibep 75 mg or Placebo). A total of 407 participants were randomized in the study, of which 400 were treated.
Participants by arm
| Arm | Count |
|---|---|
| Ensovibep 600 mg Participants received single IV infusion of ensovibep 600 mg on Day 1. | 100 |
| Ensovibep 225 mg Participants received single IV infusion of ensovibep 225 mg on Day 1. | 100 |
| Ensovibep 75 mg Participants received single IV infusion of ensovibep 75 mg on Day 1. | 101 |
| Placebo Participants received single IV infusion of placebo matching with ensovibep on Day 1. | 99 |
| Total | 400 |
Baseline characteristics
| Characteristic | Ensovibep 600 mg | Ensovibep 225 mg | Ensovibep 75 mg | Placebo | Total |
|---|---|---|---|---|---|
| Age, Continuous | 40.6 years STANDARD_DEVIATION 11.5 | 40.2 years STANDARD_DEVIATION 12.9 | 41.5 years STANDARD_DEVIATION 12.84 | 42.3 years STANDARD_DEVIATION 13.75 | 41.1 years STANDARD_DEVIATION 12.75 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 3 Participants | 0 Participants | 1 Participants | 0 Participants | 4 Participants |
| Race/Ethnicity, Customized Asian | 14 Participants | 14 Participants | 13 Participants | 16 Participants | 57 Participants |
| Race/Ethnicity, Customized Black or African American | 16 Participants | 11 Participants | 14 Participants | 11 Participants | 52 Participants |
| Race/Ethnicity, Customized Multiple | 5 Participants | 4 Participants | 6 Participants | 8 Participants | 23 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 2 Participants | 0 Participants | 4 Participants |
| Race/Ethnicity, Customized Not reported | 1 Participants | 4 Participants | 3 Participants | 1 Participants | 9 Participants |
| Race/Ethnicity, Customized Unknown | 1 Participants | 3 Participants | 0 Participants | 0 Participants | 4 Participants |
| Race/Ethnicity, Customized White | 59 Participants | 63 Participants | 62 Participants | 63 Participants | 247 Participants |
| Sex: Female, Male Female | 47 Participants | 54 Participants | 60 Participants | 57 Participants | 218 Participants |
| Sex: Female, Male Male | 53 Participants | 46 Participants | 41 Participants | 42 Participants | 182 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 100 | 0 / 98 | 0 / 102 | 0 / 300 | 2 / 100 |
| other Total, other adverse events | 51 / 100 | 40 / 98 | 40 / 102 | 131 / 300 | 53 / 100 |
| serious Total, serious adverse events | 0 / 100 | 2 / 98 | 1 / 102 | 3 / 300 | 9 / 100 |
Outcome results
Primary
Part A: Time-Weighted Change From Baseline in Log10 Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Viral Load Through Day 8
The SARS-CoV-2 viral load was measured by means of a nasopharyngeal swab, followed by quantitative reverse transcription-polymerase chain reaction assay at a central laboratory. The multiple comparison procedure-modeling methodology was used. Time-weighted change from baseline was used as viral loads were measured at multiple time points.
Time frame: Baseline (Day 1) and Days 3, 5 and 8
Population: The FAS included all participants in the randomized set for whom IV infusion of study treatment was administered. Only participants included in the analysis are reported.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ensovibep 600 mg | Part A: Time-Weighted Change From Baseline in Log10 Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Viral Load Through Day 8 | -1.99 log10 copies/milliliter (mL) | Standard Error 0.097 |
| Ensovibep 225 mg | Part A: Time-Weighted Change From Baseline in Log10 Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Viral Load Through Day 8 | -1.73 log10 copies/milliliter (mL) | Standard Error 0.093 |
| Ensovibep 75 mg | Part A: Time-Weighted Change From Baseline in Log10 Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Viral Load Through Day 8 | -1.81 log10 copies/milliliter (mL) | Standard Error 0.093 |
| Placebo | Part A: Time-Weighted Change From Baseline in Log10 Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Viral Load Through Day 8 | -1.40 log10 copies/milliliter (mL) | Standard Error 0.098 |
p-value: <0.00195% CI: [-0.86, -0.32]ANCOVA
p-value: 0.01495% CI: [-0.6, -0.07]ANCOVA
p-value: 0.00295% CI: [-0.68, -0.15]ANCOVA
Primary
Part B: Percentage of Participants With Hospitalizations and/or Emergency Room (ER) Visits Related to COVID-19 or Death From Any Cause
Percentage of participants experiencing hospitalizations \[\>= 24 hour (h) of acute care\] and/or ER visits related to COVID-19 or death from any cause up to Day 29.
Time frame: Up to Day 29
Population: The Part B of the study was not initiated based on regulatory feedback indicating that with evolving treatment options, a placebo controlled design was no longer considered to be appropriate.
| Arm | Measure | Group | Value |
|---|---|---|---|
| Unknown | Part B: Percentage of Participants With Hospitalizations and/or Emergency Room (ER) Visits Related to COVID-19 or Death From Any Cause | Any event | — |
| Unknown | Part B: Percentage of Participants With Hospitalizations and/or Emergency Room (ER) Visits Related to COVID-19 or Death From Any Cause | Hospitalizations (≥ 24 h of acute care) | — |
| Unknown | Part B: Percentage of Participants With Hospitalizations and/or Emergency Room (ER) Visits Related to COVID-19 or Death From Any Cause | Emergency room visits related to COVID-19 | — |
| Unknown | Part B: Percentage of Participants With Hospitalizations and/or Emergency Room (ER) Visits Related to COVID-19 or Death From Any Cause | Death from any cause | — |
Secondary
Part A: Apparent Total Body Clearance (CL) of Total and Free Ensovibep
Blood samples were collected to determine the CL of free ensovibep (ensovibep not bound to target) and total ensovibep (sum of ensovibep not bound to and bound to target) concentrations in serum.
Time frame: Data was summarized from pre-dose and at 15 minutes and 90 minutes after end of study drug infusion on Day 1, and at Days 3, 8, 15, 29, 61 and 91
Population: The PK analysis set included all participants with at least 1 available valid (that is, not flagged for exclusion) PK concentration measurement, who received any study treatment and with no protocol deviations that impacted PK data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Ensovibep 600 mg | Part A: Apparent Total Body Clearance (CL) of Total and Free Ensovibep | Total Ensovibep | 8.07 mL/h | Geometric Coefficient of Variation 35.4 |
| Ensovibep 600 mg | Part A: Apparent Total Body Clearance (CL) of Total and Free Ensovibep | Free Ensovibep | 7.55 mL/h | Geometric Coefficient of Variation 37.3 |
| Ensovibep 225 mg | Part A: Apparent Total Body Clearance (CL) of Total and Free Ensovibep | Total Ensovibep | 8.11 mL/h | Geometric Coefficient of Variation 36.1 |
| Ensovibep 225 mg | Part A: Apparent Total Body Clearance (CL) of Total and Free Ensovibep | Free Ensovibep | 7.64 mL/h | Geometric Coefficient of Variation 35.3 |
| Ensovibep 75 mg | Part A: Apparent Total Body Clearance (CL) of Total and Free Ensovibep | Free Ensovibep | 7.78 mL/h | Geometric Coefficient of Variation 43 |
| Ensovibep 75 mg | Part A: Apparent Total Body Clearance (CL) of Total and Free Ensovibep | Total Ensovibep | 7.48 mL/h | Geometric Coefficient of Variation 42.1 |
Secondary
Part A: Apparent Volume of Distribution (Vz) of Total and Free Ensovibep
Blood samples were collected to determine the Vz of free ensovibep (ensovibep not bound to target) and total ensovibep (sum of ensovibep not bound to and bound to target) concentrations in serum.
Time frame: Data was summarized from pre-dose and at 15 minutes and 90 minutes after end of study drug infusion on Day 1, and at Days 3, 8, 15, 29, 61 and 91
Population: The PK analysis set included all participants with at least 1 available valid (that is, not flagged for exclusion) PK concentration measurement, who received any study treatment and with no protocol deviations that impacted PK data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Ensovibep 600 mg | Part A: Apparent Volume of Distribution (Vz) of Total and Free Ensovibep | Total Ensovibep | 3230 mL | Geometric Coefficient of Variation 35 |
| Ensovibep 600 mg | Part A: Apparent Volume of Distribution (Vz) of Total and Free Ensovibep | Free Ensovibep | 2760 mL | Geometric Coefficient of Variation 46.1 |
| Ensovibep 225 mg | Part A: Apparent Volume of Distribution (Vz) of Total and Free Ensovibep | Total Ensovibep | 3310 mL | Geometric Coefficient of Variation 37.5 |
| Ensovibep 225 mg | Part A: Apparent Volume of Distribution (Vz) of Total and Free Ensovibep | Free Ensovibep | 2590 mL | Geometric Coefficient of Variation 36.4 |
| Ensovibep 75 mg | Part A: Apparent Volume of Distribution (Vz) of Total and Free Ensovibep | Total Ensovibep | 3330 mL | Geometric Coefficient of Variation 38.7 |
| Ensovibep 75 mg | Part A: Apparent Volume of Distribution (Vz) of Total and Free Ensovibep | Free Ensovibep | 2470 mL | Geometric Coefficient of Variation 45.6 |
Secondary
Part A: Area Under the Concentration-Time Curve From Time Zero to 168 Hours (AUC 0-168h) of Total and Free Ensovibep
Blood samples were collected to determine the AUC 0-168h of free ensovibep (ensovibep not bound to target) and total ensovibep (sum of ensovibep not bound to and bound to target) concentrations in serum.
Time frame: Data was summarized from pre-dose and at 15 minutes and 90 minutes after end of study drug infusion on Day 1, and at Days 3 and 8
Population: The PK analysis set included all participants with at least 1 available valid (that is, not flagged for exclusion) PK concentration measurement, who received any study treatment and with no protocol deviations that impacted PK data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Ensovibep 600 mg | Part A: Area Under the Concentration-Time Curve From Time Zero to 168 Hours (AUC 0-168h) of Total and Free Ensovibep | Total Ensovibep | 23000 h*mcg/mL | Geometric Coefficient of Variation 23.7 |
| Ensovibep 600 mg | Part A: Area Under the Concentration-Time Curve From Time Zero to 168 Hours (AUC 0-168h) of Total and Free Ensovibep | Free Ensovibep | 25200 h*mcg/mL | Geometric Coefficient of Variation 23.2 |
| Ensovibep 225 mg | Part A: Area Under the Concentration-Time Curve From Time Zero to 168 Hours (AUC 0-168h) of Total and Free Ensovibep | Free Ensovibep | 8940 h*mcg/mL | Geometric Coefficient of Variation 73.2 |
| Ensovibep 225 mg | Part A: Area Under the Concentration-Time Curve From Time Zero to 168 Hours (AUC 0-168h) of Total and Free Ensovibep | Total Ensovibep | 8570 h*mcg/mL | Geometric Coefficient of Variation 33.1 |
| Ensovibep 75 mg | Part A: Area Under the Concentration-Time Curve From Time Zero to 168 Hours (AUC 0-168h) of Total and Free Ensovibep | Free Ensovibep | 3390 h*mcg/mL | Geometric Coefficient of Variation 35.3 |
| Ensovibep 75 mg | Part A: Area Under the Concentration-Time Curve From Time Zero to 168 Hours (AUC 0-168h) of Total and Free Ensovibep | Total Ensovibep | 3020 h*mcg/mL | Geometric Coefficient of Variation 31.4 |
Secondary
Part A: Area Under the Concentration-Time Curve From Time Zero to 336 Hours (AUC 0-336h) of Total and Free Ensovibep
Blood samples were collected to determine the AUC 0-336h of free ensovibep (ensovibep not bound to target) and total ensovibep (sum of ensovibep not bound to and bound to target) concentrations in serum.
Time frame: Data was summarized from pre-dose and at 15 minutes and 90 minutes after end of study drug infusion on Day 1, and at Days 3, 8 and 15
Population: The PK analysis set included all participants with at least 1 available valid (that is, not flagged for exclusion) PK concentration measurement, who received any study treatment and with no protocol deviations that impacted PK data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Ensovibep 600 mg | Part A: Area Under the Concentration-Time Curve From Time Zero to 336 Hours (AUC 0-336h) of Total and Free Ensovibep | Total Ensovibep | 38200 h*mcg/mL | Geometric Coefficient of Variation 23.2 |
| Ensovibep 600 mg | Part A: Area Under the Concentration-Time Curve From Time Zero to 336 Hours (AUC 0-336h) of Total and Free Ensovibep | Free Ensovibep | 41800 h*mcg/mL | Geometric Coefficient of Variation 23.5 |
| Ensovibep 225 mg | Part A: Area Under the Concentration-Time Curve From Time Zero to 336 Hours (AUC 0-336h) of Total and Free Ensovibep | Total Ensovibep | 13800 h*mcg/mL | Geometric Coefficient of Variation 37.6 |
| Ensovibep 225 mg | Part A: Area Under the Concentration-Time Curve From Time Zero to 336 Hours (AUC 0-336h) of Total and Free Ensovibep | Free Ensovibep | 15300 h*mcg/mL | Geometric Coefficient of Variation 41.6 |
| Ensovibep 75 mg | Part A: Area Under the Concentration-Time Curve From Time Zero to 336 Hours (AUC 0-336h) of Total and Free Ensovibep | Total Ensovibep | 5040 h*mcg/mL | Geometric Coefficient of Variation 31.9 |
| Ensovibep 75 mg | Part A: Area Under the Concentration-Time Curve From Time Zero to 336 Hours (AUC 0-336h) of Total and Free Ensovibep | Free Ensovibep | 5620 h*mcg/mL | Geometric Coefficient of Variation 39.1 |
Secondary
Part A: Area Under the Concentration-Time Curve From Time Zero to 48 Hours (AUC 0-48h) of Total and Free Ensovibep
Blood samples were collected to determine the AUC 0-48h of free ensovibep (ensovibep not bound to target) and total ensovibep (sum of ensovibep not bound to and bound to target) concentrations in serum.
Time frame: Data was summarized from pre-dose and at 15 minutes and 90 minutes after end of study drug infusion on Day 1, and at Day 3
Population: The PK analysis set included all participants with at least 1 available valid (that is, not flagged for exclusion) PK concentration measurement, who received any study treatment and with no protocol deviations that impacted PK data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Ensovibep 600 mg | Part A: Area Under the Concentration-Time Curve From Time Zero to 48 Hours (AUC 0-48h) of Total and Free Ensovibep | Free Ensovibep | 8290 h*mcg/mL | Geometric Coefficient of Variation 32.1 |
| Ensovibep 600 mg | Part A: Area Under the Concentration-Time Curve From Time Zero to 48 Hours (AUC 0-48h) of Total and Free Ensovibep | Total Ensovibep | 7520 h*mcg/mL | Geometric Coefficient of Variation 35.3 |
| Ensovibep 225 mg | Part A: Area Under the Concentration-Time Curve From Time Zero to 48 Hours (AUC 0-48h) of Total and Free Ensovibep | Free Ensovibep | 2800 h*mcg/mL | Geometric Coefficient of Variation 156.2 |
| Ensovibep 225 mg | Part A: Area Under the Concentration-Time Curve From Time Zero to 48 Hours (AUC 0-48h) of Total and Free Ensovibep | Total Ensovibep | 2830 h*mcg/mL | Geometric Coefficient of Variation 35.7 |
| Ensovibep 75 mg | Part A: Area Under the Concentration-Time Curve From Time Zero to 48 Hours (AUC 0-48h) of Total and Free Ensovibep | Total Ensovibep | 999 h*mcg/mL | Geometric Coefficient of Variation 34.4 |
| Ensovibep 75 mg | Part A: Area Under the Concentration-Time Curve From Time Zero to 48 Hours (AUC 0-48h) of Total and Free Ensovibep | Free Ensovibep | 1120 h*mcg/mL | Geometric Coefficient of Variation 36.7 |
Secondary
Part A: Area Under the Concentration-Time Curve From Time Zero to Infinity (AUCinfinity) of Total and Free Ensovibep
Blood samples were collected to determine the AUCinfinity of free ensovibep (ensovibep not bound to target) and total ensovibep (sum of ensovibep not bound to and bound to target) concentrations in serum.
Time frame: Data was summarized from pre-dose and at 15 minutes and 90 minutes after end of study drug infusion on Day 1, and at Days 3, 8, 15, 29, 61 and 91
Population: The PK analysis set included all participants with at least 1 available valid (that is, not flagged for exclusion) PK concentration measurement, who received any study treatment and with no protocol deviations that impacted PK data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Ensovibep 600 mg | Part A: Area Under the Concentration-Time Curve From Time Zero to Infinity (AUCinfinity) of Total and Free Ensovibep | Total Ensovibep | 75400 h*mcg/mL | Geometric Coefficient of Variation 33.5 |
| Ensovibep 600 mg | Part A: Area Under the Concentration-Time Curve From Time Zero to Infinity (AUCinfinity) of Total and Free Ensovibep | Free Ensovibep | 80100 h*mcg/mL | Geometric Coefficient of Variation 40.6 |
| Ensovibep 225 mg | Part A: Area Under the Concentration-Time Curve From Time Zero to Infinity (AUCinfinity) of Total and Free Ensovibep | Total Ensovibep | 27600 h*mcg/mL | Geometric Coefficient of Variation 36.3 |
| Ensovibep 225 mg | Part A: Area Under the Concentration-Time Curve From Time Zero to Infinity (AUCinfinity) of Total and Free Ensovibep | Free Ensovibep | 29400 h*mcg/mL | Geometric Coefficient of Variation 34.8 |
| Ensovibep 75 mg | Part A: Area Under the Concentration-Time Curve From Time Zero to Infinity (AUCinfinity) of Total and Free Ensovibep | Total Ensovibep | 9930 h*mcg/mL | Geometric Coefficient of Variation 41 |
| Ensovibep 75 mg | Part A: Area Under the Concentration-Time Curve From Time Zero to Infinity (AUCinfinity) of Total and Free Ensovibep | Free Ensovibep | 9540 h*mcg/mL | Geometric Coefficient of Variation 45.8 |
Secondary
Part A: Area Under the Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Total and Free Ensovibep
Blood samples were collected to determine the AUClast of free ensovibep (ensovibep not bound to target) and total ensovibep (sum of ensovibep not bound to and bound to target) concentrations in serum.
Time frame: Data was summarized from pre-dose and at 15 minutes and 90 minutes after end of study drug infusion on Day 1, and at Days 3, 8, 15, 29, 61 and 91
Population: The PK analysis set included all participants with at least 1 available valid (that is, not flagged for exclusion) PK concentration measurement, who received any study treatment and with no protocol deviations that impacted PK data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Ensovibep 600 mg | Part A: Area Under the Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Total and Free Ensovibep | Free Ensovibep | 68200 h*mcg/mL | Geometric Coefficient of Variation 84.4 |
| Ensovibep 600 mg | Part A: Area Under the Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Total and Free Ensovibep | Total Ensovibep | 63300 h*mcg/mL | Geometric Coefficient of Variation 87.6 |
| Ensovibep 225 mg | Part A: Area Under the Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Total and Free Ensovibep | Free Ensovibep | 22500 h*mcg/mL | Geometric Coefficient of Variation 126.9 |
| Ensovibep 225 mg | Part A: Area Under the Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Total and Free Ensovibep | Total Ensovibep | 21100 h*mcg/mL | Geometric Coefficient of Variation 122 |
| Ensovibep 75 mg | Part A: Area Under the Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Total and Free Ensovibep | Total Ensovibep | 7950 h*mcg/mL | Geometric Coefficient of Variation 67.1 |
| Ensovibep 75 mg | Part A: Area Under the Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Total and Free Ensovibep | Free Ensovibep | 8380 h*mcg/mL | Geometric Coefficient of Variation 67.9 |
Secondary
Part A: Observed Maximum Serum Concentration (Cmax) of Total and Free Ensovibep
Blood samples were collected to determine the Cmax of free ensovibep (ensovibep not bound to target) and total ensovibep (sum of ensovibep not bound to and bound to target) concentrations in serum.
Time frame: Data was summarized from pre-dose and at 15 minutes and 90 minutes after end of study drug infusion on Day 1, and at Days 3, 8, 15, 29, 61 and 91
Population: The Pharmacokinetic (PK) analysis set included all participants with at least 1 available valid (that is, not flagged for exclusion) PK concentration measurement, who received any study treatment and with no protocol deviations that impacted PK data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Ensovibep 600 mg | Part A: Observed Maximum Serum Concentration (Cmax) of Total and Free Ensovibep | Total Ensovibep | 187 microgram (mcg) per mL | Geometric Coefficient of Variation 25.3 |
| Ensovibep 600 mg | Part A: Observed Maximum Serum Concentration (Cmax) of Total and Free Ensovibep | Free Ensovibep | 210 microgram (mcg) per mL | Geometric Coefficient of Variation 26.3 |
| Ensovibep 225 mg | Part A: Observed Maximum Serum Concentration (Cmax) of Total and Free Ensovibep | Total Ensovibep | 70.4 microgram (mcg) per mL | Geometric Coefficient of Variation 27.5 |
| Ensovibep 225 mg | Part A: Observed Maximum Serum Concentration (Cmax) of Total and Free Ensovibep | Free Ensovibep | 78.1 microgram (mcg) per mL | Geometric Coefficient of Variation 31.5 |
| Ensovibep 75 mg | Part A: Observed Maximum Serum Concentration (Cmax) of Total and Free Ensovibep | Total Ensovibep | 25.1 microgram (mcg) per mL | Geometric Coefficient of Variation 38.4 |
| Ensovibep 75 mg | Part A: Observed Maximum Serum Concentration (Cmax) of Total and Free Ensovibep | Free Ensovibep | 29.3 microgram (mcg) per mL | Geometric Coefficient of Variation 46.4 |
Secondary
Part A: Percentage of Participants With Hospitalizations and/or ER Visits Related to COVID-19 or Death From Any Cause
Percentage of participants experiencing hospitalizations (\>= 24 h of acute care) and/or ER visits related to COVID-19 or death from any cause up to Day 29 were presented along with relative risk to placebo.
Time frame: Up to Day 29
Population: The FAS included all participants in the randomized set for whom IV infusion of study treatment was administered.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ensovibep 600 mg | Part A: Percentage of Participants With Hospitalizations and/or ER Visits Related to COVID-19 or Death From Any Cause | Hospitalizations (≥ 24 h of acute care) | 0.0 percentage of participants |
| Ensovibep 600 mg | Part A: Percentage of Participants With Hospitalizations and/or ER Visits Related to COVID-19 or Death From Any Cause | Emergency room visits related to COVID-19 | 1.0 percentage of participants |
| Ensovibep 600 mg | Part A: Percentage of Participants With Hospitalizations and/or ER Visits Related to COVID-19 or Death From Any Cause | Death from any cause | 0.0 percentage of participants |
| Ensovibep 600 mg | Part A: Percentage of Participants With Hospitalizations and/or ER Visits Related to COVID-19 or Death From Any Cause | Any event | 1.0 percentage of participants |
| Ensovibep 225 mg | Part A: Percentage of Participants With Hospitalizations and/or ER Visits Related to COVID-19 or Death From Any Cause | Any event | 3.0 percentage of participants |
| Ensovibep 225 mg | Part A: Percentage of Participants With Hospitalizations and/or ER Visits Related to COVID-19 or Death From Any Cause | Death from any cause | 0.0 percentage of participants |
| Ensovibep 225 mg | Part A: Percentage of Participants With Hospitalizations and/or ER Visits Related to COVID-19 or Death From Any Cause | Emergency room visits related to COVID-19 | 1.0 percentage of participants |
| Ensovibep 225 mg | Part A: Percentage of Participants With Hospitalizations and/or ER Visits Related to COVID-19 or Death From Any Cause | Hospitalizations (≥ 24 h of acute care) | 2.0 percentage of participants |
| Ensovibep 75 mg | Part A: Percentage of Participants With Hospitalizations and/or ER Visits Related to COVID-19 or Death From Any Cause | Any event | 0.0 percentage of participants |
| Ensovibep 75 mg | Part A: Percentage of Participants With Hospitalizations and/or ER Visits Related to COVID-19 or Death From Any Cause | Death from any cause | 0.0 percentage of participants |
| Ensovibep 75 mg | Part A: Percentage of Participants With Hospitalizations and/or ER Visits Related to COVID-19 or Death From Any Cause | Hospitalizations (≥ 24 h of acute care) | 0.0 percentage of participants |
| Ensovibep 75 mg | Part A: Percentage of Participants With Hospitalizations and/or ER Visits Related to COVID-19 or Death From Any Cause | Emergency room visits related to COVID-19 | 0.0 percentage of participants |
| Placebo | Part A: Percentage of Participants With Hospitalizations and/or ER Visits Related to COVID-19 or Death From Any Cause | Death from any cause | 2.0 percentage of participants |
| Placebo | Part A: Percentage of Participants With Hospitalizations and/or ER Visits Related to COVID-19 or Death From Any Cause | Hospitalizations (≥ 24 h of acute care) | 5.1 percentage of participants |
| Placebo | Part A: Percentage of Participants With Hospitalizations and/or ER Visits Related to COVID-19 or Death From Any Cause | Emergency room visits related to COVID-19 | 5.1 percentage of participants |
| Placebo | Part A: Percentage of Participants With Hospitalizations and/or ER Visits Related to COVID-19 or Death From Any Cause | Any event | 6.1 percentage of participants |
Secondary
Part A: Terminal Elimination Half-Life (T1/2) of Total and Free Ensovibep
Blood samples were collected to determine the T1/2 of free ensovibep (ensovibep not bound to target) and total ensovibep (sum of ensovibep not bound to and bound to target) concentrations in serum.
Time frame: Data was summarized from pre-dose and at 15 minutes and 90 minutes after end of study drug infusion on Day 1, and at Days 3, 8, 15, 29, 61 and 91
Population: The PK analysis set included all participants with at least 1 available valid (that is, not flagged for exclusion) PK concentration measurement, who received any study treatment and with no protocol deviations that impacted PK data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Ensovibep 600 mg | Part A: Terminal Elimination Half-Life (T1/2) of Total and Free Ensovibep | Total Ensovibep | 274 hour | Geometric Coefficient of Variation 54 |
| Ensovibep 600 mg | Part A: Terminal Elimination Half-Life (T1/2) of Total and Free Ensovibep | Free Ensovibep | 262 hour | Geometric Coefficient of Variation 67.7 |
| Ensovibep 225 mg | Part A: Terminal Elimination Half-Life (T1/2) of Total and Free Ensovibep | Total Ensovibep | 290 hour | Geometric Coefficient of Variation 53.8 |
| Ensovibep 225 mg | Part A: Terminal Elimination Half-Life (T1/2) of Total and Free Ensovibep | Free Ensovibep | 234 hour | Geometric Coefficient of Variation 48.3 |
| Ensovibep 75 mg | Part A: Terminal Elimination Half-Life (T1/2) of Total and Free Ensovibep | Total Ensovibep | 309 hour | Geometric Coefficient of Variation 39.8 |
| Ensovibep 75 mg | Part A: Terminal Elimination Half-Life (T1/2) of Total and Free Ensovibep | Free Ensovibep | 215 hour | Geometric Coefficient of Variation 60.6 |
Secondary
Part A: Terminal Elimination Rate Constant (Lambda z) of Total and Free Ensovibep
Blood samples were collected to determine the lambda z of free ensovibep (ensovibep not bound to target) and total ensovibep (sum of ensovibep not bound to and bound to target) concentrations in serum.
Time frame: Data was summarized from pre-dose and at 15 minutes and 90 minutes after end of study drug infusion on Day 1, and at Days 3, 8, 15, 29, 61 and 91
Population: The PK analysis set included all participants with at least 1 available valid (that is, not flagged for exclusion) PK concentration measurement, who received any study treatment and with no protocol deviations that impacted PK data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Ensovibep 600 mg | Part A: Terminal Elimination Rate Constant (Lambda z) of Total and Free Ensovibep | Free Ensovibep | 0.003 per hour | Geometric Coefficient of Variation 69.6 |
| Ensovibep 600 mg | Part A: Terminal Elimination Rate Constant (Lambda z) of Total and Free Ensovibep | Total Ensovibep | 0.003 per hour | Geometric Coefficient of Variation 52.1 |
| Ensovibep 225 mg | Part A: Terminal Elimination Rate Constant (Lambda z) of Total and Free Ensovibep | Total Ensovibep | 0.002 per hour | Geometric Coefficient of Variation 50.6 |
| Ensovibep 225 mg | Part A: Terminal Elimination Rate Constant (Lambda z) of Total and Free Ensovibep | Free Ensovibep | 0.003 per hour | Geometric Coefficient of Variation 48.3 |
| Ensovibep 75 mg | Part A: Terminal Elimination Rate Constant (Lambda z) of Total and Free Ensovibep | Total Ensovibep | 0.002 per hour | Geometric Coefficient of Variation 39.5 |
| Ensovibep 75 mg | Part A: Terminal Elimination Rate Constant (Lambda z) of Total and Free Ensovibep | Free Ensovibep | 0.003 per hour | Geometric Coefficient of Variation 61.2 |
Secondary
Part A: Time to Reach the Maximum Concentration (Tmax) of Total and Free Ensovibep
Blood samples were collected to determine the Tmax of free ensovibep (ensovibep not bound to target) and total ensovibep (sum of ensovibep not bound to and bound to target) concentrations in serum.
Time frame: Data was summarized from pre-dose and at 15 minutes and 90 minutes after end of study drug infusion on Day 1, and at Days 3, 8, 15, 29, 61 and 91
Population: The PK analysis set included all participants with at least 1 available valid (that is, not flagged for exclusion) PK concentration measurement, who received any study treatment and with no protocol deviations that impacted PK data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Ensovibep 600 mg | Part A: Time to Reach the Maximum Concentration (Tmax) of Total and Free Ensovibep | Total Ensovibep | 0.935 hour | Geometric Coefficient of Variation 457.5 |
| Ensovibep 600 mg | Part A: Time to Reach the Maximum Concentration (Tmax) of Total and Free Ensovibep | Free Ensovibep | 1.01 hour | Geometric Coefficient of Variation 473.8 |
| Ensovibep 225 mg | Part A: Time to Reach the Maximum Concentration (Tmax) of Total and Free Ensovibep | Total Ensovibep | 1.30 hour | Geometric Coefficient of Variation 693.5 |
| Ensovibep 225 mg | Part A: Time to Reach the Maximum Concentration (Tmax) of Total and Free Ensovibep | Free Ensovibep | 1.09 hour | Geometric Coefficient of Variation 516.6 |
| Ensovibep 75 mg | Part A: Time to Reach the Maximum Concentration (Tmax) of Total and Free Ensovibep | Total Ensovibep | 1.05 hour | Geometric Coefficient of Variation 573.6 |
| Ensovibep 75 mg | Part A: Time to Reach the Maximum Concentration (Tmax) of Total and Free Ensovibep | Free Ensovibep | 1.24 hour | Geometric Coefficient of Variation 810.1 |
Secondary
Part A: Time to Sustained Clinical Recovery
Sustained clinical recovery was defined as follows; 1. All symptoms from the modified Food and Drug Administration (FDA) COVID-19 questionnaire scored as moderate or severe at baseline were subsequently scored as mild or absent, and 2. All symptoms from the modified FDA COVID-19 questionnaire scored as mild or absent at baseline were subsequently scored as absent, with no subsequent worsening, up to Day 29.
Time frame: Up to Day 29
Population: The FAS included all participants in the randomized set for whom IV infusion of study treatment was administered. Only participants included in the analysis are reported.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ensovibep 600 mg | Part A: Time to Sustained Clinical Recovery | 23.0 days |
| Ensovibep 225 mg | Part A: Time to Sustained Clinical Recovery | 15.0 days |
| Ensovibep 75 mg | Part A: Time to Sustained Clinical Recovery | 14.0 days |
| Placebo | Part A: Time to Sustained Clinical Recovery | 29.0 days |
Secondary
Part B: Change From Baseline in Log10 SARS-CoV-2 Viral Load Through Day 8
The SARS-CoV-2 viral load was measured by means of a nasopharyngeal swab, followed by quantitative reverse transcription-polymerase chain reaction assay at a central laboratory. The multiple comparison procedure-modeling methodology was used.
Time frame: Baseline (Day 1) and Days 3, 5 and 8
Population: The Part B of the study was not initiated based on regulatory feedback indicating that with evolving treatment options, a placebo controlled design was no longer considered to be appropriate.
Secondary
Part B: Percentage of Participants With Treatment-Emergent Anti-Drug Antibody (ADA) Response to Ensovibep
Treatment-emergent ADA is defined as any participant with a 1. 2-fold (1 dilution) increase in titer than the minimum required dilution if no ADAs were detected at baseline (treatment-induced ADA); or, 2. 4-fold (2 dilutions) increase in titer compared with baseline if ADAs were detected at baseline (treatment-boosted ADA).
Time frame: Pre-dose on Day 1 and Days 15, 29, 61 and 91 postdose of Ensovibep
Population: The Part B of the study was not initiated based on regulatory feedback indicating that with evolving treatment options, a placebo controlled design was no longer considered to be appropriate.
Secondary
Part B: Time to Sustained Clinical Recovery
Sustained clinical recovery was defined as follows; 1. All symptoms from the modified FDA COVID-19 questionnaire scored as moderate or severe at baseline were subsequently scored as mild or absent, and 2. All symptoms from the modified FDA COVID-19 questionnaire scored as mild or absent at baseline were subsequently scored as absent, with no subsequent worsening, up to Day 29.
Time frame: Up to Day 29
Population: The Part B of the study was not initiated based on regulatory feedback indicating that with evolving treatment options, a placebo controlled design was no longer considered to be appropriate.