A Dose Finding, Efficacy and Safety Study of Ensovibep (MP0420) in Ambulatory Adult Patients With Symptomatic COVID-19

Phase 2

Terminated

Conditions: COVID-19

Interventions: Drug: Placebo
Drug: ensovibep

Registration Number: NCT04828161

Lead Sponsor: Novartis Pharmaceuticals

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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 407

Inclusion Criteria

Men and women ≥ 18 years of age on the day of inclusion (no upper limit).
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.
Positive test for SARS-CoV-2 in upper respiratory swab on the day of dosing (rapid antigen test).
Understand and agree to comply with the planned study procedures.
The patient or legally authorized representative give signed informed consent.

Part A

Exclusion Criteria

Requiring hospitalization at time of screening, or at time of study drug administration.
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.
Known allergies to any of the components used in the formulation of the ensovibep or placebo.
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.
Any serious concomitant systemic disease, condition, or disorder that, in the opinion of the investigator, should preclude participation in this study.
Any co-morbidity requiring surgery within 7 days of dosing, or that is considered life-threatening within 29 days of dosing.
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.
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.
Are pregnant or breast feeding.
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).
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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Phase 2 / Part A, Placebo	Placebo	Phase 2 / Part A: Placebo
Phase 2 / Part A, ensovibep active treatment arm 1	ensovibep	Phase 2 / Part A: ensovibep active treatment arm 1
Phase 2 / Part A, ensovibep active treatment arm 2	ensovibep	Phase 2 / Part A: ensovibep active treatment arm 2
Phase 2 / Part A, ensovibep active treatment arm 3	ensovibep	Phase 2 / Part A: ensovibep active treatment arm 3
Phase 3/ Part B, Placebo arm	Placebo	Phase 3/ Part B: Placebo. Part B was not initiated.
Phase 3/ Part B, ensovibep active treatment arm 4	ensovibep	Phase 3/ Part B: ensovibep active treatment. Part B was not initiated.

Primary Outcome Measures

Name	Time	Method
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.
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.

Secondary Outcome Measures

Name	Time	Method
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 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: 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: 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: 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 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).
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: 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 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.

Trial Locations

Locations (48): Jasper Summit Research, LLC
🇺🇸
Jasper, Alabama, United States
Benchmark Southern California
🇺🇸
Colton, California, United States
Ascada Research
🇺🇸
Fullerton, California, United States
Pacific Neuropsychiatric Specialists
🇺🇸
Mission Viejo, California, United States
Providence Family Medical Center
🇺🇸
Redondo Beach, California, United States
Future Innovative Treatments
🇺🇸
Colorado Springs, Colorado, United States
Boward Infectious Disease and Primary Care
🇺🇸
Margate, Florida, United States
Panax Clinical Research, LLC
🇺🇸
Miami Lakes, Florida, United States
Suncoast Research Group, LLC
🇺🇸
Miami, Florida, United States
Life Spring Research Foundation
🇺🇸
Miami, Florida, United States
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Jasper Summit Research, LLC
🇺🇸Jasper, Alabama, United States