A Dose Finding, Efficacy and Safety Study of Ensovibep (MP0420) in Ambulatory Adult Patients With Symptomatic COVID-19
- Conditions
- COVID-19
- Interventions
- Drug: PlaceboDrug: 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
- 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
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Requiring hospitalization at time of screening, or at time of study drug administration.
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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.
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Known allergies to any of the components used in the formulation of the ensovibep or placebo.
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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.
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Any serious concomitant systemic disease, condition, or disorder that, in the opinion of the investigator, should preclude participation in this study.
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Any co-morbidity requiring surgery within 7 days of dosing, or that is considered life-threatening within 29 days of dosing.
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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.
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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.
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Are pregnant or breast feeding.
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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:
- 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.
- 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.
- Male sterilization (at least 6 months prior to screening). The vasectomized male partner should be the sole partner for that patient.
- 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).
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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 3/ Part B, ensovibep active treatment arm 4 ensovibep Phase 3/ Part B: ensovibep active treatment. Part B was not initiated. 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.
- 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: 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.
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.
Trial Locations
- Locations (48)
Durgabai Deshmukh Hospital & Research Centre
🇮🇳Vidyanagar, Hyderabad, India
Palm Beach Research Center
🇺🇸West Palm Beach, Florida, United States
Panax Clinical Research, LLC
🇺🇸Miami Lakes, Florida, United States
Jasper Summit Research, LLC
🇺🇸Jasper, Alabama, United States
Clinical Research of Rock Hill
🇺🇸Rock Hill, South Carolina, United States
Providence Family Medical Center
🇺🇸Redondo Beach, California, United States
Debreceni Egyetem
🇭🇺Debrecen, Hungary
Epic Medical Research
🇺🇸Red Oak, Texas, United States
VitaLink Research
🇺🇸Greenville, South Carolina, United States
BAPS Pramukhswami Hospital
🇮🇳Surat, Gujarat, India
Enhancing Care Foundation
🇿🇦Durban, South Africa
Family Practice Center
🇺🇸McAllen, Texas, United States
Clinresco Centres (Pty) Ltd
🇿🇦Kempton Park, South Africa
King George Hospital
🇮🇳Visakhapatnam, Andhra Pradesh, India
UMC Utrecht
🇳🇱Utrecht, Netherlands
Jongaie Research
🇿🇦Pretoria, South Africa
Wits Clinical Research
🇿🇦Soweto, South Africa
VHS-Infectious Disease Medical Centre
🇮🇳Chennai, Tamil Nadu, India
Suncoast Research Group, LLC
🇺🇸Miami, Florida, United States
Life Spring Research Foundation
🇺🇸Miami, Florida, United States
1960 Family Practice, PA
🇺🇸Houston, Texas, United States
AdventHealth Tampa
🇺🇸Tampa, Florida, United States
Fairway Medical Clinic
🇺🇸Houston, Texas, United States
DJW Navorsing
🇿🇦Krugersdorp, South Africa
Monroe Biomedical Research
🇺🇸Monroe, North Carolina, United States
Zion Urgent Care Clinic
🇺🇸Katy, Texas, United States
Benchmark Southern California
🇺🇸Colton, California, United States
Pacific Neuropsychiatric Specialists
🇺🇸Mission Viejo, California, United States
Ascada Research
🇺🇸Fullerton, California, United States
Future Innovative Treatments
🇺🇸Colorado Springs, Colorado, United States
Boward Infectious Disease and Primary Care
🇺🇸Margate, Florida, United States
IACT Health
🇺🇸Columbus, Georgia, United States
Jefferson City Medical Group
🇺🇸Jefferson City, Missouri, United States
Great Lakes Clinical Trials
🇺🇸Chicago, Illinois, United States
Bio-Medical Research, LLC
🇺🇸Miami, Florida, United States
Centennial Medical Group - Research Department
🇺🇸Elkridge, Maryland, United States
Gwinnett Research Institute
🇺🇸Buford, Georgia, United States
Wilmington Health
🇺🇸Wilmington, North Carolina, United States
Sandton Medical Research Centre
🇿🇦Sandton, Gauteng, South Africa
Grant Medical College & Sir J. J. Group of Hospitals
🇮🇳Mumbai, Maharashtra, India
Dr JM Engelbrecht Trial Site
🇿🇦Somerset West, Western Cape, South Africa
Government Medical College
🇮🇳Aurangabad, Maharashtra, India
Government Medical College and Hospital
🇮🇳Nagpur, Maharashtra, India
All India Institute of Medical Sciences - Nagpur
🇮🇳Nagpur, Maharashtra, India
Shetty's Hospital
🇮🇳Bengaluru, Karnataka, India
St. Theresa's Hospital
🇮🇳Hyderabad, Telangana, India
FARMOVS (Pty) Ltd
🇿🇦Bloemfontein, Free State, South Africa
George Provincial Hospital
🇿🇦George, Western Cape, South Africa