A unit of Saurashtra Medicare LLP, 1st Floor, Room no. 01, Opp. Vishveshwar Mahadev Temple, Mavdi Main Road Rajkot-360004 Rajkot GUJARAT
912816195000
jayeshdobariya@yahoo.co.in
Dr Nagalingeswaran Kumarasamy
VHS Infectious Diseases Medical Centre Chennai
VHS Infectious Diseases Medical Centre, CART Clinical Research Site,Clinical Research Department 1st floor, Room no-3, Rajiv Gandhi Salai, Taramani, Chennai - 600113, Tamilnadu Chennai TAMIL NADU
(1) ICD-10 Condition: B972||Coronavirus as the cause of diseases classified elsewhere,
Intervention / Comparator Agent
Type
Name
Details
Comparator Agent
NA
NA
Intervention
Part A:
ensovibep
Route: Intravenous
Dose: 10 mL vials are used containing 15 mg/mL ensovibep provided in isotonic buffer matrix.
Patients in Part A will be assigned on Day 1 at Visit 1 to one of the following 4 treatment arms in a ratio of 1:1:1:1 and will be dosed accordingly:
• Ensovibep 75 mg • Ensovibep 225 mg • Ensovibep 600 mg • Placebo
Placebo: Isotonic saline will be used as placebo
Intervention
Part B: ensovibep
Route: Intravenous
Dose: 5 mL vials are used containing15 mg/mL ensovibep provided in isotonic buffer matrix.
Patients in Part B will be assigned on Day 1 at Visit 1 to one of the following 2 treatment arms in a ratio of 1:1
• Ensovibep (optimal safe and efficacious dose, selected in Part A) • Placebo
Placebo: placebo consisting of the formulation buffer.
Inclusion Criteria
Age From
18.00 Year(s)
Age To
95.00 Year(s)
Gender
Both
Details
Patients eligible for inclusion in this study must meet all the following criteria:
1. Men or 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.
ExclusionCriteria
Details
Patients meeting any of the following criteria are not eligible for inclusion in this study.
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 antiinflammatory 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:
a. 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.
b.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.
c. Male sterilization (at least 6 months prior to screening). The vasectomized male partner should be the sole partner for that patient.
d. use of oral, injected or implanted hormonal methods of contraception or placement of an IUD or 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.
Comorbidities defining clinically vulnerable patients (with high risk for progression to serious COVID-19 disease), for example obesity or diabetes, are generally not exclusion criteria.
Method of Generating Random Sequence
Other
Method of Concealment
Centralized
Blinding/Masking
Participant, Investigator, Outcome Assessor and Date-entry Operator Blinded
Primary Outcome
Outcome
TimePoints
Part A•To assess the effect of ensovibep, compared to placebo, in reducing SARS-CoV-2 viral load through Day 8.
Part B • 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
Part A Endpoint: Time-weighted change from baseline (measured at Day 3, Day 5, and Day 8) in log10 SARS-CoV-2 viral load in nasopharyngeal swabs through Day 8.
Part B Endpoint: Proportion of patients experiencing 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 Outcome
Outcome
TimePoints
• 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.
Proportion of patients experiencing 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 up to Day 29
Time to sustained clinical recovery, defined as (a) all symptoms from the modified FDA COVID-19 symptom list scored as moderate or severe at baseline are subsequently scored as mild or absent, AND (b) all symptoms from the modified FDA COVID-19 symptom list scored as mild or absent at baseline are subsequently scored as absent, with no subsequent worsening up to Day 29.
•To evaluate safety and tolerability of ensovibep
Proportion of patients up to end of study with:
a. Serious adverse events (SAEs), including death from any cause
b. AEs of Special Interest (AESIs), including infusion-related reactions (IRRs) CTCAE grade 2 or higher
2. Vital signs
3. Clinical laboratory measurements.
• To characterize the pharmacokinetics (PK) of ensovibep.
Free and total ensovibep concentration in serum and calculated PK parameters.
• To assess the effect of ensovibep, compared to placebo, in reducing SARS-CoV-2 viral load through Day 8.
Change from baseline in log10 SARS-CoV-2 viral load in nasopharyngeal swabs at Day 3, Day 5, and 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 (pharmacokinetic, efficacy and safety).
Proportion of patients exhibiting treatment-emergent ADAs (TE-ADA) over time.
• To evaluate safety and tolerability of ensovibep.
Proportion of patients up to end of study with:
a. Serious adverse events (SAEs), including death from any cause
b. AEs of Special Interest (AESIs), including infusion-related reactions (IRRs) CTCAE grade 2 or higher
2. Vital signs
3. Clinical laboratory measurements.
Target Sample Size
Total Sample Size="400" Sample Size from India="103" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This is a randomized, double-blind, placebo-controlled, multicenter study of ensovibep (MP0420) in ambulatory adult patients with symptomatic COVID-19.
The study has two parts:
A Phase 2 dose-ranging study to select the best dose over the therapeutic range (Part A) to progress into Phase 3, and a confirmatory Phase 3 safety and efficacy study of the dose determined in Part A (Part B).
Screening will be used to determine eligibility. Randomization and treatment will be conducted on Day 1 (screening can optionally be done up to 3 days earlier, or also at Day 1). Study duration for individual patients is 91 ± 7 days for both Parts.
Part A
This dose-ranging part of the study will include at least 400 randomized patients in four arms (3 active arms and one placebo arm), randomized 1:1:1:1 to receive ensovibep (75 mg, 225 mg, or 600 mg) or placebo, administered as a single intravenous (i.v.) infusion over 60 minutes, and stratified by risk for COVID-19 disease progression (“high-risk patients†versus “not at high-risk patientsâ€).
Part B
Recruitment will begin in Part B once the most safe and efficacious dose has been selected from Part A based on the Day 29 data analysis. Part B will recruit 1717 patients randomized 1:1 to either the selected dose of ensovibep or placebo, administered as a single i.v. infusion over 60 minutes. An interim analysis for early efficacy will be conducted when at least 50% of patients have completed the Day 29 assessments. Patients will be stratified by risk for COVID-19 disease progression (“high-risk patients†versus “not at high-risk patientsâ€).