Clinical trial NCT04828161: A Dose Finding, Efficacy and Safety Study of Ensovibep (MP0420) in Ambulatory Adult Patients With Symptomatic COVID-19
Official title: A Randomized, Double-blind, Placebo-controlled, Multicenter Study of Ensovibep (MP0420) in Ambulatory Adult Patients With Symptomatic COVID-19 - The "EMPATHY" Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: COVID-19
Keywords: ensovibep
COVID-19 treatment, symptom reduction, viral load reduction,
EMPATHY
SARS-CoV-2
designed ankyrin repeat protein (DARPin®)
angiotensin-converting enzyme 2 (ACE2)
Lead sponsor: Novartis
Sponsor class: INDUSTRY
Collaborators: name: Molecular Partners AG
First posted: 2021-04-01
Enrollment: 407
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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
Primary purpose: TREATMENT

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.

Eligibility 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.

Primary outcomes:
measure: Part A: Time-Weighted Change From Baseline in Log10 Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Viral Load Through Day 8
timeFrame: Baseline (Day 1) and Days 3, 5 and 8
measure: Part B: Percentage of Participants With Hospitalizations and/or Emergency Room (ER) Visits Related to COVID-19 or Death From Any Cause
timeFrame: Up to Day 29
Secondary outcomes:
measure: Part A: Percentage of Participants With Hospitalizations and/or ER Visits Related to COVID-19 or Death From Any Cause
timeFrame: Up to Day 29
measure: Part A: Time to Sustained Clinical Recovery
timeFrame: Up to Day 29
measure: Part A: Observed Maximum Serum Concentration (Cmax) of Total and Free Ensovibep
timeFrame: 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
measure: 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
timeFrame: 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
measure: Part A: Area Under the Concentration-Time Curve From Time Zero to 48 Hours (AUC 0-48h) of Total and Free Ensovibep
timeFrame: 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
measure: Part A: Area Under the Concentration-Time Curve From Time Zero to 168 Hours (AUC 0-168h) of Total and Free Ensovibep
timeFrame: 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
measure: Part A: Area Under the Concentration-Time Curve From Time Zero to 336 Hours (AUC 0-336h) of Total and Free Ensovibep
timeFrame: 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
measure: Part A: Area Under the Concentration-Time Curve From Time Zero to Infinity (AUCinfinity) of Total and Free Ensovibep
timeFrame: 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
measure: Part A: Time to Reach the Maximum Concentration (Tmax) of Total and Free Ensovibep
timeFrame: 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
measure: Part A: Apparent Total Body Clearance (CL) of Total and Free Ensovibep
timeFrame: 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
measure: Part A: Terminal Elimination Rate Constant (Lambda z) of Total and Free Ensovibep
timeFrame: 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
measure: Part A: Terminal Elimination Half-Life (T1/2) of Total and Free Ensovibep
timeFrame: 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
measure: Part A: Apparent Volume of Distribution (Vz) of Total and Free Ensovibep
timeFrame: 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
measure: Part B: Change From Baseline in Log10 SARS-CoV-2 Viral Load Through Day 8
timeFrame: Baseline (Day 1) and Days 3, 5 and 8
measure: Part B: Time to Sustained Clinical Recovery
timeFrame: Up to Day 29
measure: Part B: Percentage of Participants With Treatment-Emergent Anti-Drug Antibody (ADA) Response to Ensovibep
timeFrame: Pre-dose on Day 1 and Days 15, 29, 61 and 91 postdose of Ensovibep
Other outcomes:
Locations:
city: Jasper
country: United States
facility: Jasper Summit Research, LLC
state: Alabama
city: Colton
country: United States
facility: Benchmark Southern California
state: California
city: Fullerton
country: United States
facility: Ascada Research
state: California
city: Mission Viejo
country: United States
facility: Pacific Neuropsychiatric Specialists
state: California
city: Redondo Beach
country: United States
facility: Providence Family Medical Center
state: California
city: Colorado Springs
country: United States
facility: Future Innovative Treatments
state: Colorado
city: Margate
country: United States
facility: Boward Infectious Disease and Primary Care
state: Florida
city: Miami Lakes
country: United States
facility: Panax Clinical Research, LLC
state: Florida
city: Miami
country: United States
facility: Suncoast Research Group, LLC
state: Florida
city: Miami
country: United States
facility: Life Spring Research Foundation
state: Florida
city: Miami
country: United States
facility: Bio-Medical Research, LLC
state: Florida
city: Tampa
country: United States
facility: AdventHealth Tampa
state: Florida
city: West Palm Beach
country: United States
facility: Palm Beach Research Center
state: Florida
city: Buford
country: United States
facility: Gwinnett Research Institute
state: Georgia
city: Columbus
country: United States
facility: IACT Health
state: Georgia
city: Chicago
country: United States
facility: Great Lakes Clinical Trials
state: Illinois
city: Elkridge
country: United States
facility: Centennial Medical Group - Research Department
state: Maryland
city: Jefferson City
country: United States
facility: Jefferson City Medical Group
state: Missouri
city: Monroe
country: United States
facility: Monroe Biomedical Research
state: North Carolina
city: Wilmington
country: United States
facility: Wilmington Health
state: North Carolina
city: Greenville
country: United States
facility: VitaLink Research
state: South Carolina
city: Rock Hill
country: United States
facility: Clinical Research of Rock Hill
state: South Carolina
city: Houston
country: United States
facility: Fairway Medical Clinic
state: Texas
city: Houston
country: United States
facility: 1960 Family Practice, PA
state: Texas
city: Katy
country: United States
facility: Zion Urgent Care Clinic
state: Texas
city: McAllen
country: United States
facility: Family Practice Center
state: Texas
city: Red Oak
country: United States
facility: Epic Medical Research
state: Texas
city: Debrecen
country: Hungary
facility: Debreceni Egyetem
city: Visakhapatnam
country: India
facility: King George Hospital
state: Andhra Pradesh
city: Surat
country: India
facility: BAPS Pramukhswami Hospital
state: Gujarat
city: Vidyanagar
country: India
facility: Durgabai Deshmukh Hospital & Research Centre
state: Hyderabad
city: Bengaluru
country: India
facility: Shetty's Hospital
state: Karnataka
city: Aurangabad
country: India
facility: Government Medical College
state: Maharashtra
city: Mumbai
country: India
facility: Grant Medical College & Sir J. J. Group of Hospitals
state: Maharashtra
city: Nagpur
country: India
facility: Government Medical College and Hospital
state: Maharashtra
city: Nagpur
country: India
facility: All India Institute of Medical Sciences - Nagpur
state: Maharashtra
city: Chennai
country: India
facility: VHS-Infectious Disease Medical Centre
state: Tamil Nadu
city: Hyderabad
country: India
facility: St. Theresa's Hospital
state: Telangana
city: Utrecht
country: Netherlands
facility: UMC Utrecht
city: Bloemfontein
country: South Africa
facility: FARMOVS (Pty) Ltd
state: Free State
city: Sandton
country: South Africa
facility: Sandton Medical Research Centre
state: Gauteng
city: George
country: South Africa
facility: George Provincial Hospital
state: Western Cape
city: Somerset West
country: South Africa
facility: Dr JM Engelbrecht Trial Site
state: Western Cape
city: Durban
country: South Africa
facility: Enhancing Care Foundation
city: Kempton Park
country: South Africa
facility: Clinresco Centres (Pty) Ltd
city: Krugersdorp
country: South Africa
facility: DJW Navorsing
city: Pretoria
country: South Africa
facility: Jongaie Research
city: Soweto
country: South Africa
facility: Wits Clinical Research
Study officials:
References: