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

COVID-19 Clinical Trial

— EMPATHY  

Official title:

A Randomized, Double-blind, Placebo-controlled, Multicenter Study of Ensovibep (MP0420) in Ambulatory Adult Patients With Symptomatic COVID-19 - The "EMPATHY" Trial

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04828161
• Other study ID #: MP0420-CP302
• Secondary ID: 2021-000890-10CS
• Status: Terminated
• Phase: Phase 2/Phase 3
• Start date: May 10, 2021
• Est. completion date: January 27, 2022

Study information

• Verified date: December 2022
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 407
• Est. completion date: January 27, 2022
• Est. primary completion date: November 18, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• COVID-19

Intervention

Drug:
• ensovibep
IV on day 1 only.
• Placebo
IV on day 1 only.

Locations

Country	Name	City	State
Hungary	Debreceni Egyetem	Debrecen
India	Government Medical College	Aurangabad	Maharashtra
India	Shetty's Hospital	Bengaluru	Karnataka
India	VHS-Infectious Disease Medical Centre	Chennai	Tamil Nadu
India	St. Theresa's Hospital	Hyderabad	Telangana
India	Grant Medical College & Sir J. J. Group of Hospitals	Mumbai	Maharashtra
India	All India Institute of Medical Sciences - Nagpur	Nagpur	Maharashtra
India	Government Medical College and Hospital	Nagpur	Maharashtra
India	BAPS Pramukhswami Hospital	Surat	Gujarat
India	Durgabai Deshmukh Hospital & Research Centre	Vidyanagar	Hyderabad
India	King George Hospital	Visakhapatnam	Andhra Pradesh
Netherlands	UMC Utrecht	Utrecht
South Africa	FARMOVS (Pty) Ltd	Bloemfontein	Free State
South Africa	Enhancing Care Foundation	Durban
South Africa	George Provincial Hospital	George	Western Cape
South Africa	Clinresco Centres (Pty) Ltd	Kempton Park
South Africa	DJW Navorsing	Krugersdorp
South Africa	Jongaie Research	Pretoria
South Africa	Sandton Medical Research Centre	Sandton	Gauteng
South Africa	Dr JM Engelbrecht Trial Site	Somerset West	Western Cape
South Africa	Wits Clinical Research	Soweto
United States	Gwinnett Research Institute	Buford	Georgia
United States	Great Lakes Clinical Trials	Chicago	Illinois
United States	Future Innovative Treatments	Colorado Springs	Colorado
United States	Benchmark Southern California	Colton	California
United States	IACT Health	Columbus	Georgia
United States	Centennial Medical Group - Research Department	Elkridge	Maryland
United States	Ascada Research	Fullerton	California
United States	VitaLink Research	Greenville	South Carolina
United States	1960 Family Practice, PA	Houston	Texas
United States	Fairway Medical Clinic	Houston	Texas
United States	Jasper Summit Research, LLC	Jasper	Alabama
United States	Jefferson City Medical Group	Jefferson City	Missouri
United States	Zion Urgent Care Clinic	Katy	Texas
United States	Boward Infectious Disease and Primary Care	Margate	Florida
United States	Family Practice Center	McAllen	Texas
United States	Bio-Medical Research, LLC	Miami	Florida
United States	Life Spring Research Foundation	Miami	Florida
United States	Suncoast Research Group, LLC	Miami	Florida
United States	Panax Clinical Research, LLC	Miami Lakes	Florida
United States	Pacific Neuropsychiatric Specialists	Mission Viejo	California
United States	Monroe Biomedical Research	Monroe	North Carolina
United States	Epic Medical Research	Red Oak	Texas
United States	Providence Family Medical Center	Redondo Beach	California
United States	Clinical Research of Rock Hill	Rock Hill	South Carolina
United States	AdventHealth Tampa	Tampa	Florida
United States	Palm Beach Research Center	West Palm Beach	Florida
United States	Wilmington Health	Wilmington	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals	Molecular Partners AG

Countries where clinical trial is conducted

United States,  Hungary,  India,  Netherlands,  South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	Baseline (Day 1) and Days 3, 5 and 8
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.	Up to Day 29
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.	Up to Day 29
Secondary	Part A: Time to Sustained Clinical Recovery	Sustained clinical recovery was defined as follows; 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; 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.	Up to Day 29
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.	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
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.	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
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.	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
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.	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
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.	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
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.	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
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.	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
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.	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
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.	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
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.	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
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.	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
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.	Baseline (Day 1) and Days 3, 5 and 8
Secondary	Part B: Time to Sustained Clinical Recovery	Sustained clinical recovery was defined as follows; All symptoms from the modified FDA COVID-19 questionnaire scored as moderate or severe at baseline were subsequently scored as mild or absent, and; 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.	Up to Day 29
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; 2-fold (1 dilution) increase in titer than the minimum required dilution if no ADAs were detected at baseline (treatment-induced ADA); or,; 4-fold (2 dilutions) increase in titer compared with baseline if ADAs were detected at baseline (treatment-boosted ADA).	Pre-dose on Day 1 and Days 15, 29, 61 and 91 postdose of Ensovibep