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

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Terminated

CT.gov ID

NCT04828161

Collaborator

Molecular Partners AG (Industry)

407

Enrollment

Locations

Arms

8.6

Actual Duration (Months)

6.4

Patients Per Site

0.7

Patients Per Site Per Month

Study Details

Study Description

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 and adolescent ambulatory patients

Condition or Disease	Intervention/Treatment	Phase
COVID-19	Drug: ensovibep Drug: Placebo	Phase 2/Phase 3

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 COVID-19 symptoms through Day 29.
To assess the effect of ensovibep, compared to placebo, on post-acute COVID-19 symptoms from Day 29 up to Day 91
To evaluate the effect of ensovibep, compared to placebo, on general health status up to Day 91
To evaluate the immunogenicity of ensovibep.
To evaluate the effect of ensovibep on SARS-COV-2 mutation emergence

Study Design

Study Type:

Interventional

Actual Enrollment :

407 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

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 3Parallel: 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

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

Double Blind: two or more parties are unaware of the intervention assignment Masked roles are: Subject, Caregiver, Investigator or Outcomes Assessor.

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

May 10, 2021

Actual Primary Completion Date :

Nov 18, 2021

Actual Study Completion Date :

Jan 27, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Phase 2 / Part A, ensovibep active treatment arm 1 Phase 2 / Part A: ensovibep active treatment arm 1	Drug: ensovibep IV on day 1 only. Other Names: MP0420
Experimental: Phase 2 / Part A, ensovibep active treatment arm 2 Phase 2 / Part A: ensovibep active treatment arm 2	Drug: ensovibep IV on day 1 only. Other Names: MP0420
Experimental: Phase 2 / Part A, ensovibep active treatment arm 3 Phase 2 / Part A: ensovibep active treatment arm 3	Drug: ensovibep IV on day 1 only. Other Names: MP0420
Placebo Comparator: Phase 2 / Part A, Placebo Phase 2 / Part A: Placebo	Drug: Placebo IV on day 1 only.
Experimental: Phase 3/ Part B, ensovibep active treatment arm 4 Phase 3/ Part B: ensovibep active treatment	Drug: ensovibep IV on day 1 only. Other Names: MP0420
Placebo Comparator: Phase 3/ Part B, Placebo arm Phase 3/ Part B: Placebo	Drug: Placebo IV on day 1 only.

Outcome Measures

Primary Outcome Measures

Part A - SARS-CoV-2 viral load [8 days (days 0, 3, 5 and 8)]
Time-weighted change from baseline (measured at Day 3, Day 5, and Day 8) in SARS-CoV-2 viral load in nasopharyngeal swabs through Day 8
Part B - Occurrence of hospitalizations or death [up to day 29]
Proportion of patients experiencing hospitalizations (≥ 24 hours of acute care) related to COVID-19 or death from any cause up to Day 29.

Secondary Outcome Measures

Part A - Occurrence of hospitalizations, emergency room visits or death [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.
Part A - Time to sustained clinical recovery [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.
Part A - Serious adverse events (SAEs), AEs of Special Interest (AESIs), vital signs and clinical laboratory measurements. [up to day 91]
In order to evaluate the safety and tolerability of ensovibep, the proportion of patients up to end of study with: (a) SAEs, including death from any cause and (b) AESIs, including infusion-related reactions (IRRs) CTCAE grade 2 or higher, will be assessed. Vital signs and clinical laboratory measurements will be assessed too.
Part A - Ensovibep Maximum Plasma Concentration [Cmax]). [up to day 91]
Cmax is the observed maximum concentration.
Part A - Ensovibep PK parameter - AUClast [up to day 91]
AUClast is the area under the concentration-time curve from time zero to the time of the last quantifiable concentration.
Part B - Time to sustained clinical recovery [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. at Day 1, 3, 5, 8, 15, 22 and 29) in SARS-CoV-2 viral load in nasal or nasopharyngeal swabs through Day 29
Part B - SARS-CoV-2 viral load [up to day 29]
Time-weighted change from baseline (measured at Day 1, 3, 5, 8, 15, 22 and 29) in SARS-CoV-2 viral load in nasal or nasopharyngeal swabs through Day 29
Part B - Proportion of patients with post-acute COVID-19 symptoms [from Day 29 up to day 91]
To assess the effect of ensovibep, compared to placebo, on post-acute COVID-19 symptoms
Part B - Effect of ensovibep, compared to placebo, on general health status [up to day 91]
Change from baseline in MCS and PCS scores from Short Form Health Survey (SF-36) questionnaire up to Day 91
Part B - treatment-emergent ADAs (TE-ADA) [up to day 91]
evaluate the immunogenicity of ensovibep evaluate the immunogenicity of ensovibep during the study and its clinical relevance (pharmacokinetic, efficacy and safety), proportion of patients exhibiting TE-ADA over time will be determined.
Part B - TEAEs, SAEs, AESIs, vital signs and clinical laboratory measurements [up to day 91]
In order to evaluate the safety and tolerability of ensovibep, the proportion of patients up to end of study with: (a) Treatment Emergent Adverse events (TEAEs) (ab) SAEs, including death from any cause and (bc) AESIs, will be assessed. Vital signs and clinical laboratory measurements will be assessed too.

Eligibility Criteria

Criteria

Ages Eligible for Study:

12 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Part A Inclusion Criteria:

Males or females ≥ 18 years of age on the day of inclusion (no upper limit).
Presence of two or more COVID-19 symptoms and onset within 7 days prior to 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).
Understands and agrees to comply with the planned study procedures.
The patient or legally authorized representative gives 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.
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-inflammatories [NSAIDs]) are permitted. Prior use of steroids for management of COVID-19 symptoms may be permitted, provided they can be stopped at study entry based on investigator judgement.Prior vaccination for COVID-19 is permitted.

Part B Inclusion Criteria:

Males or females ≥ 12 years of age on the day of inclusion (no upper limit) and with a body weight of ≥ 40kg
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 within 24 hours prior to dosing (rapid antigen test)
Presence of at least one of the following medical conditions or factors that places patients at higher risk for progression to severe COVID-19.

Age ≥ 60 years
Obesity [Body Mass Index (BMI) ≥30 kg/m2, or if age 12-17 years, have BMI ≥95th percentile for their age and gender based on CDC growth charts]
Chronic kidney disease
Diabetes
Hypertension
Immunosuppressive disease or immunosuppressive treatment
Cardiovascular disease (including congenital heart disease)
Chronic lung diseases
Cancer
Sickle cell disease
Neurodevelopmental disorders
Other medical conditions that confer medical complexity (for example, genetic or metabolic syndromes and severe congenital anomalies)
Having a medical-related technological dependence [for example, tracheostomy, gastrostomy, or positive pressure ventilation (not related to COVID-19)]

The patient or legally authorized representative understands and agrees to comply with the planned study procedures.
The patient, legally authorized representative, or parent/legal guardian gives signed informed consent and adolescents provide assent.

Part B 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 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 current SARS-CoV-2) that in the opinion of the investigator could constitute a risk when receiving study medication.
Any serious, unstable 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 10 days of dosing, or that is considered life-threatening within 29 days of dosing.
Prior use of ensovibep or participation in clinical trials in which ensovibep was studied.
Prior or concurrent use of any medication for treatment of the current COVID-19,infection, including antiviral agents (approved [e.g. remdesivir, Paxlovid, molnupiravir] or experimental [e.g. hydroxychloroquine, ivermectin]), convalescent serum, anti-viral antibodies, immunosuppressives or immunomodulators. Long-term treatment at stable doses for pre-existing conditions (e.g. anti-HIV medications, steroids (systemic or inhalational) for asthma, COPD, etc.) are permitted. Prior use of steroids for management of COVID-19 may be permitted provided they can be stopped before study dosing based on investigator judgement. 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 unless it occurred within the last 6 months prior to randomization. Patients who have been vaccinated against COVID19 (irrespective of product used and number of doses administered) qualify as prior vaccination.
Confirmed prior infection with SARS-CoV-2 within 6 months prior to randomization. The prior SARS-CoV-2 infection must have been confirmed by a direct diagnostic test (eg. rapid antigen test, RT-PCR). Novartis Confidential Page 59 of 131 Amended Clinical Trial Protocol Protocol No. MP0420-CP302 V02 (Track Changes) (CSKO136A12201J)
Are concurrently enrolled or were enrolled within the last 30 days or within 5 halflives (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 effective methods of contraception at the time of dosing and for 13 weeks after dosing of study drug.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Jasper Summit Research, LLC	Jasper	Alabama	United States	35501
2	Cognitive Clinical Trials, LLC	Phoenix	Arizona	United States	85044
3	Benchmark Southern California	Colton	California	United States	92324
4	Ascada Research	Fullerton	California	United States	92835
5	Collaborative Neuroscience Research, LLC	Long Beach	California	United States	90806
6	Pacific Neuropsychiatric Specialists	Mission Viejo	California	United States	92691
7	South Bay CRI	Torrance	California	United States	90503
8	Future Innovative Treatments	Colorado Springs	Colorado	United States	80907
9	Accel Research Sites - DeLand Clinical Research Unit	DeLand	Florida	United States	32720
10	Broward Infectious Disease and Primary Care	Margate	Florida	United States	33063
11	Panax Clinical Research, LLC	Miami Lakes	Florida	United States	33014
12	Goji Group - Research Trials Group	Miami Lakes	Florida	United States	33016
13	Suncoast Research Group, LLC	Miami	Florida	United States	33135
14	Life Spring Research Foundation	Miami	Florida	United States	33155
15	Bio-Medical Research, LLC	Miami	Florida	United States	33184
16	AdventHealth Tampa	Tampa	Florida	United States	33613
17	Palm Beach Research Center	West Palm Beach	Florida	United States	33409
18	Gwinnett Research Institute	Buford	Georgia	United States	30519
19	IACT Health	Columbus	Georgia	United States	31904
20	Great Lakes Clinical Trials	Chicago	Illinois	United States	60640
21	University of Maryland School of Medicine	Baltimore	Maryland	United States	21201
22	First Call Urgent Care	Laurel	Maryland	United States	20723
23	Jefferson City Medical Group	Jefferson City	Missouri	United States	65109
24	Monroe Biomedical Research	Monroe	North Carolina	United States	28112
25	Wilmington Health	Wilmington	North Carolina	United States	28405
26	Clinical Research of Rock Hill	Rock Hill	South Carolina	United States	29732
27	VitaLink Research Union	Union	South Carolina	United States	29379
28	Mercy Family Clinic	Dallas	Texas	United States	75211
29	Fairway Medical Clinical	Houston	Texas	United States	77087
30	1960 Family Practice, PA	Houston	Texas	United States	77090
31	Zion Urgent Care Clinic	Katy	Texas	United States	77494
32	Family Practice Center	McAllen	Texas	United States	78501
33	Epic Medical Research	Red Oak	Texas	United States	75154
34	Care Access Research Redmond	Redmond	Washington	United States	98052
35	Semmelweis Egyetem	Budapest		Hungary	1083
36	Debreceni Egyetem	Debrecen		Hungary	4031
37	Clinexpert Cooridination Office	Gyöngyös		Hungary	3200
38	Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont	Szeged		Hungary	6725
39	King George Hospital	Visakhapatnam	Andhra Pradesh	India	530002
40	BAPS Pramukhswami Hospital	Surat	Gujarat	India	395009
41	Rhythm Heart Institute	Vadodara	Gujarat	India	390022
42	Durgabai Deshmukh Hospital & Research Centre	Vidyanagar	Hyderabad	India	500044
43	Shetty's Hospital	Bengaluru	Karnataka	India	560068
44	Government Medical College	Aurangabad	Maharashtra	India	431001
45	Government Medical College and Hospital	Nagpur	Maharashtra	India	440003
46	All India Institute of Medical Sciences - Nagpur	Nagpur	Maharashtra	India	441108
47	VHS-Infectious Disease Medical Centre	Chennai	Tamil Nadu	India	600113
48	St. Theresa's Hospital	Hyderabad	Telangana	India	500018
49	St. George's Hospital	Mumbai		India	400001
50	UMC Utrecht	Utrecht		Netherlands	3584 CW
51	Medicome Sp. z o.o.	Oświęcim		Poland	32-600
52	Centrum Medyczne Medyk	Rzeszów		Poland	35-326
53	ETG Skierniewice	Skierniewice		Poland	96-100
54	ETG Lodz	Łódź		Poland	90-302
55	Sandton Medical Research Centre	Sandton	Gauteng	South Africa	2196
56	Excellentis Clinical Trial Consultants	George	Western Cape	South Africa	6529
57	Dr JM Engelbrecht Trial Site	Somerset West	Western Cape	South Africa	7130
58	FARMOVS (Pty) Ltd	Bloemfontein		South Africa	9301
59	Enhancing Care Foundation	Durban		South Africa	4052
60	Clinresco Centres (Pty) Ltd	Kempton Park		South Africa	1619
61	DJW Navorsing	Krugersdorp		South Africa	1739
62	Dr A Jacovides and Partners	Midrand		South Africa	1685
63	Jongaie Research	Pretoria		South Africa	183
64	Wits Clinical Research	Soweto		South Africa	2013