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COVID-19Phase 2/3EMPATHYNCT04828161

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

A Phase 2/3 study testing ensovibep in people with COVID-19, run by Novartis Pharmaceuticals at 48 sites in 5 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
COVID-19
What is being tested?
ensovibep
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
407 participants
Where
48 sitesin 5 countries
Study dates
10 May 2021to 27 Jan 2022
Phase
Phase 2/3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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:
  11. 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.
  12. 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.
  13. Male sterilization (at least 6 months prior to screening). The vasectomized male partner should be the sole partner for that patient.
  14. 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).
  15. 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.

Trial locations and contacts

48 sites in 5 countries.

48 sites in 5 countries

United States27 sites

  • Gwinnett Research Institute

    Buford, Georgia, 30519

  • Great Lakes Clinical Trials

    Chicago, Illinois, 60640

  • Future Innovative Treatments

    Colorado Springs, Colorado, 80907

  • Benchmark Southern California

    Colton, California, 92324

  • IACT Health

    Columbus, Georgia, 31904

  • Centennial Medical Group - Research Department

    Elkridge, Maryland, 21075

  • Ascada Research

    Fullerton, California, 92835

  • VitaLink Research

    Greenville, South Carolina, 29615

  • Fairway Medical Clinic

    Houston, Texas, 77087

  • 1960 Family Practice, PA

    Houston, Texas, 77090

  • Jasper Summit Research, LLC

    Jasper, Alabama, 35501

  • Jefferson City Medical Group

    Jefferson City, Missouri, 65109

  • Zion Urgent Care Clinic

    Katy, Texas, 77494

  • Boward Infectious Disease and Primary Care

    Margate, Florida, 33063

  • Family Practice Center

    McAllen, Texas, 78501

  • Suncoast Research Group, LLC

    Miami, Florida, 33135

  • Life Spring Research Foundation

    Miami, Florida, 33155

  • Bio-Medical Research, LLC

    Miami, Florida, 33184

  • Panax Clinical Research, LLC

    Miami Lakes, Florida, 33014

  • Pacific Neuropsychiatric Specialists

    Mission Viejo, California, 92691

  • Monroe Biomedical Research

    Monroe, North Carolina, 28112

  • Epic Medical Research

    Red Oak, Texas, 75154

  • Providence Family Medical Center

    Redondo Beach, California, 90277

  • Clinical Research of Rock Hill

    Rock Hill, South Carolina, 29732

  • AdventHealth Tampa

    Tampa, Florida, 33613

  • Palm Beach Research Center

    West Palm Beach, Florida, 33409

  • Wilmington Health

    Wilmington, North Carolina, 28412

Other trials in United States

India10 sites

  • Shetty's Hospital

    Bengaluru, Karnataka, 560068

  • VHS-Infectious Disease Medical Centre

    Chennai, Tamil Nadu, 600113

  • Government Medical College

    Chhatrapati Sambhajinagar, Maharashtra, 431001

  • St. Theresa's Hospital

    Hyderabad, Telangana, 500018

  • Grant Medical College & Sir J. J. Group of Hospitals

    Mumbai, Maharashtra, 400008

  • Government Medical College and Hospital

    Nagpur, Maharashtra, 440003

  • All India Institute of Medical Sciences - Nagpur

    Nagpur, Maharashtra, 441108

  • BAPS Pramukhswami Hospital

    Surat, Gujarat, 395009

  • Durgabai Deshmukh Hospital & Research Centre

    Vidyānagar, Hyderabad, 500044

  • King George Hospital

    Visakhapatnam, Andhra Pradesh, 530002

Other trials in India

South Africa9 sites

  • FARMOVS (Pty) Ltd

    Bloemfontein, Free State, 9301

  • Enhancing Care Foundation

    Durban, 4052

  • George Provincial Hospital

    George, Western Cape, 6529

  • Clinresco Centres (Pty) Ltd

    Kempton Park, 1619

  • DJW Navorsing

    Krugersdorp, 1739

  • Jongaie Research

    Pretoria, 183

  • Sandton Medical Research Centre

    Sandton, Gauteng, 2196

  • Dr JM Engelbrecht Trial Site

    Somerset West, Western Cape, 7130

  • Wits Clinical Research

    Soweto, 2013

Other trials in South Africa

Hungary1 site

  • Debreceni Egyetem

    Debrecen, 4031

Other trials in Hungary

Netherlands1 site

  • UMC Utrecht

    Utrecht, 3584 CW

Other trials in Netherlands

About this study

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

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.

Read the 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.

Conditions
COVID-19
Being tested
ensovibep, Placebo
Keywords
ensovibep, COVID-19 treatment, symptom reduction, viral load reduction,, EMPATHY, SARS-CoV-2, designed ankyrin repeat protein (DARPin®), angiotensin-converting enzyme 2 (ACE2)
Medical subject headings
COVID-19

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ensovibepDrug

    Also called MP0420

    IV on day 1 only.

  • PlaceboDrug

    IV on day 1 only.

Study groups in NCT04828161
Study groupRoleWhat they receive
Phase 2 / Part A, ensovibep active treatment arm 1ExperimentalPhase 2 / Part A: ensovibep active treatment arm 1
Receives: Drug: ensovibep
Phase 2 / Part A, ensovibep active treatment arm 2ExperimentalPhase 2 / Part A: ensovibep active treatment arm 2
Receives: Drug: ensovibep
Phase 2 / Part A, ensovibep active treatment arm 3ExperimentalPhase 2 / Part A: ensovibep active treatment arm 3
Receives: Drug: ensovibep
Phase 2 / Part A, PlaceboPlacebo comparatorPhase 2 / Part A: Placebo
Receives: Drug: Placebo
Phase 3/ Part B, ensovibep active treatment arm 4ExperimentalPhase 3/ Part B: ensovibep active treatment. Part B was not initiated.
Receives: Drug: ensovibep
Phase 3/ Part B, Placebo armPlacebo comparatorPhase 3/ Part B: Placebo. Part B was not initiated.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Baseline (Day 1) and Days 3, 5 and 8

  2. 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.

    Measured: Up to Day 29

Secondary outcomes (16)

  1. 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.

    Measured: Up to Day 29

  2. Part A: Time to Sustained Clinical Recovery

    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.

    Measured: Up to Day 29

  3. 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.

    Measured: 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

  4. 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.

    Measured: 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

  5. 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.

    Measured: 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

  6. 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.

    Measured: 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

  7. 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.

    Measured: 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

  8. 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.

    Measured: 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

  9. 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.

    Measured: 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

  10. 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.

    Measured: 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

  11. 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.

    Measured: 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

  12. 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.

    Measured: 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

  13. 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.

    Measured: 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

  14. 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.

    Measured: Baseline (Day 1) and Days 3, 5 and 8

  15. Part B: Time to Sustained Clinical Recovery

    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.

    Measured: Up to Day 29

  16. 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

    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).

    Measured: Pre-dose on Day 1 and Days 15, 29, 61 and 91 postdose of Ensovibep

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Apr 2021
  2. Study start10 May 2021
  3. Primary completion18 Nov 2021
  4. Study completion27 Jan 2022

Why it stopped: Phase 2 completed as planned. Due to the evolving landscape of treatments for COVID-19, the placebo-controlled Phase 3 design will not proceed. No patients were actively participating at the time of termination.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
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
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
407 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04828161
Sponsor's protocol ID
MP0420-CP302
Other IDs
2021-000890-10, CSKO136A12201J
Acronym
EMPATHY
Status last verified
Jan 2026
First submitted
24 Mar 2021
Last updated
27 Jan 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on https://www.clinicalstudydatarequest.com/.

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing ensovibep in people with COVID-19, run by Novartis Pharmaceuticals at 48 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 27 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 48 sites in United States, India, South Africa, Hungary, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 18 Jan 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part A: Time-Weighted Change From Baseline in Log10 Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Viral Load Through Day 8 (time frame: Baseline (Day 1) and Days 3, 5 and 8). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04828161.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jan 2026.

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