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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04828161
Recruitment Status : Terminated (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.)
First Posted : April 1, 2021
Last Update Posted : August 8, 2022
Sponsor:
Collaborator:
Molecular Partners AG
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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

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Study Type : Interventional  (Clinical Trial)
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 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 : November 18, 2021
Actual Study Completion Date : January 27, 2022

Resource links provided by the National Library of Medicine


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 Name: 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 Name: 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 Name: 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 Name: MP0420

Placebo Comparator: Phase 3/ Part B, Placebo arm
Phase 3/ Part B: Placebo
Drug: Placebo
IV on day 1 only.




Primary Outcome Measures :
  1. Part A - SARS-CoV-2 viral load [ Time Frame: 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

  2. Part B - Occurrence of hospitalizations or death [ Time Frame: 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 :
  1. Part A - Occurrence of hospitalizations, emergency room visits or death [ Time Frame: 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.

  2. Part A - Time to sustained clinical recovery [ Time Frame: 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.

  3. Part A - Serious adverse events (SAEs), AEs of Special Interest (AESIs), vital signs and clinical laboratory measurements. [ Time Frame: 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.

  4. Part A - Ensovibep Maximum Plasma Concentration [Cmax]). [ Time Frame: up to day 91 ]
    Cmax is the observed maximum concentration.

  5. Part A - Ensovibep PK parameter - AUClast [ Time Frame: up to day 91 ]
    AUClast is the area under the concentration-time curve from time zero to the time of the last quantifiable concentration.

  6. Part B - Time to sustained clinical recovery [ Time Frame: 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


  7. Part B - SARS-CoV-2 viral load [ Time Frame: 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

  8. Part B - Proportion of patients with post-acute COVID-19 symptoms [ Time Frame: from Day 29 up to day 91 ]
    To assess the effect of ensovibep, compared to placebo, on post-acute COVID-19 symptoms

  9. Part B - Effect of ensovibep, compared to placebo, on general health status [ Time Frame: up to day 91 ]
    Change from baseline in MCS and PCS scores from Short Form Health Survey (SF-36) questionnaire up to Day 91

  10. Part B - treatment-emergent ADAs (TE-ADA) [ Time Frame: 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.

  11. Part B - TEAEs, SAEs, AESIs, vital signs and clinical laboratory measurements [ Time Frame: 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Part A Inclusion Criteria:

  1. Males or females ≥ 18 years of age on the day of inclusion (no upper limit).
  2. 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.
  3. Positive test for SARS-CoV-2 in upper respiratory swab on the day of dosing (rapid antigen test).
  4. Understands and agrees to comply with the planned study procedures.
  5. The patient or legally authorized representative gives 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.
  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-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:

  1. Males or females ≥ 12 years of age on the day of inclusion (no upper limit) and with a body weight of ≥ 40kg
  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 within 24 hours prior to dosing (rapid antigen test)
  4. 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)]
  5. The patient or legally authorized representative understands and agrees to comply with the planned study procedures.
  6. The patient, legally authorized representative, or parent/legal guardian gives signed informed consent and adolescents provide assent.

Part B 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 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 current SARS-CoV-2) that in the opinion of the investigator could constitute a risk when receiving study medication.
  5. Any serious, unstable 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 10 days of dosing, or that is considered life-threatening within 29 days of dosing.
  7. Prior use of ensovibep or participation in clinical trials in which ensovibep was studied.
  8. 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.
  9. 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.
  10. 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)
  11. 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.
  12. Are pregnant or breast feeding.
  13. 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04828161


Locations
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Sponsors and Collaborators
Novartis Pharmaceuticals
Molecular Partners AG
Layout table for additonal information
Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT04828161    
Other Study ID Numbers: MP0420-CP302
2021-000890-10 ( EudraCT Number )
CSKO136A12201J ( Other Identifier: Novartis Pharmaceuticals )
First Posted: April 1, 2021    Key Record Dates
Last Update Posted: August 8, 2022
Last Verified: August 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

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/.

URL: https://www.clinicalstudydatarequest.com/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
ensovibep
COVID-19 treatment, symptom reduction, viral load reduction,
EMPATHY
SARS-COV-2
designed ankyrin repeat protein (DARPin®)
angiotensin-converting enzyme 2 (ACE2)
Additional relevant MeSH terms:
Layout table for MeSH terms
COVID-19
Respiratory Tract Infections
Infections
Pneumonia, Viral
Pneumonia
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases