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A Dose Finding, Efficacy and Safety Study of Ensovibep (MP0420) in Ambulatory Adult 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
Results First Posted : January 18, 2023
Last Update Posted : January 18, 2023
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 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 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.

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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 Adult 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. Part B was not initiated.
Drug: ensovibep
IV on day 1 only.
Other Name: MP0420

Placebo Comparator: Phase 3/ Part B, Placebo arm
Phase 3/ Part B: Placebo. Part B was not initiated.
Drug: Placebo
IV on day 1 only.




Primary Outcome Measures :
  1. 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 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.

  2. Part B: Percentage of Participants With Hospitalizations and/or Emergency Room (ER) Visits Related to COVID-19 or Death From Any Cause [ Time Frame: Up to Day 29 ]
    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.


Secondary Outcome Measures :
  1. Part A: Percentage of Participants With Hospitalizations and/or ER Visits Related to COVID-19 or Death From Any Cause [ Time Frame: Up to Day 29 ]
    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.

  2. Part A: Time to Sustained Clinical Recovery [ Time Frame: Up to Day 29 ]

    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.

  3. Part A: Observed Maximum Serum Concentration (Cmax) of Total and Free Ensovibep [ Time Frame: 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 ]
    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.

  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 [ Time Frame: 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 ]
    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.

  5. Part A: Area Under the Concentration-Time Curve From Time Zero to 48 Hours (AUC 0-48h) of Total and Free Ensovibep [ Time Frame: 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 ]
    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.

  6. Part A: Area Under the Concentration-Time Curve From Time Zero to 168 Hours (AUC 0-168h) of Total and Free Ensovibep [ Time Frame: 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 ]
    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.

  7. Part A: Area Under the Concentration-Time Curve From Time Zero to 336 Hours (AUC 0-336h) of Total and Free Ensovibep [ Time Frame: 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 ]
    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.

  8. Part A: Area Under the Concentration-Time Curve From Time Zero to Infinity (AUCinfinity) of Total and Free Ensovibep [ Time Frame: 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 ]
    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.

  9. Part A: Time to Reach the Maximum Concentration (Tmax) of Total and Free Ensovibep [ Time Frame: 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 ]
    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.

  10. Part A: Apparent Total Body Clearance (CL) of Total and Free Ensovibep [ Time Frame: 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 ]
    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.

  11. Part A: Terminal Elimination Rate Constant (Lambda z) of Total and Free Ensovibep [ Time Frame: 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 ]
    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.

  12. Part A: Terminal Elimination Half-Life (T1/2) of Total and Free Ensovibep [ Time Frame: 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 ]
    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.

  13. Part A: Apparent Volume of Distribution (Vz) of Total and Free Ensovibep [ Time Frame: 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 ]
    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.

  14. Part B: Change From Baseline in Log10 SARS-CoV-2 Viral Load Through Day 8 [ Time Frame: Baseline (Day 1) and Days 3, 5 and 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.

  15. Part B: Time to Sustained Clinical Recovery [ Time Frame: Up to Day 29 ]

    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.

  16. Part B: Percentage of Participants With Treatment-Emergent Anti-Drug Antibody (ADA) Response to Ensovibep [ Time Frame: Pre-dose on Day 1 and Days 15, 29, 61 and 91 postdose of 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).



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:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

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
Show Show 48 study locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Molecular Partners AG
  Study Documents (Full-Text)

Documents provided by Novartis ( Novartis Pharmaceuticals ):
Study Protocol  [PDF] October 19, 2021
Statistical Analysis Plan  [PDF] December 7, 2021

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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
Results First Posted: January 18, 2023
Last Update Posted: January 18, 2023
Last Verified: December 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:
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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