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

NCT04828161 | Terminated Phase 2 Results DMC FDA Drug

• 3 other identifiers: MP0420-CP3022021-000890-10CSKO136A12201J
• Study Type: interventional
• Target: 407
• Locations: 5 countries
• Sites: 48

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.

Conditions

COVID-19

Keywords

ensovibep; COVID-19 treatment, symptom reduction, viral load reduction,; EMPATHY; SARS-CoV-2; designed ankyrin repeat protein (DARPin®); angiotensin-converting enzyme 2 (ACE2)

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (16)

• Part A: Percentage of Participants With Hospitalizations and/or ER 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

• Part A: Observed Maximum Serum Concentration (Cmax) of Total and Free Ensovibep

  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

• 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

  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

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

  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

Study Arms (6)

Phase 2 / Part A, ensovibep active treatment arm 1

EXPERIMENTAL

Phase 2 / Part A: ensovibep active treatment arm 1

Drug: ensovibep

Phase 2 / Part A, ensovibep active treatment arm 2

EXPERIMENTAL

Phase 2 / Part A: ensovibep active treatment arm 2

Drug: ensovibep

Phase 2 / Part A, ensovibep active treatment arm 3

EXPERIMENTAL

Phase 2 / Part A: ensovibep active treatment arm 3

Drug: ensovibep

Phase 2 / Part A, Placebo

PLACEBO COMPARATOR

Phase 2 / Part A: Placebo

Drug: Placebo

Phase 3/ Part B, ensovibep active treatment arm 4

EXPERIMENTAL

Phase 3/ Part B: ensovibep active treatment. Part B was not initiated.

Drug: ensovibep

Phase 3/ Part B, Placebo arm

PLACEBO COMPARATOR

Phase 3/ Part B: Placebo. Part B was not initiated.

Drug: Placebo

Interventions

ensovibep DRUG

IV on day 1 only.

Also known as: MP0420

Phase 2 / Part A, ensovibep active treatment arm 1; Phase 2 / Part A, ensovibep active treatment arm 2; Phase 2 / Part A, ensovibep active treatment arm 3; Phase 3/ Part B, ensovibep active treatment arm 4

Placebo DRUG

IV on day 1 only.

Phase 2 / Part A, Placebo; Phase 3/ Part B, Placebo arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 on the day of dosing (rapid antigen test).
• Understand and agree to comply with the planned study procedures.
• The patient or legally authorized representative give signed informed consent.

You may not qualify if:

• 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 or with an oxygen saturation ≤ 93% on room air (SpO2) 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 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-inflammatory drugs \[NSAIDs\]) are permitted. Prior vaccination for COVID-19 is permitted.
• 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.
• Are pregnant or breast feeding.
• 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:
• 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.
• 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.
• Male sterilization (at least 6 months prior to screening). The vasectomized male partner should be the sole partner for that patient.
• 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).
• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead
• Molecular Partners AG: collaborator

Study Sites (48)

Jasper Summit Research, LLC

Jasper, Alabama, 35501, United States

Location

Benchmark Southern California

Colton, California, 92324, United States

Location

Ascada Research

Fullerton, California, 92835, United States

Location

Pacific Neuropsychiatric Specialists

Mission Viejo, California, 92691, United States

Location

Providence Family Medical Center

Redondo Beach, California, 90277, United States

Location

Future Innovative Treatments

Colorado Springs, Colorado, 80907, United States

Location

Boward Infectious Disease and Primary Care

Margate, Florida, 33063, United States

Location

Suncoast Research Group, LLC

Miami, Florida, 33135, United States

Location

Life Spring Research Foundation

Miami, Florida, 33155, United States

Location

Bio-Medical Research, LLC

Miami, Florida, 33184, United States

Location

Panax Clinical Research, LLC

Miami Lakes, Florida, 33014, United States

Location

AdventHealth Tampa

Tampa, Florida, 33613, United States

Location

Palm Beach Research Center

West Palm Beach, Florida, 33409, United States

Location

Gwinnett Research Institute

Buford, Georgia, 30519, United States

Location

IACT Health

Columbus, Georgia, 31904, United States

Location

Great Lakes Clinical Trials

Chicago, Illinois, 60640, United States

Location

Centennial Medical Group - Research Department

Elkridge, Maryland, 21075, United States

Location

Jefferson City Medical Group

Jefferson City, Missouri, 65109, United States

Location

Monroe Biomedical Research

Monroe, North Carolina, 28112, United States

Location

Wilmington Health

Wilmington, North Carolina, 28412, United States

Location

VitaLink Research

Greenville, South Carolina, 29615, United States

Location

Clinical Research of Rock Hill

Rock Hill, South Carolina, 29732, United States

Location

Fairway Medical Clinic

Houston, Texas, 77087, United States

Location

1960 Family Practice, PA

Houston, Texas, 77090, United States

Location

Zion Urgent Care Clinic

Katy, Texas, 77494, United States

Location

Family Practice Center

McAllen, Texas, 78501, United States

Location

Epic Medical Research

Red Oak, Texas, 75154, United States

Location

Debreceni Egyetem

Debrecen, 4031, Hungary

Location

King George Hospital

Visakhapatnam, Andhra Pradesh, 530002, India

Location

BAPS Pramukhswami Hospital

Surat, Gujarat, 395009, India

Location

Durgabai Deshmukh Hospital & Research Centre

Vidyānagar, Hyderabad, 500044, India

Location

Shetty's Hospital

Bengaluru, Karnataka, 560068, India

Location

Government Medical College

Aurangabad, Maharashtra, 431001, India

Location

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

Mumbai, Maharashtra, 400008, India

Location

Government Medical College and Hospital

Nagpur, Maharashtra, 440003, India

Location

All India Institute of Medical Sciences - Nagpur

Nagpur, Maharashtra, 441108, India

Location

VHS-Infectious Disease Medical Centre

Chennai, Tamil Nadu, 600113, India

Location

St. Theresa's Hospital

Hyderabad, Telangana, 500018, India

Location

UMC Utrecht

Utrecht, 3584 CW, Netherlands

Location

FARMOVS (Pty) Ltd

Bloemfontein, Free State, 9301, South Africa

Location

Sandton Medical Research Centre

Sandton, Gauteng, 2196, South Africa

Location

George Provincial Hospital

George, Western Cape, 6529, South Africa

Location

Dr JM Engelbrecht Trial Site

Somerset West, Western Cape, 7130, South Africa

Location

Enhancing Care Foundation

Durban, 4052, South Africa

Location

Clinresco Centres (Pty) Ltd

Kempton Park, 1619, South Africa

Location

DJW Navorsing

Krugersdorp, 1739, South Africa

Location

Jongaie Research

Pretoria, 183, South Africa

Location

Wits Clinical Research

Soweto, 2013, South Africa

Location

Related Links

• A Plain Language Trial Summary is available on www.novctrd.com

MeSH Terms

Conditions

COVID-19

Interventions

ensovibep

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Limitations and Caveats

Part B was not initiated based on regulatory feedback indicating that with evolving treatment options, a placebo controlled design was no longer considered to be appropriate. 2 patients randomized to ensovibep 225 mg didn't receive treatment they were randomized to: 1 patient received no active drug as infusion was not prepared correctly; 1 patient received lower dose (\<75 mg) as infusion was interrupted. For Safety set, these 2 were reported in placebo and ensovibep 75 mg arms, respectively.

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@Novartis.com

+1 862 778 8300

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: * Double Blind: two or more parties are unaware of the intervention assignment * Masked roles are: Subject, Caregiver, Investigator or Outcomes Assessor.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: * 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

Study Record Dates

• First Submitted: March 24, 2021
• First Posted: April 1, 2021
• Study Start: May 10, 2021
• Primary Completion: November 18, 2021
• Study Completion: January 27, 2022
• Last Updated: January 27, 2026
• Results First Posted: January 18, 2023

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share

Locations

HU (1); NL (1); IN (10); US (27); ZA (9)