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

Novartis

Status and phase: Terminated; Phase 3; Phase 2

Conditions: COVID-19

Treatments: Drug: ensovibep; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT04828161

MP0420-CP302

CSKO136A12201J (Other Identifier)

2021-000890-10 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 407 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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407 participants in 6 patient groups, including a placebo group

Phase 2 / Part A, ensovibep active treatment arm 1

Experimental group

Description:

Phase 2 / Part A: ensovibep active treatment arm 1

Treatment:

Drug: ensovibep

Phase 2 / Part A, ensovibep active treatment arm 2

Experimental group

Description:

Phase 2 / Part A: ensovibep active treatment arm 2

Treatment:

Drug: ensovibep

Phase 2 / Part A, ensovibep active treatment arm 3

Experimental group

Description:

Phase 2 / Part A: ensovibep active treatment arm 3

Treatment:

Drug: ensovibep

Phase 2 / Part A, Placebo

Placebo Comparator group

Description:

Phase 2 / Part A: Placebo

Treatment:

Drug: Placebo

Phase 3/ Part B, ensovibep active treatment arm 4

Experimental group

Description:

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

Treatment:

Drug: ensovibep

Phase 3/ Part B, Placebo arm

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo