Safety, Tolerability and PK of Ensovibep (MP0420 - a New Candidate With Potential for Treatment of COVID-19)

Study Overview
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Brief Summary
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This study will investigate how ensovibep is distributed throughout the body, the safety and the tolerability of ensovibep in healthy volunteers

Official Title
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A Phase 1, First-time-in-human, Dose Ascending Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of MP0420 (a Novel Drug Candidate With Potential for Treatment of COVID-19) in Healthy Volunteers

Conditions
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COVID-19

Intervention / Treatment
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* Drug: Ensovibep
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male or female subjects between ages of 18-65 years Body mass index of 18.0-35.0 kg/m2 Non-smokers for at least 3 months Deemed healthy on the basis of a clinical history, physical examination, ECG, vital signs, and laboratory tests of blood and urine Agree to follow the contraception requirements of the trial Able to give fully informed written consent. Exclusion Criteria: Positive tests for hepatitis B & C, HIV Severe adverse reaction to any drug Drug or alcohol abuse Use of over-the-counter medication (with the exception of paracetamol [acetaminophen]) during the 7 days before the first dose of trial medication, or prescribed medication during the 28 days before first dose of trial medication Any vaccination within 4 weeks before dose of trial medication Participation in other clinical trials of unlicensed medicines within the previous 3 months Loss of more than 400 mL blood within the previous 3 months Vital signs outside the acceptable range Clinically relevant abnormal findings at the screening assessment Acute or chronic illness Clinically relevant abnormal medical history or concurrent medical condition Possibility that volunteer will not cooperate Females who are pregnant or lactating, or who are sexually active and not using a reliable method of contraception.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Parallel (Part A) Sequential (Part B and Part C)
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ensovibep dose 1 (infusion)<br> | Drug: Ensovibep<br>* The study will start with a low-dose cohort and after a safety review escalate to the higher dose cohorts. 3 IV infusion, 2 IV bolus, 4 subcutaneous and 4 intramuscular cohorts are planned. Subjects receive one or two administration(s) on day 1, depending on the cohort.<br>* Other names: COVID-19 treatment;|
| Experimental: ensovibep dose 2 (infusion)<br> | Drug: Ensovibep<br>* The study will start with a low-dose cohort and after a safety review escalate to the higher dose cohorts. 3 IV infusion, 2 IV bolus, 4 subcutaneous and 4 intramuscular cohorts are planned. Subjects receive one or two administration(s) on day 1, depending on the cohort.<br>* Other names: COVID-19 treatment;|
| Experimental: ensovibep dose 3 (infusion)<br> | Drug: Ensovibep<br>* The study will start with a low-dose cohort and after a safety review escalate to the higher dose cohorts. 3 IV infusion, 2 IV bolus, 4 subcutaneous and 4 intramuscular cohorts are planned. Subjects receive one or two administration(s) on day 1, depending on the cohort.<br>* Other names: COVID-19 treatment;|
| Placebo Comparator: placebo (infusion)<br> | Drug: Placebo<br>* One administration at day 1 by infusion.<br>|
| Experimental: ensovibep dose 4 (IV bolus)<br> | Drug: Ensovibep<br>* The study will start with a low-dose cohort and after a safety review escalate to the higher dose cohorts. 3 IV infusion, 2 IV bolus, 4 subcutaneous and 4 intramuscular cohorts are planned. Subjects receive one or two administration(s) on day 1, depending on the cohort.<br>* Other names: COVID-19 treatment;|
| Experimental: ensovibep dose 5 (IV bolus)<br> | Drug: Ensovibep<br>* The study will start with a low-dose cohort and after a safety review escalate to the higher dose cohorts. 3 IV infusion, 2 IV bolus, 4 subcutaneous and 4 intramuscular cohorts are planned. Subjects receive one or two administration(s) on day 1, depending on the cohort.<br>* Other names: COVID-19 treatment;|
| Experimental: ensovibep dose 6 (SC injection)<br> | Drug: Ensovibep<br>* The study will start with a low-dose cohort and after a safety review escalate to the higher dose cohorts. 3 IV infusion, 2 IV bolus, 4 subcutaneous and 4 intramuscular cohorts are planned. Subjects receive one or two administration(s) on day 1, depending on the cohort.<br>* Other names: COVID-19 treatment;|
| Experimental: ensovibep dose 7 (SC injection)<br> | Drug: Ensovibep<br>* The study will start with a low-dose cohort and after a safety review escalate to the higher dose cohorts. 3 IV infusion, 2 IV bolus, 4 subcutaneous and 4 intramuscular cohorts are planned. Subjects receive one or two administration(s) on day 1, depending on the cohort.<br>* Other names: COVID-19 treatment;|
| Experimental: ensovibep dose 8 (SC injection)<br> | Drug: Ensovibep<br>* The study will start with a low-dose cohort and after a safety review escalate to the higher dose cohorts. 3 IV infusion, 2 IV bolus, 4 subcutaneous and 4 intramuscular cohorts are planned. Subjects receive one or two administration(s) on day 1, depending on the cohort.<br>* Other names: COVID-19 treatment;|
| Experimental: ensovibep dose 9 (SC injection)<br> | Drug: Ensovibep<br>* The study will start with a low-dose cohort and after a safety review escalate to the higher dose cohorts. 3 IV infusion, 2 IV bolus, 4 subcutaneous and 4 intramuscular cohorts are planned. Subjects receive one or two administration(s) on day 1, depending on the cohort.<br>* Other names: COVID-19 treatment;|
| Experimental: ensovibep dose 10 (IM injection)<br> | Drug: Ensovibep<br>* The study will start with a low-dose cohort and after a safety review escalate to the higher dose cohorts. 3 IV infusion, 2 IV bolus, 4 subcutaneous and 4 intramuscular cohorts are planned. Subjects receive one or two administration(s) on day 1, depending on the cohort.<br>* Other names: COVID-19 treatment;|
| Experimental: ensovibep dose 11 (IM injection)<br> | Drug: Ensovibep<br>* The study will start with a low-dose cohort and after a safety review escalate to the higher dose cohorts. 3 IV infusion, 2 IV bolus, 4 subcutaneous and 4 intramuscular cohorts are planned. Subjects receive one or two administration(s) on day 1, depending on the cohort.<br>* Other names: COVID-19 treatment;|
| Experimental: ensovibep dose 12 (IM injection)<br> | Drug: Ensovibep<br>* The study will start with a low-dose cohort and after a safety review escalate to the higher dose cohorts. 3 IV infusion, 2 IV bolus, 4 subcutaneous and 4 intramuscular cohorts are planned. Subjects receive one or two administration(s) on day 1, depending on the cohort.<br>* Other names: COVID-19 treatment;|
| Experimental: ensovibep dose 13 (IM injection)<br> | Drug: Ensovibep<br>* The study will start with a low-dose cohort and after a safety review escalate to the higher dose cohorts. 3 IV infusion, 2 IV bolus, 4 subcutaneous and 4 intramuscular cohorts are planned. Subjects receive one or two administration(s) on day 1, depending on the cohort.<br>* Other names: COVID-19 treatment;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vital Signs: Blood Pressure Systolic and Diastolic (mmHg) |  | up to day 100 (EOS) | 
| Vital Signs: Heart Rate (bmp) |  | up to day 100 (EOS) | 
| Vital Signs: Tympanic Temperature (°C) |  | up to day 100 (EOS) | 
| Vital Signs: Oxygen Saturation (SpO2%) |  | up to day 100 (EOS) | 
| Cardiac Safety assessed by 12-lead Electrocardiogram (ECG) |  | up to day 100 (EOS) | 
| Physical Examination | For safety purpose, the following will be examined during full physical examinations: general appearance; head, ears, eyes, nose and throat; thyroid; lymph nodes; back and neck; heart; chest; lungs; abdomen; skin; and extremities; and the following systems will be assessed: musculoskeletal and neurological. | up to day 100 (EOS) | 
| Number of subjects with Laboratory Abnormalities |  | up to day 100 (EOS) | 
| Assessment of local tolerability | Number of subjects with reaction at the injection site. The injection site is assessed for any pain, tenderness, erythema and induration. | up to day 100 (EOS) | 
| Number of subjects with Adverse Events |  | up to day 100 (EOS) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Observed maximum concentration (Cmax) | The maximum observed concentration (Cmax) is estimated based on the serum concentrations. | up to day 100 (EOS) | 
| Time to Cmax (Tmax) |  | up to day 100 (EOS) | 
| The area under the serum concentration-time curve (AUC) |  | up to day 100 (EOS) | 
| Apparent total body clearance of the drug from plasma (CL) |  | up to day 100 (EOS) | 
| The apparent volume of distribution during terminal phase after drug administration (Vz) |  | up to day 100 (EOS) | 
| Terminal Elimination Half-Life (T½) |  | up to day 100 (EOS) | 
| Proportion of subjects with treatment-emergent anti-drug antibodies (ADA) |  | up to day 100 (EOS) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ensovibep, COVID-19 treatment, SARS-CoV-2, Corona, designed ankyrin repeat protein (DARPin®), angiotensin-converting enzyme 2 (ACE2)