Phase 1 Study to Assess Safety, Tolerability, PD, PK, Immunogenicity of IV NTR-441 Solution in Healthy Volunteers and COVID-19 Patients

Study Overview
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Brief Summary
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This first-in-human clinical study is a Phase 1a/ 1b, randomized, double-blind, placebo-controlled study to assess the safety, tolerability, and PK/PD of NTR-441 in healthy subjects and patients with COVID-19 after single ascending IV infusion doses and multiple ascending IV infusion doses.

Official Title
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A Randomized, Placebo-controlled, Double-blind, Single-ascending-dose and Multiple-ascending-dose, Phase 1 Study to Assess the Safety and Tolerability, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of IV NTR-441 Solution in HV Adults and COVID-19 Patients

Conditions
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Covid19

Intervention / Treatment
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* Drug: NTR-441
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Healthy volunteers: Inclusion Criteria: Male or female, non-smoker, ≥18 and ≤55 years of age, with Body Mass Index (BMI) > 18.5 and < 32.0 kg/m2 Healthy with no clinically significant findings, determined by medical evaluation (medical history, physical examination, vital signs, 12-lead ECG, and clinical laboratory evaluations) at Screening Subject is able to understand and is willing to comply with all study requirements, and willing to follow the instructions of the study staff. Subject voluntarily agrees to participate in this study. Exclusion Criteria: Pregnancy, nursing, and/or breastfeeding. Study participant has a history of an anaphylactic reaction. Subject has used an investigational drug within 30 days (or 5 half-lives whichever is longer) prior to the first dose of study drug. Has received any prescription or nonprescription over-the-counter (except occasional use of acetaminophen, paracetamol or ibuprofen) medication, topical medications, vitamins, dietary or herbal during the last 14 days or 5 half-lives, whichever is longer. Subject has a positive urine test for drugs of abuse at the screening visit or admission. Regular consumption of alcohol within 6 months prior to Screening or use of illicit substances within 3 months prior to screening. Subject has positive test for SARS-CoV-2 infection, human immunodeficiency virus (HIV), chronic or active hepatitis B, or active hepatitis C. Donation or loss of blood or plasma within 4 weeks prior to initial dosing. Subject has a history or current evidence of a serious and/or unstable cardiovascular, respiratory, gastrointestinal, hematologic, autoimmune, mental or other medical disorder, including cirrhosis or malignancy; a history of a psychiatric disorder that will affect the subject's ability to participate in the study. Subject has a clinically relevant abnormal ECG; abnormal laboratory values. Subject has hypertension. COVID-19 patients: Inclusion Criteria: Male or female, non-smoker, ≥18 years of age. Participant has active laboratory-confirmed SARS-CoV-2 infection. Participant must be hospitalized for COVID-19 pneumonia. Ability to provide informed consent personally, or by a legally acceptable representative if the participant is unable to do so. Exclusion Criteria: Pregnancy, nursing, and/or breastfeeding. History of an anaphylactic reaction. In the opinion of the clinical team, progression to death is imminent and inevitable within the next 24 hours, irrespective of the provision of treatments. Severely immune-compromised participants. Participant known to test positive for human immunodeficiency virus (HIV), chronic or active hepatitis B, or active hepatitis C. Any other clinical conditions that in the opinion of the Investigator would make the participants unsuitable for the study. Prior treatment with any investigational drug therapy against coronavirus infection within 5 half-lives, prior to enrollment Participants who have received an experimental (or, in future, potentially a licensed) immunization or remdesivir against coronavirus remain eligible. Participation in another clinical study with the study intervention administered from 30 days or 5 half-lives whichever is longer. Anticipated transfer to another hospital which is not a study site during the intervention period.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 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: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Randomized, placebo-controlled, double-blind, single-ascending-dose and multiple-ascending-dose
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NTR-441<br>Single Ascending Dose; Multiple Ascending Dose. | Drug: NTR-441<br>* NTR-441<br>|
| Placebo Comparator: Placebo<br>Single Ascending Dose; Multiple Ascending Dose. | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate safety and tolerability of single and multiple ascending doses of NTR-441 solution administered intravenously (IV) to adults | Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 following a single or multiple IV of NTR-441. | 60 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measurement of maximum plasma concentration (Cmax) | Maximum plasma concentration | 15 days | 
| Measurement of time of maximum plasma concentration (Tmax) | Time of maximum plasma concentration | 14 days | 
| Measurement of area under the concentration-time curve | Area under the concentration-time curve from predose to the time of the last quantifiable concentration | 15 days | 
| Measurement of the terminal elimination rate (λz) | Terminal elimination rate | 15 days | 
| Measurement of terminal elimination half-life (t½) | Terminal elimination half-life | 15 days | 
| Measurement of total body clearance (CL/F) | Total body clearance | 15 days | 
| Measurement of apparent volume of distribution | Apparent volume of distribution | 15 days | 
| To assess for immunogenicity of NTR-441 following single ascending and multiples ascending doses of NTR-441 solution administered IV to adults | Concentration of anti-drug antibodies of NTR-441 following single and multiples doses of NTR-441 solution administered IV | 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Covid 19