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

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

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.

Study Overview

• Status: Terminated
• Conditions: Covid19
• Intervention / Treatment: Drug: Placebo; Drug: NTR-441

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 1

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria
    • Klinik Favoriten
  • Vienna, Austria
    • Medical University Vienna, Department of Clinical Pharmacology
• Ukraine
  • Kyiv, Ukraine
    • Kyiv City Clinical Hospital#1
  • Vinnytsia, Ukraine
    • Vinnytsa City Clinical Hospital # 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 97 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Neutrolis

Study record dates

Study Major Dates

• Study Start (Actual): April 14, 2021
• Primary Completion (Actual): December 12, 2022
• Study Completion (Actual): June 6, 2023

Study Registration Dates

• First Submitted: May 4, 2021
• First Submitted That Met QC Criteria: June 24, 2021
• First Posted (Actual): June 28, 2021

Study Record Updates

• Last Update Posted (Estimated): January 19, 2024
• Last Update Submitted That Met QC Criteria: January 18, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Covid 19
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: NTR441-1001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No