Clinical trial NCT04941183: Phase 1 Study to Assess Safety, Tolerability, PD, PK, Immunogenicity of IV NTR-441 Solution in Healthy Volunteers and COVID-19 Patients
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Covid19
Keywords: Covid 19
Lead sponsor: Neutrolis
Sponsor class: INDUSTRY
First posted: 2021-06-28
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Randomized, placebo-controlled, double-blind, single-ascending-dose and multiple-ascending-dose
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: To evaluate safety and tolerability of single and multiple ascending doses of NTR-441 solution administered intravenously (IV) to adults
timeFrame: 60 days
Secondary outcomes:
measure: Measurement of maximum plasma concentration (Cmax)
timeFrame: 15 days
measure: Measurement of time of maximum plasma concentration (Tmax)
timeFrame: 14 days
measure: Measurement of area under the concentration-time curve
timeFrame: 15 days
measure: Measurement of the terminal elimination rate (λz)
timeFrame: 15 days
measure: Measurement of terminal elimination half-life (t½)
timeFrame: 15 days
measure: Measurement of total body clearance (CL/F)
timeFrame: 15 days
measure: Measurement of apparent volume of distribution
timeFrame: 15 days
measure: To assess for immunogenicity of NTR-441 following single ascending and multiples ascending doses of NTR-441 solution administered IV to adults
timeFrame: 30 days
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Klinik Favoriten
city: Vienna
country: Austria
facility: Medical University Vienna, Department of Clinical Pharmacology
city: Kyiv
country: Ukraine
facility: Kyiv City Clinical Hospital#1
city: Vinnytsia
country: Ukraine
facility: Vinnytsa City Clinical Hospital # 1
Study officials:
References: