Phase 1 Study to Assess Safety, Tolerability, PD, PK, Immunogenicity of IV NTR-441 Solution in Healthy Volunteers and COVID-19 Patients
- Registration Number
- NCT04941183
- Lead Sponsor
- Neutrolis
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 52
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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description NTR-441 NTR-441 Single Ascending Dose; Multiple Ascending Dose. Placebo Placebo Single Ascending Dose; Multiple Ascending Dose.
- Primary Outcome Measures
Name Time Method To evaluate safety and tolerability of single and multiple ascending doses of NTR-441 solution administered intravenously (IV) to adults 60 days Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 following a single or multiple IV of NTR-441.
- Secondary Outcome Measures
Name Time Method To assess for immunogenicity of NTR-441 following single ascending and multiples ascending doses of NTR-441 solution administered IV to adults 30 days Concentration of anti-drug antibodies of NTR-441 following single and multiples doses of NTR-441 solution administered IV
Measurement of terminal elimination half-life (t½) 15 days Terminal elimination half-life
Measurement of maximum plasma concentration (Cmax) 15 days Maximum plasma concentration
Measurement of time of maximum plasma concentration (Tmax) 14 days Time of maximum plasma concentration
Measurement of area under the concentration-time curve 15 days Area under the concentration-time curve from predose to the time of the last quantifiable concentration
Measurement of the terminal elimination rate (λz) 15 days Terminal elimination rate
Measurement of total body clearance (CL/F) 15 days Total body clearance
Measurement of apparent volume of distribution 15 days Apparent volume of distribution
Trial Locations
- Locations (4)
Klinik Favoriten
🇦🇹Vienna, Austria
Medical University Vienna, Department of Clinical Pharmacology
🇦🇹Vienna, Austria
Kyiv City Clinical Hospital#1
🇺🇦Kyiv, Ukraine
Vinnytsa City Clinical Hospital # 1
🇺🇦Vinnytsia, Ukraine