Single Ascending Dose Safety and Tolerability of NTS-104 Healthy Adults

NCT ID: NCT05547438

Last Updated: 2023-05-26

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-04-28
• Study Completion Date: 2023-08-07

Brief Summary

NTS-104 TRIS will be administered as a single intravenous dose to healthy subjects at doses of 0.8, 4, 8 and 16 mg/kg in 4 Cohorts. Each cohort of 8 subjects will begin with dosing 2 sentinel subjects with one being given the investigational product and one the placebo. If no safety issues arise, dosing the remaining subjects in the cohort will begin. A Safety Review Committee will review the safety and pharmacokinetic data before approving escalation to the next dose level.

Detailed Description

This is a randomized, , placebo-controlled, Phase 1, single-dose, dose-escalation study to assess the safety, tolerability, and PK of IV NTS-104 in healthy participants. The study is composed of a screening period, a treatment day, and a follow-up period. The study will enroll 4 cohorts with 8 participants in each cohort. Participants in each cohort will be randomized 3:1 to receive either a single IV administration of NTS-104 or placebo. Cohort 1 will be administered 0.8 mg/kg (Cohort 1) with proposed subsequent doses of 4 mg/kg (Cohort 2), 8 mg/kg (Cohort 3), and 16 mg/kg (Cohort 4). Two additional cohorts of 8 participants each, Cohorts 5 and 6, may be enrolled if the human equivalent dose to the no-observed-adverse-effect level (NOAEL) dose in rats is not reached or if exposure limits are not exceeded in the first 4 cohorts. Each cohort will start with a sentinel pair of participants, with 1 participant assigned to NTS-104 Tris (Arm 1) and 1 participant randomized to placebo (Arm 2). If there are no safety concerns identified at 48 hours, the remainder of the cohort will be dosed, with 5 participants randomized to NTS-104 Tris (Arm 1) and 1 participant assigned to placebo (Arm 2).

Conditions

Acute Ischemic Stroke

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Treatment Arm 1

0.8, 4, 8, or 16 mg/mL NTS-104 solution for IV infusion

Group Type: EXPERIMENTAL

NTS-104 TRIS

Intervention Type: DRUG

Subjects will receive a single IV infusion of either 0.8, 4, 8, or 16 mg/mL NTS-104 depending on the Cohort number

Treatment Arm 2

Single administration of placebo at the same volume and duration

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Subjects will be administered an IV infusion of placebo and the same duration and volume as the subjects administered NTS-104 TRIS in the cohort

Interventions

NTS-104 TRIS

Subjects will receive a single IV infusion of either 0.8, 4, 8, or 16 mg/mL NTS-104 depending on the Cohort number

Intervention Type: DRUG

Placebo

Subjects will be administered an IV infusion of placebo and the same duration and volume as the subjects administered NTS-104 TRIS in the cohort

Intervention Type: DRUG

Other Intervention Names

IP; Buffer

Eligibility Criteria

Inclusion Criteria

1. Participants who provide written informed consent to participate in the study.

2. Healthy males and females between 18 and 65 years (inclusive) of age at the time of signing informed consent.

3. Body mass index (BMI) of 18 to 32 kg/m2 (inclusive) and weighing at least 50 kg at screening.

4. Participants in general good health in the opinion of the Investigator as determined by medical history; vital signs; and physical, neurological, and suicidal ideation examinations.

5. Blood pressure and heart rate within normal limits (blood pressure: systolic 90 to 140 mmHg and diastolic 50 to 90 mmHg; heart rate: 45 to 100 beats per minute) at screening and at admission on Day -1.

6. Female participants must have a negative serum pregnancy test at screening and at admission and be willing and able to use a medically acceptable method of birth control - Acceptable methods of birth control in this study must start one complete menstrual cycle (and at least 30 days) prior to the first day of dosing and continue until 4 weeks after the final follow-up visit.

• Acceptable methods of birth control include abstinence, tubal ligation, bilateral tubal occlusion, progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable and implantable), combined hormonal contraception (i.e., estrogen- and progestogen-containing), IUS and IUD.
• Female participants of non-childbearing potential are defined as either postmenopausal (evidence of menopause based on a combination of amenorrhea for at least one year confirmed with pre-admission serum follicle-stimulating hormone level [>30 IU/L]), or surgical sterilization (evidence of hysterectomy and/or bilateral oophorectomy).
• Male participants with a partner who might become pregnant must use reliable forms of contraception during the trial and 4 weeks afterward. Surgical sterilization (vasectomy with documentation of azoospermia) and a barrier method (condom).
• The participant's female partner uses oral contraceptives (combined hormonal contraception), injectable progesterone or subdermal implants, and the male partner uses a barrier method (condom)

Exclusion Criteria

1. History of significant medical disorder that, in the opinion of the Investigator, contraindicates administration of the study medications.

2. Any active or current comorbidity with the exception of topical or allergic conditions treated with topical comedication and/or non-drowsy anti-allergic medication or acetaminophen

3. Any use of current comedication at admission or during the 30 days prior to enrollment with the exception of topical dermatological medication and/or non-drowsy anti-allergic medication or acetaminophen

4. Any acute illness (e.g., acute infection) within 72 hours of study drug administration, if considered of significance by the Investigator.

5. Any clinically significant abnormality in safety laboratory tests at screening or admission, in particular a screening TSH test

6. Positive human immunodeficiency virus, hepatitis B, or hepatitis C serology at screening.

7. Specifically, any history or current diagnosis of hepatic impairment at screening and Day - 1

8. Specifically, any history or current diagnosis of renal impairment at screening

9. Specifically, a history of type 1 diabetes mellitus or current type 2 diabetes.

10. Any abnormality on the neurological examination, at screening or enrollment

11. Positive Columbia-Suicide Severity Rating Scale (C-SSRS).

12. Participation in another clinical trial with drugs received within 3 months prior to dosing (calculated from the previous study's last dosing date).

13. Participant who is an active smoker and/or has smoked or used nicotine or nicotine- containing products (e.g., nicotine patch, gum, e-cigarettes) within the past 6 months before enrollment.

14. The use of ketogenic diets within 12 months prior to enrollment.

15. Electrocardiogram (ECG) with clinically significant findings recorded at screening or admission.

17. Positive coronavirus disease 2019 (COVID-19) test determined at screening and admission (nasal swab).

18. Known history of alcohol or drug abuse in the past 5 years. 19. Positive urinary drug or cotinine screen determined at screening and admission.

20. Positive serum alcohol screen determined during the screening period and on admission.

21. Any other condition, which in the Investigator's opinion, would not make the participant a good candidate for the study.

22. Blood donation of 500 mL (1 pint) or more: 56 days before the screening visit and until after the follow-up visit.

23. Plasma donation: 7 days before the screening visit and until after the follow-up visit.

24. Grapefruit, grapefruit juice, star fruit, pomegranate, and Seville oranges: 7 days before screening and until after the follow-up visit

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Parexel

INDUSTRY

Sponsor Role: collaborator

NeuroTrauma Sciences, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Marc de Somer, MD

Role: STUDY_DIRECTOR

NeuroTrauma Sciences, LLC

Locations

Parexel International EPCU Baltimore 7th floor

Baltimore, Maryland, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Marilyn S Dar

Role: CONTACT

m.dar@neurotraumasciences.com

18455361733

Tina Lamidi

Role: CONTACT

tina.lamidi@parexel.com

240-506-4435

Facility Contacts

Ronald Goldwater, MD

Role: primary

Shannon Marriott, PA-C

Role: backup

Other Identifiers

CLN-22-411

Identifier Type: -

Identifier Source: org_study_id