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

NCT05547438 | Unknown Phase 1 DMC FDA Drug

• 1 other identifier: CLN-22-411
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

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.

Conditions

Acute Ischemic Stroke

Outcome Measures

Primary Outcomes (5)

• Adverse Events and Serious Adverse Events

  Treatment emergent adverse events reported by the participant or observed by the Investigator

  Day -28 to Day 8

• Change from Baseline in Physical Examination

  Any change in appearance, eyes, ears, nose, head, throat, neck, chest, lungs, heart, abdomen, extremities, skin, and neurologic examination including mental status from the screening physical to the physical on Day 8

  Day -28 to Day 8

• Change in Baseline Vital Signs

  Any change in vital signs will include blood pressure and heart rate at supine position after the participant has sat quietly for at least 5 minutes, from screening to Day 8.

  Day -28 to Day 8

• Concomitant Medication Use

  Change in use of concomitant medication taken from screening to after the IP administration

  Day -1 to Day 8

• Change in QTcF Determined by Electrocardiogram

  Any change in the QTcF from screening determined significant by the Investigator.

  Day -28 to Day 8

Secondary Outcomes (8)

• Cmax

  Blood will be drawn from each patient prior to the start of the infusion, at 30, 60, 75, 90, 105, 120, 150, and 180 minutes after the infusion as well as at 4, 6, 8, 12, 24, 36, and 48 hours after the infusion.

• Tmax

  Blood will be drawn from each patient prior to the start of the infusion, at 30, 60, 75, 90, 105, 120, 150, and 180 minutes after the infusion as well as at 4, 6, 8, 12, 24, 36, and 48 hours after the infusion.

• AUC(0-t)

  Blood will be drawn from each patient prior to the start of the infusion, at 30, 60, 75, 90, 105, 120, 150, and 180 minutes after the infusion as well as at 4, 6, 8, 12, 24, 36, and 48 hours after the infusion.

• AUC(inf)

  Blood will be drawn from each patient prior to the start of the infusion, at 30, 60, 75, 90, 105, 120, 150, and 180 minutes after the infusion as well as at 4, 6, 8, 12, 24, 36, and 48 hours after the infusion.

• Elimination rate constant (λz)

  Blood will be drawn from each patient prior to the start of the infusion, at 30, 60, 75, 90, 105, 120, 150, and 180 minutes after the infusion as well as at 4, 6, 8, 12, 24, 36, and 48 hours after the infusion.

Study Arms (2)

Treatment Arm 1

EXPERIMENTAL

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

Drug: NTS-104 TRIS

Treatment Arm 2

PLACEBO COMPARATOR

Single administration of placebo at the same volume and duration

Drug: Placebo

Interventions

NTS-104 TRIS 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

Also known as: IP

Treatment Arm 1

Placebo 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

Also known as: Buffer

Treatment Arm 2

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants who provide written informed consent to participate in the study.
• Healthy males and females between 18 and 65 years (inclusive) of age at the time of signing informed consent.
• Body mass index (BMI) of 18 to 32 kg/m2 (inclusive) and weighing at least 50 kg at screening.
• 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.
• 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.
• 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)

You may not qualify if:

• History of significant medical disorder that, in the opinion of the Investigator, contraindicates administration of the study medications.
• 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
• 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
• Any acute illness (e.g., acute infection) within 72 hours of study drug administration, if considered of significance by the Investigator.
• Any clinically significant abnormality in safety laboratory tests at screening or admission, in particular a screening TSH test
• Positive human immunodeficiency virus, hepatitis B, or hepatitis C serology at screening.
• Specifically, any history or current diagnosis of hepatic impairment at screening and Day - 1
• Specifically, any history or current diagnosis of renal impairment at screening
• Specifically, a history of type 1 diabetes mellitus or current type 2 diabetes.
• Any abnormality on the neurological examination, at screening or enrollment
• Positive Columbia-Suicide Severity Rating Scale (C-SSRS).
• Participation in another clinical trial with drugs received within 3 months prior to dosing (calculated from the previous study's last dosing date).
• 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.
• The use of ketogenic diets within 12 months prior to enrollment.
• Electrocardiogram (ECG) with clinically significant findings recorded at screening or admission.

Sponsors & Collaborators

• NeuroTrauma Sciences, LLC: lead
• Parexel: collaborator

Study Sites (1)

Parexel International EPCU Baltimore 7th floor

Baltimore, Maryland, 21225, United States

RECRUITING

MeSH Terms

Conditions

Ischemic Stroke

Interventions

Buffers

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Laboratory Chemicals; Specialty Uses of Chemicals; Chemical Actions and Uses

Study Officials

• Marc de Somer, MD

  NeuroTrauma Sciences, LLC

  STUDY DIRECTOR

Central Study Contacts

Marilyn S Dar

CONTACT

18455361733; m.dar@neurotraumasciences.com

Tina Lamidi

CONTACT

240-506-4435; tina.lamidi@parexel.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Single ascending doses with review of safety, tolerability and pk prior to next dose level

Study Record Dates

• First Submitted: September 12, 2022
• First Posted: September 21, 2022
• Study Start: April 28, 2023
• Primary Completion: July 27, 2023
• Study Completion: August 7, 2023
• Last Updated: May 26, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)