A Study to Investigate the Safety, Tolerability, and Pharmacokinetics of KYN-5356 in Healthy Subjects Aged 18 to 55 Years

NCT06225115 | Completed Phase 1 FDA Drug

• 1 other identifier: KYN5356-CL-001
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

This first-in-human clinical trial with a randomized, double-blind, placebo-controlled, dose-escalation study design is regarded as standard to test the safety, tolerability, and pharmacokinetics of KYN-5356. The study comprises 3 parts: Part 1: Single Ascending Dose study Part 2: Multiple Ascending Dose study Part 3: Food Effect study The aim of Parts 1 and 2 of the study is to evaluate the safety and tolerability following single and multiple ascending doses of KYN-5356. The secondary aim is to evaluate the pharmacokinetics (PK) of escalating single and multiple doses of KYN-5356. In Part 2, cerebrospinal fluid will be sampled to explore PK and pharmacodynamic effects of KYN-5356. The potential effect of food intake on the disposition of KYN-5356 following a single oral dose will be evaluated in Part 3. Part 3 is an open-label, randomized, 2 period, 2 sequence design.

Conditions

Cognitive Dysfunction; Schizophrenia

Outcome Measures

Primary Outcomes (1)

• Treatment-Emergent Adverse Events

  All cohorts

  Initiation of dosing through the last follow-up visit after the last dose, approximately 8 days in the MAD and 5 days after dosing in the SAD and the Food Effect parts of the study

Secondary Outcomes (9)

• PK parameters: Cmax [SAD]

  Baseline (predose) through 72 hours post dosing

• PK parameters: tmax [SAD]

  Baseline (predose) through 72 hours post dosing

• PK parameters: AUCinf [SAD]

  Baseline (predose) through 72 hours post dosing

• PK parameters: Cmax on Day 1 [MAD]

  Baseline (predose) through 24 hours post first dosing

• PK parameters: tmax on Day 1 [MAD]

  Baseline (predose) through 24 hours post first dosing

Study Arms (9)

SAD Cohort 1

EXPERIMENTAL

Single-Ascending Dose Cohort 1. Intervention: KYN-5356 A mg or placebo, single dose, oral tablet

Drug: KYN-5356; Drug: placebo

SAD Cohort 2

EXPERIMENTAL

Single-Ascending Dose Cohort 2. Intervention: KYN-5356 B mg or placebo, single dose, oral tablet

Drug: KYN-5356; Drug: placebo

SAD Cohort 3

EXPERIMENTAL

Single-Ascending Dose Cohort 3. Intervention: KYN-5356 C mg or placebo, single dose, oral tablet

Drug: KYN-5356; Drug: placebo

SAD Cohort 4

EXPERIMENTAL

Single-Ascending Dose Cohort 4. Intervention: KYN-5356 D mg or placebo, single dose, oral tablet

Drug: KYN-5356; Drug: placebo

SAD Cohort 5

EXPERIMENTAL

Single-Ascending Dose Cohort 5. Intervention: KYN-5356 E mg or placebo, single dose, oral tablet

Drug: KYN-5356; Drug: placebo

MAD Cohort 1

EXPERIMENTAL

Multiple-Ascending Dose Cohort 1. Intervention: KYN-5356 G mg or placebo, oral tablets for 7 days

Drug: KYN-5356; Drug: placebo

MAD Cohort 2

EXPERIMENTAL

Multiple-Ascending Dose Cohort 2. Intervention: KYN-5356 H mg or placebo, oral tablets for 7 days

Drug: KYN-5356; Drug: placebo

MAD Cohort 3

EXPERIMENTAL

Multiple-Ascending Dose Cohort 3. Intervention: KYN-5356 I mg or placebo, oral tablets for 7 days

Drug: KYN-5356; Drug: placebo

Food Effect Cohort

EXPERIMENTAL

Intervention: KYN-5356 J mg, single dose, oral tablets in fasted or fed state.

Drug: KYN-5356

Interventions

KYN-5356 DRUG

KYN-5356, oral tablet

Food Effect Cohort; MAD Cohort 1; MAD Cohort 2; MAD Cohort 3; SAD Cohort 1; SAD Cohort 2; SAD Cohort 3; SAD Cohort 4; SAD Cohort 5

placebo DRUG

placebo, oral tablet

MAD Cohort 1; MAD Cohort 2; MAD Cohort 3; SAD Cohort 1; SAD Cohort 2; SAD Cohort 3; SAD Cohort 4; SAD Cohort 5

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subject understands the study procedures and agrees to participate by providing written informed consent prior to any study procedures.
• Subject is between 18 and 55 years of age (inclusive), on the date of signing the informed consent form.
• Subject has a body mass index between 18 and 30 kg/m2, inclusive.
• A female subject is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: Not a woman of childbearing potential or a woman of childbearing potential who agrees to follow the contraceptive guidance (highly effective birth control method) from Screening until end of the study. Note: Males should use appropriate contraceptive method from Screening until end of the study.
• Subject is judged to be in good health by the Principal Investigator based upon the results of a medical history, physical examination, vital signs, 12-lead ECG, and clinical laboratory safety tests.
• Subject is willing to adhere to the study requirements and restrictions.

You may not qualify if:

• Subject has positive serology for HBsAg, HCV, or HIV, or history of hepatitis from any cause with the exception of hepatitis A that was resolved at least 3 months prior to first dosing of the Investigational Medicinal Product.
• Subject has any illness judged by the Principal Investigator as clinically significant, in the 3 months prior to first dosing of the Investigational Medicinal Product.
• Subject has a suicidality score of "yes" on item 4 or item 5 of the suicidal ideation section of the C-SSRS, if this ideation occurred in the past 6 months, or "yes" on any item of the suicidal behavior section, except for the "Non-Suicidal Self-Injurious Behavior" (item also included in the suicidal behavior section), if this behavior occurred in the past 2 years.
• Subject has a history or current sign or symptom of psychiatric or neurologic disease.
• Subject has a history of head trauma in the past year and/or current seizures.
• Subject is a smoker (use of tobacco products in the previous 3 months from Screening) or uses nicotine or nicotine-containing products and has a positive urine cotinine test at Screening or Admission.
• Subject has a history of alcohol and/or illicit drug abuse within 2 years of entry or has a positive screening test for alcohol and/or drugs of abuse at Screening or Admission.
• Subject consumes caffeine containing beverages exceeding 500 mg caffeine per day (5 cups of coffee) during the off-site days during the study.
• Subject has regular excessive consumption of alcohol within 6 months prior to Screening (7 drinks/week for females, 14 drinks/week for males where 1 drink = 150 mL of wine or 360 mL of beer or 45 mL of hard liquor).
• Subject has a history or current sign or symptom of a cardiovascular, renal, or metabolic bone disease or disease of bone remodeling, or any history of endocrine disease, including an abnormal laboratory result for pre-specified clinical laboratory safety parameters related to these conditions.
• Subject has a history or presence of clinically significant abnormalities detected on 12-lead ECG of either rhythm or conduction. A first-degree atrioventricular block will not be considered as a significant abnormality. Subject has QTcF \> 450 ms (mean values per parameter will be considered) detected on the 12-lead ECG at Screening or Admission.
• Presence or sequelae of gastrointestinal, liver, kidney (creatinine clearance \<85 mL/min, using the Cockcroft-Gault formula), or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs at Screening or Admission.
• Subject has a history of malignancy within the past 5 years prior to Screening with the exception of excised and curatively treated non-metastatic cell carcinoma of the skin which is considered cured with minimal risk of recurrence.
• Subject tests positive for SARS-CoV-2 at Admission.
• Subject uses any prescription drugs, herbal supplements, within 4 weeks prior to initial dosing, and/or over-the-counter medication, dietary supplements (vitamins included) within 2 weeks prior to initial dosing, other than what is allowed per protocol.

Sponsors & Collaborators

• Kynexis B.V.: lead
• Parexel: collaborator

Study Sites (1)

Parexel Los Angeles Early Phase Clinical Unit

Glendale, California, 91206, United States

Location

MeSH Terms

Conditions

Cognitive Dysfunction; Schizophrenia

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders

Study Officials

• Hakop Gevorkyan, MD, MBA

  Parexel

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2023
• First Posted: January 25, 2024
• Study Start: December 21, 2023
• Primary Completion: October 7, 2024
• Study Completion: October 7, 2024
• Last Updated: December 4, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)