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

Schizophrenia Clinical Trial

Official title:

A First in Human Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Oral Doses of KYN-5356 in Adult, Healthy Subjects

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06225115
• Other study ID #: KYN5356-CL-001
• Status: Recruiting
• Phase: Phase 1
• Start date: December 21, 2023
• Est. completion date: July 2024

Study information

• Verified date: March 2024
• Source: Kynexis B.V.
• Contact: Hakop Gevorkyan, MD, MBA
• Phone: 818-254-1600
• Email: Mike.Proshyan[@]parexel.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: July 2024
• Est. primary completion date: July 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

• Additional exclusion criteria for subjects in the MAD Part in view of lumbar puncture for cerebrospinal fluid (CSF) sampling and the ERP assessment.

• 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.

• Subject received vaccination 1 month before admission or plans to receive vaccination during the study.

• Use of other investigational drugs/devices within 5 half-lives of the drug from enrollment (time of the subject signing the informed consent form), or within 30 days, whichever is longer.

• Donation or loss of 400 mL or more of blood within 8 weeks prior to initial dosing.

• Plasma donation (> 200 mL) within 7 days prior to first dosing.

• Resting vital signs at Screening (blood pressure > 140/90 mmHg, heart rate > 90 beats per minute, respiratory rate > 20 breaths per minute, and clinically significant elevated body temperature), or any clinically significant abnormalities in vital signs requiring intervention in the opinion of the Investigator. Up to 2 repeat measurements are permitted to confirm eligibility.

Related Conditions & MeSH terms

• Cognitive Dysfunction
• Schizophrenia

Intervention

Drug:
• KYN-5356
KYN-5356, oral tablet
• placebo
placebo, oral tablet

Locations

Country	Name	City	State
United States	Parexel Los Angeles Early Phase Clinical Unit	Glendale	California

Sponsors (2)

Lead Sponsor	Collaborator
Kynexis B.V.	Parexel

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	PK parameters: Cmax [SAD]	Maximum plasma concentration determined directly from the concentration-time profile. For each dose in SAD part.	Baseline (predose) through 72 hours post dosing
Secondary	PK parameters: tmax [SAD]	Time of maximum plasma concentration determined directly from the concentration-time profile. For each dose in SAD part.	Baseline (predose) through 72 hours post dosing
Secondary	PK parameters: AUCinf [SAD]	Area under the concentration-time curve from pre-dose (time 0) extrapolated to infinite time calculated using the linear-log trapezoidal rule. For each dose in SAD part.	Baseline (predose) through 72 hours post dosing
Secondary	PK parameters: Cmax on Day 1 [MAD]	Maximum plasma concentration determined directly from the concentration-time profile. For each dose in MAD part	Baseline (predose) through 24 hours post first dosing
Secondary	PK parameters: tmax on Day 1 [MAD]	Time of maximum plasma concentration determined directly from the concentration-time profile. For each dose in MAD part.	Baseline (predose) through 24 hours post first dosing
Secondary	PK parameters: Cmax,ss [MAD]	Maximum observed plasma concentration during a dosing interval at steady state. For each dose in MAD part.	Baseline (predose) through 72 hours post dosing on Day 7.
Secondary	PK parameters: tmax,ss [MAD]	Time of maximum plasma concentration determined directly from the concentration-time profile at steady state. For each dose in MAD part.	Baseline (predose) through 72 hours post dosing on Day 7.
Secondary	PK parameters: AUCinf [MAD]	Area under the concentration-time curve from pre-dose (time 0) extrapolated to infinite time calculated using the linear-log trapezoidal rule. For each dose in MAD part.	Baseline (predose) through 72 hours post dosing on Day 7.
Secondary	PK parameters: AUCtau on Days 1 and 7 [MAD]	Area under the concentration-time curve over the dosing interval. For each dose in MAD part	Baseline (predose) through 72 hours post dosing on Day 7.