Cognitive DysfunctionPhase 1NCT06225115
A Study to Investigate the Safety, Tolerability, and Pharmacokinetics of KYN-5356 in Healthy Subjects Aged 18 to 55 Years
A Phase 1 study testing KYN-5356 in people with Cognitive Dysfunction and Schizophrenia, run by Kynexis B.V. at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Cognitive Dysfunction, Schizophrenia
- What is being tested?
- KYN-5356
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 72 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Dec 2023to 7 Oct 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 21Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Parexel Los Angeles Early Phase Clinical Unit
Glendale, California, 91206
About this study
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
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:
Read more
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
- Being tested
- KYN-5356, placebo
- Medical subject headings
- Cognitive Dysfunction, Schizophrenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KYN-5356Drug
KYN-5356, oral tablet
placeboDrug
placebo, oral tablet
| Study group | Role | What they receive |
|---|---|---|
| SAD Cohort 1 | Experimental | Single-Ascending Dose Cohort 1. Intervention: KYN-5356 A mg or placebo, single dose, oral tablet Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: Drug: KYN-5356; Drug: placebo |
| Food Effect Cohort | Experimental | Intervention: KYN-5356 J mg, single dose, oral tablets in fasted or fed state. Receives: Drug: KYN-5356 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Treatment-Emergent Adverse Events
All cohorts
Measured: 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]
Maximum plasma concentration determined directly from the concentration-time profile. For each dose in SAD part.
Measured: Baseline (predose) through 72 hours post dosing
PK parameters: tmax [SAD]
Time of maximum plasma concentration determined directly from the concentration-time profile. For each dose in SAD part.
Measured: Baseline (predose) through 72 hours post dosing
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.
Measured: Baseline (predose) through 72 hours post dosing
PK parameters: Cmax on Day 1 [MAD]
Maximum plasma concentration determined directly from the concentration-time profile. For each dose in MAD part
Measured: Baseline (predose) through 24 hours post first dosing
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.
Measured: Baseline (predose) through 24 hours post first dosing
PK parameters: Cmax,ss [MAD]
Maximum observed plasma concentration during a dosing interval at steady state. For each dose in MAD part.
Measured: Baseline (predose) through 96 hours post dosing on Day 7.
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.
Measured: Baseline (predose) through 96 hours post dosing on Day 7.
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
Measured: Baseline (predose) through 96 hours post dosing on Day 7.
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.
Measured: Baseline (predose) through 96 hours post dosing on Day 7.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jan 2024
- Study start21 Dec 2023
- Primary completion7 Oct 2024
- Study completion7 Oct 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cognitive DysfunctionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 72 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kynexis B.V.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Parexel
- Responsible party
- Sponsor
- Investigators
- Hakop Gevorkyan, MD, MBA, Principal investigator, Parexel
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06225115
- Sponsor's protocol ID
- KYN5356-CL-001
- Status last verified
- Dec 2024
- First submitted
- 20 Dec 2023
- Last updated
- 4 Dec 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT06225115
- Acronym / sponsor ID
- KYN5356-CL-001
- Conditions
- Cognitive Dysfunction, Schizophrenia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 72 participants (actual)
- Lead sponsor
- Kynexis B.V.Industry (pharma, biotech, devices)
- Collaborators
- Parexel
- Study start
- 21 Dec 2023 (actual)
- Primary completion
- 7 Oct 2024 (actual)
- Study completion
- 7 Oct 2024 (actual)
- First posted
- 25 Jan 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 9
| Arm | Type | Receives |
|---|---|---|
| SAD Cohort 1 | Experimental | Drug: KYN-5356, Drug: placeboSingle-Ascending Dose Cohort 1. Intervention: KYN-5356 A mg or placebo, single dose, oral tablet |
| SAD Cohort 2 | Experimental | Drug: KYN-5356, Drug: placeboSingle-Ascending Dose Cohort 2. Intervention: KYN-5356 B mg or placebo, single dose, oral tablet |
| SAD Cohort 3 | Experimental | Drug: KYN-5356, Drug: placeboSingle-Ascending Dose Cohort 3. Intervention: KYN-5356 C mg or placebo, single dose, oral tablet |
| SAD Cohort 4 | Experimental | Drug: KYN-5356, Drug: placeboSingle-Ascending Dose Cohort 4. Intervention: KYN-5356 D mg or placebo, single dose, oral tablet |
| SAD Cohort 5 | Experimental | Drug: KYN-5356, Drug: placeboSingle-Ascending Dose Cohort 5. Intervention: KYN-5356 E mg or placebo, single dose, oral tablet |
| MAD Cohort 1 | Experimental | Drug: KYN-5356, Drug: placeboMultiple-Ascending Dose Cohort 1. Intervention: KYN-5356 G mg or placebo, oral tablets for 7 days |
| MAD Cohort 2 | Experimental | Drug: KYN-5356, Drug: placeboMultiple-Ascending Dose Cohort 2. Intervention: KYN-5356 H mg or placebo, oral tablets for 7 days |
| MAD Cohort 3 | Experimental | Drug: KYN-5356, Drug: placeboMultiple-Ascending Dose Cohort 3. Intervention: KYN-5356 I mg or placebo, oral tablets for 7 days |
| Food Effect Cohort | Experimental | Drug: KYN-5356Intervention: KYN-5356 J mg, single dose, oral tablets in fasted or fed state. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (21 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| KYN-5356KYN-5356, oral tablet | Drug | 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 |
| placeboplacebo, oral tablet | Drug | MAD Cohort 1, MAD Cohort 2, MAD Cohort 3, SAD Cohort 1, SAD Cohort 2, SAD Cohort 3, SAD Cohort 4, SAD Cohort 5 |
Primary outcome
Treatment-Emergent Adverse Events
Time frame: 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
All cohorts
9 secondary outcomes
PK parameters: Cmax [SAD]
Time frame: Baseline (predose) through 72 hours post dosing
PK parameters: tmax [SAD]
Time frame: Baseline (predose) through 72 hours post dosing
PK parameters: AUCinf [SAD]
Time frame: Baseline (predose) through 72 hours post dosing
PK parameters: Cmax on Day 1 [MAD]
Time frame: Baseline (predose) through 24 hours post first dosing
PK parameters: tmax on Day 1 [MAD]
Time frame: Baseline (predose) through 24 hours post first dosing
PK parameters: Cmax,ss [MAD]
Time frame: Baseline (predose) through 96 hours post dosing on Day 7.
PK parameters: tmax,ss [MAD]
Time frame: Baseline (predose) through 96 hours post dosing on Day 7.
PK parameters: AUCtau on Days 1 and 7 [MAD]
Time frame: Baseline (predose) through 96 hours post dosing on Day 7.
PK parameters: AUCinf [MAD]
Time frame: Baseline (predose) through 96 hours post dosing on Day 7.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Dec 2024.
- Individual participant dataSharing planned: No
Related trials for Cognitive Dysfunction
Recruiting
Early Motor-Cognitive Integrative Training on Cognitive and Motor Performance in Patients With Aneurysmal Subarachnoid Hemorrhage
Subarachnoid Aneurysm Hemorrhage
Recruiting
HEARS-NPS: Addressing Hearing Loss as a Common Unmet Contributor of Neuropsychiatric Symptoms
Alzheimer Disease, Dementia
RecruitingObservational study
Locus Coeruleus and CCHS (Congenital Central Hypoventilation Syndrome)
Ondine Syndrome (Congenital Central Hypoventilation Syndrome)
RecruitingPhase 1
PET Imaging of Phosphodiesterase-4 (PDE4) in Volunteers With Alzheimer Disease (AD) or Mild Cognitive Impairment (MCI)
Alzheimer s Disease, Mild Cognitive Impairment
RecruitingObservational study
Community-based Screening for Alzheimer's Disease
Alzheimer's Disease(AD), Mild Cognitive Impairment (MCI)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hakop Gevorkyan, MD, MBA principal investigator
Parexel
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing KYN-5356 in people with Cognitive Dysfunction and Schizophrenia, run by Kynexis B.V. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Treatment-Emergent Adverse Events (time frame: 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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Dec 2024.