Leucettinib-21 First-in-Human Phase 1 in Healthy Volunteers and Subjects With Down Syndrome and Alzheimer's Disease

NCT06206824 | Recruiting Phase 1

• 2 other identifiers: OP1125222023-507075-22
• Study Type: interventional
• Target: 164
• Locations: 1 country
• Sites: 1

Brief Summary

Leucettinib-21 First-in-Human Phase 1 Study in 6 Parts: Single (Part 1 and 5) and Multiple (Part 3 and 6) Ascending Doses, and Food-Effect (Part 2) in Healthy Subjects, and Single Dose (Part 4) in People with Down Syndrome (DS) and Alzheimer's Disease (AD). For Parts 1, 3, 4, 5 and 6, safety and tolerability of an oral administration of Leucettinib-21 will be assessed as primary objectives. Pharmacokinetics and pharmacodynamic biomarkers will be investigated as secondary objectives. For Part 2, the effect of high fat meal will be evaluated on the pharmacokinetics parameters after an oral administration of Leucettinib-21.

Conditions

Healthy Volunteers; Down Syndrome; Alzheimer's Disease

Outcome Measures

Primary Outcomes (6)

• Part 1 : Safety and tolerability of Leucettinib-21 after single administration at 6 increasing doses in healthy male subjects.

  Assessment of systemic tolerability and safety

  Part 1 : Up to 8 days following administration

• Part 2 : Effect of food on the PK parameters after an oral administration of Leucettinib-21 in healthy male subjects in high fat breakfast condition vs. under fasted conditions.

  Plasma PK assessments

  Part 2 : Up to 8 days following administration

• Part 3 : Safety and tolerability of Leucettinib-21 after multiple administration at 3 increasing doses in healthy male subjects

  Assessment of systemic tolerability and safety

  Part 3 : Up to 21 days following administration

• Part 4 : Safety and tolerability of Leucettinib-21 after single administration at 1 dose in Down Syndrome individuals and patients with Alzheimer's disease

  Assessment of systemic tolerability and safety

  Part 4 : Up to 8 days following administration

• Part 5 : Number of participants with treatment-related adverse events after single administration of Leucettinib-21 at 3 increasing doses in healthy male and female subjects.

  Assessment of systemic tolerability and safety: * Adverse Events * Vital signs * Physical examination * ECG * Biological tests

  Part 5 : Up to 8 days following administration

• Part 6 : Number of participants with treatment-related adverse events after repeated administration of Leucettinib-21 at 1 dose for 14 days in healthy male subjects

  Assessment of systemic tolerability and safety: * Adverse Events * Vital signs * Physical examination * ECG * Biological tests * Psychometric tests (REST-SPER / FOCU SHIF) * Insulin, glucagon and somatostatin dosage * NT-pro BNP and troponin

  Part 6 : Up to 21 days following administration

Secondary Outcomes (3)

• PK of Leucettinib-21

  Up to 24 hours following Leucettinib-21 administration

• PD of Leucettinib-21

  Up to 4 hours following Leucettinib-21 administration

• Activity of DYRK1A

  Up to 8 hours following Leucettinib-21 administration

Study Arms (6)

Part 1 : Single Ascending Doses in Healthy Volunteers

EXPERIMENTAL

A total of 48 healthy male volunteers will be randomized into six consecutive single ascending dose cohorts of 8 subjects, 6 receiving one dose of Leucettinib-21 and 2 receiving placebo.

Drug: Leucettinib-21

Part 2 : Food-Effect in Healthy Volunteers

EXPERIMENTAL

A total of 12 healthy male volunteers will be randomly assigned to one of two sequences in this cross over study part. All subjects will receive the same one dose of Leucettinib-21 in each sequence.

Drug: Leucettinib-21

Part 3 : Multiple Ascending Doses over 14 days in Healthy Volunteers

EXPERIMENTAL

A total of 36 healthy male volunteers will be randomized into three consecutive multiple ascending doses cohorts of 12 subjects, 9 receiving one dose of Leucettinib-21 and 3 receiving placebo everyday for 14 days.

Drug: Leucettinib-21

Part 4 : Single Dose in People with Down Syndrome and Alzheimer's Disease

EXPERIMENTAL

A total of 12 people with Down Syndrome and 12 people with Alzheimer's Disease will receive the same one dose of Leucettinib-21.

Drug: Leucettinib-21

Part 5 : Single Ascending Doses in Healthy Volunteers

EXPERIMENTAL

A total of 32 healthy volunteers will be randomized into three consecutive single ascending dose cohorts, of 16 male and female subjects for the first cohort, 12 receiving one dose of Leucettinib-21 and 4 receiving placebo, and 8 male subjects for the two following cohorts, 6 receiving one dose of Leucettinib-21 and 2 receiving placebo.

Drug: Leucettinib-21

Part 6 : Single dose over 14 days in Healthy Volunteers

EXPERIMENTAL

A total of 12 healthy male volunteers will be randomized into one cohort of 12 subjects, 9 receiving one dose of Leucettinib-21 and 3 receiving placebo everyday for 14 days.

Drug: Leucettinib-21

Interventions

Leucettinib-21 DRUG

See arm's description.

Part 1 : Single Ascending Doses in Healthy Volunteers; Part 2 : Food-Effect in Healthy Volunteers; Part 3 : Multiple Ascending Doses over 14 days in Healthy Volunteers; Part 4 : Single Dose in People with Down Syndrome and Alzheimer's Disease; Part 5 : Single Ascending Doses in Healthy Volunteers; Part 6 : Single dose over 14 days in Healthy Volunteers

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Part 5: Healthy male and female aged to 18-55 years inclusive / Part 6: Healthy male aged to 18-55 years inclusive
• Part 1, 2, 3, 5 \& 6 for males: Must agree to adhere to the contraception requirements: use of condom by the male subject plus an effective method of contraception for the subject partner of childbearing potential from the time of informed consent signature up to 4 months after last IMP administration. Highly effective method of birth control such as combined hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), intra uterine devices (IUDs), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, true abstinence is acceptable when it is in line with the subject's preferred and usual lifestyle) / Part 5 for females of childbearing potential: Must agree to adhere to the contraception requirements: use for the subject of a highly effective method of birth control (defined as methods that can achieve a failure rate less than 1per 100 per year when used consistently and correctly) restricted to non-hormonal intra uterine device or non-hormonal intra uterine system, vasectomized partner and use of a second form of contraception. Hormonal methods of contraception whichever the mode of administration are not permitted. The following acceptable methods can be used as a second form of contraception during the study: partner's use of a condom or the subject's use of an occlusive cap \[diaphragm or cervical/vault caps\] with spermicidal foam, gel, film, cream, or suppository from the time of informed consent signature and for 4 months after the last study drug administration. True sexual abstinence when this is in line with the preferred and usual lifestyle of the subject is acceptable. Periodic abstinence (e.g., calendar ovulation, symptothermal, post-ovulation methods), declaration of abstinence for the duration of the trial and withdrawal are NOT acceptable methods of contraception / Part 5 for females of non-childbearing potential: female subjects who are postmenopausal (defined as spontaneous amenorrhea for at least 1 year or spontaneous amenorrhea for at least 6 months confirmed by follicle-stimulating hormone \[FSH\] result of ≥ 40 IU/mL) are eligible for this study and female subjects with surgical sterilization (i.e., bilateral tubal ligation/salpingectomy, hysterectomy) also;
• Non-smoker subject or smoker of not more than 5 cigarettes a day;
• Parts 1, 2, 3 \& 6: Body Mass Index (BMI) between 18.5 and 28,0 (kg/m2) inclusive, with body weight between 60 and 100 kg inclusive, at Screening and Day -1 / Part 5: Body Mass Index (BMI) between 18.5 and 28,0 (kg/m2) inclusive, with body weight between 50 and 100 kg inclusive, at Screening and Day -1;
• Considered as healthy after a comprehensive clinical assessment (detailed medical history and complete physical examination);
• Normal Blood Pressure (BP), oxygen saturation and Heart Rate (HR) at the screening visit after 10 minutes in supine position:
• mmHg ≤ Systolic Blood Pressure (SBP) ≤ 140 mmHg,
• mmHg ≤ Diastolic Blood Pressure (DBP) ≤ 90 mmHg,
• bpm ≤ HR ≤ 90 bpm,
• Or considered NCs by investigators;
• Normal ECG recording on a 12-lead ECG at the screening visit:
• ≤ PR \< 210 ms,
• QRS \< 120 ms,
• QTcf ≤ 430 ms for male,
• No sign of any trouble of sinusal automatism,

You may not qualify if:

• Any relevant history or presence of significant diseases that would interfere with the assessment according the population except stabilized pathology with associated treatment for more than 3 months and known in the medical history;
• Patients considered unable to complete study assessments, according the investigator judgment;
• History of cancer in the past 5 years;
• History of inflammatory disease with potential for central nervous system involvement;
• Positive urine drug testing or alcohol testing at Screening or Day -1;
• Positive Hepatitis B surface (HBs) antigen or anti Hepatitis C Virus (HCV) antibody, or positive results for Human Immunodeficiency Virus (HIV) 1 or 2 tests.

Sponsors & Collaborators

• Perha Pharmaceuticals: lead
• France 2030 program: collaborator
• European Innovation Council: collaborator
• Fondation Jérôme Lejeune: collaborator

Study Sites (1)

Eurofins Optimed

Gières, 38610, France

RECRUITING

MeSH Terms

Conditions

Down Syndrome; Alzheimer Disease

Condition Hierarchy (Ancestors)

Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn; Dementia; Brain Diseases; Central Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Central Study Contacts

Laurent MEIJER, Dr

CONTACT

+33(0)608605834; meijer@perha-pharma.com

Emilie CHRETIEN, Dr

CONTACT

+33(0)222554572; chretien@perha-pharma.com

Study Design

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

Study Record Dates

• First Submitted: December 20, 2023
• First Posted: January 16, 2024
• Study Start: January 18, 2024
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: December 10, 2025

Record last verified: 2025-12

Locations

FR (1)