A Phase 1 Trial of LH-001 vs Placebo in Healthy Participants

Chien-Liang Lin

Status and phase: Begins enrollment this month; Phase 1

Conditions: Healthy

Treatments: Drug: Placebo; Drug: LH-001

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT06546449

2024W0061

1U01AG068822-01 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

The purpose of this clinical trial is to evaluate the safety and tolerability of LH-001 when administered as an oral, single or multiple dose(s) at ascending dose levels in healthy participants.

Full description

This is a first-in-human, randomized, double-blinded, placebo-controlled study. This study consists of two parts: (1) single ascending doses in 4 cohorts (SAD) and (2) 14-day multiple ascending doses in 3 cohorts (MAD). Cohorts may be added or removed if needed due to safety considerations or deviations of actual PK parameters from predicted values.

The SAD study consists of a screening visit, a 2-day inpatient stay (Day 1-2), a return visit for safety assessments on Day 3 and 4, and a follow-up by phone on Day 8.

The MAD study consists of a screening visit, a 2-day inpatient stay (Day 1-2), daily return for dosing and safety assessments (Day 3-13), a 2-day inpatient stay (Day 14-15), and a follow-up by phone (Day 21).

Enrollment: 56 estimated patients

Sex: All

Ages: 18 to 60 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• 1. Healthy males or females aged 18-60 years 2. Must provide written informed consent 3. Physically and mentally able and willing to participate in the safety and other assessments including staying overnight 4. BMI 18-26 kg/m2 5. Sexually active male participants, sexually active female participants of childbearing potential, and their sexual partners are to adhere to the contraception requirements. These requirements include utilizing highly effective birth control (including hormonal methods, intrauterine devices, and/or barrier methods) from the screening phase through the completion of the last study follow-up. Note, the barrier method may not be used as a standalone method and must be combined with an additional approved method.

Exclusion criteria

• 1. History or presence of gastrointestinal, renal, or hepatic disease or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs 2. History or presence of major disorder of any other major organ system (cardiovascular, respiratory, central nervous system, or endocrine system) 3. History or presence of cancer 4. Any clinically important illness, medical/surgical procedure, or trauma within 4 weeks prior to dosing 5. History or presence of alcohol or substance abuse 6. History of chronic or current use of recreational or illicit drugs 7. History of, or treatment for, major psychiatric illness 8. History of, or treatment for, seizures or epilepsy 9. Pregnant or breast-feeding females 10. History of, or treatment for, an autoimmune disease (e.g., Rheumatoid Arthritis, Multiple Sclerosis, Myasthenia Gravis, etc.) 11. History of asplenia, hyposplenia, or splenectomy 12. History or presence of drug hypersensitivity 13. Poor venous access 14. Receipt of investigational therapy within 4 months prior to screening 15. Current or previous use of systemic corticosteroids or other systemic immunosuppressive agents 4 weeks prior to dosing 16. Current or previous use of NMDA antagonists 4 weeks prior to dosing 17. Clinically significant findings in the opinion of the investigator in the laboratory, physical examination, or vital sign assessments 18. Evidence of active Hepatitis B, Hepatitis C, or HIV on laboratory testing 19. Any clinically significant ECG abnormality in the opinion of the investigator 20. Plasma or blood donation within the last 4 weeks 21. Positive drug or alcohol screen 22. Any contraindication to or unable to tolerate a LP, for those who consented to the procedure, including the use of anti-coagulant medications. Daily administration of 81 mg aspirin will be allowed 23. Any concurrent condition that, in the opinion of the investigator, would interfere with the evaluation of LH-001 24. Participants who answer "Yes" on the C-SSRS Suicidal Ideation Item 4 (Active Suicidal Ideation with Some Intent to Act, Without Specific Plan) and whose most recent episode meeting criteria for this C-SSRS Item 4 occurred within the last 6 months, OR Subjects who answer "Yes" on the C-SSRS Suicidal Ideation Item 5 (Active Suicidal Ideation with Specific Plan and Intent) and whose most recent episode meeting criteria for this CSSRS Item 5 occurred within the last 6 months OR Subjects who answer "Yes" on any of the 5 C-SSRS Suicidal Behavior Items (actual attempt, interrupted attempt, aborted attempt, preparatory acts, or behavior) and whose most recent episode meeting criteria for any of these 5 C-SSRS Suicidal Behavior Items occurred in the last 2 years

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Quadruple Blind

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56 participants in 9 patient groups, including a placebo group

SAD Cohort 1

Experimental group

Description:

Participants will be administered a single 12.5 mg dose of LH-001

Treatment:

Drug: LH-001

SAD Cohort 2

Experimental group

Description:

Participants will be administered a single 25 mg dose of LH-001

Treatment:

Drug: LH-001

SAD Cohort 3

Experimental group

Description:

Participants will be administered a single 50 mg dose of LH-001

Treatment:

Drug: LH-001

SAD Cohort 4

Experimental group

Description:

Participants will be administered a single 100 mg dose of LH-001

Treatment:

Drug: LH-001

MAD Cohort 1

Experimental group

Description:

Participants will be administered multiple 25 mg doses of LH-001

Treatment:

Drug: LH-001

MAD Cohort 2

Experimental group

Description:

Participants will be administered multiple 50 mg doses of LH-001

Treatment:

Drug: LH-001

MAD Cohort 3

Experimental group

Description:

Participants will be administered multiple 100 mg doses of LH-001

Treatment:

Drug: LH-001

SAD Placebo cohorts 1, 2, 3 and 4

Placebo Comparator group

Description:

Participants will be administered a single dose of placebo

Treatment:

Drug: Placebo

MAD Placebo cohorts 1, 2 and 3

Placebo Comparator group

Description:

Participants will be administered multiple doses of placebo

Treatment:

Drug: Placebo