A Study to Evaluate the Safety, Tolerability, and Efficacy of CB03-154 in Adult Patients With Focal Epilepsy

NCT06612775 | Not Yet Recruiting Phase 2

• 1 other identifier: CB03-154-EP201
• Study Type: interventional
• Target: 180
• Locations: 0 countries
• Sites: N/A

Brief Summary

CB03-154 is an investigational drug developed by Shanghai Zhimeng Biopharma Inc. for the treatment of Focal Epilepsy.

Conditions

Focal Epilepsy

Outcome Measures

Primary Outcomes (2)

• To assess the efficacy of CB03-154 compared to placebo on focal seizure frequency in adults with focal epilepsy taking 1 to 3 AEDs in the double-blind period (DBP).

  Median percent change (MPC) in monthly (28 days) focal seizure frequency from baseline to the entire period of DBP for CB03-154 versus placebo.

  From baseline to the entire period of double-blind period, assessed up to 20 weeks.

• To assess the safety and tolerability by evaluating the frequency and severity of adverse events (AEs) /serious adverse events (SAEs) of CB03-154 in adults with focal epilepsy taking 1 to 3 AEDs in the DBP.

  Severity and frequency/incidence of associated AEs/serious adverse events (SAEs).

  From the entire period of double-blind period of 12 weeks to the post-treatment follow-up period of 2 weeks(+7 days), assessed up to 17 weeks.

Secondary Outcomes (6)

• To evaluate the 50% CB03-154 response rates in comparison to placebo in the DBP.

  From baseline to the entire period of double-blind period, assessed up to 20 weeks.

• To evaluate trends in focal seizure frequency over time in the DBP.

  From baseline to the entire period of double-blind period, assessed up to 20 weeks.

• Maximum Plasma Concentration (Cmax).

  On Day 7, Day 15, Day 29, and Day 85 in the period of double-blind period.

• Use the Hamilton Depression Rating Scale (HAMD-17) to assess the effect of CB03-154 vs placebo on seizure severity and impact in adults with focal epilepsy taking 1 to 3 AEDs in the DBP.

  In the entire period of double-blind period, assessed up to 12 weeks.

• Clinical Global Impression of Change (CGI-C) scores during the DBP.

  In the entire period of double-blind period, assessed up to 12 weeks.

Study Arms (4)

CB03-154 5mg and Placebo 15mg

EXPERIMENTAL

Participants will receive CB03-154 5mg and Placebo 15mg orally once daily for 12 weeks.

Drug: Test drug CB03-154 5mg group

CB03-154 10mg and Placebo 10mg

EXPERIMENTAL

Participants will receive CB03-154 10mg and Placebo 10mg orally once daily for 12 weeks.

Drug: Test drug CB03-154 10mg group

CB03-154 20mg

EXPERIMENTAL

Participants will receive CB03-154 20mg orally once daily for 12 weeks.

Drug: Test drug CB03-154 20mg group

Placebo 20mg

PLACEBO COMPARATOR

Participants will receive Placebo 20mg orally once daily for 12 weeks.

Drug: Placebo group

Interventions

Test drug CB03-154 5mg group DRUG

CB03-154 tablet (5mg/tablet) once daily.

CB03-154 5mg and Placebo 15mg

Test drug CB03-154 10mg group DRUG

Two CB03-154 tablets (5mg/tablet) once daily.

CB03-154 10mg and Placebo 10mg

Test drug CB03-154 20mg group DRUG

Four CB03-154 tablets (5mg/tablet) once daily.

CB03-154 20mg

Placebo group DRUG

Four Placebo tablets once daily.

Placebo 20mg

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability of the subjects or his/her authorized representative be fully informed of the nature and risks of the study and give informed consent in writing prior to entering the study.
• Male and female aged 18 to 70 years, inclusive.
• kg/m2 ≤BMI ≤ 34.0 kg/m2.
• Diagnosis (≥2 years) of focal epilepsy according to the International League Against Epilepsy \[ILAE\] Classification of Epilepsy (2017).
• Prior neuroimaging within the last 5 years and documentation are available to rule out progressive structural central nervous system abnormalities at the time of the diagnosis of epilepsy.
• Treatment with a stable dose of 1 to 3 allowable current AEDs for at least one month prior to screening, during baseline, and throughout the duration of the DBP.
• Prior to screening and during baseline period, subjects must have at least 6 focal seizures without status epilepticus, with or without focal to bilateral tonic-clonic.
• If a female, must be:
• Postmenopausal, defined as amenorrhea for at least 12 months, and confirmed by blood follicle stimulating hormone (FSH) at Screening, OR
• Surgically sterile with a documented hysterectomy, partial hysterectomy, bilateral oophorectomy, or bilateral tubal ligation at least 6 months prior to Screening, OR
• If of child-bearing potential, heterosexually active females with male partners must be using an acceptable and highly effective method of contraception at least one menstrual cycle before first study drug administration and continuing until at least 3 months after the last dose of the study drug. If a female subject is abstinent, she must agree to use an acceptable and highly effective form of birth control as above once she becomes heterosexually active during the study.
• If a female of child-bearing potential, must have a negative pregnancy test result at Screening and Check-in.
• If a male, if heterosexually sexually active with a female partner of child-bearing potential and has not had a vasectomy, must agree to use a highly effective method of contraception and deemed appropriate by the Investigator and must not donate sperm during the study and for 3 months after the last dose of study drug.
• Able to keep accurate seizure diaries.

You may not qualify if:

• Subject has had documented previous EEGs indicating other patterns of epilepsy besides the focal epilepsy prior to dosing the study drug.
• Subject has seizures secondary to drugs or alcohol use, ongoing infection, metabolic diseases or progressive central nervous system diseases or lesions at the investigator's assessments.
• Subject has the history of pseudo seizures, conversion disorders, or other non-epileptic seizure conditions, or other non-epileptic ictal events that could be confused with seizures at the investigator's discretion and/or EEG evidence.
• Subject has the presence or previous history of Lennox-Gastaut syndrome, some other related syndrome or evidence of both focal and generalized epilepsy at investigator's decisions.
• Subject has the history of status epilepticus within 6 months prior to screening.
• Subject has only uncountably repetitive seizures occurring within 6 months prior to screening.
• Subject has the history of neurosurgery for seizures \<1 year prior to enrolment, or radiosurgery \<2 years prior to enrolment. Subjects has the implantment and activation of vagus nerve stimulation (VNS), deep brain stimulation (DBS), or other neurostimulation for epilepsy treatment \<1 year prior to enrolment, or with stimulation parameters that have been stable for \<3 months prior to enrolment, or with anticipated left battery lifetime shorter than trial duration.
• Subject has any of the following findings will be excluded:
• A history or family history of unexplained syncope;
• A history of presence of long QT syndrome; QTcF \> 450 msec prior to first dose of the study drug; a family history of long QT syndromes or sudden death of unknown cause;
• Bundle branch blocks or atrioventricular or other conduction abnormalities that are clinically significant according to the Investigator and/or with a PR interval ≥220ms, or HR\<50bpm at rest in ECGs or vital signs, prior to first dose of the study drug;
• A history of venous thrombosis, or a history or presence of medical conditions indicating unresolved high risks of thrombophilia or hypercoagulability including but not limited to protein C deficiency, protein S deficiency, antithrombin deficiency, antiphospholipid syndrome, Budd-Chiari syndrome, myeloproliferative neoplasm including Chronic myeloid leukemia (CML), polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF), autoimmune diseases (especially systemic lupus erythematosus (SLE) or antiphospholipid syndrome or vasculitis), nephrotic syndrome, paroxysmal nocturnal hemoglobinuria, uncured malignancy, unstoppable estrogen containing oral or injection contraception or hormone replacement therapy, postpartum period within 2 months, or other medical conditions at the investigator and the medical monitor's judgements;
• Venous ultrasound examinations on bilateral lower extremes indicating DVT;
• The estimated glomerular filtration rate (eGFR) at screening is \<60mL/min and the calculated result of female is ×0.85.
• Subject has any clinically significant abnormalities on physical examination, vital signs, laboratory tests or ECG prior to first dose of the study drug which could jeopardize or would compromise the subject's safety or ability to participate in this study as deemed by the Investigator and the Medical monitor.

Sponsors & Collaborators

• Shanghai Zhimeng Biopharma, Inc.: lead

MeSH Terms

Conditions

Epilepsies, Partial

Interventions

Population Groups

Condition Hierarchy (Ancestors)

Epilepsy; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Demography; Population Characteristics

Study Design

• Study Type: interventional
• Phase: phase 2
• 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: September 19, 2024
• First Posted: September 25, 2024
• Study Start: September 1, 2024
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: September 25, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share