A Study to Evaluate the Preliminary Efficacy and Safety of Terfenadine in Patients With Relapsing-Remitting Multiple Sclerosis

Phase 2RecruitingNCT07827716

Chuan Qin100 enrolled

Overview

The goal of this clinical trial is to evaluate the safety and tolerability of terfenadine when added to standard first-line disease-modifying therapy in adults with multiple sclerosis. The study will also explore whether adding terfenadine may help improve disease-related outcomes. Researchers will compare participants who receive terfenadine plus standard first-line disease-modifying therapy with participants who receive standard first-line disease-modifying therapy alone. Participants will: Be randomly assigned to receive either terfenadine plus standard first-line disease-modifying therapy or standard first-line disease-modifying therapy alone. Take terfenadine 60 mg once daily at bedtime for 1 month if assigned to the terfenadine group. Attend study visits during screening, treatment, and follow-up over 12 months. Have physical examinations, vital sign checks, laboratory tests, electrocardiograms, imaging assessments, neurological evaluations, and collection of blood, stool, and cerebrospinal fluid samples at scheduled visits.

Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system that can cause neurological disability and disease progression. Current disease-modifying therapies can reduce relapses and MRI disease activity, but limitations remain in preventing disability progression and promoting remyelination or neuroprotection. Terfenadine is a histamine H1 receptor antagonist. Preclinical evidence suggests that histamine signaling may be involved in immune and inflammatory processes relevant to MS. This study will evaluate the safety and tolerability of terfenadine as an adjunct to standard first-line disease-modifying therapy and explore its potential clinical effects in people with MS. This is a single-center, open-label, randomized controlled clinical trial. Approximately 100 participants will be enrolled and randomly assigned in a 2:1 ratio to a terfenadine treatment group or a control group. Participants in the terfenadine group will receive terfenadine 60 mg orally once daily at bedtime for 1 month in addition to standard first-line disease-modifying therapy. Participants in the control group will receive standard first-line disease-modifying therapy alone. Participants will be followed for 12 months. Study assessments will include physical examinations, vital signs, laboratory tests, electrocardiograms, imaging examinations, neurological and functional assessments, quality-of-life assessments, and collection of blood, stool, and cerebrospinal fluid samples at scheduled visits. Safety will be assessed throughout the study by recording and following adverse events and by reviewing relevant clinical and laboratory findings.

Study Type

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Male or female participants aged 18 to 65 years, inclusive. 2. Diagnosis of multiple sclerosis (MS) according to the 2024 revised McDonald diagnostic criteria. 3. Women of childbearing potential must have a negative pregnancy test and agree to use effective contraception during the study. 4. Participants must be able to understand the study requirements and provide written informed consent. If applicable, informed consent may be provided by the participant's legally authorized representative. Exclusion Criteria: 1. Use of drugs that may interact with terfenadine through CYP3A4 inhibition, including certain azole antifungal agents or macrolide antibiotics. 2. Congenital long QT syndrome, atrioventricular block, abnormal baseline QTc interval (\>450 ms in males or \>470 ms in females), hypokalemia or hypomagnesemia, or concomitant use of drugs known to prolong the QT interval. 3. Significant hepatic dysfunction. 4. Active or clinically significant infection. 5. Secondary demyelinating diseases of the central nervous system. 6. Vascular, genetic, metabolic, neoplastic, toxic, or other diseases that may cause central nervous system demyelination or neurological symptoms that could interfere with study assessments. 7. Myocardial infarction, unstable ischemic heart disease, stroke, or New York Heart Association (NYHA) class IV heart failure within 12 weeks before screening. 8. Pregnancy, breastfeeding, or plans to become pregnant during the study period. 9. Inability or unwillingness to comply with the study follow-up schedule or study procedures. 10. Contraindication to lumbar puncture. 11. Inability or unwillingness to undergo the required magnetic resonance imaging (MRI) examinations. 12. Participation in another clinical trial within 3 months before screening.

Outcomes

Primary Outcomes

Safety and tolerability of terfenadine during the treatment period

Safety and tolerability will be assessed by the incidence and severity of adverse events and serious adverse events, as well as changes or clinically significant abnormalities in vital signs, physical examinations, clinical laboratory tests, electrocardiograms, and imaging examinations.

Time frame: Baseline through 1 month

Secondary Outcomes

Safety and tolerability during the 12-month follow-up period

Time frame: Baseline through 12 months

Change from baseline in cerebrospinal fluid white blood cell count

Cerebrospinal fluid white blood cell count will be measured at baseline, Month 1, and Month 12, and the change from baseline will be evaluated.

Time frame: Baseline, Month 1, and Month 12

Change from baseline in cerebrospinal fluid albumin quotient

Cerebrospinal fluid albumin quotient will be measured at baseline, Month 1, and Month 12, and the change from baseline will be evaluated.

Time frame: Baseline, Month 1, and Month 12

Change from baseline in cerebrospinal fluid neurofilament light chain (NfL)

Cerebrospinal fluid neurofilament light chain (NfL) level will be measured at baseline, Month 1, and Month 12 in pg/mL, and the change from baseline will be evaluated.

Time frame: Baseline, Month 1, and Month 12

Change from baseline in cerebrospinal fluid oligoclonal bands (OCB)

Cerebrospinal fluid oligoclonal bands (OCB) will be assessed at baseline, Month 1, and Month 12, and the change from baseline will be evaluated.

Time frame: Baseline, Month 1, and Month 12

Change from baseline in cerebrospinal fluid kappa free light chain (kFLC)

Cerebrospinal fluid kappa free light chain (kFLC) level will be measured at baseline, Month 1, and Month 12 in mg/L, and the change from baseline will be evaluated.

Time frame: Baseline, Month 1, and Month 12

Change from baseline in cerebrospinal fluid IgG index

Cerebrospinal fluid IgG index will be measured at baseline, Month 1, and Month 12, and the change from baseline will be evaluated.

Time frame: Baseline, Month 1, and Month 12

Change from baseline in serum neurofilament light chain (NfL)

Serum neurofilament light chain (NfL) levels will be measured at baseline and during follow-up. Changes in serum NfL from baseline will be evaluated at Month 1, Month 3, Month 6, and Month 12.

Time frame: Baseline, Month 1, Month 3, Month 6, and Month 12

Change from baseline in Expanded Disability Status Scale (EDSS) score

Neurological disability will be assessed using the Expanded Disability Status Scale (EDSS), which ranges from 0 to 10, with higher scores indicating greater disability and a worse outcome. The change in EDSS score from baseline will be evaluated at Month 1, Month 6, and Month 12.

Time frame: Baseline, Month 1, Month 6, and Month 12

Change from baseline in Timed 25-Foot Walk (T25FW) walking speed

Walking function will be assessed using the Timed 25-Foot Walk (T25FW). The change in T25FW walking speed from baseline will be evaluated at Month 3, Month 6, and Month 12.

Time frame: Baseline, Month 3, Month 6, and Month 12

Change from baseline in Nine-Hole Peg Test (9HPT) completion time

Upper limb motor function will be assessed using the Nine-Hole Peg Test (9HPT). The change in the time required to complete the 9HPT from baseline will be evaluated at Month 3, Month 6, and Month 12.

Time frame: Baseline, Month 3, Month 6, and Month 12

Change from baseline in Symbol Digit Modalities Test (SDMT) score

Cognitive function will be assessed using the Symbol Digit Modalities Test (SDMT), which ranges from 0 to 110, with higher scores indicating better cognitive processing speed. The change in SDMT score from baseline will be evaluated at Month 6 and Month 12.

Time frame: Baseline, Month 6, and Month 12

Change from baseline in Multiple Sclerosis Functional Composite (MSFC) score

Overall functional status will be assessed using the Multiple Sclerosis Functional Composite (MSFC), a standardized composite measure of neurological function based on the Timed 25-Foot Walk, 9-Hole Peg Test, and Paced Auditory Serial Addition Test. The MSFC score is expressed as a standardized z-score, with higher scores indicating better functional performance. The change in MSFC score from baseline will be evaluated at Month 6 and Month 12.

Time frame: Baseline, Month 6, and Month 12

Change from baseline in EQ-5D-5L score

Health-related quality of life will be assessed using the 5-Level EuroQol 5-Dimension questionnaire (EQ-5D-5L). The descriptive system consists of five dimensions, each rated from 1 to 5, with higher dimension scores indicating more severe problems. The EQ-5D-5L responses may be converted to an index value using the applicable value set, with higher index values indicating better health-related quality of life. The change in EQ-5D-5L score from baseline will be evaluated at Month 1 and Month 12.

Time frame: Baseline, Month 1, and Month 12

Confirmed disability progression (CDP) rate at Month 6

Confirmed disability progression will be evaluated at Month 6. CDP will be defined as an increase in EDSS score of at least 1.0 point for participants with a baseline EDSS score of 5.5 or lower, or at least 0.5 point for participants with a baseline EDSS score greater than 5.5, or an increase of at least 20% in T25FW completion time or 9HPT completion time.

Time frame: Baseline to Month 6

Annualized relapse rate at Month 12

Disease relapse will be assessed throughout the study, and the annualized relapse rate will be evaluated through Month 12. The annualized relapse rate at Month 12 will be compared between the terfenadine treatment group and the active comparator group.

Time frame: Baseline through Month 12

MRI T2 lesion activity at Month 12

Brain and spinal cord MRI findings will be evaluated at Month 12. The assessment will include the number of new or enlarging T2 hyperintense lesions, changes from baseline in cumulative T2 lesion number and lesion volume, and the proportion of participants without new T2 hyperintense lesions.

Time frame: Baseline and Month 12

Gadolinium-enhancing T1 lesions on brain MRI at Month 12

Brain MRI findings will be evaluated at Month 12. The assessment will include the change from baseline in the number of gadolinium-enhancing T1 lesions and the proportion of participants without gadolinium-enhancing lesions.

Time frame: Baseline and Month 12

A Study to Evaluate the Preliminary Efficacy and Safety of Terfenadine in Patients With Relapsing-Remitting Multiple Sclerosis

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts