Exploratory Study of Dipraglurant (ADX48621) for the Treatment of Patients With Blepharospasm

Study Overview
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Brief Summary
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This study is designed to assess the safety and tolerability of dipraglurant in patients with blepharospasm (BSP) (randomized 1:1:1 to receive dipraglurant 50 mg, 100 mg or placebo) and explore the efficacy of 50 mg and 100 mg immediate release tablets (versus placebo) on the severity and frequency of BSP signs and symptoms using objective measures, clinical ratings and patient reported outcomes.

Official Title
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Exploratory Phase 2a Randomized, Double-blind, Placebo-controlled Study of Dipraglurant (ADX48621) Immediate Release Tablets in Patients With Blepharospasm

Conditions
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Blepharospasm, Dystonia

Intervention / Treatment
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* Drug: Dipraglurant
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with an established diagnosis of idiopathic benign essential blepharospasm Must have had prior response to to botulinum toxin (BoNT) reported on last 2 consecutive injection cycles Last injection of BoNT at least 8 weeks prior to Screening assessments Patient is experiencing features of Blepharospasm (BSP) of moderate severity/frequency at study entry. Exclusion Criteria: BSP that is known or suspected to be associated with a known cause such as neuroleptic exposure, brain injury or lesion, stroke, Parkinson's disease, or related Parkinsonisms History of surgical intervention (e.g., deep brain stimulation) or orbital myectomy for dystonia Disabling eyelid opening apraxia Other neurological disease (including psychiatric disease and/or cognitive impairment) that, in the opinion of the investigator, would affect the patient's ability to complete study assessments. Other significant medical condition that may affect the safety of the patient or preclude adequate participation in the study. Other protocol-defined inclusion and exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dipraglurant 50 mg<br> | Drug: Dipraglurant<br>* Oral tablet<br>* Other names: ADX48621;|
| Experimental: Dipraglurant 100 mg<br> | Drug: Dipraglurant<br>* Oral tablet<br>* Other names: ADX48621;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Oral matching placebo tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of dipraglurant as measured by incidence of adverse events | The primary outcome will be testing the safety and tolerability of dipraglurant in patients with blepharospasm based on the incidence of adverse events reported by patients and/or as identified by the Investigator based on clinical assessments conducted during the study. | Baseline to Day 2 | 
| Computerized Motor Objective Rater (CMOR) analysis of blinking activity | Video analysis, by an independent rater, of the mean proportion of eye closure time, severity of periocular spasms, and blink rate. Decreased eye closure time, severity of periocular spasms and blink rate indicates improvement of blepharospasm symptoms. | Baseline to Day 2 | 
| Skintronics wearable analysis of blinking activity | Analysis of blinking activity as recorded on the Skintronics wearable device. Decreased blink activity indicates improvement of blepharospasm symptoms. | Baseline to Day 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Jankovic Rating Scale (JRS) severity score | The JRS is a clinician rated scale for blepharospasm. The intensity of eyelid spasms is measured based on a 5 point grading system where 0 indicates no symptoms and 4 indicates the most severe symptoms. | Baseline to Day 2 | 
| Jankovic Rating Scale (JRS) frequency score | The JRS is a clinician rated scale for blepharospasm. The frequency of eyelid spasms is measured based on a 5 point grading system where 0 indicates no symptoms and 4 indicates highest frequency symptoms. | Baseline to Day 2 | 
| Global Dystonia Severity Rating Scale (GDS) | The GDS is a clinician rated scale for the assessment of dystonia severity across multiple body regions. Each body region is rated on a scale from 0-10 where 0 represents no dystonia and 10 represents severe dystonia. | Baseline to Day 2 | 
| Blepharospasm Phenotyping Tool (BPT) | The BPT is a clinician rated scale assessing 4 major phenotypic elements of blepharospasm using a 4 point scale for severity and frequency, where 0 indicates no symptoms and 4 indicates the highest frequency and/or most severe symptoms. | Baseline to Day 2 | 
| Blepharospasm Severity Rating Scale (BSRS) | The BSRS is a clinician rated scale for rating severity of blepharospasm based on 6 clinical features of the condition. A total score is generated based on the combined score for severity and frequency and where a higher value indicates more severe symptoms. | Baseline to Day 2 | 
| Clinician's Global Impression of Severity (CGI-S) score | The CGI-S score is used by the Investigator to determine, in a global sense, how severe the patients blepharospasm is in the context of other blepharospasm patients. Increased scores indicate more severe symptoms. | Baseline to Day 2 | 
| Blepharospasm Disability Index (BSDI) | The BSDI is a 6 item patient rated disability scale that measures how blepharospasm effects activities of daily living. Each item is scored on a 5 point scale to produce a total score of up to 30, where a higher individual item score and a higher total score indicate greater disability to the patient. | Baseline to Day 2 | 
| Patient Global Impression of Change (PGI-C) score | The PGI-C score is a patient reported outcome that assesses how much the blepharospasm symptoms have improved or worsened. A score of 0 indicates no change, negative scores down to -3 indicate worsening, and positive scores of up to 3 indicate improvement. | Baseline to Day 2 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Blepharospasm, Dystonia