A Phase 1/2 Study of VX-670 in Adult Participants With Myotonic Dystrophy 1 (DM1)

Study Overview
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Brief Summary
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The purpose of the study is to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of VX-670 at different single and multiple doses in participants with DM1.

Official Title
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A Phase 1/2, Randomized, Double-blind, Placebo-controlled Single- and Multiple-dose Escalation Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of VX-670 in Adult Subjects With Myotonic Dystrophy Type 1

Conditions
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Myotonic Dystrophy Type 1 (DM1)

Intervention / Treatment
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* Drug: VX-670
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: - Documented clinical diagnosis of DM1 with age of onset greater than (>) 1 year of age and documented positive genetic test for DM1 in the subject with cytosine thymine guanine (CTG) repeat of at least 100 Key Exclusion Criteria: - History of any illness or any clinical condition as pre-specified in the protocol Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 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: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A: Single Ascending Dose<br>Participants will be randomized to receive a single dose of different dose levels of VX-670. | Drug: VX-670<br>* Solution for intravenous administration.<br>|
| Placebo Comparator: Part A: Placebo<br>Participants will be randomized to receive single dose of placebo matched to VX-670. | Drug: Placebo<br>* Solution for intravenous administration.<br>|
| Experimental: Part B: Single and Multiple Ascending Dose<br>Participants will be randomized to receive single and multiple doses of different dose levels of VX-670. The dose levels will be determined based on the data from Part A. | Drug: VX-670<br>* Solution for intravenous administration.<br>|
| Placebo Comparator: Part B: Placebo<br>Participants will be randomized to receive single or multiple doses of placebo matched to VX-670. | Drug: Placebo<br>* Solution for intravenous administration.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Parts A and B: Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) |  | Part A: From Baseline up to Day 42; Part B: From Baseline and up to Day 168 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A: Maximum Observed Concentration (Cmax) of VX-670 and its Active Component in Plasma |  | From Day 1 up to Day 42 | 
| Part A: Area Under the Concentration Versus Time Curve (AUC) of VX-670 and its Active Component in Plasma |  | From Day 1 up to Day 42 | 
| Part B: Maximum Observed Concentration (Cmax) of VX-670 and its Active Component in Plasma After Each Dose |  | From Day 1 up to Day 168 | 
| Part B: Area Under the Concentration Versus Time Curve (AUC) of VX-670 and its Active Component in Plasma After Each Dose |  | From Day 1 up to Day 168 | 
| Part B: Concentration of VX-670 and its Active Component in Muscle |  | Baseline and at Day 15 | 
| Part B: Change in Splicing Index in Muscle Biopsy |  | Baseline and at Day 15 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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DM1, DM2, Myotonic Dystrophy 1, Myotonic Dystrophy 2, Myotonic Dystrophy Type 1 (DM1), Myotonic Dystrophy, DM, Myotonia, Dystrophy Myotonic, Myotonic Disorders, Steinert Disease, Vertex, Entrada, VX-670, VX670, PMO, ASO, Myotonic Muscular Dystrophy, Muscular Disorders, Atrophic, Muscular Diseases, Musculoskeletal Diseases, Neuromuscular Diseases, Nervous System Diseases, Genetic Diseases, Inborn, Heredodegenerative Disorders, Nervous System, Neurodegenerative Diseases, Muscular Dystrophies