VX-670 for Myotonic dystrophy type 1

Inclusion criteria

• {"criterion_text":"- 3. Body mass index (BMI) <35.0 kg/m2, inclusive, and a total body weight >40 kg."}
• {"criterion_text":"- 4. Subjects (male and female) between the ages of 18 to 64 years, inclusive. Women of childbearing potential may be enrolled as allowed by local regulatory guidance."}
• {"criterion_text":"- 5. Documented clinical diagnosis of DM1 with age of onset >1 year of age and documented positive genetic test for DM1."}
• {"criterion_text":"- 7. Part B: Ambulatory, defined as having the ability to complete 10-meter walk/run timed test unassisted (e.g., without the use of a cane or walker) or with the use of a brace or other orthotic device only."}
• {"criterion_text":"- 8. Part B: Evidence of myotonia, defined by HOT of ≥2 seconds."}
• {"criterion_text":"- 9. Part B: Evidence of weakness, defined by percent predicted QMT of hand grip of 5 to 80%"}
• {"criterion_text":"- 6. Left ventricular ejection fraction (LVEF) >55% within the past 3 months."}

Exclusion criteria

• {"criterion_text":"- 1. History of any illness or any clinical condition that, in the opinion of the investigator or the subject’s general practitioner, might confound the results of or participation in the study or pose an additional risk in administering study drug to the subject. This may include, but is not limited to, history of relevant drug or food allergies; history of cardiovascular or central nervous system disease (other than DM1); history or presence of clinically significant pathology; had major surgery or had significant trauma within 4 weeks before the first study drug dose;history of mental disease; significant intellectual or behavioral disability; and history of cancer, except for squamous cell skin cancer, basal cell skin cancer, and Stage 0 cervical carcinoma in situ (all 3 diagnosed ≥ 3 years ago with no recurrence in the past 3 years)."}
• {"criterion_text":"- 11. Clinically significant liver disease, even if intermittent."}
• {"criterion_text":"- 12. History of cardiac anomalies."}
• {"criterion_text":"- 13. Clinically significant kidney disease."}
• {"criterion_text":"- 14. Exposure to any other investigational nucleic acid, cell and genetic therapies, including siRNA, ASO, mRNA within 6 months before Day 1 or 5 half-lives of investigational agent (confirmed at Screening), whichever is longer."}
• {"criterion_text":"- 15. Exposure to any other investigational drugs or devices within 1 month before Day 1"}
• {"criterion_text":"- 16. Part B: Any contraindication to a muscle biopsy in the opinion of the investigator including but not limited to: a limb injury, bleeding diathesis, ascites, or significant atrophy of the tibialis anterior muscles."}
• {"criterion_text":"- 17. Thyroid dysfunction that is untreated (if on thyroid hormone replacement therapy, need to have adequate and stable replacement over the previous 6 months)."}
• {"criterion_text":"- 18. Diabetes that is uncontrolled, in the opinion of the Investigator."}
• {"criterion_text":"- 2. History of febrile illness or other acute illness that has not fully resolved within 14 days before the first dose of study drug."}
• {"criterion_text":"- 3. Median QTcF of triplicate standard 12-lead ECGs >450 msec at Screening."}
• {"criterion_text":"- 4. For female subjects: Females who are currently breastfeeding or pregnant or planning to become pregnant during the study or within 180 days after the last dose of study drug. a. For male subjects: Male subjects with a female partner who is pregnant, nursing, or planning to become pregnant during the study or within 180 days after the last dose of study drug."}
• {"criterion_text":"- 5. Blood donation (of approximately 1 pint [500 mL] or more) within 56 days before the first dose of study drug."}
• {"criterion_text":"- 6. Use of the substances, activities, or devices within the specified duration before the first study drug dose."}
• {"criterion_text":"- 7. A screen positive for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, or antibodies against human immunodeficiency virus 1 or 2 (HIV1 and HIV2 Abs)."}
• {"criterion_text":"- 8. Hypersensitivity to any component of the investigational drug product or placebo"}
• {"criterion_text":"- 10. Abnormal and clinically significant values for clinical chemistry, hematology, coagulation, or urinalysis parameters at Screening unless explained by disease or are benign in nature (such as Gilbert’s disease)."}

Primary endpoints

• {"endpoint_text":"- Parts A and B: Safety and tolerability of VX-670 based on the assessment of adverse events (AEs), laboratory test results, standard 12-lead electrocardiograms (ECGs), vital signs, Columbia Suicide Severity Rating Scale (C-SSRS)","definition_or_measurement_approach":"Assessment of adverse events (AEs), clinical laboratory tests, standard 12-lead ECGs, vital signs, and Columbia Suicide Severity Rating Scale (C-SSRS)."}

Secondary endpoints

• {"endpoint_text":"- Parts A: PK parameter estimates of VX-670 and PMO-0221a derived from plasma concentration time data","definition_or_measurement_approach":"Pharmacokinetic parameter estimates derived from plasma concentration-time data for VX-670 and its active molecule PMO-0221a."}
• {"endpoint_text":"- Part B: - PK parameter estimates of VX-670 and PMO-0221a derived from plasma concentration time data - PK parameter estimates of VX-670 and PMO-0221a derived from muscle concentration data - Change from baseline in splicing index in tibialis anterior muscle biopsy","definition_or_measurement_approach":"Part B PK endpoints: plasma and muscle concentration-based PK parameter estimates for VX-670 and PMO-0221a; pharmacodynamic endpoint: change from baseline in splicing index measured in tibialis anterior muscle biopsy."}

Methods

• MyTomorrows CT Landing Page (patient-facing online recruitment platform) – versions / materials present for EN/FR/NL/DE/ES/IT
• Google Ads campaigns (MyTomorrows / DM1 Ad copies) aimed at patients (materials in EN/FR/NL/DE/ES/IT)
• Posters and Flyers (site posters/flyers) in local languages for participating sites
• Recruitment brochure and PI-to-patient invitation letters (country/language-specific)
• PI-to-Doctor letters and site outreach materials to healthcare professionals
• Patient Navigator scripts (to support telephone/online navigator outreach)

Belgium

Earliest CTIS Part Ii Submission Date

16-02-2024

Latest Decision Or Authorization Date

16-04-2024

Processing Time Days

60

Number Of Sites

1

Number Of Participants

3

France

Earliest CTIS Part Ii Submission Date

16-02-2024

Latest Decision Or Authorization Date

16-04-2024

Processing Time Days

60

Number Of Sites

1

Number Of Participants

5

Spain

Earliest CTIS Part Ii Submission Date

14-02-2024

Latest Decision Or Authorization Date

16-04-2024

Processing Time Days

62

Number Of Sites

1

Number Of Participants

2

Italy

Earliest CTIS Part Ii Submission Date

29-02-2024

Latest Decision Or Authorization Date

16-04-2024

Processing Time Days

47

Number Of Sites

2

Number Of Participants

4

Germany

Earliest CTIS Part Ii Submission Date

18-01-2024

Latest Decision Or Authorization Date

16-04-2024

Processing Time Days

89

Number Of Sites

2

Number Of Participants

4

Netherlands

Earliest CTIS Part Ii Submission Date

12-03-2024

Latest Decision Or Authorization Date

22-03-2024

Processing Time Days

10

Number Of Sites

2

Number Of Participants

2

Primary sponsor

Full Name

Vertex Pharmaceuticals Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States