A Phase 1/2 Study of VX-670 in Adult Subjects with Myotonic Dystrophy Type 1

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Vertex Pharmaceuticals Inc.

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

Trial duration

11 Dec 2024 → ongoing

Decision date (initial)

2024-03-19

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Vertex Pharmaceuticals Inc.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Pharmacodynamic

Part A: To evaluate the safety and tolerability of single ascending doses of VX 670 in subjects with myotonic dystrophy type 1 (DM1)
Part B: To evaluate the safety and tolerability of single and multiple ascending doses of VX 670 in subjects with DM1

Secondary objectives 2

1. Part A: To evaluate the plasma PK of VX-670 and its active molecule, PMO 0221a, after administration of single ascending doses of VX-670 in adult subjects with DM1
2. Part B: • To evaluate the plasma PK of VX-670 and PMO-0221a after single and multiple ascending doses of VX-670 in adult subjects with DM1 • To evaluate the muscle PK of VX-670 and PMO-0221a in adult subjects with DM1 • To evaluate the muscle spliceopathy in adult subjects with DM1

Conditions and MedDRA coding

Myotonic Dystrophy

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. 3. Body mass index (BMI) <35.0 kg/m2, inclusive, and a total body weight >40 kg.
2. 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.
3. 5. Documented clinical diagnosis of DM1 with age of onset >1 year of age and documented positive genetic test for DM1.
4. 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.
5. 8. Part B: Evidence of myotonia, defined by HOT of ≥2 seconds.
6. 9. Part B: Evidence of weakness, defined by percent predicted QMT of hand grip of 5 to 80%
7. 6. Left ventricular ejection fraction (LVEF) >55% within the past 3 months.

Exclusion criteria 17

1. 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).
2. 2. History of febrile illness or other acute illness that has not fully resolved within 14 days before the first dose of study drug.
3. 3. Median QTcF of triplicate standard 12-lead ECGs >450 msec at Screening.
4. 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.
5. 5. Blood donation (of approximately 1 pint [500 mL] or more) within 56 days before the first dose of study drug.
6. 6. Use of the substances, activities, or devices within the specified duration before the first study drug dose.
7. 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).
8. 8. Hypersensitivity to any component of the investigational drug product or placebo
9. 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).
10. 11. Clinically significant liver disease, even if intermittent.
11. 12. History of cardiac anomalies.
12. 13. Clinically significant kidney disease.
13. 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.
14. 15. Exposure to any other investigational drugs or devices within 1 month before Day 1
15. 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.
16. 17. Thyroid dysfunction that is untreated (if on thyroid hormone replacement therapy, need to have adequate and stable replacement over the previous 6 months).
17. 18. Diabetes that is uncontrolled, in the opinion of the Investigator.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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)

Secondary endpoints 2

1. Parts A: PK parameter estimates of VX-670 and PMO-0221a derived from plasma concentration time data
2. 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

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Vertex Pharmaceuticals Inc.

Sponsor organisation

Vertex Pharmaceuticals Inc.

Address

50 Northern Avenue

City

Boston

Postcode

02210-1862

Country

United States

Scientific contact point

Organisation

Vertex Pharmaceuticals Inc.

Contact name

Clinical Trials and Medical Info

Public contact point

Organisation

Vertex Pharmaceuticals Inc.

Contact name

Clinical Trials and Medical Info

Locations

6 EU/EEA countries · 9 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 148 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

10 submissions — initial application plus substantial / non-substantial modifications