A Phase 1/2a Dose-Escalating Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ARO-DM1 in Subjects With Type 1 Myotonic Dystrophy Who are ≥18 to ≤65 Years

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Sarepta Therapeutics Inc.

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Decision date (initial)

2026-01-30

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Arrowhead Pharmaceuticals, Inc.

External identifiers

EU CT number

2024-513579-42-00

ClinicalTrials.gov

NCT06138743

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacodynamic, Dose response, Pharmacokinetic

-To evaluate the safety, tolerability, PK, and PD of escalating single and multiple doses of ARO DM1 in subjects with DM1
-To evaluate the efficacy of multiple doses of ARO-DM1 in subjects with DM1 (Cohort 5 only)

Conditions and MedDRA coding

Type 1 Myotonic Dystrophy

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Males and females who are ≥18 to ≤65 years of age at the time of informed consent.
2. A genetically confirmed diagnosis of DM1 with DMPK CTG repeat length ≥100 based on Screening evaluation or source verifiable medical records.
3. Have clinician-assessed signs of DM1 including clinically apparent myotonia equivalent to hand opening time of at least 2 seconds (in the opinion of the Investigator).
4. Had the onset of clinically significant DM1 symptoms after the age of 12 years.
5. Can walk for at least 10 meters independently at Screening (orthoses allowed; canes and walkers are not allowed).
6. Subjects of childbearing potential must agree to use highly effective contraception in addition to a condom during the study and for at least 90 days following the end of the study or last dose of study drug, whichever is later. Subjects must not donate sperm or eggs during the study and for at least 90 days following the end of the study or last dose of study drug, whichever is later.

Exclusion criteria 22

1. Body mass index ≥40 kg/m2.
2. Treatment with anti-myotonia medication (or medications that can improve myotonia) within a period of 5 half-lives of the medication prior to performing screening assessment. Subjects must not use anti-myotonia medication for the duration of the study.
3. History of inadequately controlled diabetes.
4. Any contraindications to muscle biopsy.
5. Any condition that, in the opinion of the Investigator, would make the subject unsuitable for inclusion, or could interfere with the subject’s ability to participate in or completing the study.
6. Confirmed diagnosis of congenital DM1.
7. Screening values of coagulation parameters including platelet count, INR, prothrombin time, and activated partial thromboplastin time (APTT) should be within normal ranges. Subjects with non-clinically significant and stable out-of-range values may be eligible to enroll in the study at the discretion of the Investigator.
8. Intellectual disability or significant behavioral neuropsychiatric manifestation.
9. A history of torsade de pointes, ventricular rhythm disturbances (eg, ventricular tachycardia or fibrillation), heart block (excluding first-degree block, being PR interval prolongation only), congenital long QT syndrome, corrected QTc value >450 ms in males and >470 ms in females, new ST segment elevation or depression, or new Q wave on ECG. Subjects with a history of atrial arrhythmias should be discussed with the Medical Monitor. Symptomatic heart failure (per New York Heart Association guidelines), unstable angina, myocardial infarction, severe cardiovascular disease (ejection fraction <20%), transient ischemic attack, or cerebrovascular accident within 24 weeks prior to first dose.
10. Seropositive for hepatitis B (positive hepatitis B virus surface antigen at Screening) or hepatitis C (HCV) at Screening, (positive for anti-HCV antibody must be confirmed with positive HCV-RNA test for exclusion).
11. Active infection that, in the opinion of the PI, would interfere with the subject’s ability safely tolerate and/or complete the study.
12. History of malignancy within the last 2 years except for adequately treated basal cell carcinoma, squamous cell skin cancer, superficial bladder tumors, or in situ cervical cancer. Subjects with other curatively treated malignancies who have no evidence of metastatic disease and >2-year disease-free interval may be entered following approval by the Medical Monitor.
13. Recent history of or current drug and/or alcohol abuse (at the discretion of the site PI).
14. Presence of risk for increased or uncontrolled bleeding and/or risk of bleeding that is not managed optimally and could place a subject at an increased risk for intraoperative or postoperative bleeding. These could include, anticipated need, in the opinion of the Investigator, for administration of any antiplatelet or anticoagulant around each biopsy procedure, and underlying disorders of the coagulation cascade, platelet function, or platelet count (eg, hemophilia, Von Willebrand’s disease, liver disease).
15. History of poorly controlled thyroid dysfunction per discretion of the PI.
16. Untreated or poorly controlled epilepsy.
17. Uncontrolled hypertension.
18. History of TA biopsy within 3 months of Day 1 or planning to undergo tibialis anterior (TA) biopsies (outside of this study) during the study period.
19. Recent treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) prior to first dose or current participation in an investigational study.
20. Current concomitant use of theophylline (including duration of study).
21. Clinically significant cardiac, liver, or renal disease (please refer to the protocol for details).
22. HIV infection, as shown by the presence of anti-HIV antibody (seropositive) at Screening.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Incidence, frequency, and severity of treatment-emergent adverse events (TEAEs) and treatment-related AEs in subjects with DM1 over time through the end of study (EOS)

Secondary endpoints 1

1. Plasma PK of ARO-DM1 in subjects with DM1.

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Sarepta Therapeutics Inc.

Sponsor organisation

Sarepta Therapeutics Inc.

Address

215 1st Street

City

Cambridge

Postcode

02142-1213

Country

United States

Scientific contact point

Organisation

Arrowhead Pharmaceuticals Inc.

Contact name

Jiyeon Denninger

Public contact point

Organisation

Arrowhead Pharmaceuticals Inc.

Contact name

Jiyeon Denninger

Third parties 16

Locations

4 EU/EEA countries · 12 investigational sites

By country

Investigational sites

Results and documents

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

Documents 92 files

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

Application history

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