A Randomized, Placebo-Controlled, Multiple Ascending Dose Study Assessing Safety, Tolerability, Pharmacodynamics, Efficacy, and Pharmacokinetics of DYNE-101 Administered to Participants with Myotonic Dystrophy Type 1
- Conditions
- DM1Myotonic Dystrophy Type 1100283021002839610029317
- Registration Number
- NL-OMON56459
- Lead Sponsor
- Dyne Therapeutics, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 5
1. Age 18 to < 50 years, at the time of signing the informed consent.
2. Diagnosis of DM1 confirmed by molecular genetics with trinucleotide repeat
size > 100.
3. Age of onset of DM1 muscle symptoms >= 12 years
4. Clinically apparent myotonia equivalent to hand opening time of at least 2
seconds in the opinion of the Investigator
5. Hand grip strength and ankle dorsiflexion strength
a. Hand grip strength averaged from both sides >= 20% and <= 80% (± 5%) predicted
for age, sex, and height at screening
b. Ankle dorsiflexion strength averaged from both sides >= 20% and <= 80% (±10%)
predicted for age, sex, and height at screening.
Note: two sets of functional assessments must be performed during the Screening
period. Participants must meet inclusion criterion #5 on both sets of
functional assessments for study eligibility.
6. Able to complete 10MWT, stair ascend/descend, and 5×STS at screening without
the use of assistive devices such as canes, walkers, or orthoses. The use of
submalleolar orthoses and inserts or supports that do not extend above the
malleolus are permitted during testing
7. Body mass index (BMI) < 35kg/m2
8. If being treated with testosterone, on a stable replacement dose for 30 days
prior to screening
9. Participants must agree to follow protocol-specified contraception guidance
as described in Section 10.4.
10. Female participants must not be pregnant or breastfeeding
11. Capable of giving signed informed consent as described in Section 10.1.3 of
the protocol, which includes compliance with the requirements and restrictions
listed in the informed consent form (ICF) and in the protocol
12. Willingness and ability of participant to comply with and tolerate
scheduled visits, dosing
administration plan, and study assessments, including multiple needle muscle
biopsy
procedures over the duration of the study
1. Previous or ongoing medical condition, medical history, physical findings,
or laboratory abnormalities that in the opinion of the Investigator could
affect safety, make it unlikely that dosing schedule and follow-up will be
correctly completed, and/or impair the assessment and interpretation of study
results
2. History of major surgical procedure within 12 weeks prior to the start of
investigative product administration or an expectation of a major surgical
procedure (eg, implantation of cardiac defibrillator) during course of the
study
3. History of anaphylaxis
4. History of clinically significant liver disease or ongoing treatment for
liver disease
5. History of clinically significant hematologic disease or have any of the
following hematologic results at Screening: platelets or hemoglobin below the
lower limit of normal for age and sex.
6. History of clinically significant kidney disease, ongoing treatment for
kidney disease (treatment for hypertension is permitted) or estimated
glomerular filtration rate (eGFR) < 60 mL/min as calculated with the Chronic
Kidney Disease Epidemiology Collaboration (CKD-EPI) Cystatin C Equation (Inker
et al. 2012) at screening
7. Active malignancy or history within the last 5 years, except for basal or
squamous cell carcinoma of the skin or carcinoma in situ of the cervix that has
been successfully treated
8. Recent history (within previous 12 months) of drug or alcohol abuse
9. Medical condition other than DM1 that would significantly impact ambulation
or participation in functional assessments
10. Current insulin-dependent diabetes mellitus or uncontrolled diabetes
mellitus, congestive heart failure, symptomatic cardiomyopathy, symptomatic
coronary artery disease, multiple sclerosis, or other serious medical illness
11. Second- or third-degree heart block, symptomatic first-degree heart block,
atrial flutter, atrial fibrillation, ventricular arrhythmias, pacemakers,
implanted defibrillator, or is receiving medication for treatment of cardiac
arrhythmia
12. Treatment with medications that can improve myotonia of clinical functional
endpoints within a period of 5 half-lives of the medication prior to performing
screening assessments. May include but not limited to mexiletine, phenytoin,
carbamazepine, procainamide, disopyramide, ranolazine, flecainide, lamotrigine,
nifedipine, acetazolamide, clomipramine, imipramine, amitriptyline, taurine,
quinine, or metformin.
13. Use of anticoagulant such as warfarin or a direct oral anticoagulant (eg,
dabigatran) due to the increased risk of bleeding
14. Current treatment with immunosuppressive therapy
15. Receipt of another investigational drug, biologic agent, or device within 5
half-lives (if known) of the agent, or within 4 months prior to the start of
Screening, whichever is longer. Individuals previously treated with
oligonucleotide therapies (including small interfering RNA [siRNA]) may be
eligible if the last dose of the investigational drug was received >= 3 years ago
16. ECG with the corrected QT interval by Fridericia*s Formula (QTcF) >= 450 ms
in men and QTcF >= 460 ms in women, PR >= 240 ms, left bundle-branch block, or a
conduction defect, which is clinically significant in the opinion of the
Investigator
17. Percent predicted forced vital capacity (F
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method