A Safety andTolerability Study of Multiple Doses of ISIS-DMPKRx in Adults With Myotonic Dystrophy Type 1

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2022
• Main ID: NCT02312011
• Date of registration: 04/12/2014
• Prospective Registration: No
• Primary sponsor: Ionis Pharmaceuticals, Inc.
• Public title: A Safety andTolerability Study of Multiple Doses of ISIS-DMPKRx in Adults With Myotonic Dystrophy Type 1
• Scientific title: A Phase 1/2a Blinded, Placebo-Controlled Study to Assess the Safety, Tolerability, and Dose-range Finding of Multiple Ascending Doses of ISIS 598769 Administered Subcutaneously to Adult Patients With Myotonic Dystrophy Type 1
• Date of first enrolment: December 2014
• Target sample size: 48
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02312011
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Investigator, Outcomes Assessor).
• Phase: Phase 1/Phase 2

Countries of recruitment

United States

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Must have given written informed consent (signed and dated) and any authorizations
required by local law and be able to comply with all study requirements

2. Males or females aged 20 to 55 years old at the time of informed consent

3. Satisfy the following:

1. Females: non-pregnant and non-lactating, surgically sterile, post menopausal,
abstinent, or if engaged in sexual relations of child-bearing potential, subject
is using an acceptable contraceptive method from the time of signing the informed
consent until at least 14 weeks after the last dose of Study Drug.

2. Males: surgically sterile, abstinent or if engaged in sexual relations with a
female of child-bearing potential, the subject must be using an acceptable
contraceptive method from the time of signing the informed consent form until at
least 14 weeks after the last dose of Study Drug.

4. BMI <35.0 kg/m2

5. Genetic confirmation of DM1 with DMPK CTG repeat length = 100

6. Onset of DM1 symptoms after the age of 12

7. Clinically apparent myotonia equivalent to hand opening time of at least 2 seconds, in
the opinion of the Investigator

8. Ambulatory (orthoses allowed, canes and walkers not allowed) and able to walk at least
25 meters at screening

Exclusion Criteria:

1. Clinically significant abnormalities in medical history (e.g., previous acute coronary
syndrome within 6 months of screening, major surgery within 3 months of screening) or
physical examination

2. Clinically significant abnormalities in screening laboratory values that would render
the subject unsuitable for inclusion

3. Active infection requiring systemic antiviral or antimicrobial therapy that will not
be completed prior to Study Day 1

4. Unwilling or unable to comply with study procedures (e.g., muscle biopsies), including
follow-up, as specified by this protocol, or unwillingness to cooperate fully with the
Investigator

5. Known history of or previous positive test for human immunodeficiency virus (HIV),
hepatitis C, or chronic hepatitis B

6. Active malignancy or history within last 5 years, except for basal or squamous cell
carcinoma of the skin, carcinoma in situ of the cervix that has been successfully
treated, or pilomatricoma

7. Treatment with another investigational drug, biologic agent, or device within one
month of screening, or 5 half-lives of investigational agent, whichever is longer; any
history of previous treatment with an oligonucleotide (including siRNA)

8. Recent history of or current drug or alcohol abuse

9. History of bleeding tendency or ongoing oral anticoagulation

10. Developmental delay, intellectual disability, or significant behavioral
neuropsychiatric manifestations

11. Thyroid dysfunction that is untreated (if on thyroid hormone replacement therapy, need
to have adequate and stable replacement over the previous 6 months)

12. Implanted device for the treatment of cardiac problems (i.e., pacemaker or
defibrillator)

13. Clinically significant abnormal ECG or echocardiogram, or significant symptoms of
cardiac dysfunction at Screening

14. Have a seizure disorder

15. If being treated with testosterone, on a stable replacement dose (i.e., for
hypogonadism)

16. Treatment with corticosteroids within 8 weeks prior to the first dose of Study Drug

17. History of hypersensitivity to local anesthetics to be used in the biopsy procedure or
components thereof

18. Treatment with anti-myotonia medication within 30 days prior to screening. May
include, but not be limited to: Phenytoin, Carbamazepine, Procainamide, Disopyramide,
Nifedipine, Acetazolamide, Clomipramine, Imipramine, Amytriptiline, Taurine, Quinine,
Mexiletine

19. Have any condition, which, in the opinion of the investigator would make the subject
unsuitable for inclusion, or could interfere with the subject participating in or
completing the study



Age minimum: 20 Years
Age maximum: 55 Years
Gender: All

Health Condition(s) or Problem(s) studied

Myotonic Dystrophy Type 1

Intervention(s)

Drug: IONIS-DMPKRx

Drug: Placebo

Primary Outcome(s)

Safety (The number of participants with adverse events) [Time Frame: Participants will be followed for the duration of the study; an expected 24 - 32 weeks]

Tolerability (The number of participants with adverse events) [Time Frame: Participants will be followed for the duration of the study; an expected 24 -32 weeks]

Secondary Outcome(s)

Plasma Pharmacokinetics (Cmax, Tmax) [Time Frame: Plasma at 0.5, 1, 1.5, 2, 4, 6, 8, 12 and 24 hours after dosing.]

Urine Pharmacokinetics (Amount of drug excreted in the urine) [Time Frame: 0-24 hours post-dosing]

Secondary ID(s)

ISIS 598769-CS2

Source(s) of Monetary Support

Please refer to primary and secondary sponsors