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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02312011
Recruitment Status : Completed
First Posted : December 9, 2014
Last Update Posted : December 6, 2022
Information provided by (Responsible Party):
Ionis Pharmaceuticals, Inc.

Brief Summary:
This study will test the safety, tolerability, and pharmacokinetics of multiple escalating doses of ISIS-DMPKRx administered subcutaneously to adult patients with DM1.

Condition or disease Intervention/treatment Phase
Myotonic Dystrophy Type 1 Drug: IONIS-DMPKRx Drug: Placebo Phase 1 Phase 2

Detailed Description:
This is a Phase 1/2a multicenter, blinded, placebo-controlled study of ISIS-DMPK Rx in adult patients with DM1.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 48 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official 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
Study Start Date : December 2014
Actual Primary Completion Date : July 2016
Actual Study Completion Date : August 2016

Arm Intervention/treatment
Experimental: IONIS-DMPKRx

IONIS DMPKRx is administered subcutaneously over the course of 6 weeks for dose levels 1, 2, 3, 4, and 5.

IONIS DMPKRx is administered subcutaneously over the course of 12 weeks for dose levels 4 or 5.

Other Name: ISIS 598769

Placebo Comparator: Placebo
A placebo is administered subcutaneously over the course of 6 weeks. A placebo is administered subcutaneously over the course of 12 weeks.
Drug: Placebo

Primary Outcome Measures :
  1. 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 ]
    The number of participants with adverse events

  2. 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 ]
    The number of participants with adverse events

Secondary Outcome Measures :
  1. Plasma Pharmacokinetics (Cmax, Tmax) [ Time Frame: Plasma at 0.5, 1, 1.5, 2, 4, 6, 8, 12 and 24 hours after dosing. ]
    • the maximal observed plasma drug concentration (Cmax)
    • the time to reach Cmax (Tmax)
    • the area under the plasma concentration time curve from the time of the subcutaneous dose to the last collected sample (24 hours after dosing)

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

Information from the National Library of Medicine

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Ages Eligible for Study:   20 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02312011

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United States, California
Stanford University Medical Center
Stanford, California, United States, 94305
United States, Florida
University of Florida
Gainesville, Florida, United States, 32610
United States, Kansas
University of Kansas Medical Center
Kansas City, Kansas, United States, 66103
United States, Maryland
Kennedy Krieger Institute
Baltimore, Maryland, United States, 21205
United States, New York
University of Rochester
Rochester, New York, United States, 14642
United States, Ohio
The Ohio State University
Columbus, Ohio, United States, 43221
United States, Texas
Houston Methodist
Houston, Texas, United States, 77030
United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84132
Sponsors and Collaborators
Ionis Pharmaceuticals, Inc.
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Responsible Party: Ionis Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT02312011    
Other Study ID Numbers: ISIS 598769-CS2
First Posted: December 9, 2014    Key Record Dates
Last Update Posted: December 6, 2022
Last Verified: December 2022
Keywords provided by Ionis Pharmaceuticals, Inc.:
Myotonic Dystrophy
Adult onset
Neuromuscular Disease
Additional relevant MeSH terms:
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Myotonic Dystrophy
Muscular Dystrophies
Muscular Disorders, Atrophic
Muscular Diseases
Musculoskeletal Diseases
Myotonic Disorders
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Nervous System Diseases
Neuromuscular Diseases
Genetic Diseases, Inborn