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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 : June 25, 2018
Sponsor:
Information provided by (Responsible Party):
Ionis Pharmaceuticals, Inc.

Tracking Information
First Submitted Date  ICMJE December 4, 2014
First Posted Date  ICMJE December 9, 2014
Last Update Posted Date June 25, 2018
Study Start Date  ICMJE December 2014
Actual Primary Completion Date July 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 20, 2018)
  • 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
  • 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
Original Primary Outcome Measures  ICMJE
 (submitted: December 8, 2014)
  • Safety (The number of participants with adverse events) [ Time Frame: Patricipants will be followed for the duration of the study; an expected 24 weeks ]
    The number of participants with adverse events
  • Tolerability (The number of participants with adverse events) [ Time Frame: Patricipants will be followed for the duration of the study; an expected 24 weeks ]
    The number of participants with adverse events
Change History Complete list of historical versions of study NCT02312011 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: December 10, 2014)
  • 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)
  • Urine Pharmacokinetics (Amount of drug excreted in the urine) [ Time Frame: 0-24 hours post-dosing ]
    Amount of drug excreted in the urine
Original Secondary Outcome Measures  ICMJE
 (submitted: December 8, 2014)
  • 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 subcutanous dose to the last collected sample (24 hours after dosing)
  • Urine Pharmacokinetics (Amount of drug excreated in the urine) [ Time Frame: 0-24 hours post-dosing ]
    Amount of drug excreated in the urine
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Safety andTolerability Study of Multiple Doses of ISIS-DMPKRx in Adults With Myotonic Dystrophy Type 1
Official Title  ICMJE 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
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.
Detailed Description This is a Phase 1/2a multicenter, blinded, placebo-controlled study of ISIS-DMPK Rx in adult patients with DM1.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Myotonic Dystrophy Type 1
Intervention  ICMJE
  • Drug: IONIS-DMPKRx
    Drug
    Other Name: ISIS 598769
  • Drug: Placebo
    Placebo
Study Arms  ICMJE
  • 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.

    Intervention: Drug: IONIS-DMPKRx
  • 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.
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 2, 2016)
48
Original Estimated Enrollment  ICMJE
 (submitted: December 8, 2014)
36
Actual Study Completion Date  ICMJE August 2016
Actual Primary Completion Date July 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 20 Years to 55 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02312011
Other Study ID Numbers  ICMJE ISIS 598769-CS2
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Ionis Pharmaceuticals, Inc.
Study Sponsor  ICMJE Ionis Pharmaceuticals, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Ionis Pharmaceuticals, Inc.
Verification Date June 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP