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

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Brief Title

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

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

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 Phase

Phase 1/Phase 2

Study Type

Interventional


Primary Outcome

Safety (The number of participants with adverse events)

Secondary Outcome

 Plasma Pharmacokinetics (Cmax, Tmax)

Condition

Myotonic Dystrophy Type 1

Intervention

IONIS-DMPKRx

Study Arms / Comparison Groups

 IONIS-DMPKRx
Description:  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.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

48

Start Date

December 2014

Completion Date

August 2016

Primary Completion Date

July 2016

Eligibility 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
      

Gender

All

Ages

20 Years - 55 Years

Accepts Healthy Volunteers

No

Contacts

, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT02312011

Organization ID

ISIS 598769-CS2


Responsible Party

Sponsor

Study Sponsor

Ionis Pharmaceuticals, Inc.


Study Sponsor

, , 


Verification Date

June 2018