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

NCT ID: NCT02312011

Last Updated: 2022-12-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-12-31
• Study Completion Date: 2016-08-31

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.

Conditions

Myotonic Dystrophy Type 1

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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.

Group Type: EXPERIMENTAL

IONIS-DMPKRx

Intervention Type: DRUG

Drug

Placebo

A placebo is administered subcutaneously over the course of 6 weeks. A placebo is administered subcutaneously over the course of 12 weeks.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo

Interventions

IONIS-DMPKRx

Drug

Intervention Type: DRUG

Placebo

Placebo

Intervention Type: DRUG

Other Intervention Names

ISIS 598769

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

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ionis Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Stanford University Medical Center

Stanford, California, United States

University of Florida

Gainesville, Florida, United States

University of Kansas Medical Center

Kansas City, Kansas, United States

Kennedy Krieger Institute

Baltimore, Maryland, United States

University of Rochester

Rochester, New York, United States

The Ohio State University

Columbus, Ohio, United States

Houston Methodist

Houston, Texas, United States

University of Utah

Salt Lake City, Utah, United States

Countries

United States

References

Thornton CA, Moxley RT 3rd, Eichinger K, Heatwole C, Mignon L, Arnold WD, Ashizawa T, Day JW, Dent G, Tanner MK, Duong T, Greene EP, Herbelin L, Johnson NE, King W, Kissel JT, Leung DG, Lott DJ, Norris DA, Pucillo EM, Schell W, Statland JM, Stinson N, Subramony SH, Xia S, Bishop KM, Bennett CF. Antisense oligonucleotide targeting DMPK in patients with myotonic dystrophy type 1: a multicentre, randomised, dose-escalation, placebo-controlled, phase 1/2a trial. Lancet Neurol. 2023 Mar;22(3):218-228. doi: 10.1016/S1474-4422(23)00001-7.

Reference Type: DERIVED

PMID: 36804094 (View on PubMed)

Other Identifiers

ISIS 598769-CS2

Identifier Type: -

Identifier Source: org_study_id