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

Myotonic Dystrophy Type 1 Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02312011
• Other study ID #: ISIS 598769-CS2
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: December 2014
• Est. completion date: August 2016

Study information

• Verified date: December 2022
• Source: Ionis Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: August 2016
• Est. primary completion date: July 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Myotonic Dystrophy
• Myotonic Dystrophy Type 1

Intervention

Drug:
• IONIS-DMPKRx
Drug
• Placebo
Placebo

Locations

Country	Name	City	State
United States	Kennedy Krieger Institute	Baltimore	Maryland
United States	The Ohio State University	Columbus	Ohio
United States	University of Florida	Gainesville	Florida
United States	Houston Methodist	Houston	Texas
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	University of Rochester	Rochester	New York
United States	University of Utah	Salt Lake City	Utah
United States	Stanford University Medical Center	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Ionis Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety (The number of participants with adverse events)	The number of participants with adverse events	Participants will be followed for the duration of the study; an expected 24 - 32 weeks
Primary	Tolerability (The number of participants with adverse events)	The number of participants with adverse events	Participants will be followed for the duration of the study; an expected 24 -32 weeks
Secondary	Plasma Pharmacokinetics (Cmax, Tmax)	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)	Plasma at 0.5, 1, 1.5, 2, 4, 6, 8, 12 and 24 hours after dosing.
Secondary	Urine Pharmacokinetics (Amount of drug excreted in the urine)	Amount of drug excreted in the urine	0-24 hours post-dosing