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

Ionis Pharmaceuticals, Inc.8 sites in 1 country48 target enrollmentDecember 2014

ConditionsMyotonic Dystrophy Type 1

InterventionsPlacebo IONIS-DMPKRx

DrugsIONIS-DMPKRx Placebo

Overview

Phase: Phase 1
Intervention: Placebo
Conditions: Myotonic Dystrophy Type 1
Sponsor: Ionis Pharmaceuticals, Inc.
Enrollment: 48
Locations: 8
Primary Endpoint: Tolerability (The number of participants with adverse events)
Status: Completed
Last Updated: 3 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

December 2014

End Date

August 2016

Last Updated

3 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Ionis Pharmaceuticals, Inc.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•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
•Males or females aged 20 to 55 years old at the time of informed consent
•Satisfy the following:
•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.
•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.
•BMI \<35.0 kg/m2
•Genetic confirmation of DM1 with DMPK CTG repeat length ≥ 100
•Onset of DM1 symptoms after the age of 12
•Clinically apparent myotonia equivalent to hand opening time of at least 2 seconds, in the opinion of the Investigator
•Ambulatory (orthoses allowed, canes and walkers not allowed) and able to walk at least 25 meters at screening

Exclusion Criteria

•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
•Clinically significant abnormalities in screening laboratory values that would render the subject unsuitable for inclusion
•Active infection requiring systemic antiviral or antimicrobial therapy that will not be completed prior to Study Day 1
•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
•Known history of or previous positive test for human immunodeficiency virus (HIV), hepatitis C, or chronic hepatitis B
•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
•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)
•Recent history of or current drug or alcohol abuse
•History of bleeding tendency or ongoing oral anticoagulation
•Developmental delay, intellectual disability, or significant behavioral neuropsychiatric manifestations

Arms & Interventions

Placebo

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

Intervention: Placebo

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: IONIS-DMPKRx

Outcomes

Primary Outcomes

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

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

Secondary Outcomes

Plasma Pharmacokinetics (Cmax, Tmax)(Plasma at 0.5, 1, 1.5, 2, 4, 6, 8, 12 and 24 hours after dosing.)
Urine Pharmacokinetics (Amount of drug excreted in the urine)(0-24 hours post-dosing)