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

NCT02312011 | Completed Phase 1

• 1 other identifier: ISIS 598769-CS2
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 8

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.

Conditions

Myotonic Dystrophy Type 1

Keywords

Myotonic Dystrophy; DM1; Adult onset; Neuromuscular Disease; DMPKRx

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (2)

• 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

Study Arms (2)

IONIS-DMPKRx

EXPERIMENTAL

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.

Drug: IONIS-DMPKRx

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

IONIS-DMPKRx DRUG

Drug

Also known as: ISIS 598769

IONIS-DMPKRx

Placebo DRUG

Placebo

Placebo

Eligibility Criteria

• Age: 20 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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
• Thyroid dysfunction that is untreated (if on thyroid hormone replacement therapy, need to have adequate and stable replacement over the previous 6 months)
• Implanted device for the treatment of cardiac problems (i.e., pacemaker or defibrillator)
• Clinically significant abnormal ECG or echocardiogram, or significant symptoms of cardiac dysfunction at Screening
• Have a seizure disorder
• If being treated with testosterone, on a stable replacement dose (i.e., for hypogonadism)
• Treatment with corticosteroids within 8 weeks prior to the first dose of Study Drug

Sponsors & Collaborators

• Ionis Pharmaceuticals, Inc.: lead

Study Sites (8)

Stanford University Medical Center

Stanford, California, 94305, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66103, United States

Location

Kennedy Krieger Institute

Baltimore, Maryland, 21205, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

The Ohio State University

Columbus, Ohio, 43221, United States

Location

Houston Methodist

Houston, Texas, 77030, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

Related Publications (1)

• 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.

  PMID: 36804094 DERIVED

MeSH Terms

Conditions

Myotonic Dystrophy; Neuromuscular Diseases

Condition Hierarchy (Ancestors)

Muscular Dystrophies; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Myotonic Disorders; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 4, 2014
• First Posted: December 9, 2014
• Study Start: December 1, 2014
• Primary Completion: July 1, 2016
• Study Completion: August 1, 2016
• Last Updated: December 6, 2022

Record last verified: 2022-12

Locations

US (8)