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Myotonic Dystrophy Type 1Phase 1/2NCT02312011

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

A Phase 1/2 study testing IONIS-DMPKRx in people with Myotonic Dystrophy Type 1, run by Ionis Pharmaceuticals, Inc. at 8 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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. Read more about this study

Who is it for?
Ages 20 to 55 years
Conditions the study is for
Myotonic Dystrophy Type 1
What is being tested?
IONIS-DMPKRx
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
48 participants
Where
8 sitesUnited States
Study dates
Dec 2014to Aug 2016
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 20 to 55 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • 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
Show all 10Show fewer
  • 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

Who cannot join

  • 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
Show all 19Show fewer
  • 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
  • History of hypersensitivity to local anesthetics to be used in the biopsy procedure or components thereof
  • 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
  • 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

Trial locations and contacts

8 sites in 1 country.

8 sites in 1 country

United States8 sites

  • Kennedy Krieger Institute

    Baltimore, Maryland, 21205

  • The Ohio State University

    Columbus, Ohio, 43221

  • University of Florida

    Gainesville, Florida, 32610

  • Houston Methodist

    Houston, Texas, 77030

  • University of Kansas Medical Center

    Kansas City, Kansas, 66103

  • University of Rochester

    Rochester, New York, 14642

  • University of Utah

    Salt Lake City, Utah, 84132

  • Stanford University Medical Center

    Stanford, California, 94305

Other trials in United States

About this study

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

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

Read the detailed description

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

Being tested
IONIS-DMPKRx, Placebo
Keywords
Myotonic Dystrophy, DM1, Adult onset, Neuromuscular Disease, DMPKRx
Medical subject headings
Myotonic Dystrophy, Neuromuscular Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IONIS-DMPKRxDrug

    Also called ISIS 598769

    Drug

  • PlaceboDrug

    Placebo

Study groups in NCT02312011
Study groupRoleWhat they receive
IONIS-DMPKRxExperimentalIONIS 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.
Receives: Drug: IONIS-DMPKRx
PlaceboPlacebo comparatorA placebo is administered subcutaneously over the course of 6 weeks. A placebo is administered subcutaneously over the course of 12 weeks.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Safety (The number of participants with adverse events)

    The number of participants with adverse events

    Measured: Participants will be followed for the duration of the study; an expected 24 - 32 weeks

  2. Tolerability (The number of participants with adverse events)

    The number of participants with adverse events

    Measured: Participants will be followed for the duration of the study; an expected 24 -32 weeks

Secondary outcomes (2)

  1. 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)

    Measured: Plasma at 0.5, 1, 1.5, 2, 4, 6, 8, 12 and 24 hours after dosing.

  2. Urine Pharmacokinetics (Amount of drug excreted in the urine)

    Amount of drug excreted in the urine

    Measured: 0-24 hours post-dosing

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Dec 2014 (estimated)
  2. Study startDec 2014
  3. Primary completionJul 2016
  4. Study completionAug 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
48 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02312011
Sponsor's protocol ID
ISIS 598769-CS2
Status last verified
Dec 2022
First submitted
4 Dec 2014
Last updated
6 Dec 2022
Results posted
No
Data monitoring committee
No

Publications

  • 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.

    PubMed 36804094

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing IONIS-DMPKRx in people with Myotonic Dystrophy Type 1, run by Ionis Pharmaceuticals, Inc. at 8 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02312011, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Dec 2022.

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