Efficacy and Safety of IONIS-PKKRx for Preventive Treatment of Chronic Migraine
Condition: Chronic Migraine
MeSH terms: Migraine Disorders
Intervention: IONIS-PKKRx (ISIS 546254); Placebo
Intervention description: Those randomized to IONIS-PKKRx (ISIS 546254) will receive subcutaneous injections containing 1.00 mL (200mg) of IONIS- PKKRx (ISIS 546254) weekly for weeks 1-16.; Those randomized to placebo will receive subcutaneous injections 1.00 mL (200mg) weekly for weeks 1-16.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Masking description: At randomization (Visit 2), neither the subject nor the investigator will be aware to which treatment group the subject has been assigned. Investigational product will be drawn and administered in a double blind format. If needed, for safety and proper treatment of the subject, the investigator can unblind the subject's treatment assignment to determine which treatment has been assigned and institute appropriate follow-up care. When possible, Sponsor and Clinvest should be notified prior to unblinding study drug.
Enrollment: 30.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: migraine

Summary:

      The purpose of this study is to evaluate the safety, tolerability, and changes in the number
      of migraine and headache days with repeated subcutaneous administration of IONIS-PKKRx (ISIS
      546254) or placebo in subjects with chronic migraine.
    

Eligibility criteria:

        Inclusion Criteria:

        Potential subjects must meet the following criteria at the screening visit to enter this
        study:

          1. male or female, in otherwise good health, 18 to 65 years of age.

          2. history of chronic migraine meeting the diagnostic criteria listed in the
             International Classification of Headache Disorders (ICHD-III beta version, 2013), as
             follows:

             a. History of frequent headaches suggestive of chronic migraine (15 or greater days of
             qualifying headaches per month) for at least three months prior to screening b.
             Verification of headache frequency through prospectively collected baseline
             information during the 28-day run-in phase demonstrating headaches on at least 15
             days, with at least 8 days per month fulfilling any ONE of the following; i. Qualify
             as being a migraine attack ii. Relieved by migraine specific acute medications

          3. onset of migraine before age 50.

          4. stable pattern of migraine pattern for at least 3 months prior to screening.

          5. not currently taking a migraine preventive OR has been taking a stable dose of a
             preventive for at least 30 days prior to screening and agrees to not start, stop, or
             change medication and/or dosage during the study period.

             i. Subjects on migraine preventative should have stable headache pattern ii.
             Injections of onabotulinumtoxinA are allowable if subject has completed at least 2
             injection cycles and agrees to maintain a regular injection cycle for the duration of
             the study

        Exclusion Criteria:

        Potential subjects meeting any of the following criteria will be excluded from entering
        this study:

          1. unable to understand the study requirements, the informed consent, or complete
             headache records as required per protocol.

          2. pregnant, actively trying to become pregnant, or breast-feeding.

          3. history of medication overuse (MO) of opioids, or butalbital, as defined by ICHD-3
             beta criteria and/or MO during baseline period.

          4. history of substance abuse and/or dependence, in the opinion of the Investigator.

          5. unstable neurological condition or a significantly abnormal neurological examination
             with focal signs or signs of increased intracranial pressure.