Clinical Trial: Efficacy and Safety of IONIS-PKKRx for Preventive Treatment of Chronic Migraine

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

Official Title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of ISIS 546254 for Preventive Treatment of Chronic Migraine

Brief 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.

Detailed Summary:

This is a double-blind, placebo-controlled, randomized, multi-center study in subjects with chronic migraine. The study will consist of 7 office visits, 6 Sample collection visits and 3 phone call assessments. Subjects agreeing to participate in the study and meeting the entry criteria assessed at the screening visit, will begin a 28 day baseline period to confirm their diagnosis, and establish a baseline frequency of migraine and headache days. During the baseline period, subjects will continue treating their migraines in their usual manner. They will monitor headache activity, migraine related symptoms, and medication usage with an electronic daily headache diary.

Subjects who, after completing the baseline, continue to meet entrance criteria will be eligible to enter into the 4 month treatment phase. They will be randomized according to the Clinvest generated randomization schedule. A total of 30 randomized subjects will enter the treatment phase receiving IONIS-PKKRx (ISIS 546254; SC) or placebo in a 1:1 design. Study drug or placebo will be administered weekly for 16 weeks. A short phone call to assess any treatment related adverse events will take place 1 and 2 days after randomization. Daily electronic diary assessments will collect headache frequency and severity, associated migraine symptoms, acute medication usage, and the emergence of unusual symptoms and adverse events. Subjects will return to the site at weeks 4, 8, and 12 for investigational product (IP) accountability/dispensing, medication and medication updates, biomarker/lab sample collection, and assessment of adverse events. An end of treatment visit will take place 16 weeks after randomization.

Subjects will have a follow-up safety visit one month after their last dosage of IP ) for assessment of any adverse events (AE) and satisfaction and a final saf
Sponsor: Smith, Timothy R., M.D.

Current Primary Outcome:

• Comparison of Adverse Events [ Time Frame: Treatment period through the end of the follow-up period, up to 28 weeks ]
  Compare the number of adverse events and laboratory abnormalities through the study for subjects treated with ISIS 546254 vs. placebo.
• Change in Migraine Days [ Time Frame: Comparing baseline to treatment period, up to 16 weeks ]
  Compare the efficacy of ISIS 546254 in the preventive treatment of chronic migraine, measured by mean change in the monthly migraine days comparing baseline to the final month of the 4-month treatment period for subjects treated with ISIS 546254 vs. placebo.

Original Primary Outcome: Same as current

Current Secondary Outcome:

• Change in Headache Severity [ Time Frame: Comparing baseline to treatment period, up to 16 weeks ]
  Evaluate the efficacy of ISIS 546254 in the preventive treatment of chronic migraine, measured by mean change in the monthly headache severity comparing baseline to the final month of the 4-month treatment period for subjects treated with ISIS 546254 vs. placebo. Headache severity scale ranges from 1 (Mild) to 3 (Severe).
• Change in Headache Days [ Time Frame: Comparing baseline to treatment period, up to 16 weeks ]
  Compare the efficacy of ISIS 546254 in the preventive treatment of chronic migraine, measured by mean change in the monthly headache days comparing baseline to the final month of the 4-month treatment period for subjects treated with ISIS 546254 vs. placebo.
• Proportion of Subjects Reporting a ≥ 50% Reduction in the Number of Migraine Headaches [ Time Frame: Comparing baseline to treatment period, up to 16 weeks ]
  Compare the proportion of patients meeting 50% response criteria, response defined as a ≥ 50% reduction in the number of headaches from baseline to the final month of the 4-month treatment period for subjects treated with ISIS 546254 vs. placebo.
• Frequency of Migraine Headache Days Requiring Use of Migraine Medication [ Time Frame: Comparing baseline to treatment period, up to 16 weeks ]
  Compare the change in frequency in the number of headache days requiring use of medication for the treatment of migraine or headache pain (i.e., acute and rescue or breakthrough medication use) from baseline to the final month of the 4-month treatment period for subjects treated with ISIS 546254 vs. placebo.
• Change in Migraine Specific Quality of Life (MSQ) Questionnaire Score [ Time Frame: Comparing baseline to treatment period, up to 16 weeks ]
  Compare change from baseline to the final month of the 4-month treatment period in the Migraine Specific Quality of Life (MSQ) Questionnaire for subjects treated with ISIS 546254 vs. placebo.
• Physician Global Impress of Change (PGIC) Score [ Time Frame: Evaluating the treatment period, but collected at the end of treatment, up to 16 weeks ]
  Compare the end of treatment month 4 in the physician global impress of change (PGIC) for subjects treated with ISIS 546254 vs. placebo.
• Subject Global Impress of Change (SGIC) Score [ Time Frame: Evaluating the treatment period, but collected at the end of treatment, up to 16 weeks ]
  Compare the end of treatment month 4 in the subjects' global impression of change (SGIC) for subjects treated with ISIS 546254 vs. placebo.

Original Secondary Outcome: Same as current

Information By: Smith, Timothy R., M.D.

Dates:
Date Received: March 27, 2017
Date Started: May 1, 2017
Date Completion: December 31, 2017
Last Updated: April 10, 2017
Last Verified: April 2017