Clinical trial NCT03108469: Efficacy and Safety of IONIS-PKKRx for Preventive Treatment of Chronic Migraine
Official title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of ISIS 546254 for Preventive Treatment of Chronic Migraine
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Migraine
Keywords: migraine
Lead sponsor: Smith, Timothy R., M.D.
Sponsor class: INDIV
Collaborators: name: Clinvest Research, LLC
name: Ionis Pharmaceuticals, Inc.
First posted: 2017-04-11
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 description: 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 safety phone call 2 months following their last office visit (3 months after last dose of IP) for assessment of any adverse events (AE). Subjects will continue to complete headache diaries through Visit 7. Subjects will also have hematology samples collected every other week starting after Visit 2 through Day 154.

Safety and tolerability will be monitored by the Investigators. Patients who discontinue study treatment prematurely should complete any follow-up visits associated with the most recent dose and should move into and complete the Follow-up Phase.

Subjects will undergo sampling for (pharmacokinetics) PK, coagulation, chemistry, hematology, and optional future biomedical research, as specified in the schedule of procedures.

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.

Primary outcomes:
measure: Migraine Days
timeFrame: Comparing baseline to treatment period, up to 16 weeks
Secondary outcomes:
measure: Headache Severity
timeFrame: Comparing baseline to treatment period, up to 16 weeks
measure: Headache Days
timeFrame: Comparing baseline to treatment period, up to 16 weeks
measure: Number of Subjects Reporting a ≥ 50% Reduction in the Number of Migraine Headaches
timeFrame: Comparing baseline to treatment period, up to 16 weeks
measure: Count of Migraine Headache Days Requiring Use of Migraine Medication
timeFrame: Comparing baseline to treatment period, up to 16 weeks
measure: Migraine Specific Quality of Life (MSQ) Questionnaire Score
timeFrame: Comparing baseline to treatment period, up to 16 weeks
measure: Physician Global Impress of Change (PGIC) Score
timeFrame: Evaluating the treatment period, but collected at the end of treatment, up to 16 weeks
measure: Subject Global Impress of Change (SGIC) Score
timeFrame: Evaluating the treatment period, but collected at the end of treatment, up to 16 weeks
Other outcomes:
Locations:
city: Saint Peters
country: United States
facility: StudyMetrix
state: Missouri
city: Springfield
country: United States
facility: Clinvest Research, LLC
state: Missouri
Study officials:
affiliation: Clinvest Research, LLC
name: Timothy R Smith, MD
role: PRINCIPAL_INVESTIGATOR
References: