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

This study is currently recruiting participants.
Verified October 2017 by Timothy Smith, Smith, Timothy R., M.D.
Sponsor:
ClinicalTrials.gov Identifier:
NCT03108469
First Posted: April 11, 2017
Last Update Posted: October 5, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborators:
Clinvest Research, LLC
Ionis Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Timothy Smith, Smith, Timothy R., M.D.
  Purpose
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.

Condition Intervention Phase
Chronic Migraine Drug: IONIS-PKKRx (ISIS 546254) Other: Placebo Phase 2

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

Resource links provided by NLM:


Further study details as provided by Timothy Smith, Smith, Timothy R., M.D.:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 30
Actual Study Start Date: August 1, 2017
Estimated Study Completion Date: December 31, 2017
Estimated Primary Completion Date: December 31, 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: IONIS-PKKRx (ISIS 546254)
Those randomized to IONIS-PKKRx (ISIS 546254) will receive subcutaneous injections containing 1.00 mL (200mg) weekly for weeks 1-16.
Drug: IONIS-PKKRx (ISIS 546254)
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.
Placebo Comparator: Placebo
Those randomized to placebo will receive subcutaneous injections containing 1.00 mL (200mg) weekly for weeks 1-16.
Other: Placebo
Those randomized to placebo will receive subcutaneous injections 1.00 mL (200mg) weekly for weeks 1-16.

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

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03108469


Contacts
Contact: Heather Manley, MS 417-841-3664 hmanley@clinvest.com
Contact: Jim Sly, MS 417-841-3673 jsly@clinvest.com

Locations
United States, Missouri
StudyMetrix Recruiting
Saint Peters, Missouri, United States, 63303
Contact: Donna Straatmann, RN    636-387-5100      
Contact: Sheri Rocco, LPN    636-387-5100      
Principal Investigator: Timothy R Smith, MD         
Sub-Investigator: Jill Stoneman, NP         
Clinvest Research, LLC Recruiting
Springfield, Missouri, United States, 65807
Contact: Melody Luebbert, LPN    417-883-7889      
Contact: Marjorie Cheesman, LPN    417-883-7889      
Principal Investigator: Timothy R Smith, MD         
Sub-Investigator: Carol A Matthews, DNP, FNP         
Sub-Investigator: David G True, DO         
Sponsors and Collaborators
Smith, Timothy R., M.D.
Clinvest Research, LLC
Ionis Pharmaceuticals, Inc.
Investigators
Principal Investigator: Timothy R Smith, MD Clinvest Research, LLC
  More Information

Responsible Party: Timothy Smith, Principal Investigator, Smith, Timothy R., M.D.
ClinicalTrials.gov Identifier: NCT03108469     History of Changes
Other Study ID Numbers: 15-001IS
First Submitted: March 27, 2017
First Posted: April 11, 2017
Last Update Posted: October 5, 2017
Last Verified: October 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Timothy Smith, Smith, Timothy R., M.D.:
migraine

Additional relevant MeSH terms:
Migraine Disorders
Headache Disorders, Primary
Headache Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases