Chronic MigrainePhase 2NCT03108469
Efficacy and Safety of IONIS-PKKRx for Preventive Treatment of Chronic Migraine
A Phase 2 study testing IONIS-PKKRx (ISIS 546254) in people with Chronic Migraine, run by Smith, Timothy R., M.D. at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Chronic Migraine
- What is being tested?
- IONIS-PKKRx (ISIS 546254)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 2 sitesUnited States
- Study dates
- 1 Aug 2017to 26 Apr 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Potential subjects must meet the following criteria at the screening visit to enter this study:
- male or female, in otherwise good health, 18 to 65 years of age.
- history of chronic migraine meeting the diagnostic criteria listed in the International Classification of Headache Disorders (ICHD-III beta version, 2013), as follows:
- 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
- onset of migraine before age 50.
- stable pattern of migraine pattern for at least 3 months prior to screening.
- 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.
- 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
Who cannot join
- Potential subjects meeting any of the following criteria will be excluded from entering this study:
- unable to understand the study requirements, the informed consent, or complete headache records as required per protocol.
- pregnant, actively trying to become pregnant, or breast-feeding.
- history of medication overuse (MO) of opioids, or butalbital, as defined by ICHD-3 beta criteria and/or MO during baseline period.
- history of substance abuse and/or dependence, in the opinion of the Investigator.
- unstable neurological condition or a significantly abnormal neurological examination with focal signs or signs of increased intracranial pressure.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
StudyMetrix
City of Saint Peters, Missouri, 63303
Clinvest Research, LLC
Springfield, Missouri, 65807
About this study
Official title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of ISIS 546254 for Preventive Treatment of Chronic Migraine
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.
Read the 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.
- Conditions
- Chronic Migraine
- Being tested
- IONIS-PKKRx (ISIS 546254), Placebo
- Keywords
- migraine
- Medical subject headings
- Migraine Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IONIS-PKKRx (ISIS 546254)Drug
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.
PlaceboOther
Those randomized to placebo will receive subcutaneous injections 1.00 mL (200mg) weekly for weeks 1-16.
| Study group | Role | What they receive |
|---|---|---|
| IONIS-PKKRx (ISIS 546254) | Active comparator | Those randomized to IONIS-PKKRx (ISIS 546254) will receive subcutaneous injections containing 1.00 mL (200mg) weekly for weeks 1-16. Receives: Drug: IONIS-PKKRx (ISIS 546254) |
| Placebo | Placebo comparator | Those randomized to placebo will receive subcutaneous injections containing 1.00 mL (200mg) weekly for weeks 1-16. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Migraine Days
Compare the efficacy of ISIS 546254 in the preventive treatment of chronic migraine, measured by the number of monthly migraine days comparing baseline to the final month of the 4-month treatment period for subjects treated with ISIS 546254 vs. placebo.
Measured: Comparing baseline to treatment period, up to 16 weeks
Secondary outcomes (7)
Headache Severity
Evaluate the efficacy of ISIS 546254 in the preventive treatment of chronic migraine, measured by 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).
Measured: Comparing baseline to treatment period, up to 16 weeks
Headache Days
Compare the efficacy of ISIS 546254 in the preventive treatment of chronic migraine, measured by the number of monthly headache days comparing baseline to the final month of the 4-month treatment period for subjects treated with ISIS 546254 vs. placebo.
Measured: Comparing baseline to treatment period, up to 16 weeks
Number of Subjects Reporting a ≥ 50% Reduction in the Number of Migraine Headaches
Compare the number 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.
Measured: Comparing baseline to treatment period, up to 16 weeks
Count of Migraine Headache Days Requiring Use of Migraine Medication
Compare the count of 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.
Measured: Comparing baseline to treatment period, up to 16 weeks
Migraine Specific Quality of Life (MSQ) Questionnaire Score
Compare scores 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.
The MSQ total score is derived from the summation of fourteen questions on the MSQ. Answer options for the MSQ are coded as: 1 = None of the time, 2 = A little bit of the time, 3 = Some of the time, 4 = A good bit of the time, 5 = Most of the time, 6 = All of the time. The range of total MSQ score for each time point is 14 to 84, with higher scores indicating more effects of migraine on the subject's daily activities.
Measured: Comparing baseline to treatment period, up to 16 weeks
Physician Global Impress of Change (PGIC) Score
Compare the end of treatment month 4 in the physician global impress of change (PGIC) for subjects treated with ISIS 546254 vs. placebo.
The PGIC is a one item questionnaire asking, "Since the beginning of treatment in this study, how would you describe this patient's change (if any) in their overall status?". The answer option for the PGIC is coded as: 3 = Very Much Improved, 2 = Much Improved, 1 = Minimally Improved, 0 = No Change, -1 = Minimally Worse, -2 = Much Worse, -3 = Very Much Worse, with negative scores indicating the subject's overall status has decreased while in the study and positive scores indicating the subject's overall status has increased while in the study.
Measured: Evaluating the treatment period, but collected at the end of treatment, up to 16 weeks
Subject Global Impress of Change (SGIC) Score
Compare the end of treatment month 4 in the subjects' global impression of change (SGIC) for subjects treated with ISIS 546254 vs. placebo.
The SGIC is a one item questionnaire asking, "Since the beginning of treatment in this study, how would you describe the change (if any) in your overall status?". The answer option for the SGIC is coded as: 3 = Very Much Improved, 2 = Much Improved, 1 = Minimally Improved, 0 = No Change, -1 = Minimally Worse, -2 = Much Worse, -3 = Very Much Worse, with negative scores indicating the subject's overall status has decreased while in the study and positive scores indicating the subject's overall status has increased while in the study.
Measured: Evaluating the treatment period, but collected at the end of treatment, up to 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Apr 2017
- Study start1 Aug 2017
- Primary completion26 Apr 2019
- Study completion26 Apr 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Chronic MigraineStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Smith, Timothy R., M.D.
- Collaborators
- Clinvest Research, LLC, Ionis Pharmaceuticals, Inc.
- Responsible party
- Principal investigator, Timothy Smith, Smith, Timothy R., M.D.
- Investigators
- Timothy R Smith, MD, Principal investigator, Clinvest Research, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03108469
- Sponsor's protocol ID
- 15-001IS
- Status last verified
- Feb 2020
- First submitted
- 27 Mar 2017
- Last updated
- 12 Feb 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of ISIS 546254 for Preventive Treatment of Chronic Migraine
- ClinicalTrials.gov ID
- NCT03108469
- Acronym / sponsor ID
- 15-001IS
- Conditions
- Chronic Migraine
- Keywords
- migraine
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Smith, Timothy R., M.D.
- Collaborators
- Clinvest Research, LLC, Ionis Pharmaceuticals, Inc.
- Study start
- 1 Aug 2017 (actual)
- Primary completion
- 26 Apr 2019 (actual)
- Study completion
- 26 Apr 2019 (actual)
- First posted
- 11 Apr 2017 (actual)
- Results
- Posted 5 Feb 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| IONIS-PKKRx (ISIS 546254) | Active comparator | Drug: 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. |
| Placebo | Placebo comparator | Other: PlaceboThose randomized to placebo will receive subcutaneous injections containing 1.00 mL (200mg) weekly for weeks 1-16. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Potential subjects must meet the following criteria at the screening visit to enter this study:
- male or female, in otherwise good health, 18 to 65 years of age.
- history of chronic migraine meeting the diagnostic criteria listed in the International Classification of Headache Disorders (ICHD-III beta version, 2013), as follows:
- onset of migraine before age 50.
- stable pattern of migraine pattern for at least 3 months prior to screening.
Key exclusion criteria (6 listed)
- Potential subjects meeting any of the following criteria will be excluded from entering this study:
- unable to understand the study requirements, the informed consent, or complete headache records as required per protocol.
- pregnant, actively trying to become pregnant, or breast-feeding.
- history of medication overuse (MO) of opioids, or butalbital, as defined by ICHD-3 beta criteria and/or MO during baseline period.
- history of substance abuse and/or dependence, in the opinion of the Investigator.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Drug | IONIS-PKKRx (ISIS 546254) |
| PlaceboThose randomized to placebo will receive subcutaneous injections 1.00 mL (200mg) weekly for weeks 1-16. | Other | Placebo |
Primary outcome
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 the number of monthly migraine days comparing baseline to the final month of the 4-month treatment period for subjects treated with ISIS 546254 vs. placebo.
7 secondary outcomes
Headache Severity
Time frame: Comparing baseline to treatment period, up to 16 weeks
Headache Days
Time frame: Comparing baseline to treatment period, up to 16 weeks
Number of Subjects Reporting a ≥ 50% Reduction in the Number of Migraine Headaches
Time frame: Comparing baseline to treatment period, up to 16 weeks
Count of Migraine Headache Days Requiring Use of Migraine Medication
Time frame: Comparing baseline to treatment period, up to 16 weeks
Migraine Specific Quality of Life (MSQ) Questionnaire Score
Time frame: Comparing baseline to treatment period, up to 16 weeks
Physician Global Impress of Change (PGIC) Score
Time frame: Evaluating the treatment period, but collected at the end of treatment, up to 16 weeks
Subject Global Impress of Change (SGIC) Score
Time frame: Evaluating the treatment period, but collected at the end of treatment, up to 16 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Feb 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Timothy R Smith, MD principal investigator
Clinvest Research, LLC
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing IONIS-PKKRx (ISIS 546254) in people with Chronic Migraine, run by Smith, Timothy R., M.D. at 2 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 8 inclusion and 6 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 12 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 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 phase mean?
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?
Yes. Results are posted in the registry (first posted 5 Feb 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Migraine Days (time frame: Comparing baseline to treatment period, up to 16 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 12 Feb 2020.