Trial Outcomes & Findings for Efficacy and Safety of IONIS-PKKRx for Preventive Treatment of Chronic Migraine (NCT NCT03108469)

NCT ID: NCT03108469

Last Updated: 2020-02-12

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 30 participants
• Primary outcome timeframe: Comparing baseline to treatment period, up to 16 weeks
• Results posted on: 2020-02-12

Participant Flow

Participant milestones

Measure	IONIS-PKKRx (ISIS 546254) Those randomized to IONIS-PKKRx (ISIS 546254) received subcutaneous injections containing 1.00 mL (200mg/mL) weekly for weeks 1-16.	Placebo Those randomized to placebo will receive subcutaneous injections containing 1.00 mL weekly for weeks 1-16.
Overall Study STARTED	15	15
Overall Study COMPLETED	11	11
Overall Study NOT COMPLETED	4	4

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	IONIS-PKKRx (ISIS 546254) n=15 Participants Those randomized to IONIS-PKKRx (ISIS 546254) received subcutaneous injections containing 1.00 mL (200mg/mL) weekly for weeks 1-16.	Placebo n=15 Participants Those randomized to placebo will receive subcutaneous injections containing 1.00 mL weekly for weeks 1-16.	Total n=30 Participants Total of all reporting groups
Age, Continuous	35.6 years STANDARD_DEVIATION 13.04 • n=5 Participants	38.4 years STANDARD_DEVIATION 10.83 • n=7 Participants	37.16 years STANDARD_DEVIATION 12.08 • n=5 Participants
Sex: Female, Male Female	13 Participants n=5 Participants	12 Participants n=7 Participants	25 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	14 Participants n=5 Participants	15 Participants n=7 Participants	29 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	15 Participants n=5 Participants	14 Participants n=7 Participants	29 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	15 participants n=5 Participants	15 participants n=7 Participants	30 participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	IONIS-PKKRx (ISIS 546254) n=15 Participants Those randomized to IONIS-PKKRx (ISIS 546254) received subcutaneous injections containing 1.00 mL (200mg/mL) weekly for weeks 1-16.	Placebo n=15 Participants Those randomized to placebo will receive subcutaneous injections containing 1.00 mL weekly for weeks 1-16.
Migraine Days Baseline	14.267 Days Standard Error 1.48	14.133 Days Standard Error 1.17
Migraine Days Treatment Month	11.067 Days Standard Error 2.08	9.867 Days Standard Error 1.80

SECONDARY outcome

Timeframe: Comparing baseline to treatment period, up to 16 weeks

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).

Outcome measures

Measure	IONIS-PKKRx (ISIS 546254) n=15 Participants Those randomized to IONIS-PKKRx (ISIS 546254) received subcutaneous injections containing 1.00 mL (200mg/mL) weekly for weeks 1-16.	Placebo n=15 Participants Those randomized to placebo will receive subcutaneous injections containing 1.00 mL weekly for weeks 1-16.
Headache Severity Baseline	1.605 units on a scale Standard Error 0.106	1.538 units on a scale Standard Error 0.084
Headache Severity Treatment Month	1.202 units on a scale Standard Error 0.146	0.994 units on a scale Standard Error 0.170

SECONDARY outcome

Timeframe: 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 headache days comparing baseline to the final month of the 4-month treatment period for subjects treated with ISIS 546254 vs. placebo.

Outcome measures

Measure	IONIS-PKKRx (ISIS 546254) n=15 Participants Those randomized to IONIS-PKKRx (ISIS 546254) received subcutaneous injections containing 1.00 mL (200mg/mL) weekly for weeks 1-16.	Placebo n=15 Participants Those randomized to placebo will receive subcutaneous injections containing 1.00 mL weekly for weeks 1-16.
Headache Days Baseline	22.267 Days Standard Error 1.27	23.733 Days Standard Error 0.86
Headache Days Treatment Month	17.733 Days Standard Error 2.11	14.333 Days Standard Error 1.76

SECONDARY outcome

Timeframe: Comparing baseline to treatment period, up to 16 weeks

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.

Outcome measures

Measure	IONIS-PKKRx (ISIS 546254) n=15 Participants Those randomized to IONIS-PKKRx (ISIS 546254) received subcutaneous injections containing 1.00 mL (200mg/mL) weekly for weeks 1-16.	Placebo n=15 Participants Those randomized to placebo will receive subcutaneous injections containing 1.00 mL weekly for weeks 1-16.
Number of Subjects Reporting a ≥ 50% Reduction in the Number of Migraine Headaches	2 Participants	6 Participants

SECONDARY outcome

Timeframe: Comparing baseline to treatment period, up to 16 weeks

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.

Outcome measures

Measure	IONIS-PKKRx (ISIS 546254) n=15 Participants Those randomized to IONIS-PKKRx (ISIS 546254) received subcutaneous injections containing 1.00 mL (200mg/mL) weekly for weeks 1-16.	Placebo n=15 Participants Those randomized to placebo will receive subcutaneous injections containing 1.00 mL weekly for weeks 1-16.
Count of Migraine Headache Days Requiring Use of Migraine Medication Baseline	7.2 Days Standard Error 1.64	14.733 Days Standard Error 2.09
Count of Migraine Headache Days Requiring Use of Migraine Medication Treatment Month	4.733 Days Standard Error 1.64	7.733 Days Standard Error 2.00

SECONDARY outcome

Timeframe: Comparing baseline to treatment period, up to 16 weeks

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.

Outcome measures

Measure	IONIS-PKKRx (ISIS 546254) n=15 Participants Those randomized to IONIS-PKKRx (ISIS 546254) received subcutaneous injections containing 1.00 mL (200mg/mL) weekly for weeks 1-16.	Placebo n=15 Participants Those randomized to placebo will receive subcutaneous injections containing 1.00 mL weekly for weeks 1-16.
Migraine Specific Quality of Life (MSQ) Questionnaire Score Baseline	50.133 score on a scale Standard Error 2.40	50.133 score on a scale Standard Error 2.63
Migraine Specific Quality of Life (MSQ) Questionnaire Score Treatment Month	41.133 score on a scale Standard Error 3.46	40.733 score on a scale Standard Error 3.16

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	IONIS-PKKRx (ISIS 546254) n=15 Participants Those randomized to IONIS-PKKRx (ISIS 546254) received subcutaneous injections containing 1.00 mL (200mg/mL) weekly for weeks 1-16.	Placebo n=15 Participants Those randomized to placebo will receive subcutaneous injections containing 1.00 mL weekly for weeks 1-16.
Physician Global Impress of Change (PGIC) Score	0.867 units on a scale Standard Error 0.215	1.00 units on a scale Standard Error 0.258

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	IONIS-PKKRx (ISIS 546254) n=15 Participants Those randomized to IONIS-PKKRx (ISIS 546254) received subcutaneous injections containing 1.00 mL (200mg/mL) weekly for weeks 1-16.	Placebo n=15 Participants Those randomized to placebo will receive subcutaneous injections containing 1.00 mL weekly for weeks 1-16.
Subject Global Impress of Change (SGIC) Score	0.867 units on a scale Standard Error 0.291	1.13 units on a scale Standard Error 0.350

Adverse Events

IONIS-PKKRx (ISIS 546254)

Serious events: 0 serious events

Other events: 15 other events

Deaths: 0 deaths

Placebo

Serious events: 2 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Measure	IONIS-PKKRx (ISIS 546254) n=15 participants at risk Those randomized to IONIS-PKKRx (ISIS 546254) received subcutaneous injections containing 1.00 mL (200mg/mL) weekly for weeks 1-16.	Placebo n=15 participants at risk Those randomized to placebo will receive subcutaneous injections containing 1.00 mL weekly for weeks 1-16.
Surgical and medical procedures Gastrectomy	0.00% 0/15 • 196 days	6.7% 1/15 • Number of events 1 • 196 days
Hepatobiliary disorders Cholecystitis	0.00% 0/15 • 196 days	6.7% 1/15 • Number of events 1 • 196 days

Other adverse events

Measure	IONIS-PKKRx (ISIS 546254) n=15 participants at risk Those randomized to IONIS-PKKRx (ISIS 546254) received subcutaneous injections containing 1.00 mL (200mg/mL) weekly for weeks 1-16.	Placebo n=15 participants at risk Those randomized to placebo will receive subcutaneous injections containing 1.00 mL weekly for weeks 1-16.
General disorders Pain	0.00% 0/15 • 196 days	26.7% 4/15 • Number of events 4 • 196 days
Respiratory, thoracic and mediastinal disorders Sinus congestion	6.7% 1/15 • Number of events 1 • 196 days	26.7% 4/15 • Number of events 4 • 196 days
General disorders Injection site erythema	100.0% 15/15 • Number of events 96 • 196 days	0.00% 0/15 • 196 days
General disorders Injection site induration	60.0% 9/15 • Number of events 31 • 196 days	0.00% 0/15 • 196 days
General disorders Injection site pain	73.3% 11/15 • Number of events 51 • 196 days	0.00% 0/15 • 196 days
General disorders Injection site pruritus	33.3% 5/15 • Number of events 23 • 196 days	0.00% 0/15 • 196 days
Gastrointestinal disorders Nausea	6.7% 1/15 • Number of events 1 • 196 days	20.0% 3/15 • Number of events 3 • 196 days

Additional Information

Jim Sly

Clinvest Research

Phone: 4178413673

Email: jsly@clinvest.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place