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Study to Evaluate the Efficacy and Safety of AMG 301 in Migraine Prevention

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ClinicalTrials.gov Identifier: NCT03238781
Recruitment Status : Completed
First Posted : August 3, 2017
Results First Posted : February 7, 2020
Last Update Posted : February 7, 2020
Sponsor:
Information provided by (Responsible Party):
Amgen

Brief Summary:
To evaluate the effect of AMG 301 compared to placebo on the change from the baseline period in monthly migraine days in subjects with migraine.

Condition or disease Intervention/treatment Phase
Chronic Migraine or Episodic Migraine Drug: Placebo Drug: AMG 301 Phase 2

Detailed Description:
A Phase 2a, randomized, double-blind, placebo-controlled, 3-arm parallel group study to evaluate the efficacy and safety of AMG 301 in subjects with chronic migraine or episodic migraine.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 343 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Phase 2a Randomized Double-blind Placebo Controlled Study to Evaluate the Efficacy and Safety of AMG 301 in Migraine Prevention
Actual Study Start Date : September 6, 2017
Actual Primary Completion Date : October 16, 2018
Actual Study Completion Date : February 4, 2019

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Migraine
MedlinePlus related topics: Migraine

Arm Intervention/treatment
Placebo Comparator: Placebo
Participants randomized to Placebo were administered 6 subcutaneous (SC) injections on day 1 and weeks 2, 4, 6, 8 and 10 during the 12 week double-blind treatment period.
Drug: Placebo
Placebo was presented in identical containers, stored/packaged the same as AMG 301. All injections were administered within 30 minutes on treatment days.

Experimental: AMG 301 210 mg Q4W
Participants randomized to AMG 301 210 mg every fourth week (Q4W) received a total of 3 AMG 301 subcutaneous (SC) injections (70 mg/mL in each injection) plus 3 matching placebo injections on day 1 and weeks 4 and 8. Participants also received 6 SC placebo injections on weeks 2, 6, and 10 during the 12 week double-blind treatment period.
Drug: AMG 301
AMG 301 was packaged in 5 mL clear glass vials containing 1 mL of 70 mg/mL of AMG 301. All injections were administered within 30 minutes on treatment days.

Experimental: AMG 301 420 mg Q2W
Participants randomized to AMG 301 420 mg every second week (Q2W) received a total of 6 AMG 301 subcutaneous (SC) injections (70 mg/mL in each injection) on day 1 and weeks 2, 4, 6, 8, and 10 during the 12 week double-blind treatment period.
Drug: AMG 301
AMG 301 was packaged in 5 mL clear glass vials containing 1 mL of 70 mg/mL of AMG 301. All injections were administered within 30 minutes on treatment days.




Primary Outcome Measures :
  1. Change From Baseline in Monthly Migraine Days to the Last 4 Weeks of the 12 Week Double-Blind Treatment Period [ Time Frame: Baseline Day -28 to Day -1; Weeks 9-12 ]

    A migraine day is any calendar day from the eDiary in which the participant experienced a migraine headache. A migraine headache is a headache with or without aura, lasting for >= 4 hours, and meeting >=1 of the criteria:

    1. >= 2 pain features (unilateral, throbbing, moderate to severe, exacerbated with exercise/physical activity)
    2. >= 1 symptoms (nausea and/or vomiting, photophobia and phonophobia) If the participant took a migraine-specific medication during aura or to treat headache, it was counted as a migraine day.

    Days without eDiary data in each monthly interval are handled by proration.

    Negative change from baseline values indicated improvement (i.e. fewer migraine days after treatment as compared to baseline).



Secondary Outcome Measures :
  1. Percentage of Participants Who Responded, Defined as At Least a 50% Reduction From the Baseline Period in Monthly Migraine Days in the Last 4 Weeks of the 12-Week Double-Blind Treatment Period [ Time Frame: Baseline Day -28 to Day -1; Weeks 9-12 ]
    Responders are participants who had at least a 50% reduction from baseline in monthly migraine days during the last 4 weeks of treatment in the 12-week double blind period.

  2. Change From Baseline Period in Monthly Acute Migraine-Specific Medication Days in the Last 4 Weeks of the 12-Week Double-Blind Treatment Period [ Time Frame: Baseline Day -28 to Day -1; Weeks 9-12 ]

    Number of days on which acute headache medications (triptans and ergotamine-derivatives, alone or in combination) are used as recorded in eDiary. Monthly acute headache medication treatment days at baseline are the number of acute headache medication treatment days in the baseline period. Days without eDiary data are handled by proration.

    Negative change from baseline values indicate improvement (i.e. fewer days requiring acute migraine-specific medications after treatment as compared to baseline).


  3. Change From Baseline in Mean Physical Impairment Domain Scores as Measured by the Migraine Physical Function Impact Diary (MPFID) Over the Last 4 Weeks of the 12-Week Double-Blind Treatment Period [ Time Frame: Baseline Day -28 to Day -1; Weeks 9-12 ]

    Participants complete the MPFID every day during baseline (Days -28 to Day -1) and the 12-week Double Blind Treatment Period. The MPFID has 2 domains, Impact on Everyday Activities (7 items) and Physical Impairment (5 items), and 1 stand-alone global question that provides an assessment of the overall impact of migraine on participants' everyday activities. The recall period for each item is the past 24 hours.

    The Physical Impairment Domain Score is reported here. A participant's response to the difficulty of the 5 physical impairment items is measured using a 5-point scale, with difficulty measurements ranging from 1 to 5. The sum was rescaled to a 0 to 100 scale, with 0=no difficulty and 100=unable to do (maximum burden). Negative change from baseline values indicate improvement in migraine impact.


  4. Change From Baseline in Mean Impact on Everyday Activity Domain Scores as Measured by the Migraine Physical Function Impact Diary (MPFID) Over the Last 4 Weeks of the 12-Week Double-Blind Treatment Period [ Time Frame: Baseline Day -28 to Day -1; Weeks 9-12 ]

    Participants complete the MPFID every day during baseline (Days -28 to Day -1) and the 12-week Double Blind Treatment Period. The MPFID has 2 domains, Impact on Everyday Activities (7 items) and Physical Impairment (5 items), and 1 stand-alone global question that provides an assessment of the overall impact of migraine on participants' everyday activities. The recall period for each item is the past 24 hours.

    The Impact on Everyday Activities Domain Score is reported here. A participant's response to the Impact on Everyday Activities 7 items is measured using a 5-point scale, with difficulty measurements ranging from 1 to 5. The sum was rescaled to a 0 to 100 scale, with 0=no difficulty and 100=unable to do (maximum burden). Negative change from baseline values indicate improvement in migraine impact.


  5. Participants With Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: Day 1 up to Week 30 (12 weeks of double-blind treatment plus 18 weeks follow-up after last dose of investigational product) ]

    Adverse events (AEs) were graded according to the Common Terminology Criteria for Adverse Events (CTCAE), version 4, where:

    Grade 1 = Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated; Grade 2 = Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL); Grade 3 = Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL; Grade 4 = Life-threatening consequences; urgent intervention indicated Grade 5 = Death related to AE.


  6. Percentage of Participants Who Met Hy's Law Criteria at Baseline and On Study [ Time Frame: Baseline: Day 1 On study: Weeks 4, 6, 12, 20, 28 ]

    Hy's law predicts potential for drug-related hepatotoxicity. Hy's Law cases have three components:

    • The drug causes hepatocellular injury, generally defined as an elevated alanine aminotransferase (ALT) or aspartate aminotransferase (AST) by 3-fold or greater above the upper limit of normal (ULN).
    • Among participants showing such aminotransferase elevations, they also have elevation of their serum total bilirubin of greater than 2 times the ULN, without findings of cholestasis (defined as serum alkaline phosphatase activity less than 2 times the upper limit of normal).
    • No other reason can be found to explain the combination of increased aminotransferase and serum total bilirubin, such as viral hepatitis, alcohol abuse, ischemia, preexisting liver disease, or another drug capable of causing the observed injury.

  7. Percentage of Participants With Aminotransferase Test Abnormalities > 3 Times the Upper Limit of Normal (ULN) at Baseline and On Study [ Time Frame: Baseline: Day 1 On study: Weeks 4, 6, 12, 20, 28 ]
    Aminotransferase tests included alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Percentage of participants with results that were greater than 3 * ULN for either test are reported.

  8. Percentage of Participants With Total Bilirubin Test Abnormalities > 2 Times the Upper Limit of Normal (ULN) at Baseline and On Study [ Time Frame: Baseline: Day 1 On study: Weeks 4, 6, 12, 20, 28 ]
    Percentage of participants with total bilirubin results that were greater than 2 * ULN are reported.

  9. Percentage of Participants With Systolic Blood Pressure (SBP) in Categories by Visit [ Time Frame: Day 1, Weeks 2, 4, 6, 8, 10, 12,16, 20, 24, 28 ]
    Participant was expected to be in a supine position (or the most recumbent position possible) in a rested and calm state for at least 5 minutes before blood pressure assessments were conducted. Blood pressure units are millimeters of mercury (mmHg).

  10. Percentage of Participants With Diastolic Blood Pressure (DBP) in Categories by Visit [ Time Frame: Day 1, Weeks 2, 4, 6, 8, 10, 12,16, 20, 24, 28 ]
    Participant was expected to be in a supine position (or the most recumbent position possible) in a rested and calm state for at least 5 minutes before blood pressure assessments were conducted. Blood pressure units are millimeters of mercury (mmHg).

  11. Percentage of Participants With Pulse Rate in Categories by Visit [ Time Frame: Day 1, Weeks 2, 4, 6, 8, 10, 12,16, 20, 24, 28 ]
    Participant was expected to be in a supine position (or the most recumbent position possible) in a rested and calm state for at least 5 minutes before pulse assessments were conducted. Pulse rate units are beats per minute (BPM)

  12. Percentage of Participants With Temperature in Categories by Visit [ Time Frame: Day 1, Weeks 2, 4, 6, 8, 10, 12,16, 20, 24, 28 ]
    Participant was expected to be in a supine position (or the most recumbent position possible) in a rested and calm state for at least 5 minutes before vital sign assessments were conducted. Temperature units are reported in degrees Celsius (C).

  13. Percentage of Participants With Respiratory Rates in Categories by Visit [ Time Frame: Day 1, Weeks 2, 4, 6, 8, 10, 12,16, 20, 24, 28 ]
    Participant was expected to be in a supine position (or the most recumbent position possible) in a rested and calm state for at least 5 minutes before vital sign assessments were conducted. Respiratory rate (RR) is reported in breaths/minute.



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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adults ≥ 18 to ≤ 60 years of age at the time of signing the informed consent form.
  • History of migraine (with or without aura) for ≥ 12 months before screening according to the International Headache Society (IHS) Classification ICHD-III (Headache Classification Committee of the International Headache Society, 2013)
  • Migraine frequency: ≥ 4 migraine days per month on average across the 3 months before screening.
  • Failed at least 1 medication for prophylactic treatment of migraine due to tolerability or lack of efficacy

Exclusion Criteria:

  • Older than 50 years of age at migraine onset.
  • History of cluster headache, hemiplegic migraine headache.
  • Unable to differentiate migraine from other headaches.
  • Migraine with continuous pain, in which the subject does not experience any pain-free periods (of any duration) during the 1 month before the screening period.
  • History or evidence of any other clinically significant disorder, condition or disease that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion.

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): NCT03238781


Locations
Show Show 49 study locations
Sponsors and Collaborators
Amgen
Investigators
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Study Director: MD Amgen
  Study Documents (Full-Text)

Documents provided by Amgen:
Study Protocol  [PDF] October 17, 2017
Statistical Analysis Plan  [PDF] October 31, 2018

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT03238781    
Other Study ID Numbers: 20150308
2017-000630-57 ( EudraCT Number )
First Posted: August 3, 2017    Key Record Dates
Results First Posted: February 7, 2020
Last Update Posted: February 7, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the link below.
URL: https://www.amgen.com/datasharing

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Amgen:
Migraine
Headache
Prevention
Prophylaxis
Additional relevant MeSH terms:
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Migraine Disorders
Headache Disorders, Primary
Headache Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases