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

A Phase 2a Randomized Double-blind Placebo Controlled Study to Evaluate the Efficacy and Safety of AMG 301 in Migraine Prevention

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.

Study Overview

• Status: Completed
• Conditions: Chronic Migraine or Episodic Migraine
• Intervention / Treatment: Drug: Placebo; Drug: AMG 301

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.

• Study Type: Interventional
• Enrollment (Actual): 343
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Innsbruck, Austria, 6020
    • Research Site
  • Klagenfurt, Austria, 9020
    • Research Site
  • Wien, Austria, 1090
    • Research Site
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T3M 1M4
      • Research Site
  • British Columbia
    • Surrey, British Columbia, Canada, V3Z 2N6
      • Research Site
  • Ontario
    • Markham, Ontario, Canada, L3R 9X3
      • Research Site
    • Toronto, Ontario, Canada, M4S 1Y2
      • Research Site
  • Quebec
    • Levis, Quebec, Canada, G6W 0M6
      • Research Site
    • Montreal, Quebec, Canada, H2W 1V1
      • Research Site
• Czechia
  • Brno, Czechia, 616 00
    • Research Site
  • Praha 2, Czechia, 120 00
    • Research Site
  • Praha 4, Czechia, 140 59
    • Research Site
  • Prerov, Czechia, 750 02
    • Research Site
• Denmark
  • Aarhus, Denmark, 8000
    • Research Site
  • Glostrup, Denmark, 2600
    • Research Site
  • Viborg, Denmark, 8800
    • Research Site
• Finland
  • Helsinki, Finland, 00100
    • Research Site
  • Helsinki, Finland, 00930
    • Research Site
  • Jyvaskyla, Finland, 40100
    • Research Site
  • Oulu, Finland, 90220
    • Research Site
  • Turku, Finland, 20100
    • Research Site
• Germany
  • Berlin, Germany, 10117
    • Research Site
  • Berlin, Germany, 10435
    • Research Site
  • Hamburg, Germany, 20251
    • Research Site
  • Kiel, Germany, 24149
    • Research Site
  • Leipzig, Germany, 04107
    • Research Site
• Sweden
  • Stockholm, Sweden, 112 45
    • Research Site
  • Stockholm, Sweden, 114 33
    • Research Site
• United States
  • California
    • Long Beach, California, United States, 90806
      • Research Site
    • Santa Monica, California, United States, 90404
      • Research Site
  • Colorado
    • Boulder, Colorado, United States, 80301
      • Research Site
  • Connecticut
    • East Hartford, Connecticut, United States, 06118
      • Research Site
    • Stamford, Connecticut, United States, 06905
      • Research Site
  • Florida
    • Jacksonville, Florida, United States, 32216
      • Research Site
    • Orlando, Florida, United States, 32801
      • Research Site
    • West Palm Beach, Florida, United States, 33407
      • Research Site
  • Massachusetts
    • Worcester, Massachusetts, United States, 01605
      • Research Site
  • Michigan
    • Ann Arbor, Michigan, United States, 48104
      • Research Site
  • Missouri
    • Saint Louis, Missouri, United States, 63141
      • Research Site
    • Saint Peters, Missouri, United States, 63303
      • Research Site
  • New York
    • Plainview, New York, United States, 11803
      • Research Site
  • North Carolina
    • Greensboro, North Carolina, United States, 27405
      • Research Site
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Research Site
  • Tennessee
    • Memphis, Tennessee, United States, 38119
      • Research Site
    • Nashville, Tennessee, United States, 37203
      • Research Site
  • Texas
    • Austin, Texas, United States, 78731
      • Research Site
    • Dallas, Texas, United States, 75214
      • Research Site
    • Round Rock, Texas, United States, 78681
      • Research Site
  • Utah
    • Salt Lake City, Utah, United States, 84109
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

3

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Monthly Migraine Days to the Last 4 Weeks of the 12 Week Double-Blind Treatment Period	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: >= 2 pain features (unilateral, throbbing, moderate to severe, exacerbated with exercise/physical activity); >= 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).	Baseline Day -28 to Day -1; Weeks 9-12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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.	Baseline Day -28 to Day -1; Weeks 9-12
Change From Baseline Period in Monthly Acute Migraine-Specific Medication Days in the Last 4 Weeks of the 12-Week Double-Blind Treatment Period	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).	Baseline Day -28 to Day -1; Weeks 9-12
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	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.	Baseline Day -28 to Day -1; Weeks 9-12
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	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.	Baseline Day -28 to Day -1; Weeks 9-12
Participants With Treatment-Emergent Adverse Events (TEAEs)	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.	Day 1 up to Week 30 (12 weeks of double-blind treatment plus 18 weeks follow-up after last dose of investigational product)
Percentage of Participants Who Met Hy's Law Criteria at Baseline and On Study	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.	Baseline: Day 1 On study: Weeks 4, 6, 12, 20, 28
Percentage of Participants With Aminotransferase Test Abnormalities > 3 Times the Upper Limit of Normal (ULN) at Baseline and On Study	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.	Baseline: Day 1 On study: Weeks 4, 6, 12, 20, 28
Percentage of Participants With Total Bilirubin Test Abnormalities > 2 Times the Upper Limit of Normal (ULN) at Baseline and On Study	Percentage of participants with total bilirubin results that were greater than 2 * ULN are reported.	Baseline: Day 1 On study: Weeks 4, 6, 12, 20, 28
Percentage of Participants With Systolic Blood Pressure (SBP) in Categories by Visit	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).	Day 1, Weeks 2, 4, 6, 8, 10, 12,16, 20, 24, 28
Percentage of Participants With Diastolic Blood Pressure (DBP) in Categories by Visit	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).	Day 1, Weeks 2, 4, 6, 8, 10, 12,16, 20, 24, 28
Percentage of Participants With Pulse Rate in Categories by Visit	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)	Day 1, Weeks 2, 4, 6, 8, 10, 12,16, 20, 24, 28
Percentage of Participants With Temperature in Categories by Visit	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).	Day 1, Weeks 2, 4, 6, 8, 10, 12,16, 20, 24, 28
Percentage of Participants With Respiratory Rates in Categories by Visit	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.	Day 1, Weeks 2, 4, 6, 8, 10, 12,16, 20, 24, 28

Collaborators and Investigators

• Sponsor: Amgen

Publications and helpful links

General Publications

• Ashina M, Dolezil D, Bonner JH, Zhou L, Klatt J, Picard H, Mikol DD. A phase 2, randomized, double-blind, placebo-controlled trial of AMG 301, a pituitary adenylate cyclase-activating polypeptide PAC1 receptor monoclonal antibody for migraine prevention. Cephalalgia. 2021 Jan;41(1):33-44. doi: 10.1177/0333102420970889. Epub 2020 Nov 24.

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 6, 2017
• Primary Completion (ACTUAL): October 16, 2018
• Study Completion (ACTUAL): February 4, 2019

Study Registration Dates

• First Submitted: August 1, 2017
• First Submitted That Met QC Criteria: August 1, 2017
• First Posted (ACTUAL): August 3, 2017

Study Record Updates

• Last Update Posted (ACTUAL): February 7, 2020
• Last Update Submitted That Met QC Criteria: January 24, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: Migraine; Headache; Prevention; Prophylaxis
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Migraine Disorders
• Other Study ID Numbers: 20150308; 2017-000630-57 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
• IPD Sharing 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.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No