Study of Sustained Benefit of AMG334 in Adult Episodic Migraine Patients

Amgen

Status and phase: Completed; Phase 4

Conditions: Episodic Migraine

Treatments: Drug: Oral Prophylactic; Drug: AMG334

Study type: Interventional

Funder types: Industry

Identifiers

NCT03927144

CAMG334A2401 (Other Identifier)

2018-001228-20 (EudraCT Number)

AMG334A2401

Details and patient eligibility

About

The purpose of this study is to compare the sustained long-term benefit between two treatment paradigms of migraine prophylactic agents (erenumab versus a control arm of oral prophylactics) in episodic migraine patients who have previously failed 1 to 2 prophylactic migraine treatments.

Enrollment: 621 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Written informed consent must be obtained before any assessment is performed.
• Adults greater than or equal to 18 years of age upon entry into screening.
• Documented history of migraine (with or without aura) greater than or equal to 12 months prior to screening according to the International Classification of Headache Disorders-3rd Edition (ICHD-3).
• Greater than or equal to 4 and less than 15 days per month of migraine symptoms (based on ICHD-3 criteria) on average across 3 months prior to screening based on retrospective reporting.
• Less than 15 days per month of headache symptoms (i.e., migraine and non-migraine).
• Subjects in need for switching by documented failure of 1 or 2 prophylactic treatments in the last 6 months due to either lack of efficacy or poor tolerability. For subjects with 1 prior treatment failure, the failure should have occurred in the last 6 months. For subjects with 2 prior treatment failures, the second treatment failure should have occurred in the last 6 months.
• During baseline: Confirmed migraine frequency of 4 to 14 migraine days and less than 15 days of headache symptoms.
• During baseline: greater than or equal to 80% compliance with the headache diary.

Exclusion criteria

• Subjects meeting any of the following criteria are not eligible for inclusion in this study.

  • Older than 50 years of age at migraine onset.
  • History of cluster headache or hemiplegic migraine headache.
  • Unable to differentiate migraine from other headaches.
  • Lack of efficacy or poor tolerability with greater than 2 treatments from the 7 medication categories for prophylactic treatment of migraine after an adequate therapeutic trial.

• Efficacy failure is defined as no meaningful reduction in headache frequency, duration, and/or severity after administration of the medication for at least 6 weeks at the generally accepted therapeutic dose(s) based on the investigator's assessment.

• Tolerability failure is defined as documented discontinuation due to adverse events of the respective medication during the last 6 months prior to screening.

• The following scenarios do not constitute lack of therapeutic response:

• Lack of sustained response to a medication.

• Patient decision to halt treatment due to improvement.

• Used a prohibited medication from the 7 categories of prior prophylactic medications within 3 months prior to the start of and during baseline for a non-migraine indication if dose is not stable

• Exposure to botulinum toxin in the head and/or neck region within 4 months.

• Taken the following for any indication in any month during the 2 months prior to the start of the baseline period:

  • Ergotamines or triptans on greater than or equal to 10 days per month, or Simple analgesics (non-steroidal anti-inflammatory drugs [NSAIDs], acetaminophen) on greater than or equal to 15 days per month, or
  • Opioid- or butalbital-containing analgesics on greater than or equal to 4 days per month.

• Device, or procedure that potentially may interfere with the intensity or number of migraine days within 2 months prior to the start of or during baseline.

• History of major psychiatric disorders (such as schizophrenia or bipolar disorder) or current evidence of depression. Subjects with anxiety disorder and/or major depressive disorders are permitted in the study if they are considered by the investigator to be stable and are taking no more than 1 medication for each disorder. Subjects must have been on a stable dose within the 3 months prior to the start of the baseline period.

• History of seizure disorder or other significant neurological conditions other than migraine. Note: a single childhood febrile seizure is not exclusionary.

• History of malignancy of any organ system (other than localized basal cell carcinoma of the skin or in situ cervical cancer), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.

• Human immunodeficiency virus (HIV) infection by history.

• History or evidence of any other unstable or clinically significant medical condition or clinically significant vital sign, laboratory, or electrocardiogram (ECG) abnormality during that could pose a risk to subject safety or interfere with the study evaluation.

• Myocardial infarction, stroke, transient ischemic attack, unstable angina, or coronary artery bypass surgery or other re-vascularization procedures within 6 months prior to screening.

• Score "yes" on item 4 or item 5 of the Suicidal Ideation section of the C-SSRS, if this ideation occurred in the past 6 months, or "yes" on any item of the Suicidal Behavior section, except for the "Non-Suicidal Self-Injurious Behavior" (item also included in the Suicidal Behavior section), if this behavior occurred in the past 2 years.

• Evidence of drug or alcohol abuse or dependence, based on Investigator discretion within 12 months.

• Pregnant or nursing (lactating) women.

• Women of child-bearing potential must use contraception during dosing with study treatment.

• Use of other investigational drugs within 5 half-lives of enrollment, or until the expected pharmacodynamic effect has returned to baseline, whichever is longer.

• History of hypersensitivity to any of the study drugs or its excipients or to drugs of similar chemical classes.

• Previous exposure to AMG334 or exposure to any other prophylactic CGRP-targeted therapy (prior to the study).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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621 participants in 2 patient groups

AMG334 70 mg/140 mg

Experimental group

Description:

Participants were randomized to receive 70 mg or 140 mg of AMG334 as a subcutaneous injection once per month for 52 weeks in the Core Phase. Participants were permitted to switch to an approved oral prophylactic based on treatment failure status and at the investigator's and participant's discretion. Participants who completed visits through Week 52 of the Core Phase were eligible to participate in the 52-week Extension Phase of the study.

Treatment:

Drug: AMG334

Drug: Oral Prophylactic

Oral Prophylactic

Active Comparator group

Description:

Participants were randomized to receive a standard of care (SOC) locally approved oral prophylactic migraine medication once per day for 52 weeks in the Core Phase, as prescribed per local country labels. Participants were permitted to switch to a different approved oral prophylactic based on treatment failure status and at the investigator's and participant's discretion. Participants who completed visits through Week 52 of the Core Phase were eligible to participate in the 52-week Extension Phase of the study.

Treatment:

Drug: AMG334

Drug: Oral Prophylactic