A Study to Evaluate the Efficacy and Safety of Erenumab in Adults With Medication Overuse Headache

Amgen

Status and phase: Completed; Phase 4

Conditions: Migraine Headache

Treatments: Drug: Erenumab 70 mg; Drug: Erenumab 140 mg; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT03971071

2018-003342-16 (EudraCT Number)

20170703

Details and patient eligibility

About

Study 20170703 is a phase 4, randomized, double-blind, parallel-group, placebo-controlled study to evaluate the efficacy and safety of erenumab against placebo in participants with chronic migraine (CM) who have a history of at least 1 preventive treatment failure and are diagnosed with medication overuse headache (MOH).

Full description

Study 20170703 is a phase 4, randomized, double-blind, double-dummy, parallel-group, placebo-controlled study to evaluate the safety and efficacy of erenumab against placebo in a CM population with MOH and prior history of treatment failure. Participants will be enrolled based on fulfilment of the International Classification of Headache Disorders, 3rd Edition (ICHD-3) CM and MOH criteria and will not be advised to early discontinue acute medication.

Participants who successfully complete the 24-week double-blind treatment period (DBTP) of the study will be offered an opportunity to continue in an open-label treatment period (OLTP) of 28-weeks duration. Participants who received erenumab treatment during the DBTP will continue to receive the same erenumab dose during the OLTP. Participants who received placebo during the DBTP will be allocated in a 1:1 ratio to receive either erenumab 70 mg or 140 mg SC QM during the OLTP. All participants will remain blinded to their original DBTP treatment assignment.

Enrollment: 620 patients

Sex: All

Ages: 18 to 99 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Eligibility criteria will be evaluated during the up to 3-week screening period (part 1) and a 4-week baseline period (part 2). At the end of baseline period, participants who successfully met eligibility criteria will be randomized on study.

Key Inclusion Criteria Part 1: To be assessed during the 3-week screening period, prior to the baseline period. Participants are eligible to be included in the study only if all of the following criteria apply:

• Participant has provided informed consent prior to initiation of any study-specific activities/procedures
• Age ≥ 18 years on entry into the study
• Documented history of migraine without aura and/or migraine with aura according to the ICHD-3 classification for ≥ 12 months at screening
• Documented history of CM for a minimal duration of 6 months before screening
• Current diagnosis of MOH
• History of treatment failure with at least 1 preventive treatment as defined as treatment discontinuation due to lack of efficacy, adverse event or general poor tolerability

Key Exclusion Criteria Part 1

Participants are excluded from the study if any of the following criteria apply:

Disease Related

• Age > 50 years at migraine onset or > 65 years at CM onset
• History of hemiplegic migraine, cluster headache or other trigeminal autonomic cephalalgia
• Current concomitant diagnosis of a secondary type of headache other than MOH
• No therapeutic response in prevention of migraine after an adequate therapeutic trial of > 3 preventive treatment categories
• Changes in drug regimen (ie, changes in dose or frequency of use) of an allowed migraine preventive medication within 2 months prior to start of baseline
• Received botulinum toxin in the head and/or neck region within 4 months prior to screening
• Documented history of treatment with an anti-calcitonin gene-related peptide product preventive treatment
• Anticipated to require any excluded medication/device or procedure during the study

Other Medical Conditions

• History or evidence of unstable or clinically significant medical condition that, in the opinion of the investigator or Amgen's physician, if consulted, would pose a risk to participant safety or interfere with the study evaluation, procedures or completion
• Evidence of "recreational use" of illicit drugs within 12 months prior to screening, based on medical records, self-report, or a positive drug test performed during screening.

Key Inclusion Criteria Part 2. To be assessed at the end of the baseline period and prior to enrollment into DBTP. Based on information collected through the electronic diary (eDiary) during the baseline period, the following requirements must be met:

-≥ 14 headache days during the 28-day baseline period out of which ≥ 8 headache days meet criteria as migraine days

• Observation of acute migraine medication overuse during the baseline period. Medication overuse at baseline is defined as:
• ≥ 10 days of combination treatment OR
• ≥ 10 days of short-acting opioids/opioid-containing medication OR
• ≥ 10 days of triptans, ergots, OR
• ≥ 15 days of nonsteroidal anti-inflammatory drugs or simple analgesics intake
• At least 2 acute headache medication days per week for each week with at least 5 diary days
• Demonstrated at least 80% compliance with the eDiary (eg, must complete eDiary items on at least 23 out of 28 days during the baseline period)

Key Exclusion Criteria Part 2

Study Procedures

• Changed or planning to change the dose of an allowed concomitant medication that may have migraine preventive effect during baseline period or post-randomization
• Unstable or clinically significant medical condition that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to participant safety or interfere with the study evaluation, procedures or completion

Contraception, pregnancy or breastfeeding

• Unwillingness to maintain acceptable contraception method, when applicable
• Evidence of pregnancy or breastfeeding per participant self-report, medical records or positivity on baseline pregnancy screening tests, through end of study

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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620 participants in 3 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

After participants complete the baseline period and are found eligible, they will be enrolled and randomized in a 1:1:1 ratio to either erenumab (70 mg or 140 mg) or placebo.

Treatment:

Drug: Placebo

Erenumab 70 mg

Active Comparator group

Description:

After participants complete the baseline period and are found eligible, they will be enrolled and randomized in a 1:1:1 ratio to either erenumab (70 mg or 140 mg) or placebo.

Treatment:

Drug: Erenumab 70 mg

Erenumab 140 mg

Active Comparator group

Description:

After participants complete the baseline period and are found eligible, they will be enrolled and randomized in a 1:1:1 ratio to either erenumab (70 mg or 140 mg) or placebo.

Treatment:

Drug: Erenumab 140 mg