Study to Evaluate the Efficacy and Safety of Erenumab (AMG 334) in Migraine Prevention

Amgen

Status and phase: Completed; Phase 2

Conditions: Migraine

Treatments: Drug: Erenumab; Drug: Placebo; Drug: Erenumab PFS; Drug: Erenumab AI/Pen

Study type: Interventional

Funder types: Industry

Identifiers

NCT01952574

2012-005331-90 (EudraCT Number)

20120178

Details and patient eligibility

About

A study to evaluate the effect of erenumab compared to placebo on the change from baseline in monthly migraine days in participants with episodic migraine.

Full description

The study is composed of an initial screening phase (up to 3 weeks), a 4-week baseline phase, a 12-week double-blind treatment phase (DBTP), an open-label treatment phase (OLTP) for up to 256 weeks, and an 8-week safety follow-up (12 weeks after the last dose of investigational product [IP]).

In the DBTP participants were to be randomized in a 3:2:2:2 ratio to placebo, erenumab 7 mg, erenumab 21 mg, or erenumab 70 mg.

During the open-label treatment phase, participants were to receive erenumab 70 mg QM from week 12 to week 264. After implementation of Protocol Amendment 3 (07 April 2016), participants remaining in the OLTP increased their dose to erenumab 140 mg QM up to week 264. The safety follow-up increased from an 8-week safety follow-up to a 12-week safety follow-up (16 weeks after the last dose of investigational product).

During the OLTP participants enrolled at sites in the United States could enroll in an optional clinical home use (CHU) substudy, per a country-specific protocol amendment dated 20 June 2016. Participants in the CHU substudy were to be randomized 1:1 into 1 of 2 treatment groups: erenumab 140 mg using a prefilled syringe or erenumab 140 mg using an autoinjector/pen. Day 1 of the CHU substudy corresponded with any OLTP study visit up through Week 256, as long as the participant had received at least 2 doses of erenumab 140 mg. During the CHU substudy, participants initially self-administered IP under site supervision on substudy day 1, and then self-administered IP at home on substudy days 29 and 57.

Enrollment: 483 patients

Sex: All

Ages: 18 to 60 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• History of migraine for more than12 months prior to screening
• Migraine frequency: ≥ 4 and ≤ 14 migraine days per month in each of the 3 months prior to screening and during baseline phase
• Headache frequency: < 15 headache days per month (with > 50% of the headache days being migraine days) in each of the 3 months prior to screening and during baseline phase
• Demonstrated at least 80% compliance with the eDiary during baseline phase

Exclusion criteria

• Older than 50 years of age at migraine onset

• History of cluster headache or basilar or hemiplegic migraine headache

• Unable to differentiate migraine from other headaches

• No therapeutic response with > 2 of the following eight medication categories for prophylactic treatment of migraine after an adequate therapeutic trial. Medication categories are:

  • Category 1: Divalproex sodium, sodium valproate
  • Category 2: Topiramate
  • Category 3: Beta blockers (for example: atenolol, bisoprolol, metoprolol, nadolol, nebivolol, pindolol, propranolol, timolol)
  • Category 4: Tricyclic antidepressants (for example: amitriptyline, nortriptyline, protriptyline)
  • Category 5: Venlafaxine, desvenlafaxine, duloxetine, milnacipran
  • Category 6: Flunarizine, verapamil
  • Category 7: Lisinopril, candesartan
  • Category 8: Butterbur, feverfew, magnesium (≥ 600 mg/day), riboflavin (≥ 100 mg/day)

• Overuse of acute migraine medications in any month during the 3 months prior to screening or during screening

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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483 participants in 6 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Participants received placebo on day 1 and at weeks 4 and 8 by subcutaneous injection during the double-blind treatment phase. In the open-label treatment phase participants received 70 mg erenumab QM from week 12 to week 264 (last dose). After Protocol Amendment 3, participants still on study had their dose increased to 140 mg QM.

Treatment:

Drug: Placebo

Drug: Erenumab

Erenumab 7 mg QM

Experimental group

Description:

Participants received erenumab 7 mg on day 1 and at weeks 4 and 8 by subcutaneous injection during the double-blind treatment phase. In the open-label treatment phase participants received 70 mg erenumab QM from week 12 to week 264 (last dose). After Protocol Amendment 3, participants still on study had their dose increased to 140 mg QM.

Treatment:

Drug: Erenumab

Erenumab 21 mg QM

Experimental group

Description:

Participants received erenumab 21 mg on day 1 and at weeks 4 and 8 by subcutaneous injection during the double-blind treatment phase. In the open-label treatment phase participants received 70 mg erenumab QM from week 12 to week 264 (last dose). After Protocol Amendment 3, participants still on study had their dose increased to 140 mg QM.

Treatment:

Drug: Erenumab

Erenumab 70 mg QM

Experimental group

Description:

Participants received erenumab 70 mg on day 1 and at weeks 4 and 8 by subcutaneous injection during the double-blind treatment phase. In the open-label treatment phase participants received 70 mg erenumab QM from week 12 to week 264 (last dose). After Protocol Amendment 3, participants still on study had their dose increased to 140 mg QM.

Treatment:

Drug: Erenumab

CHU Substudy: Erenumab 140 mg PFS

Experimental group

Description:

Participants in the open-label treatment phase in the United States randomized to self-administer 140 mg erenumab via two 70 mg injections using a prefilled syringe (PFS) on CHU substudy day 1 (under study site supervision), and at home on day 29 (week 4) and day 57 (week 8).

Treatment:

Drug: Erenumab PFS

CHU Substudy: Erenumab 140 mg AI/Pen

Experimental group

Description:

Participants in the open-label treatment phase in the United States randomized to self-administer 140 mg erenumab via two 70 mg injections using an autoinjector/pen (AI)/pen) on CHU substudy day 1 (under study site supervision), and at home on day 29 (week 4) and day 57 (week 8).

Treatment:

Drug: Erenumab AI/Pen