A Study Evaluating the Effectiveness of AMG 334 Injection in Preventing Migraines in Adults Having Failed Other Therapies

Phase 3

Completed

• Conditions: Episodic Migraine
• Interventions: Biological: AMG334 (70 mg) Pre-Filled Syringe (PFS); Biological: Placebo Pre-Filled Syringe (PFS)

• Registration Number: NCT03096834
• Lead Sponsor: Novartis Pharmaceuticals

Brief Summary

The purpose of this study is to determine if AMG 334 is effective in treating migraines in patients who have failed other preventive migraine treatments.

Detailed Description

This study was a double blind, placebo-controlled, randomized trial in adult patients with episodic migraine. There was a screening period of 2 weeks to assess initial eligibility, and a 4-week baseline period. After randomization, participants entered the double-blind treatment epoch (DBTE) and had clinic visits for 12 weeks. All participants who completed the DBTE were eligible to enter the Open-Label Treatment Epoch (OLTE) for up to 156 weeks. All participants had a 12 week Follow-Up Epoch and a a Follow-Up visit 16 weeks after the last dose of AMG334 unless the participant continued on commercially available AMG334. Participants who had demonstrated clinical benefit were eligible to enter a Post Trial Access (PTA-Open Label Treatment Epoch) of flexible duration for approximately 6 months.

Study Timeline

• Study First Submitted: 2017-03-17
• Study Start: 2017-03-20
• Study First Submitted QC: 2017-03-24
• Study First Posted: 2017-03-30
• Primary Completion: 2018-01-18
• Disposition First Submitted: 2019-09-16
• Disposition First Submitted QC: 2019-09-20
• Disposition First Posted: 2019-10-04
• Study Completion: 2021-01-28
• Results First Submitted: 2022-01-25
• Results First Submitted QC: 2022-01-25
• Status Verified: 2022-02
• Results First Posted: 2022-02-18
• Last Update Submitted: 2022-02-23
• Last Update Posted: 2022-03-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 246

Inclusion Criteria

• Documented history of migraine in the 12 months prior to screen
• 4-14 days per month of migraine symptoms
• >=80% diary compliance during the Baseline period
• Failure of previous migraine prophylactic treatments

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Exclusion Criteria

• >50 years old at migraine onset
• Pregnant or nursing
• History of cluster or hemiplegic headache
• Evidence of seizure or psychiatric disorder
• Score of over 19 on Beck Depression Inventory-2
• Active chronic pain syndrome
• Cardiac or hepatic disease

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
AMG334 140 mg DB cont on AMG334 140 mg	AMG334 (70 mg) Pre-Filled Syringe (PFS)	AMG334 70 mg subcutaneous injections (2) during DB continued on AMG334 140 mg in Open-Label Epoch
Placebo DB	Placebo Pre-Filled Syringe (PFS)	Matching placebo subcutaneous injections administered every 4 weeks during Double-Blind Epoch
Placebo in DB to AMG334 140 mg	AMG334 (70 mg) Pre-Filled Syringe (PFS)	Placebo in Double-Blind Epoch (DB) switched to AMG334 140 mg in Open-Label Epoch
AMG334 140 mg DB	AMG334 (70 mg) Pre-Filled Syringe (PFS)	AMG334 70 mg subcutaneous injections (2) administered every 4 weeks during Double-Blind Epoch

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With at Least 50% Reduction From Baseline of Monthly Migraine Days (MMD) in the Last Month (Last 4 Weeks of Treatment)	Baseline, Month 3 (last 4 weeks of treatment)	A migraine day was defined as any calendar day in which the subject experienced a qualified migraine headache defined as: with/without aura, lasting ≥ 30 minutes with at least 1 criteria: 1. ≥ 2 of following pain features: unilateral, throbbing, moderate to severe or exacerbated with exercise/physical activity, 2. ≥ 1 of the following symptoms: nausea and/or vomiting, photophobia and phonophobia. If a migraine-specific medication (ie, triptan or ergotamine) was taken during aura, or a headache, it was counted as a migraine day regardless of duration and pain features/associated symptoms.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Monthly Migraine Days (MMD) in the Last Month (Last 4 Weeks of Treatment)	Baseline, Month 3 (last 4 weeks of treatment)	A migraine day was defined as any calendar day in which the subject experienced a qualified migraine headache defined as: with/without aura, lasting ≥ 30 minutes with at least 1 criteria: 1. ≥ 2 of following pain features: unilateral, throbbing, moderate to severe or exacerbated with exercise/physical activity, 2. ≥ 1 of the following symptoms: nausea and/or vomiting, photophobia and phonophobia. If a migraine-specific medication (ie, triptan or ergotamine) was taken during aura, or a headache, it was counted as a migraine day regardless of duration and pain features/associated symptoms.
Percentage of Participants With a 75% Reduction From Baseline of Monthly Migraine Days (MMD) in the Last Month (Last 4 Weeks of Treatment)	Baseline, Month 3 (last 4 weeks of treatment)	A migraine day was defined as any calendar day in which the subject experienced a qualified migraine headache defined as: with/without aura, lasting ≥ 30 minutes with at least 1 criteria: 1. ≥ 2 of following pain features: unilateral, throbbing, moderate to severe or exacerbated with exercise/physical activity, 2. ≥ 1 of the following symptoms: nausea and/or vomiting, photophobia and phonophobia. If a migraine-specific medication (ie, triptan or ergotamine) was taken during aura, or a headache, it was counted as a migraine day regardless of duration and pain features/associated symptoms.
Change From Baseline in Physical Impairment and Everyday Activities as Measured by the Migraine Physical Function Impact Diary (MPFID) at Month 3	Baseline, Month 3 (last 4 weeks of treatment)	MPFID has 2 domains: Everyday Activities, which consisted of 7 items and Physical Impairment with 5 items using a 5-point scale. Scores were summed across each domain and were then transformed and used for analyses. Transforming MPFID domain scores ranged from 0-100, where higher scores were indicative of greater migraine impact (ie, higher burden)
Change in the Number of Monthly Acute Migraine-specific Medication Treatment Days at Month 3	Baseline, Month 3 (last 4 weeks of treatment)	Number of days on which acute migraine-specific medications were used were recorded in eDiary between each monthly IP dose. Migraine-Specific medications included two categories of medications: triptan-based migraine medications and ergotamine-based migraine medications. Monthly migraine-specific medication use at baseline was the number of migraine-specific medication treatment days in the baseline period.
Percentage of Participants With a 100% Reduction From Baseline of Monthly Migraine Days (MMD) in the Last Month (Last 4 Weeks of Treatment)	Baseline, Month 3 (last 4 weeks of treatment)	A migraine day was defined as any calendar day in which the subject experienced a qualified migraine headache defined as: with/without aura, lasting ≥ 30 minutes with at least 1 criteria: 1. ≥ 2 of following pain features: unilateral, throbbing, moderate to severe or exacerbated with exercise/physical activity, 2. ≥ 1 of the following symptoms: nausea and/or vomiting, photophobia and phonophobia. If a migraine-specific medication (ie, triptan or ergotamine) was taken during aura, or a headache, it was counted as a migraine day regardless of duration and pain features/associated symptoms.
Number of Participants Who Developed Anti-AMG334 Antibodies	Baseline up to approximately 180 weeks	Blood samples for immunogenicity testing were collected for the measurement of anti-AMG334 binding antibodies.

Trial Locations

Locations (1)

Novartis Investigative Site; 🇬🇧 London, United Kingdom