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

A 12-week Double-blind, Randomized, Multicenter Study Comparing the Efficacy and Safety of Once Monthly Subcutaneous 140 mg AMG 334 Against Placebo in Adult Episodic Migraine Patients Who Have Failed 2-4 Prophylactic Treatments (LIBERTY)

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.

Study Overview

• Status: Completed
• Conditions: Episodic Migraine
• Intervention / Treatment: Biological: Placebo Pre-Filled Syringe (PFS); Biological: AMG334 (70 mg) Pre-Filled Syringe (PFS)

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 Type: Interventional
• Enrollment (Actual): 246
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Heidelberg, Australia, 3084
    • Novartis Investigative Site
• Austria
  • Innsbruck, Austria, A 6020
    • Novartis Investigative Site
  • Vienna, Austria, 1090
    • Novartis Investigative Site
• Belgium
  • Brussel, Belgium, 1090
    • Novartis Investigative Site
  • Gent, Belgium, 9000
    • Novartis Investigative Site
  • Hasselt, Belgium, 3500
    • Novartis Investigative Site
  • Leuven, Belgium, 3000
    • Novartis Investigative Site
• Czechia
  • Czech Republic, Czechia, 18600
    • Novartis Investigative Site
  • Praha 4, Czechia, 140 59
    • Novartis Investigative Site
  • CZE
    • Prague, CZE, Czechia, 120 00
      • Novartis Investigative Site
• Denmark
  • Glostrup, Denmark, 2600
    • Novartis Investigative Site
• Finland
  • Helsinki, Finland, 00180
    • Novartis Investigative Site
  • Helsinki, Finland, 00930
    • Novartis Investigative Site
  • Turku, Finland, 20100
    • Novartis Investigative Site
• France
  • Lille Cedex, France, 59037
    • Novartis Investigative Site
  • Marseille Cedex 05, France, 13885
    • Novartis Investigative Site
  • Nice, France, 06003
    • Novartis Investigative Site
• Germany
  • Berlin, Germany, 13353
    • Novartis Investigative Site
  • Berlin, Germany, 10435
    • Novartis Investigative Site
  • Bielefeld, Germany, D 33647
    • Novartis Investigative Site
  • Bochum, Germany, 44787
    • Novartis Investigative Site
  • Erlangen, Germany, 91054
    • Novartis Investigative Site
  • Essen, Germany, 45147
    • Novartis Investigative Site
  • Hamburg, Germany, 20251
    • Novartis Investigative Site
  • Kiel, Germany, 24149
    • Novartis Investigative Site
  • Leipzig, Germany, 04107
    • Novartis Investigative Site
  • Muenchen, Germany, 81377
    • Novartis Investigative Site
  • Tübingen, Germany, 72076
    • Novartis Investigative Site
  • Wiesbaden, Germany, 65191
    • Novartis Investigative Site
• Greece
  • Glyfada, Greece, 16675
    • Novartis Investigative Site
  • Maroussi, Greece, 15125
    • Novartis Investigative Site
  • GR
    • Athens, GR, Greece, 115 25
      • Novartis Investigative Site
• Italy
  • Milano, Italy, 20133
    • Novartis Investigative Site
  • Napoli, Italy, 80138
    • Novartis Investigative Site
  • Palermo, Italy, 90127
    • Novartis Investigative Site
  • BO
    • Bologna, BO, Italy, 40139
      • Novartis Investigative Site
  • FI
    • Firenze, FI, Italy, 50139
      • Novartis Investigative Site
  • RM
    • Roma, RM, Italy, 00189
      • Novartis Investigative Site
• Netherlands
  • Leiden, Netherlands, 2333 ZA
    • Novartis Investigative Site
  • Nijmegen, Netherlands, 6532 SZ
    • Novartis Investigative Site
  • BG
    • Sittard-Geleen, BG, Netherlands, 6162 BG
      • Novartis Investigative Site
• Norway
  • Hamar, Norway, 2317
    • Novartis Investigative Site
  • Sandvika, Norway, 1337
    • Novartis Investigative Site
• Spain
  • Zaragoza, Spain, 50009
    • Novartis Investigative Site
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Novartis Investigative Site
  • Castilla Y Leon
    • Valladolid, Castilla Y Leon, Spain, 47011
      • Novartis Investigative Site
  • Catalunya
    • Barcelona, Catalunya, Spain, 08035
      • Novartis Investigative Site
  • Madrid
    • Fuenlabrada, Madrid, Spain, 28942
      • Novartis Investigative Site
    • Pozuelo de Alarcon, Madrid, Spain, 28223
      • Novartis Investigative Site
• Sweden
  • Lund, Sweden, 222 22
    • Novartis Investigative Site
  • Stockholm, Sweden, 114 33
    • Novartis Investigative Site
  • Uppsala, Sweden, SE-751 85
    • Novartis Investigative Site
  • Vallingby, Sweden, 162 68
    • Novartis Investigative Site
• Switzerland
  • Bad Zurzach, Switzerland, 5330
    • Novartis Investigative Site
  • Lausanne, Switzerland, 1011
    • Novartis Investigative Site
  • Zollikon, Switzerland, 8702
    • Novartis Investigative Site
• United Kingdom
  • London, United Kingdom, SE5 9RS
    • Novartis Investigative Site
  • East Sussex
    • Brighton, East Sussex, United Kingdom, BN2 5BE
      • Novartis Investigative Site
  • Staffordshire
    • Stoke on Trent, Staffordshire, United Kingdom, ST46QG
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo DB; Matching placebo subcutaneous injections administered every 4 weeks during Double-Blind Epoch	Biological: Placebo Pre-Filled Syringe (PFS); Subcutaneous injection of matching placebo
Experimental: AMG334 140 mg DB; AMG334 70 mg subcutaneous injections (2) administered every 4 weeks during Double-Blind Epoch	Biological: AMG334 (70 mg) Pre-Filled Syringe (PFS); Two injections of AMG 334 70 mg (equaling 140 mg total dose) will be administered via subcutaneous injection
Experimental: AMG334 140 mg DB cont on AMG334 140 mg; AMG334 70 mg subcutaneous injections (2) during DB continued on AMG334 140 mg in Open-Label Epoch	Biological: AMG334 (70 mg) Pre-Filled Syringe (PFS); Two injections of AMG 334 70 mg (equaling 140 mg total dose) will be administered via subcutaneous injection
Experimental: Placebo in DB to AMG334 140 mg; Placebo in Double-Blind Epoch (DB) switched to AMG334 140 mg in Open-Label Epoch	Biological: AMG334 (70 mg) Pre-Filled Syringe (PFS); Two injections of AMG 334 70 mg (equaling 140 mg total dose) will be administered via subcutaneous injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With at Least 50% Reduction From Baseline of Monthly Migraine Days (MMD) in the Last Month (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.	Baseline, Month 3 (last 4 weeks of treatment)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Monthly Migraine Days (MMD) in the Last Month (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.	Baseline, Month 3 (last 4 weeks of treatment)
Change From Baseline in Physical Impairment and Everyday Activities as Measured by the Migraine Physical Function Impact Diary (MPFID) at Month 3	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)	Baseline, Month 3 (last 4 weeks of treatment)
Change in the Number of Monthly Acute Migraine-specific Medication Treatment Days at Month 3	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.	Baseline, Month 3 (last 4 weeks of treatment)
Percentage of Participants With a 75% Reduction From Baseline of Monthly Migraine Days (MMD) in the Last Month (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.	Baseline, Month 3 (last 4 weeks of treatment)
Percentage of Participants With a 100% Reduction From Baseline of Monthly Migraine Days (MMD) in the Last Month (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.	Baseline, Month 3 (last 4 weeks of treatment)
Number of Participants Who Developed Anti-AMG334 Antibodies	Blood samples for immunogenicity testing were collected for the measurement of anti-AMG334 binding antibodies.	Baseline up to approximately 180 weeks

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Lampl C, Kraus V, Lehner K, Loop B, Chehrenama M, Maczynska Z, Ritter S, Klatt J, Snellman J. Safety and tolerability of erenumab in individuals with episodic or chronic migraine across age groups: a pooled analysis of placebo-controlled trials. J Headache Pain. 2022 Aug 18;23(1):104. doi: 10.1186/s10194-022-01470-4.
• Ferrari MD, Reuter U, Goadsby PJ, Paiva da Silva Lima G, Mondal S, Wen S, Tenenbaum N, Pandhi S, Lanteri-Minet M, Stites T. Two-year efficacy and safety of erenumab in participants with episodic migraine and 2-4 prior preventive treatment failures: results from the LIBERTY study. J Neurol Neurosurg Psychiatry. 2022 Mar;93(3):254-262. doi: 10.1136/jnnp-2021-327480. Epub 2021 Nov 29.
• Goadsby PJ, Reuter U, Lanteri-Minet M, Paiva da Silva Lima G, Hours-Zesiger P, Fernandes C, Wen S, Tenenbaum N, Kataria A, Ferrari MD, Klatt J. Long-Term Efficacy and Safety of Erenumab: Results From 64 Weeks of the LIBERTY Study. Neurology. 2021 Apr 28;96(22):e2724-35. doi: 10.1212/WNL.0000000000012029. Online ahead of print.
• Lanteri-Minet M, Goadsby PJ, Reuter U, Wen S, Hours-Zesiger P, Ferrari MD, Klatt J. Effect of erenumab on functional outcomes in patients with episodic migraine in whom 2-4 preventives were not useful: results from the LIBERTY study. J Neurol Neurosurg Psychiatry. 2021 May;92(5):466-472. doi: 10.1136/jnnp-2020-324396. Epub 2021 Jan 5.
• Reuter U, Goadsby PJ, Lanteri-Minet M, Wen S, Hours-Zesiger P, Ferrari MD, Klatt J. Efficacy and tolerability of erenumab in patients with episodic migraine in whom two-to-four previous preventive treatments were unsuccessful: a randomised, double-blind, placebo-controlled, phase 3b study. Lancet. 2018 Nov 24;392(10161):2280-2287. doi: 10.1016/S0140-6736(18)32534-0. Epub 2018 Oct 22.

Study record dates

Study Major Dates

• Study Start (Actual): March 20, 2017
• Primary Completion (Actual): January 18, 2018
• Study Completion (Actual): January 28, 2021

Study Registration Dates

• First Submitted: March 17, 2017
• First Submitted That Met QC Criteria: March 24, 2017
• First Posted (Actual): March 30, 2017

Study Record Updates

• Last Update Posted (Actual): March 23, 2022
• Last Update Submitted That Met QC Criteria: February 23, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: adult; Migraine; headache; erenumab; CGRP receptor agonist; aura; attack; episodic; AMG 334
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Migraine Disorders; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Calcitonin Gene-Related Peptide Receptor Antagonists; Erenumab
• Other Study ID Numbers: CAMG334A2301; 2016-002211-18 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes