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

Episodic Migraine Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03096834
• Other study ID #: CAMG334A2301
• Secondary ID: 2016-002211-18
• Status: Completed
• Phase: Phase 3
• Start date: March 20, 2017
• Est. completion date: January 28, 2021

Study information

• Verified date: February 2022
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 246
• Est. completion date: January 28, 2021
• Est. primary completion date: January 18, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Episodic Migraine
• Migraine Disorders

Intervention

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
• Placebo Pre-Filled Syringe (PFS)
Subcutaneous injection of matching placebo

Locations

Country	Name	City	State
Australia	Novartis Investigative Site	Heidelberg
Austria	Novartis Investigative Site	Innsbruck
Austria	Novartis Investigative Site	Vienna
Belgium	Novartis Investigative Site	Brussel
Belgium	Novartis Investigative Site	Gent
Belgium	Novartis Investigative Site	Hasselt
Belgium	Novartis Investigative Site	Leuven
Czechia	Novartis Investigative Site	Czech Republic
Czechia	Novartis Investigative Site	Prague	CZE
Czechia	Novartis Investigative Site	Praha 4
Denmark	Novartis Investigative Site	Glostrup
Finland	Novartis Investigative Site	Helsinki
Finland	Novartis Investigative Site	Helsinki
Finland	Novartis Investigative Site	Turku
France	Novartis Investigative Site	Lille Cedex
France	Novartis Investigative Site	Marseille Cedex 05
France	Novartis Investigative Site	Nice
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Bielefeld
Germany	Novartis Investigative Site	Bochum
Germany	Novartis Investigative Site	Erlangen
Germany	Novartis Investigative Site	Essen
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Kiel
Germany	Novartis Investigative Site	Leipzig
Germany	Novartis Investigative Site	Muenchen
Germany	Novartis Investigative Site	Tübingen
Germany	Novartis Investigative Site	Wiesbaden
Greece	Novartis Investigative Site	Athens	GR
Greece	Novartis Investigative Site	Glyfada
Greece	Novartis Investigative Site	Maroussi
Italy	Novartis Investigative Site	Bologna	BO
Italy	Novartis Investigative Site	Firenze	FI
Italy	Novartis Investigative Site	Milano
Italy	Novartis Investigative Site	Napoli
Italy	Novartis Investigative Site	Palermo
Italy	Novartis Investigative Site	Roma	RM
Netherlands	Novartis Investigative Site	Leiden
Netherlands	Novartis Investigative Site	Nijmegen
Netherlands	Novartis Investigative Site	Sittard-Geleen	BG
Norway	Novartis Investigative Site	Hamar
Norway	Novartis Investigative Site	Sandvika
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Fuenlabrada	Madrid
Spain	Novartis Investigative Site	Pozuelo de Alarcon	Madrid
Spain	Novartis Investigative Site	Santander	Cantabria
Spain	Novartis Investigative Site	Valladolid	Castilla Y Leon
Spain	Novartis Investigative Site	Zaragoza
Sweden	Novartis Investigative Site	Lund
Sweden	Novartis Investigative Site	Stockholm
Sweden	Novartis Investigative Site	Uppsala
Sweden	Novartis Investigative Site	Vallingby
Switzerland	Novartis Investigative Site	Bad Zurzach
Switzerland	Novartis Investigative Site	Lausanne
Switzerland	Novartis Investigative Site	Zollikon
United Kingdom	Novartis Investigative Site	Brighton	East Sussex
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	Stoke on Trent	Staffordshire

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

Australia,  Austria,  Belgium,  Czechia,  Denmark,  Finland,  France,  Germany,  Greece,  Italy,  Netherlands,  Norway,  Spain,  Sweden,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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