Study of Efficacy and Safety of AMG 334 in Adult Episodic Migraine Patients (EMPOwER)

A 12-week Double-blind, Randomized, Multi-center Study Comparing the Efficacy and Safety of Once Monthly Subcutaneous AMG 334 Against Placebo in Adult Episodic Migraine Patients (EMPOwER)

This study is to evaluate the efficacy and safety of AMG334 in adult patients with episodic migraine

Study Overview

• Status: Completed
• Conditions: Episodic Migraine
• Intervention / Treatment: Biological: Erenumab; Other: Placebo

Detailed Description

This study used a single-cohort, 3-treatment arm, randomized, double-blind study design in adult patients with episodic migraine. The subjects were randomized to receive either erenumab or placebo in a 2:3:3 ratio (erenumab 140 mg: erenumab 70 mg: placebo). A screening period of 2 weeks was used to assess initial eligibility, followed by a 4-week baseline period. After randomization/Day 1, visits occurred at four week intervals until Week 12, which was the End of Treatment. The final visit, Last Patient Last Visit was a Safety Follow-Up visit, which occurred 12 weeks later, at Week 24.

• Study Type: Interventional
• Enrollment (Actual): 900
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, 1061
    • Novartis Investigative Site
  • Buenos Aires, Argentina, C1012AAR
    • Novartis Investigative Site
  • Ciudad Autonoma de Bs As, Argentina, C1128AAF
    • Novartis Investigative Site
  • Cordoba, Argentina, 5001
    • Novartis Investigative Site
  • Buenos Aires
    • Caba, Buenos Aires, Argentina, C1056ABJ
      • Novartis Investigative Site
    • Caba, Buenos Aires, Argentina, C1428AQK
      • Novartis Investigative Site
    • Caba, Buenos Aires, Argentina, C1181ACH
      • Novartis Investigative Site
• India
  • Belagavi, India, 590010
    • Novartis Investigative Site
  • Mumbai, India, 400016
    • Novartis Investigative Site
  • New Delhi, India, 110029
    • Novartis Investigative Site
  • Andhra Pradesh
    • Guntur, Andhra Pradesh, India, 522 001
      • Novartis Investigative Site
  • Delhi
    • New Delhi, Delhi, India, 110 060
      • Novartis Investigative Site
    • New Delhi, Delhi, India, 110002
      • Novartis Investigative Site
  • Gujarat
    • Ahmedabad, Gujarat, India, 382428
      • Novartis Investigative Site
  • Karnataka
    • Bangalore, Karnataka, India, 560054
      • Novartis Investigative Site
    • Bangalore, Karnataka, India, 560060
      • Novartis Investigative Site
    • Mysore, Karnataka, India, 570001
      • Novartis Investigative Site
  • Kerala
    • Kochi, Kerala, India, 682 026
      • Novartis Investigative Site
    • Kochi, Kerala, India, 682027
      • Novartis Investigative Site
    • Kozhikode, Kerala, India, 673004
      • Novartis Investigative Site
    • Thiruvananthapuram, Kerala, India, 695011
      • Novartis Investigative Site
  • Maharashtra
    • Mumbai, Maharashtra, India, 400008
      • Novartis Investigative Site
    • Mumbai, Maharashtra, India, 401107
      • Novartis Investigative Site
    • Nagpur, Maharashtra, India, 400 012
      • Novartis Investigative Site
    • Nashik, Maharashtra, India, 422005
      • Novartis Investigative Site
    • Nashik, Maharashtra, India, 422 005
      • Novartis Investigative Site
    • Pune, Maharashtra, India, 411004
      • Novartis Investigative Site
  • Punjab
    • Ludhiana, Punjab, India, 141001
      • Novartis Investigative Site
  • Tamil Nadu
    • Chennai, Tamil Nadu, India, 600100
      • Novartis Investigative Site
  • Telangana
    • Hyderabad, Telangana, India, 500082
      • Novartis Investigative Site
  • Uttar Pradesh
    • Lucknow, Uttar Pradesh, India, 226014
      • Novartis Investigative Site
  • Uttarakhand
    • DehraDun, Uttarakhand, India, 248001
      • Novartis Investigative Site
  • West Bengal
    • Kolkata, West Bengal, India, 700017
      • Novartis Investigative Site
    • Kolkata, West Bengal, India, 700068
      • Novartis Investigative Site
• Korea, Republic of
  • Busan, Korea, Republic of, 47392
    • Novartis Investigative Site
  • Gwangju, Korea, Republic of, 61469
    • Novartis Investigative Site
  • Gyeonggi do, Korea, Republic of, 11765
    • Novartis Investigative Site
  • Incheon, Korea, Republic of, 22332
    • Novartis Investigative Site
  • Seoul, Korea, Republic of, 06351
    • Novartis Investigative Site
  • Seoul, Korea, Republic of, 03722
    • Novartis Investigative Site
  • Seoul, Korea, Republic of, 139-711
    • Novartis Investigative Site
  • Gyeonggi Do
    • Hwaseong si, Gyeonggi Do, Korea, Republic of, 18450
      • Novartis Investigative Site
  • KOR
    • Seoul, KOR, Korea, Republic of, 03181
      • Novartis Investigative Site
    • Seoul, KOR, Korea, Republic of, 08308
      • Novartis Investigative Site
  • Korea
    • Daejeon, Korea, Korea, Republic of, 35015
      • Novartis Investigative Site
    • Seoul, Korea, Korea, Republic of, 03080
      • Novartis Investigative Site
• Lebanon
  • Beirut, Lebanon, 1107 2020
    • Novartis Investigative Site
  • Beirut, Lebanon, 6301
    • Novartis Investigative Site
  • Beirut, Lebanon, 166378
    • Novartis Investigative Site
  • Beirut, Lebanon
    • Novartis Investigative Site
  • LBN
    • El Chouf, LBN, Lebanon, 1503201002
      • Novartis Investigative Site
• Malaysia
  • Kuala Lumpur, Malaysia, 59100
    • Novartis Investigative Site
  • MYS
    • Kuala Lumpur, MYS, Malaysia, 56000
      • Novartis Investigative Site
  • Pulau Pinang
    • Seberang Jaya, Pulau Pinang, Malaysia, 13700
      • Novartis Investigative Site
  • Selangor
    • Sungai Buloh, Selangor, Malaysia, 47000
      • Novartis Investigative Site
  • Wilayah Persekutuan
    • Kuala Lumpur, Wilayah Persekutuan, Malaysia, 50586
      • Novartis Investigative Site
• Mexico
  • Chihuahua, Mexico, 31203
    • Novartis Investigative Site
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44130
      • Novartis Investigative Site
    • Guadalajara, Jalisco, Mexico, 44610
      • Novartis Investigative Site
  • Nuevo Leon
    • Monterrey, Nuevo Leon, Mexico, 64060
      • Novartis Investigative Site
• Philippines
  • Pasig City, Philippines, 1605
    • Novartis Investigative Site
  • Quezon City, Philippines, 1102
    • Novartis Investigative Site
  • Metro Manila
    • Manila, Metro Manila, Philippines, 1000
      • Novartis Investigative Site
    • Manila, Metro Manila, Philippines, 1012
      • Novartis Investigative Site
• Singapore
  • Singapore, Singapore, 169608
    • Novartis Investigative Site
  • Singapore, Singapore, 308433
    • Novartis Investigative Site
• Taiwan
  • Chia-Yi, Taiwan, 60002
    • Novartis Investigative Site
  • Taichung, Taiwan, 40447
    • Novartis Investigative Site
  • Taichung County, Taiwan
    • Novartis Investigative Site
  • Tainan, Taiwan, 71004
    • Novartis Investigative Site
  • Tainan, Taiwan
    • Novartis Investigative Site
  • Taipei, Taiwan, 11217
    • Novartis Investigative Site
  • Taipei, Taiwan, 10449
    • Novartis Investigative Site
  • Taoyuan, Taiwan, 33305
    • Novartis Investigative Site
• Thailand
  • Bangkok, Thailand, 10330
    • Novartis Investigative Site
  • Bangkok, Thailand, 10400
    • Novartis Investigative Site
  • Chiang Mai, Thailand, 50200
    • Novartis Investigative Site
  • THA
    • Bangkok, THA, Thailand, 10400
      • Novartis Investigative Site
    • Khon Kaen, THA, Thailand, 40002
      • Novartis Investigative Site
• Vietnam
  • Hanoi, Vietnam, 100000
    • Novartis Investigative Site
  • VNM
    • Ho Chi Minh, VNM, Vietnam, 700000
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key inclusion criteria:

1. Documented history of migraine in the 12 months prior to screening
2. 4-14 days per month of migraine symptoms
3. >=80% diary compliance during the Baseline period

Key exclusion criteria:

1. >50 years old at migraine onset
2. Pregnant or nursing
3. History of cluster or hemiplegic headache
4. Evidence of seizure or major psychiatric disorder
5. Score of 19 or higher on the BDI
6. Active chronic pain syndrome
7. Cardiac or hepatic disease

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AMG334 70 mg; AMG334 70 mg: one pre-filled syringe containing 70 mg of erenumab plus one pre-filled syringe of identical placebo administered subcutaneous every 28 days	Biological: Erenumab; 70 mg/mL pre-filled syringe administered subcutaneously; Other Names: AMG334
Experimental: AMG334 140 mg; AMG334 140 mg: two pre-filled syringe containing 70 mg each of erenumab administered subcutaneous every 28 days	Biological: Erenumab; 70 mg/mL pre-filled syringe administered subcutaneously; Other Names: AMG334
Placebo Comparator: Placebo; Two pre-filled syringes containing placebo identical in appearance to erenumab	Other: Placebo; Matching placebo in pre-filled syringe administered subcutaneously

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Monthly Migraine Days at the Last Month (Month 3) of the Double-blind Treatment Period (DBTP)	A migraine day was defined as any calendar day in which the subject experienced a qualified migraine headache defined as a migraine with or without aura, lasting for ≥ 30 minutes, and meeting at least one of the following criteria: ≥ 2 of the following pain features: unilateral, throbbing, moderate to severe or exacerbated with exercise/physical activity; ≥ 1 of the following associated symptoms: nausea and/or vomiting, photophobia and phonophobia	Baseline up to Month 3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With at Least a 50% Reduction From Baseline in Monthly Migraine Days at Month 3	Achievement of at least a 50% reduction from baseline in monthly migraine days at Month 3. A migraine day was defined as any calendar day in which the subject experienced a qualified migraine headache defined as a migraine with or without aura, lasting for ≥ 30 minutes, and meeting at least one of the following criteria: ≥ 2 of the following pain features: unilateral, throbbing, moderate to severe or exacerbated with exercise/physical activity; ≥ 1 of the following associated symptoms: nausea and/or vomiting, photophobia and phonophobia	Baseline and at Month 3
Change From Baseline in 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 include two categories of medications: triptan-based migraine medications and ergotamine-based migraine medications. Monthly migraine-specific medication use at baseline is the number of migraine-specific medication treatment days in the baseline period.	Baseline up to Month 3
Change From Baseline in Headache Impact Scores as Measured by the Headache Impact Test (HIT-6) at Month 3	The HIT-6 is a short-form self-administered questionnaire based on the internet-HIT question pool. The HIT-6 was developed as a global measure of adverse headache impact to assess headache severity in the previous month and change in a patient's clinical status over a short period of time. Six items assess the frequency of pain severity, headaches limiting daily activity (household, work, school, and social). Each of the 6 questions is responded to using 1 of 5 response categories: "never," "rarely," "sometimes," "very often," or "always." For each HIT-6 item, 6, 8, 10, 11, or 13 points, respectively, are assigned to the response provided. These points were summed to produce a total HIT-6 score that ranges from 36 to 78. Scores were categorized into 4 grades, representing little or no impact (49 or less), some impact (50-55), substantial impact (56-59), and severe impact (60-78) due to headache. Lower values represent better outcomes, therefore negative change denotes improveme	Baseline up to Month 3

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.
• Wang SJ, Roxas AA Jr, Saravia B, Kim BK, Chowdhury D, Riachi N, Tai MS, Tanprawate S, Ngoc TT, Zhao YJ, Mikol DD, Pandhi S, Wen S, Mondal S, Tenenbaum N, Hours-Zesiger P. Randomised, controlled trial of erenumab for the prevention of episodic migraine in patients from Asia, the Middle East, and Latin America: The EMPOwER study. Cephalalgia. 2021 Nov;41(13):1285-1297. doi: 10.1177/03331024211024160. Epub 2021 Jun 25.

Helpful Links

• A Plain Language Trial Summary is available on novartisclinicaltrials.com

Study record dates

Study Major Dates

• Study Start (Actual): February 8, 2018
• Primary Completion (Actual): January 13, 2020
• Study Completion (Actual): January 13, 2020

Study Registration Dates

• First Submitted: November 2, 2017
• First Submitted That Met QC Criteria: November 2, 2017
• First Posted (Actual): November 6, 2017

Study Record Updates

• Last Update Posted (Actual): October 11, 2021
• Last Update Submitted That Met QC Criteria: October 7, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: adult; episodic migraine; headache; migraine; erenumab; CGRP; AMG334; Calcitonin Gene-related
• 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: CAMG334A2302

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