NCT03927144

Study of Sustained Benefit of AMG334 in Adult Episodic Migraine Patients

Completed Phase 4 Results posted Last updated 18 November 2023

What this trial tests

Phase 4 trial testing AMG334 in Episodic Migraine in 621 participants. Completed in 30 September 2022.

Timeline

15 May 2019

Primary endpoint
1 October 2021

30 September 2022

Quick facts

Lead sponsor	Amgen
Phase	Phase 4
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	621
Start date	15 May 2019
Primary completion	1 October 2021
Estimated completion	30 September 2022
Sites	112 locations across France, Italy, Finland, Netherlands, Greece, Slovakia, Belgium, Austria

Drugs / interventions tested

• AMG334 — full drug profile →
• Oral Prophylactic

Conditions studied

• Episodic Migraine — all drugs for Episodic Migraine →

Sponsor

Amgen — full company profile →

Who can join

18 and older, any sex, with Episodic Migraine. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants Who Completed Initially Assigned Treatment and Achieved at Least a 50% Reduction From Baseline in Monthly Migraine Days at Month 12 Primary · Baseline and Month 12

A migraine day was defined as any calendar day in which the participant experienced a qualified migraine headache (onset, continuation, or recurrence of the migraine headache). A qualified migraine headache was defined as a migraine with or without aura, lasting for ≥ 30 minutes, and meeting at least one of the following criteria: 1. ≥2 of the following pain features: * Unilateral * Throbbing * Moderate to severe * Exacerbated with exercise/physical activity 2. ≥1 of the following associated symptoms: * Nausea and/or vomiting * Photophobia and phonophobia If the participa

Group	Value	95% CI
AMG334 70 mg/140 mg	232
Oral Prophylactic	35

Number of Participants Who Completed Initially Assigned Treatment at Month 12 Secondary · Month 12

Group	Value	95% CI
AMG334 70 mg/140 mg	359
Oral Prophylactic	78

Cumulative Mean Change From Baseline on the Monthly Migraine Days to Week 52 Secondary · Baseline and Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44, Week 48, and Week 52

A migraine day was defined as any calendar day in which the participant experienced a qualified migraine headache (onset, continuation, or recurrence of the migraine headache). The mean of monthly migraine days was obtained cumulatively every 4 weeks across 52 weeks (for example, at Week 8 the mean will be based on data from Week 1 to Week 8; and at Week 12 the mean will be based on data from Week 1 to Week 12). The cumulative mean change from baseline in monthly migraine days was derived using difference between cumulative average of each month and baseline monthly migraine days.

Week 4

Group	Value	95% CI
AMG334 70 mg/140 mg	-2.55	± 0.17
Oral Prophylactic	-0.55	± 0.25

Week 8

Group	Value	95% CI
AMG334 70 mg/140 mg	-3.00	± 0.17
Oral Prophylactic	-1.01	± 0.25

Week 12

Group	Value	95% CI
AMG334 70 mg/140 mg	-3.27	± 0.17
Oral Prophylactic	-1.05	± 0.26

Week 16

Group	Value	95% CI
AMG334 70 mg/140 mg	-3.45	± 0.17
Oral Prophylactic	-1.22	± 0.26

Week 20

Group	Value	95% CI
AMG334 70 mg/140 mg	-3.63	± 0.17
Oral Prophylactic	-1.35	± 0.26

Week 24

Group	Value	95% CI
AMG334 70 mg/140 mg	-3.75	± 0.17
Oral Prophylactic	-1.56	± 0.26

Week 28

Group	Value	95% CI
AMG334 70 mg/140 mg	-3.84	± 0.17
Oral Prophylactic	-1.73	± 0.26

Week 32

Group	Value	95% CI
AMG334 70 mg/140 mg	-3.93	± 0.17
Oral Prophylactic	-1.91	± 0.27

Number of Responders as Measured by the Patient's Global Impression of Change (PGIC) Scale at Week 52 Secondary · Baseline and Week 52

The PGIC scale consists of one item which measures the participants' perception of change in their condition relative to the beginning of the study. Responses are rated on a 7-item response scale ranging from very much improved (7) to no change or worsened condition (1). A responder was defined as a participant with a PGIC score of at least 5 (5=moderately better, 6=better, 7=a great deal better), at Week 52 for participants who completed the treatment period at Week 52 on the initially assigned treatment.

Group	Value	95% CI
AMG334 70 mg/140 mg	314
Oral Prophylactic	39

Adverse events — posted to ClinicalTrials.gov

Time frame: Day 1 to Week 52 of the Core Phase and Day 1 to Week 52 of the Extension Phase. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Core Phase: AMG334 70mg/140mg

Serious: 15/408 (4%)

Deaths: 0/408

Core Phase: Oral Prophylactics

Serious: 9/206 (4%)

Deaths: 0/206

Extension Phase: AMG334 70mg/140mg Continuing on AMG334 70mg/140mg

Serious: 9/343 (3%)

Deaths: 0/343

Extension Phase: Oral Prophylactics Then AMG334 70mg/140mg

Serious: 4/118 (3%)

Deaths: 0/118

Serious adverse events (41 terms)

Reaction	System	Core Phase: AMG334 70mg/14…	Core Phase: Oral Prophylac…	Extension Phase: AMG334 70…	Extension Phase: Oral Prop…
Tympanic membrane perforation	Ear and labyrinth disorders	—	—	—	—
Goitre	Endocrine disorders	—	—	—	—
Ulcerative keratitis	Eye disorders	—	—	—	—
Umbilical hernia	Gastrointestinal disorders	—	—	—	—
Medical device pain	General disorders	—	—	—	—
Anaphylactic reaction	Immune system disorders	—	—	—	—
Food allergy	Immune system disorders	—	—	—	—
COVID-19 pneumonia	Infections and infestations	—	—	—	—
Diverticulitis	Infections and infestations	—	—	—	—
Gastroenteritis	Infections and infestations	—	—	—	—
Pyelonephritis acute	Infections and infestations	—	—	—	—
Ankle fracture	Injury, poisoning and procedural complications	—	—	—	—
Hand fracture	Injury, poisoning and procedural complications	—	—	—	—
Hip fracture	Injury, poisoning and procedural complications	—	—	—	—
Ligament sprain	Injury, poisoning and procedural complications	—	—	—	—
Meniscus injury	Injury, poisoning and procedural complications	—	—	—	—
Muscle hernia	Injury, poisoning and procedural complications	—	—	—	—
Procedural pain	Injury, poisoning and procedural complications	—	—	—	—
Radius fracture	Injury, poisoning and procedural complications	—	—	—	—
Wound	Injury, poisoning and procedural complications	—	—	—	—
Diastasis recti abdominis	Musculoskeletal and connective tissue disorders	—	—	—	—
Femoroacetabular impingement	Musculoskeletal and connective tissue disorders	—	—	—	—
Joint stiffness	Musculoskeletal and connective tissue disorders	—	—	—	—
Metatarsalgia	Musculoskeletal and connective tissue disorders	—	—	—	—
Papillary thyroid cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—

Other adverse events (9 terms — click to expand)

Reaction	System	Core Phase: AMG334 70mg/14…	Core Phase: Oral Prophylac…	Extension Phase: AMG334 70…	Extension Phase: Oral Prop…
COVID-19	Infections and infestations	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—
Nasopharyngitis	Infections and infestations	—	—	—	—
Fatigue	General disorders	—	—	—	—
Weight increased	Investigations	—	—	—	—
Dizziness	Nervous system disorders	—	—	—	—
Vaccination complication	Injury, poisoning and procedural complications	—	—	—	—
Paraesthesia	Nervous system disorders	—	—	—	—
Somnolence	Nervous system disorders	—	—	—	—

Most-reported serious reactions: Tympanic membrane perforation, Goitre, Ulcerative keratitis, Umbilical hernia, Medical device pain, Anaphylactic reaction, Food allergy, COVID-19 pneumonia.

Data from ClinicalTrials.gov NCT03927144 adverse events section.

Sponsor's own description

The purpose of this study is to compare the sustained long-term benefit between two treatment paradigms of migraine prophylactic agents (erenumab versus a control arm of oral prophylactics) in episodic migraine patients who have previously failed 1 to 2 prophylactic migraine treatments.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

1. Early Use of Erenumab vs Nonspecific Oral Migraine Preventives: The APPRAISE Randomized Clinical Trial.
   Pozo-Rosich P, Dolezil D, Paemeleire K, Stepien A, et al · · 2024 · cited 20× · PMID 38526461 · DOI 10.1001/jamaneurol.2024.0368
2. Migraine Prevention with Erenumab: Focus on Patient Selection, Perspectives and Outcomes.
   De Matteis E, Sacco S, Ornello R. · · 2022 · cited 5× · PMID 35411146 · DOI 10.2147/tcrm.s263825
3. Abstracts from the 17th European Headache Congress (EHC)
   · 2024