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NCT02174861

A Study to Assess the Long-term Safety and Efficacy of Erenumab (AMG 334) in Chronic Migraine Prevention.

Completed Phase 2 Results posted Last updated 12 October 2022
What this trial tests

Phase 2 trial testing Erenumab in Treatment for Prevention of Chronic Migraine in 609 participants. Completed in 26 May 2017.

Timeline
30 June 2014
Primary endpoint
26 May 2017
26 May 2017

Quick facts

Lead sponsorAmgen
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment609
Start date30 June 2014
Primary completion26 May 2017
Estimated completion26 May 2017
Sites65 locations across Denmark, Finland, Sweden, United Kingdom, Germany, Poland, Norway, Canada

Drugs / interventions tested

Conditions studied

Sponsor

Amgen — full company profile →

Who can join

Adults 18 to 66, any sex, with Treatment for Prevention of Chronic 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 With Adverse Events Primary · From first dose of erenumab in extension study 20130255 to the end of the 12-week safety follow-up period (up to 64 weeks).

Adverse events (AEs) were graded for severity using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03, where Grade 1 = mild AE, asymptomatic or mild symptoms; Grade 2 = Moderate AE; Grade 3 = Severe or medically significant but not immediately life-threatening; Grade 4 = Life-threatening consequences; urgent intervention indicated; Grade 5 = Death related to AE.

Any adverse event
GroupValue95% CI
Erenumab398
Adverse event grade ≥ 2
GroupValue95% CI
Erenumab302
Adverse event grade ≥ 3
GroupValue95% CI
Erenumab34
Adverse event grade ≥ 4
GroupValue95% CI
Erenumab0
Treatment-related adverse events
GroupValue95% CI
Erenumab114
Serious adverse events
GroupValue95% CI
Erenumab24
AE leading to discontinuation of erenumab
GroupValue95% CI
Erenumab16
Fatal adverse events
GroupValue95% CI
Erenumab0
CHU Substudy: Number of Participants Able to Administer a Full Dose of Erenumab in Home-use Primary · Day 29 (week 4) and day 57 (week 8) of the substudy

At the CHU substudy day 28 and day 56 visits, the site provided erenumab 140 mg to participants to self-administer at home on the following day. Study site staff then called the participants and asked if they administered a full, partial, or no dose of erenumab. A full dose was defined when the entire volume of both prefilled syringes or autoinjector/pens were injected.

Week 4
GroupValue95% CI
Erenumab 140 mg PFS25
Erenumab 140 mg AI/Pen26
Week 8
GroupValue95% CI
Erenumab 140 mg PFS25
Erenumab 140 mg AI/Pen25
Change From Study 20120295 Baseline in Monthly Migraine Days Secondary · 4-week baseline phase of Study 20120295 and the 4 weeks prior to the week 4, 8, 12, 24, 40, and 52 visits of Study 20130255

A migraine day was 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 either as a migraine with or without aura. The change from baseline in monthly migraine days was calculated as the number of migraine days during the 4 weeks prior to each study visit - the number of migraine days during the 4-week baseline phase.

Baseline
GroupValue95% CI
Erenumab18.11± 4.53
Change from baseline at week 4
GroupValue95% CI
Erenumab-6.72± 6.22
Change from baseline at week 8
GroupValue95% CI
Erenumab-7.38± 6.50
Change from baseline at week 12
GroupValue95% CI
Erenumab-7.63± 6.49
Change from baseline at week 24
GroupValue95% CI
Erenumab-8.36± 6.29
Change from baseline at week 40
GroupValue95% CI
Erenumab-8.72± 6.53
Change from baseline at week 52
GroupValue95% CI
Erenumab-9.29± 6.64
Percentage of Participants With at Least a 50% Reduction in Monthly Migraine Days From Study 20120295 Baseline Secondary · 4-week baseline phase of Study 20120295 and the 4 weeks prior to the week 4, 8, 12, 24, 40 and 52 visits of Study 20130255

A migraine day was 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 either as a migraine without aura or a migraine with aura. Monthly migraine days were calculated as the number of migraine days in the 4-week baseline phase and during the 4 weeks prior to each study visit. At least a 50% reduction from baseline (of study 20120295) in monthly migraine days was determined if the change in monthly migraine days from the 4-week baseline phase to the 4 weeks

Week 4
GroupValue95% CI
Erenumab39.235.3 – 43.3
Week 8
GroupValue95% CI
Erenumab45.641.6 – 49.7
Week 12
GroupValue95% CI
Erenumab45.741.6 – 49.9
Week 24
GroupValue95% CI
Erenumab53.649.2 – 58.0
Week 40
GroupValue95% CI
Erenumab55.650.9 – 60.2
Week 52
GroupValue95% CI
Erenumab59.054.0 – 63.8
Change From Study 20120295 Baseline in Monthly Acute Migraine-Specific Medication Treatment Days Secondary · 4-week baseline phase of Study 20120295 and the 4 weeks prior to the week 4, 8, 12, 24, 40 and 52 visits of Study 20130255

Monthly acute migraine-specific medication treatment days is the number of days on which migraine specific medications were used between monthly doses of study drug. Migraine-specific medications includes two categories of medications: triptan-based migraine medications and ergotamine-based migraine medications.

Baseline
GroupValue95% CI
Erenumab9.53± 7.26
Change from baseline at Week 4
GroupValue95% CI
Erenumab-3.59± 4.62
Change from baseline at Week 8
GroupValue95% CI
Erenumab-4.01± 4.96
Change from baseline at Week 12
GroupValue95% CI
Erenumab-3.96± 5.03
Change from baseline at Week 24
GroupValue95% CI
Erenumab-4.39± 4.99
Change from baseline at Week 40
GroupValue95% CI
Erenumab-4.58± 5.00
Change from baseline at Week 52
GroupValue95% CI
Erenumab-4.97± 5.33
Change From Study 20120295 Baseline in Cumulative Monthly Headache Hours Secondary · 4-week baseline phase of Study 20120295 and the 4 weeks prior to the week 4, 8, 12, 24, 40, and 52 visits of Study 20130255

The cumulative duration of any qualified headache between monthly doses of study drug regardless of acute treatment use. A qualified headache was defined as follows: * a qualified migraine headache (including an aura-only event that is treated with acute migraine-specific medication), or * a qualified non-migraine headache, which is a headache that lasted continuously for ≥ 4 hours and was not a qualified migraine headache, or * a headache of any duration for which acute headache treatment was administered.

Baseline
GroupValue95% CI
Erenumab226.84± 125.54
Change from baseline at week 4
GroupValue95% CI
Erenumab-79.38± 107.56
Change from baseline at week 8
GroupValue95% CI
Erenumab-85.24± 110.24
Change from Baseline at week 12
GroupValue95% CI
Erenumab-89.30± 111.47
Change from Baseline at week 24
GroupValue95% CI
Erenumab-100.41± 112.30
Change from Baseline at week 40
GroupValue95% CI
Erenumab-101.07± 111.77
Change from Baseline at week 52
GroupValue95% CI
Erenumab-107.44± 113.60
CHU Substudy: Number of Participants With Adverse Events Secondary · From first dose of erenumab in the CHU substudy to 28 days after last dose of erenumab in the CHU substudy; up to 12 weeks.

Adverse events were graded for severity using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Injection site reactions were derived from a Medical Dictionary for Regulatory Activities (MedDRA) query using a list of pre-specified preferred terms. An adverse device effect (ADE) is any adverse event related to the use of a medical device.

Any adverse event
GroupValue95% CI
Erenumab 140 mg PFS2
Erenumab 140 mg AI/Pen6
Adverse event grade ≥ 2
GroupValue95% CI
Erenumab 140 mg PFS1
Erenumab 140 mg AI/Pen4
Adverse event grade ≥ 3
GroupValue95% CI
Erenumab 140 mg PFS0
Erenumab 140 mg AI/Pen0
Adverse event grade ≥ 4
GroupValue95% CI
Erenumab 140 mg PFS0
Erenumab 140 mg AI/Pen0
Serious adverse events
GroupValue95% CI
Erenumab 140 mg PFS0
Erenumab 140 mg AI/Pen0
AE leading to discontinuation of erenumab
GroupValue95% CI
Erenumab 140 mg PFS0
Erenumab 140 mg AI/Pen0
Fatal adverse events
GroupValue95% CI
Erenumab 140 mg PFS0
Erenumab 140 mg AI/Pen0
Injection site reactions
GroupValue95% CI
Erenumab 140 mg PFS0
Erenumab 140 mg AI/Pen1

Adverse events — posted to ClinicalTrials.gov

Time frame: From first dose of erenumab in extension study 20130255 to the end of the 12-week safety follow-up period (up to 64 weeks).. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Erenumab
Serious: 24/609 (4%)
Deaths: 0/609

Serious adverse events (20 terms)

ReactionSystemErenumab
MigraineNervous system disorders
Intervertebral disc protrusionMusculoskeletal and connective tissue disorders
DepressionPsychiatric disorders
Myocardial bridgingCongenital, familial and genetic disorders
Abdominal painGastrointestinal disorders
OesophagitisGastrointestinal disorders
VolvulusGastrointestinal disorders
Alcoholic liver diseaseHepatobiliary disorders
AppendicitisInfections and infestations
Gastroenteritis viralInfections and infestations
PneumoniaInfections and infestations
Post procedural oedemaInjury, poisoning and procedural complications
CostochondritisMusculoskeletal and connective tissue disorders
Rotator cuff syndromeMusculoskeletal and connective tissue disorders
Medication overuse headacheNervous system disorders
PresyncopeNervous system disorders
Radicular syndromeNervous system disorders
Transient ischaemic attackNervous system disorders
Vestibular migraineNervous system disorders
AlcoholismPsychiatric disorders
Other adverse events (3 terms — click to expand)

ReactionSystemErenumab
Viral upper respiratory tract infectionInfections and infestations
Upper respiratory tract infectionInfections and infestations
SinusitisInfections and infestations

Most-reported serious reactions: Migraine, Intervertebral disc protrusion, Depression, Myocardial bridging, Abdominal pain, Oesophagitis, Volvulus, Alcoholic liver disease.

Data from ClinicalTrials.gov NCT02174861 adverse events section.

Sponsor's own description

To assess the long-term safety and efficacy of erenumab.

Publications & conference data

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

  1. Targeting dorsal root ganglia and primary sensory neurons for the treatment of chronic pain.
    Berta T, Qadri Y, Tan PH, Ji RR. · · 2017 · cited 200× · PMID 28480765 · DOI 10.1080/14728222.2017.1328057
  2. Long-term safety and efficacy of erenumab in patients with chronic migraine: Results from a 52-week, open-label extension study.
    Tepper SJ, Ashina M, Reuter U, Brandes JL, et al · · 2020 · cited 68× · PMID 32216456 · DOI 10.1177/0333102420912726
  3. Vascular safety of erenumab for migraine prevention.
    Kudrow D, Pascual J, Winner PK, Dodick DW, et al · · 2020 · cited 67× · PMID 31852816 · DOI 10.1212/wnl.0000000000008743
  4. Spotlight on Anti-CGRP Monoclonal Antibodies in Migraine: The Clinical Evidence to Date.
    Pellesi L, Guerzoni S, Pini LA. · · 2017 · cited 48× · PMID 28409893 · DOI 10.1002/cpdd.345
  5. Erenumab and galcanezumab in chronic migraine prevention: effects after treatment termination.
    Raffaelli B, Mussetto V, Israel H, Neeb L, et al · · 2019 · cited 43× · PMID 31159727 · DOI 10.1186/s10194-019-1018-8
  6. The Biology of Monoclonal Antibodies: Focus on Calcitonin Gene-Related Peptide for Prophylactic Migraine Therapy.
    Raffaelli B, Reuter U. · · 2018 · cited 43× · PMID 29616494 · DOI 10.1007/s13311-018-0622-7
  7. Long-term tolerability and nonvascular safety of erenumab, a novel calcitonin gene-related peptide receptor antagonist for prevention of migraine: A pooled analysis of four placebo-controlled trials with long-term extensions.
    Ashina M, Kudrow D, Reuter U, Dolezil D, et al · · 2019 · cited 42× · PMID 31707815 · DOI 10.1177/0333102419888222
  8. Calcitonin Gene-Related Peptide (CGRP)-Targeted Monoclonal Antibodies and Antagonists in Migraine: Current Evidence and Rationale.
    Cohen F, Yuan H, Silberstein SD. · · 2022 · cited 28× · PMID 35476215 · DOI 10.1007/s40259-022-00530-0

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