NCT04418765: DELIVER

A Study to Evaluate the Efficacy and Safety of Eptinezumab for the Prevention of Migraine in Participants That Are Not Helped by Previous Preventive Treatments

Completed Phase 3 Results posted Last updated 29 September 2023

What this trial tests

Phase 3 trial testing Eptinezumab in Migraine in 892 participants. Completed in 15 September 2022.

Timeline

1 June 2020

Primary endpoint
15 July 2021

15 September 2022

Quick facts

Lead sponsor	H. Lundbeck A/S
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	892
Start date	1 June 2020
Primary completion	15 July 2021
Estimated completion	15 September 2022
Sites	138 locations across Georgia, Denmark, France, Finland, Italy, Russia, Slovakia, Belgium

Drugs / interventions tested

• Eptinezumab (EPTINEZUMAB) — full drug profile →
• Placebo

Conditions studied

• Migraine — all drugs for Migraine →

Sponsor

H. Lundbeck A/S — full company profile →

Who can join

Adults 18 to 75, any sex, with 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.

Change From Baseline in the Number of Monthly Migraine Days (MMDs) Averaged Over Weeks 1 to 12 Primary · Baseline, Weeks 1 - 12

A migraine day was defined as any day the participant reported a headache that met criterion A, B, C, or D: Criterion A (all of the following criteria): lasted ≥4 hours, had ≥2 of the following: unilateral location; pulsating quality; moderate or severe pain intensity; aggravation by, or causing avoidance of, routine physical activity; and was accompanied by ≥1 of the following: nausea; vomiting; photophobia and phonophobia. Criterion B: lasted ≥30 minutes and the participant had an aura with the headache. Criterion C: lasted ≥30 minutes and met ≥2 of the following criteria: lasted ≥4 hours, h

Group	Value	95% CI
Placebo	-2.1	± 0.38
Eptinezumab 100 mg	-4.8	± 0.37
Eptinezumab 300 mg	-5.3	± 0.37

Percentage of Participants With ≥50% Reduction From Baseline in MMDs Averaged Over Weeks 1 to 12 Secondary · Baseline to Weeks 1 - 12

A migraine day was defined as any day the participant reported a headache that met criterion A, B, C, or D: Criterion A (all of the following criteria): lasted ≥4 hours, had ≥2 of the following: unilateral location; pulsating quality; moderate or severe pain intensity; aggravation by, or causing avoidance of, routine physical activity; and was accompanied by ≥1 of the following: nausea; vomiting; photophobia and phonophobia. Criterion B: lasted ≥30 minutes and the participant had an aura with the headache. Criterion C: lasted ≥30 minutes and met ≥2 of the following criteria: lasted ≥4 hours, h

Group	Value	95% CI
Placebo	13.1
Eptinezumab 100 mg	42.1
Eptinezumab 300 mg	49.5

Change From Baseline in the Number of MMDs Averaged Over Weeks 13 to 24 Secondary · Baseline, Weeks 13 - 24

A migraine day was defined as any day the participant reported a headache that met criterion A, B, C, or D: Criterion A (all of the following criteria): lasted ≥4 hours, had ≥2 of the following: unilateral location; pulsating quality; moderate or severe pain intensity; aggravation by, or causing avoidance of, routine physical activity; and was accompanied by ≥1 of the following: nausea; vomiting; photophobia and phonophobia. Criterion B: lasted ≥30 minutes and the participant had an aura with the headache. Criterion C: lasted ≥30 minutes and met ≥2 of the following criteria: lasted ≥4 hours, h

Group	Value	95% CI
Placebo	-2.4	± 0.39
Eptinezumab 100 mg	-5.4	± 0.39
Eptinezumab 300 mg	-6.1	± 0.39

Percentage of Participants With ≥75% Reduction From Baseline in MMDs Averaged Over Weeks 1 to 12 Secondary · Baseline to Weeks 1 - 12

A migraine day was defined as any day the participant reported a headache that met criterion A, B, C, or D: Criterion A (all of the following criteria): lasted ≥4 hours, had ≥2 of the following: unilateral location; pulsating quality; moderate or severe pain intensity; aggravation by, or causing avoidance of, routine physical activity; and was accompanied by ≥1 of the following: nausea; vomiting; photophobia and phonophobia. Criterion B: lasted ≥30 minutes and the participant had an aura with the headache. Criterion C: lasted ≥30 minutes and met ≥2 of the following criteria: lasted ≥4 hours, h

Group	Value	95% CI
Placebo	2.0
Eptinezumab 100 mg	15.7
Eptinezumab 300 mg	18.8

Change From Baseline in the Headache Impact Test (HIT-6) Score at Week 12 Secondary · Baseline, Week 12

The HIT-6 (version 1.0) is a Likert-type, self-reporting questionnaire designed to assess the impact of an occurring headache and its effect on the ability to function normally in daily life. The HIT-6 contains 6 questions, each item was rated from never to always with the following response scores: never = 6, rarely = 8, sometimes = 10, very often = 11, and always = 13. The total score for the HIT-6 was the sum of each response score ranging from 36 to 78. The life impact derived from the total score was described as followed: severe (≥60), substantial (56-59), some (50-55), little to none (≤

Group	Value	95% CI
Placebo	-3.1	± 0.61
Eptinezumab 100 mg	-6.9	± 0.61
Eptinezumab 300 mg	-8.5	± 0.60

Percentage of Participants With ≥50% Reduction From Baseline in MMDs Averaged Over Weeks 13 to 24 Secondary · Baseline to Weeks 13 - 24

A migraine day was defined as any day the participant reported a headache that met criterion A, B, C, or D: Criterion A (all of the following criteria): lasted ≥4 hours, had ≥2 of the following: unilateral location; pulsating quality; moderate or severe pain intensity; aggravation by, or causing avoidance of, routine physical activity; and was accompanied by ≥1 of the following: nausea; vomiting; photophobia and phonophobia. Criterion B: lasted ≥30 minutes and the participant had an aura with the headache. Criterion C: lasted ≥30 minutes and met ≥2 of the following criteria: lasted ≥4 hours, h

Group	Value	95% CI
Placebo	23.7
Eptinezumab 100 mg	52.3
Eptinezumab 300 mg	59.1

Percentage of Participants With ≥75% Reduction From Baseline in MMDs Averaged Over Weeks 13 to 24 Secondary · Baseline to Weeks 13 - 24

A migraine day was defined as any day the participant reported a headache that met criterion A, B, C, or D: Criterion A (all of the following criteria): lasted ≥4 hours, had ≥2 of the following: unilateral location; pulsating quality; moderate or severe pain intensity; aggravation by, or causing avoidance of, routine physical activity; and was accompanied by ≥1 of the following: nausea; vomiting; photophobia and phonophobia. Criterion B: lasted ≥30 minutes and the participant had an aura with the headache. Criterion C: lasted ≥30 minutes and met ≥2 of the following criteria: lasted ≥4 hours, h

Group	Value	95% CI
Placebo	6.8
Eptinezumab 100 mg	21.3
Eptinezumab 300 mg	27.6

Percentage of Participants With 100% Reduction From Baseline in MMDs Averaged Over Weeks 1 to 12 Secondary · Baseline to Weeks 1 - 12

A migraine day was defined as any day the participant reported a headache that met criterion A, B, C, or D: Criterion A (all of the following criteria): lasted ≥4 hours, had ≥2 of the following: unilateral location; pulsating quality; moderate or severe pain intensity; aggravation by, or causing avoidance of, routine physical activity; and was accompanied by ≥1 of the following: nausea; vomiting; photophobia and phonophobia. Criterion B: lasted ≥30 minutes and the participant had an aura with the headache. Criterion C: lasted ≥30 minutes and met ≥2 of the following criteria: lasted ≥4 hours, h

Group	Value	95% CI
Placebo	1.1
Eptinezumab 100 mg	5.9
Eptinezumab 300 mg	7.7

Percentage of Participants With ≥50% Reduction From Baseline in Monthly Headache Days (MHDs) Averaged Over Weeks 1 to 12 Secondary · Baseline to Weeks 1 - 12

A headache day was defined as a day with a headache that lasted ≥30 minutes or met the definition of a migraine day (as defined in criterion A, B, C, or D above in outcome measure 1).

Group	Value	95% CI
Placebo	12.8
Eptinezumab 100 mg	39.5
Eptinezumab 300 mg	45.7

Percentage of Participants With ≥75% Reduction From Baseline in Monthly Headache Days (MHDs) Averaged Over Weeks 1 to 12 Secondary · Baseline to Weeks 1 - 12

A headache day was defined as a day with a headache that lasted ≥30 minutes or met the definition of a migraine day (as defined in criterion A, B, C, or D above in outcome measure 1).

Group	Value	95% CI
Placebo	2.3
Eptinezumab 100 mg	15.1
Eptinezumab 300 mg	16.4

Percentage of Participants With 100% Reduction From Baseline in Monthly Headache Days (MHDs) Averaged Over Weeks 1 to 12 Secondary · Baseline to Weeks 1 - 12

A headache day was defined as a day with a headache that lasted ≥30 minutes or met the definition of a migraine day (as defined in criterion A, B, C, or D above in outcome measure 1).

Group	Value	95% CI
Placebo	1.1
Eptinezumab 100 mg	4.1
Eptinezumab 300 mg	5.3

Change From Baseline in the Number of MHDs Averaged Over Weeks 1 to 12 Secondary · Baseline, Weeks 1 - 12

A headache day was defined as a day with a headache that lasted ≥30 minutes or met the definition of a migraine day (as defined in criterion A, B, C, or D above in outcome measure 1).

Group	Value	95% CI
Placebo	-2.1	± 0.38
Eptinezumab 100 mg	-4.6	± 0.37
Eptinezumab 300 mg	-5.1	± 0.37

Adverse events — posted to ClinicalTrials.gov

Time frame: Baseline up to Week 72. Reporting threshold: 1%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo-controlled Period: Placebo

Serious: 3/298 (1%)

Deaths: 0/298

Placebo-controlled Period: Eptinezumab 100 mg

Serious: 6/299 (2%)

Deaths: 0/299

Placebo-controlled Period: Eptinezumab 300 mg

Serious: 7/294 (2%)

Deaths: 0/294

Extension Period: Placebo to Eptinezumab 100 mg

Serious: 2/145 (1%)

Deaths: 0/145

Extension Period: Placebo to Eptinezumab 300 mg

Serious: 7/148 (5%)

Deaths: 0/148

Extension Period: Eptinezumab 100 mg to Eptinezumab 100 mg

Serious: 9/288 (3%)

Deaths: 0/288

Extension Period: Eptinezumab 300 mg to Eptinezumab 300 mg

Serious: 9/284 (3%)

Deaths: 0/284

Serious adverse events (43 terms)

Reaction	System	Placebo-controlled Period:…	Placebo-controlled Period:…	Placebo-controlled Period:…	Extension Period: Placebo …	Extension Period: Placebo …	Extension Period: Eptinezu…	Extension Period: Eptinezu…
Anaphylactic reaction	Immune system disorders	—	—	—	—	—	—	—
COVID-19	Infections and infestations	—	—	—	—	—	—	—
Retinal detachment	Eye disorders	—	—	—	—	—	—	—
Cholelithiasis	Hepatobiliary disorders	—	—	—	—	—	—	—
Concussion	Injury, poisoning and procedural complications	—	—	—	—	—	—	—
Hand fracture	Injury, poisoning and procedural complications	—	—	—	—	—	—	—
Humerus fracture	Injury, poisoning and procedural complications	—	—	—	—	—	—	—
Road traffic accident	Injury, poisoning and procedural complications	—	—	—	—	—	—	—
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—
Periarthritis	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—	—	—	—
Cervical radiculopathy	Nervous system disorders	—	—	—	—	—	—	—
Migraine	Nervous system disorders	—	—	—	—	—	—	—
Psychogenic seizure	Nervous system disorders	—	—	—	—	—	—	—
Seizure	Nervous system disorders	—	—	—	—	—	—	—
Suicidal ideation	Psychiatric disorders	—	—	—	—	—	—	—
Acute myocardial infarction	Cardiac disorders	—	—	—	—	—	—	—
Conductive deafness	Ear and labyrinth disorders	—	—	—	—	—	—	—
Hypothyroidism	Endocrine disorders	—	—	—	—	—	—	—
Eye pain	Eye disorders	—	—	—	—	—	—	—
Colitis	Gastrointestinal disorders	—	—	—	—	—	—	—
Gastritis	Gastrointestinal disorders	—	—	—	—	—	—	—
Inguinal hernia	Gastrointestinal disorders	—	—	—	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—	—	—	—
Chronic sinusitis	Infections and infestations	—	—	—	—	—	—	—

Other adverse events (64 terms — click to expand)

Reaction	System	Placebo-controlled Period:…	Placebo-controlled Period:…	Placebo-controlled Period:…	Extension Period: Placebo …	Extension Period: Placebo …	Extension Period: Eptinezu…	Extension Period: Eptinezu…
COVID-19	Infections and infestations	—	—	—	—	—	—	—
Nasopharyngitis	Infections and infestations	—	—	—	—	—	—	—
Upper respiratory tract infection	Infections and infestations	—	—	—	—	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—
Migraine	Nervous system disorders	—	—	—	—	—	—	—
Fatigue	General disorders	—	—	—	—	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—
Pruritus	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—
Abdominal pain upper	Gastrointestinal disorders	—	—	—	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—	—	—	—
Gastroenteritis	Infections and infestations	—	—	—	—	—	—	—
Sinusitis	Infections and infestations	—	—	—	—	—	—	—
Urinary tract infection	Infections and infestations	—	—	—	—	—	—	—
Post vaccination syndrome	Injury, poisoning and procedural complications	—	—	—	—	—	—	—
Dizziness	Nervous system disorders	—	—	—	—	—	—	—
Dyspepsia	Gastrointestinal disorders	—	—	—	—	—	—	—
Cystitis	Infections and infestations	—	—	—	—	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—	—	—	—	—
Pyrexia	General disorders	—	—	—	—	—	—	—
Bronchitis	Infections and infestations	—	—	—	—	—	—	—
Somnolence	Nervous system disorders	—	—	—	—	—	—	—
Insomnia	Psychiatric disorders	—	—	—	—	—	—	—
Alopecia	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—
Hypertension	Vascular disorders	—	—	—	—	—	—	—
Influenza	Infections and infestations	—	—	—	—	—	—	—
Pharyngitis	Infections and infestations	—	—	—	—	—	—	—
Tonsillitis	Infections and infestations	—	—	—	—	—	—	—
Viral upper respiratory tract infection	Infections and infestations	—	—	—	—	—	—	—
Hypercholesterolaemia	Metabolism and nutrition disorders	—	—	—	—	—	—	—
Osteoarthritis	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—	—	—	—
Asthenia	General disorders	—	—	—	—	—	—	—
Blood creatine phosphokinase increased	Investigations	—	—	—	—	—	—	—
Blood pressure increased	Investigations	—	—	—	—	—	—	—
Neck pain	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—
Headache	Nervous system disorders	—	—	—	—	—	—	—
Sciatica	Nervous system disorders	—	—	—	—	—	—	—
Depressive symptom	Psychiatric disorders	—	—	—	—	—	—	—

Most-reported serious reactions: Anaphylactic reaction, COVID-19, Retinal detachment, Cholelithiasis, Concussion, Hand fracture, Humerus fracture, Road traffic accident.

Data from ClinicalTrials.gov NCT04418765 adverse events section.

Sponsor's own description

Evaluation of eptinezumab in the prevention of migraine in participants with unsuccessful prior preventive treatments.

Publications & conference data

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

1. Safety and efficacy of eptinezumab for migraine prevention in patients with two-to-four previous preventive treatment failures (DELIVER): a multi-arm, randomised, double-blind, placebo-controlled, phase 3b trial.
   Ashina M, Lanteri-Minet M, Pozo-Rosich P, Ettrup A, et al · · 2022 · cited 88× · PMID 35716692 · DOI 10.1016/s1474-4422(22)00185-5
2. Resistant and refractory migraine: clinical presentation, pathophysiology, and management.
   Ornello R, Andreou AP, De Matteis E, Jürgens TP, et al · · 2024 · cited 33× · PMID 38142636 · DOI 10.1016/j.ebiom.2023.104943
3. Eptinezumab improved patient-reported outcomes and quality of life in patients with migraine and prior preventive treatment failures.
   Goadsby PJ, Barbanti P, Lambru G, Ettrup A, et al · · 2023 · cited 19× · PMID 36583633 · DOI 10.1111/ene.15670
4. Efficacy and safety of monoclonal antibody against calcitonin gene-related peptide or its receptor for migraine patients with prior preventive treatment failure: a network meta-analysis.
   Wang X, Wen D, He Q, You C, et al · · 2022 · cited 19× · PMID 36071388 · DOI 10.1186/s10194-022-01472-2
5. Efficacy and safety of eptinezumab for migraine prevention in patients with prior preventive treatment failures: subgroup analysis of the randomized, placebo-controlled DELIVER study.
   Ashina M, Lanteri-Minet M, Ettrup A, Christoffersen CL, et al · · 2023 · cited 14× · PMID 37125484 · DOI 10.1177/03331024231170807
6. Long-term effectiveness of eptinezumab in patients with migraine and prior preventive treatment failures: extension of a randomized controlled trial.
   Ashina M, Tepper SJ, Gendolla A, Sperling B, et al · · 2023 · cited 13× · PMID 37985968 · DOI 10.1186/s10194-023-01688-w
7. Effects of eptinezumab on self-reported work productivity in adults with migraine and prior preventive treatment failure in the randomized, double-blind, placebo-controlled DELIVER study.
   Barbanti P, Goadsby PJ, Lambru G, Ettrup A, et al · · 2022 · cited 13× · PMID 36460983 · DOI 10.1186/s10194-022-01521-w
8. Revolutionizing migraine management: advances and challenges in CGRP-targeted therapies and their clinical implications.
   Özge A, Baykan B, Bıçakçı Ş, Ertaş M, et al · · 2024 · cited 11× · PMID 38938785 · DOI 10.3389/fneur.2024.1402569