NCT02542605

To Evaluate the Blockade of CGRP in Preventing PACAP-38 Induced Migraine-like Attacks With AMG 334 in Migraine Patients

Completed Phase 1 Results posted Last updated 3 June 2019

What this trial tests

Phase 1 trial testing Erenumab in Migraine in 35 participants. Completed in 8 November 2017.

Timeline

11 November 2015

Primary endpoint
28 September 2017

8 November 2017

Quick facts

Lead sponsor	Amgen
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	triple
Primary purpose	prevention
Enrollment	35
Start date	11 November 2015
Primary completion	28 September 2017
Estimated completion	8 November 2017
Sites	3 locations across Belgium, Netherlands, United States

Drugs / interventions tested

• Erenumab (ERENUMAB) — full drug profile →
• Placebo
• PACAP-38 Challenge Agent — full drug profile →

Conditions studied

• Migraine — all drugs for Migraine →

Sponsor

Amgen — full company profile →

Who can join

Adults 18 to 45, 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.

Number of Participants With a MLA Within 24 Hours of Challenge Agent Infusion Primary · Part B randomization phase day 8 plus 24 hours.

On day 1 of the double-blind randomization phase participants received 140 mg intravenous erenumab over 30 minutes or matching placebo. On day 8, participants received 10 mol/kg/minute PACAP-38 over 10 minutes and were observed for 24 hours after PACAP-38 infusion. A MLA was defined as fulfilling 1 of the 2 criteria: 1. Headache with at least 2 of the following characteristics: unilateral location, pulsating quality, moderate or severe pain intensity, aggravated by/causing avoidance of routine physical activity. Additionally, during the headache at least 1 of the following: nausea and/or vom

Participants with MLA

Group	Value	95% CI
Placebo	1
Erenumab	1

Participants without MLA

Group	Value	95% CI
Placebo	8
Erenumab	6

Number of Participants With a Headache Within 24 Hours of Challenge Agent Infusion Secondary · Part B randomization phase day 8 plus 24 hours.

On day 1 of the double-blind randomization phase participants received 140 mg intravenous erenumab over 30 minutes or matching placebo. On day 8, participants received 10 mol/kg/minute PACAP-38 over 10 minutes and were observed for 24 hours after PACAP-38 infusion.

Participants with headaches

Group	Value	95% CI
Placebo	3
Erenumab	3

Participants without headaches

Group	Value	95% CI
Placebo	6
Erenumab	4

Number of Participants With Treatment Emergent Adverse Events (TEAEs) Secondary · Part B randomization phase day 1 until EOS (up to 12 weeks).

TEAEs were summarised for days 1 to 7 after the participants received placebo or erenumab infusion on day 1 of the Part B randomization phase. TEAEs were also summarized from day 8 to end of study (EOS) after participants had received both investigational product (placebo or erenumab) and the second dose of PACAP-38 on day 8.

Participants with TEAEs from day 1 to 7

Group	Value	95% CI
Placebo	6
Erenumab	0

Participants with TEAEs from day 8 to EOS

Group	Value	95% CI
Placebo	9
Erenumab	7

Serious AEs

Group	Value	95% CI
Placebo	0
Erenumab	0

AEs with fatal outcome

Group	Value	95% CI
Placebo	0
Erenumab	0

Mean Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at Day 1, Day 8 and EOS Secondary · Part B randomization phase baseline and day 1, day 8 and EOS (week 12).

Systolic and diastolic BP was assessed during Part B of the study, and the mean change from baseline is presented for the last measurements taken following administration of placebo or erenumab on day 1 (1 hour post-dose), and following administration of PACAP-38 on day 8 (8 hours post-dose). The mean change from baseline is also presented for the EOS assessment.

1 hour post-dose day 1: systolic BP

Group	Value	95% CI
Placebo	-0.7	± 7.9
Erenumab	2.4	± 5.2

1 hour post-dose day 1: diastolic BP

Group	Value	95% CI
Placebo	1.2	± 5.7
Erenumab	0.7	± 6.4

8 hours post-dose day 8: systolic BP

Group	Value	95% CI
Placebo	-3.1	± 5.7
Erenumab	-3.7	± 6.2

8 hours post-dose day 8: diastolic BP

Group	Value	95% CI
Placebo	-3.6	± 2.9
Erenumab	-9.6	± 6.8

EOS: systolic BP

Group	Value	95% CI
Placebo	-2.6	± 9.2
Erenumab	2.6	± 3.8

EOS: diastolic BP

Group	Value	95% CI
Placebo	-0.1	± 6.4
Erenumab	1.7	± 5.9

Mean Change From Baseline in Heart Rate at Day 1, Day 8 and EOS Secondary · Part B randomization phase baseline and day 1, day 8 and EOS (week 12).

Heart rate was assessed during Part B of the study, and the mean change from baseline is presented for the last measurements taken following administration of placebo or erenumab on day 1 (1 hour post-dose), and following administration of PACAP-38 on day 8 (8 hours post-dose). The mean change from baseline is also presented for the EOS assessment.

1 hour post-dose day 1

Group	Value	95% CI
Placebo	-5.0	± 8.2
Erenumab	1.7	± 5.7

8 hours post-dose day 8

Group	Value	95% CI
Placebo	2.6	± 11.5
Erenumab	8.7	± 4.6

EOS

Group	Value	95% CI
Placebo	-0.9	± 8.6
Erenumab	2.4	± 5.5

Mean Change From Baseline in Respiratory Rate at Day 1, Day 8 and EOS Secondary · Part B randomization phase baseline and day 1, day 8 and EOS (week 12).

Respiratory rate was assessed during Part B of the study, and the mean change from baseline is presented for the last measurements taken following administration of placebo or erenumab on day 1 (1 hour post-dose), and following administration of PACAP-38 on day 8 (8 hours post-dose). The mean change from baseline is also presented for the EOS assessment.

1 hour post-dose day 1

Group	Value	95% CI
Placebo	0.8	± 2.2
Erenumab	-1.4	± 2.6

8 hours post-dose day 8

Group	Value	95% CI
Placebo	1.0	± 2.1
Erenumab	-1.0	± 3.5

EOS

Group	Value	95% CI
Placebo	1.7	± 4.0
Erenumab	1.1	± 3.7

Mean Change From Baseline in Temperature at Day 1, Day 8 and EOS Secondary · Part B randomization phase baseline and day 1, day 8 and EOS (week 12).

Temperature was assessed during Part B of the study, and the mean change from baseline is presented for the last measurements taken following administration of placebo or erenumab on day 1 (1 hour post-dose), and following administration of PACAP-38 on day 8 (8 hours post-dose). The mean change from baseline is also presented for the EOS assessment.

1 hour post-dose day 1

Group	Value	95% CI
Placebo	0.18	± 0.39
Erenumab	0.34	± 0.36

8 hours post-dose day 8

Group	Value	95% CI
Placebo	0.60	± 0.48
Erenumab	0.63	± 0.56

EOS

Group	Value	95% CI
Placebo	-0.34	± 0.47
Erenumab	0.16	± 0.41

Mean Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) at Day 8, Day 9 and EOS Secondary · Part B randomization phase baseline and day 8, day 9 and EOS (week 12).

ALP, ALT and AST were assessed during Part B of the study, and the mean change from baseline is presented for samples taken prior to administration of PACAP-38 on day 8 (pre-PACAP-38 dose), and following administration of PACAP-38 on day 9. The mean change from baseline is also presented for the EOS assessment.

Day 8 (Pre-PACAP-38 dose): ALP

Group	Value	95% CI
Placebo	-2.0	± 5.6
Erenumab	0.0	± 4.8

Day 9 (Post-PACAP-38 dose): ALP

Group	Value	95% CI
Placebo	-1.6	± 4.1
Erenumab	-0.3	± 2.3

EOS: ALP

Group	Value	95% CI
Placebo	1.0	± 12.3
Erenumab	6.1	± 9.6

Day 8 (Pre-PACAP-38 dose): ALT

Group	Value	95% CI
Placebo	-1.4	± 3.5
Erenumab	-3.0	± 4.2

Day 9 (Post-PACAP-38 dose): ALT

Group	Value	95% CI
Placebo	-2.1	± 3.5
Erenumab	-4.5	± 4.2

EOS: ALT

Group	Value	95% CI
Placebo	-2.0	± 4.7
Erenumab	3.1	± 9.4

Day 8 (Pre-PACAP-38 dose): AST

Group	Value	95% CI
Placebo	0.3	± 3.0
Erenumab	2.4	± 4.0

Day 9 (Post-PACAP-38 dose): AST

Group	Value	95% CI
Placebo	-0.8	± 2.7
Erenumab	-4.2	± 2.3

Mean Change From Baseline in Total Bilirubin at Day 8, Day 9 and EOS Secondary · Part B randomization baseline and day 8, day 9 and EOS (week 12).

Total bilirubin was assessed during Part B of the study, and the mean change from baseline is presented for samples taken prior to administration of PACAP-38 on day 8 (pre-PACAP-38 dose), and following administration of PACAP-38 on day 9. The mean change from baseline is also presented for the EOS assessment.

Day 8 (Pre-PACAP-38 dose)

Group	Value	95% CI
Placebo	-0.4211	± 3.6356
Erenumab	-1.4849	± 0.8532

Day 9 (Post-PACAP-38 dose)

Group	Value	95% CI
Placebo	3.3229	± 1.3971
Erenumab	-2.2980	± 1.0300

EOS

Group	Value	95% CI
Placebo	0.0804	± 3.0270
Erenumab	1.3191	± 3.5099

Mean Change From Baseline in Blood Urea at Day 8, Day 9 and EOS Secondary · Part B randomization baseline and day 8, day 9 and EOS (week 12).

Blood urea was assessed during Part B of the study, and the mean change from baseline is presented for samples taken prior to administration of PACAP-38 on day 8 (pre-PACAP-38 dose), and following administration of PACAP-38 on day 9. The mean change from baseline is also presented for the EOS assessment.

Day 8 (Pre-PACAP-38 dose)

Group	Value	95% CI
Placebo	0.0629	± 0.9274
Erenumab	-0.0524	± 0.5270

Day 9 (Post-PACAP-38 dose)

Group	Value	95% CI
Placebo	0.1501	± 0.7552
Erenumab	-0.5278	± 1.2592

EOS

Group	Value	95% CI
Placebo	-0.1961	± 0.7673
Erenumab	0.0570	± 1.1286

Mean Change From Baseline in Creatine Kinase at Day 8, Day 9 and EOS Secondary · Part B randomization baseline and day 8, day 9 and EOS (week 12).

Creatine Kinase was assessed during Part B of the study, and the mean change from baseline is presented for samples taken prior to administration of PACAP-38 on day 8 (pre-PACAP-38 dose), and following administration of PACAP-38 on day 9. The mean change from baseline is also presented for the EOS assessment.

Day 8 (Pre-PACAP-38 dose)

Group	Value	95% CI
Placebo	5.8	± 21.0
Erenumab	-22.4	± 51.5

Day 9 (Post-PACAP-38 dose)

Group	Value	95% CI
Placebo	-16.8	± 9.1
Erenumab	-59.3	± 65.7

EOS

Group	Value	95% CI
Placebo	8.1	± 25.3
Erenumab	-24.9	± 79.9

Mean Change From Baseline in Creatinine at Day 8, Day 9 and EOS Secondary · Part B randomization baseline and day 8, day 9 and EOS (week 12).

Creatinine was assessed during Part B of the study, and the mean change from baseline is presented for samples taken prior to administration of PACAP-38 on day 8 (pre-PACAP-38 dose), and following administration of PACAP-38 on day 9. The mean change from baseline is also presented for the EOS assessment.

Day 8 (Pre-PACAP-38 dose)

Group	Value	95% CI
Placebo	-1.9890	± 6.0835
Erenumab	-2.2526	± 3.1121

Day 9 (Post-PACAP-38 dose)

Group	Value	95% CI
Placebo	0.1450	± 7.3859
Erenumab	-1.4733	± 3.4367

EOS

Group	Value	95% CI
Placebo	3.5151	± 7.8109
Erenumab	-0.3457	± 2.6598

Adverse events — posted to ClinicalTrials.gov

Time frame: From first dose of investigational product (placebo or erenumab) up to 85 days (up to 12 weeks).. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo Day 1-7

Serious: 0/9 (0%)

Deaths: 0/9

Erenumab Day 1-7

Serious: 0/7 (0%)

Deaths: 0/7

Placebo Day 8-EOS

Serious: 0/9 (0%)

Deaths: 0/9

Erenumab Day 8-EOS

Serious: 0/7 (0%)

Deaths: 0/7

Other adverse events (49 terms — click to expand)

Reaction	System	Placebo Day 1-7	Erenumab Day 1-7	Placebo Day 8-EOS	Erenumab Day 8-EOS
Migraine	Nervous system disorders	—	—	—	—
Flushing	Vascular disorders	—	—	—	—
Headache	Nervous system disorders	—	—	—	—
Palpitations	Cardiac disorders	—	—	—	—
Fatigue	General disorders	—	—	—	—
Head discomfort	Nervous system disorders	—	—	—	—
Feeling hot	General disorders	—	—	—	—
Lacrimation increased	Eye disorders	—	—	—	—
Abdominal pain upper	Gastrointestinal disorders	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—
Feeling cold	General disorders	—	—	—	—
Dizziness	Nervous system disorders	—	—	—	—
Photosensitivity reaction	Skin and subcutaneous tissue disorders	—	—	—	—
Leukocytosis	Blood and lymphatic system disorders	—	—	—	—
Cardiac discomfort	Cardiac disorders	—	—	—	—
Hyperacusis	Ear and labyrinth disorders	—	—	—	—
Eye irritation	Eye disorders	—	—	—	—
Ocular discomfort	Eye disorders	—	—	—	—
Photophobia	Eye disorders	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—
Gastritis	Gastrointestinal disorders	—	—	—	—
Hypoaesthesia oral	Gastrointestinal disorders	—	—	—	—
Catheter site pain	General disorders	—	—	—	—
Chest discomfort	General disorders	—	—	—	—
Discomfort	General disorders	—	—	—	—
Hunger	General disorders	—	—	—	—
Malaise	General disorders	—	—	—	—
Pain	General disorders	—	—	—	—
Pyrexia	General disorders	—	—	—	—
Thirst decreased	General disorders	—	—	—	—
Bacterial infection	Infections and infestations	—	—	—	—
Cystitis	Infections and infestations	—	—	—	—
Gastroenteritis	Infections and infestations	—	—	—	—
Nasopharyngitis	Infections and infestations	—	—	—	—
Upper respiratory tract infection	Infections and infestations	—	—	—	—
Urinary tract infection	Infections and infestations	—	—	—	—
Concussion	Injury, poisoning and procedural complications	—	—	—	—
Contusion	Injury, poisoning and procedural complications	—	—	—	—
Joint lock	Musculoskeletal and connective tissue disorders	—	—	—	—
Muscle spasms	Musculoskeletal and connective tissue disorders	—	—	—	—

Data from ClinicalTrials.gov NCT02542605 adverse events section.

Sponsor's own description

Phase I, Randomized, Parallel-group, Double-Blind, Placebo-Controlled, Single Dose Study to Evaluate the Blockade of CGRP Receptor by AMG 334 in Preventing PACAP-38 Induced Migraine-like Attacks in Migraine Patients.

Publications & conference data

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

1. Novel Therapeutic Targets for Migraine.
   Nisar A, Ahmed Z, Yuan H. · · 2023 · cited 11× · PMID 36831105 · DOI 10.3390/biomedicines11020569
2. Pituitary adenylate cyclase-activating polypeptide/vasoactive intestinal peptide (Part 2): biology and clinical importance in central nervous system and inflammatory disorders.
   Moody TW, Jensen RT. · · 2021 · cited 6× · PMID 33481421 · DOI 10.1097/med.0000000000000621