Ascending Multiple-Doses of Erenumab (AMG 334) in Healthy Adults and in Migraine Patients

Study Overview
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Brief Summary
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The primary purpose of this study is to determine whether erenumab is safe and well tolerated in healthy adults and migraine patients. As part of the secondary objectives, this study will be conducted to characterize the pharmacokinetic (PK) profile of erenumab after multiple subcutaneous (SC) doses in healthy adults and migraine patients, as well as to characterize the effect of erenumab on the capsaicin induced increase in dermal blood flow after multiple SC doses in healthy adults and migraine patients.

Official Title
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Phase 1, Randomized, Double-Blind, Placebo-Controlled, Ascending Multiple-Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AMG 334 in Healthy Subjects and in Migraine Patients

Conditions
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Migraine

Intervention / Treatment
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* Drug: Erenumab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male and female subjects, as well as male or female subjects with migraines between 18 and 55 years of age, inclusive, with no history or evidence of clinically relevant medical disorders as determined by the investigator in consultation with the Amgen physician; Exclusion Criteria: - History or evidence of clinically significant disorder (including psychiatric), condition or disease that, in the opinion of the Investigator or Amgen physician would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Erenumab<br>Healthy participants and participants with migraine received subcutaneous doses of erenumab on days 1, 29 and 57. | Drug: Erenumab<br>* Administered by subcutaneous injection once a month<br>* Other names: Aimovig™;|
| Placebo Comparator: Placebo<br>Healthy participants and participants with migraine received subcutaneous doses of placebo on days 1, 29 and 57. | Drug: Placebo<br>* Administered by subcutaneous injection once a month<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events | An adverse event (AE) is defined as any untoward medical occurrence in a clinical trial participant. The event does not necessarily have a causal relationship with study treatment. The definition of adverse events includes worsening of a pre-existing medical condition. Laboratory value changes that require treatment or adjustment in current therapy are considered adverse events. Teatment-related adverse events (TRAEs) are those assessed by the investigator as being possibly related to study drug. A serious adverse event is defined as an adverse event that meets at least 1 of the following serious criteria: fatal life-threatening (places the subject at immediate risk of death) requires in-patient hospitalization or prolongation of existing hospitalization results in persistent or significant disability/incapacity congenital anomaly/birth defect other medically important serious event. | From first dose of study drug until a maximum of 168 days after last dose (225 days) | 
| Number of Participants With Suicidal Ideation and Behavior as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) | The C-SSRS is a measure of suicidal ideation and behavior. Ideation includes a wish to be dead or nonspecific thoughts about wanting to end life. Suicidal behavior includes actual attempts, interrupted or aborted attempts, and any preparatory acts. | From first dose of study drug until a maximum of 168 days after last dose (225 days) | 
| Number of Participants Who Developed Anti-erenumab Antibodies | Participants who had a negative or no result at baseline and were antibody positive postbaseline. Blood samples were first tested for anti-erenumab binding antibodies, samples testing positive for binding antibodies were also tested for neutralizing antibodies. | From first dose of study drug until a maximum of 168 days after last dose (225 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Serum Concentration (Cmax) of Erenumab | Serum concentration of erenumab was analyzed using an enzyme-linked immunosorbent assay (ELISA). | Day 1 (assessed from predose to day 28) and day 57 (assessed from predose up to day 225) | 
| Time to Maximum Observed Concentration (Tmax) of Erenumab | Serum concentration of erenumab was analyzed using an enzyme-linked immunosorbent assay (ELISA). | Day 1 (assessed from predose to day 28) and day 57 (assessed from predose up to day 225) | 
| Area Under the Serum Concentration-Time Curve From 0 to 28 Days (AUC0-28day) | Serum concentration of erenumab was analyzed using an enzyme-linked immunosorbent assay (ELISA). | Day 1 (assessed from predose to day 28) and day 57 (assessed from predose up to day 225) | 
| Area Under the Serum Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) | Serum concentration of erenumab was analyzed using an enzyme-linked immunosorbent assay (ELISA). | Day 57 (assessed from predose to day 225)) | 
| Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow | Inhibition of capsaicin-induced dermal blood flow (DBF) by erenumab was used to measure calcitonin gene-related peptide (CGRP) receptor antagonism. Capsaicin was applied at 2 sites on the volar surface of the participants' left or right forearms and a control mixture was applied to 1 site on the volar surface of either the participants' left or right forearm. Dermal blood flow was assessed by laser Doppler perfusion imaging and was done immediately before ('baseline') and 0.5 hours post-capsaicin on the surface of these 3 sites. Data reported are the least square geometric mean ratios for the post-capsaicin dermal blood flow to pre-capsaicin dermal blood flow. According to the protocol, not all cohorts had dermal blood flow measurements at all time points. | Baseline, Days 8, 57, 85, 113, 169 and 197 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Migraine