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

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Primary Purpose

Status

Completed

Phase

Phase 1

Locations

Belgium

Study Type

Interventional

Intervention

Erenumab

Placebo

About this trial

This is an interventional prevention trial for Migraine focused on measuring Migraine

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

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;

Sites / Locations

Research Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Erenumab

Placebo

Arm Description

Healthy participants and participants with migraine received subcutaneous doses of erenumab on days 1, 29 and 57.

Healthy participants and participants with migraine received subcutaneous doses of placebo on days 1, 29 and 57.

Outcomes

Primary Outcome Measures

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.

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.

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.

Secondary Outcome Measures

Maximum Observed Serum Concentration (Cmax) of Erenumab

Serum concentration of erenumab was analyzed using an enzyme-linked immunosorbent assay (ELISA).

Time to Maximum Observed Concentration (Tmax) of Erenumab

Serum concentration of erenumab was analyzed using an enzyme-linked immunosorbent assay (ELISA).

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).

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).

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.

Full Information

NCT ID

NCT01723514

First Posted

November 6, 2012

Last Updated

August 1, 2018

Sponsor

Amgen

1. Study Identification

Unique Protocol Identification Number

NCT01723514

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2018

Overall Recruitment Status

Completed

Study Start Date

November 14, 2012 (Actual)

Primary Completion Date

July 10, 2014 (Actual)

Study Completion Date

July 10, 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Amgen

4. Oversight

Data Monitoring Committee

No

5. Study Description

Brief Summary

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Migraine

Keywords

Migraine

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

48 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Erenumab

Arm Type

Experimental

Arm Description

Healthy participants and participants with migraine received subcutaneous doses of erenumab on days 1, 29 and 57.

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Healthy participants and participants with migraine received subcutaneous doses of placebo on days 1, 29 and 57.

Intervention Type

Drug

Intervention Name(s)

Erenumab

Other Intervention Name(s)

AMG-334, Aimovig™

Intervention Description

Administered by subcutaneous injection once a month

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Administered by subcutaneous injection once a month

Primary Outcome Measure Information:

Title

Number of Participants With Adverse Events

Description

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.

Time Frame

From first dose of study drug until a maximum of 168 days after last dose (225 days)

Title

Number of Participants With Suicidal Ideation and Behavior as Assessed by the Columbia Suicide Severity Rating Scale (C-SSRS)

Description

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.

Time Frame

From first dose of study drug until a maximum of 168 days after last dose (225 days)

Title

Number of Participants Who Developed Anti-erenumab Antibodies

Description

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.

Time Frame

From first dose of study drug until a maximum of 168 days after last dose (225 days)

Secondary Outcome Measure Information:

Title

Maximum Observed Serum Concentration (Cmax) of Erenumab

Description

Serum concentration of erenumab was analyzed using an enzyme-linked immunosorbent assay (ELISA).

Time Frame

Day 1 (assessed from predose to day 28) and day 57 (assessed from predose up to day 225)

Title

Time to Maximum Observed Concentration (Tmax) of Erenumab

Description

Serum concentration of erenumab was analyzed using an enzyme-linked immunosorbent assay (ELISA).

Time Frame

Day 1 (assessed from predose to day 28) and day 57 (assessed from predose up to day 225)

Title

Area Under the Serum Concentration-Time Curve From 0 to 28 Days (AUC0-28day)

Description

Serum concentration of erenumab was analyzed using an enzyme-linked immunosorbent assay (ELISA).

Time Frame

Day 1 (assessed from predose to day 28) and day 57 (assessed from predose up to day 225)

Title

Area Under the Serum Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast)

Description

Serum concentration of erenumab was analyzed using an enzyme-linked immunosorbent assay (ELISA).

Time Frame

Day 57 (assessed from predose to day 225))

Title

Ratio of Post-capsaicin Dermal Blood Flow to Pre-capsaicin Dermal Blood Flow

Description

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.

Time Frame

Baseline, Days 8, 57, 85, 113, 169 and 197

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

55 Years

Accepts Healthy Volunteers

Eligibility Criteria

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;

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

MD

Organizational Affiliation

Amgen

Official's Role

Study Director

Facility Information:

Facility Name

Research Site

City

Leuven

ZIP/Postal Code

3000

Country

Belgium

12. IPD Sharing Statement

Citations:

PubMed Identifier

28736918

Citation

de Hoon J, Van Hecken A, Vandermeulen C, Yan L, Smith B, Chen JS, Bautista E, Hamilton L, Waksman J, Vu T, Vargas G. Phase I, Randomized, Double-blind, Placebo-controlled, Single-dose, and Multiple-dose Studies of Erenumab in Healthy Subjects and Patients With Migraine. Clin Pharmacol Ther. 2018 May;103(5):815-825. doi: 10.1002/cpt.799. Epub 2017 Oct 24.

Results Reference

background

PubMed Identifier

31852816

Citation

Kudrow D, Pascual J, Winner PK, Dodick DW, Tepper SJ, Reuter U, Hong F, Klatt J, Zhang F, Cheng S, Picard H, Eisele O, Wang J, Latham JN, Mikol DD. Vascular safety of erenumab for migraine prevention. Neurology. 2020 Feb 4;94(5):e497-e510. doi: 10.1212/WNL.0000000000008743. Epub 2019 Dec 18. Erratum In: Neurology. 2020 Jun 9;94(23):1052.

Results Reference

derived

Links:

URL

http://www.amgentrials.com

Description

AmgenTrials clinical trials website

Migraine

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial