Migraine, Migraine Disorders, Migraine Headache
Conditions
Keywords
migraine, episodic migraine, chronic migraine, headache, erenumab, AMG334, aimovig, monoclonal antibody, CGRP-receptor antibody
Brief summary
This is a 128-week open-label study to assess the long-term safety and tolerabilty of the monoclonal antibody erenumab in migraine patients.
Detailed description
This was an open-label, multi-center, single arm study with flexible dosing allowing both dose adjustment and one drug holiday per patient. The study design consisted of 3 parts: * Screening Epoch (0 - 2 weeks): required for all patients to assess initial eligibility. Eligible patients came from study CAMG334ADE01 (NCT03828539). * Open-label Treatment Epoch (128 weeks): Individual patients were treated for 128 weeks. In this open-label treatment phase, the erenumab dose could be adjusted from 70 mg to 140 mg or vice versa at the discretion of the physician at any scheduled study visit. Additionally, a voluntary single treatment interruption ('drug holiday') of up to 24 weeks (approximately six months) could be introduced after at least 12 weeks of treatment in the open-label Treatment Epoch. * Follow-up Epoch (4 weeks): A Follow-Up Visit 4 weeks after the last regular study visit (8 weeks after last investigational medicinal product \[IMP\] application) was required as part of routine safety monitoring.
Interventions
BIOLOGICALErenumab
Erenumab was supplied as a pre-filled pen (auto-injector) for subcutaneous injection.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 67 Years
Healthy volunteers
No
Inclusion criteria
The study population consisted of patients with a documented history of episodic (4 - 14 baseline migraine days) or chronic migraine (≥15 baseline headache days), who had been successfully randomized to clinical trial CAMG334ADE01. Key inclusion Criteria: * Signed informed consent must be obtained prior to participation in the study * Patient is capable of understanding the nature, significance and implications of the clinical trial. * Adults ≥18 years of age upon entry into screening Key
Exclusion criteria
* Use of a prophylactic migraine medication within five plasma clearance half-lives, or a device or procedure within one month prior to the start of the Open-label Treatment Epoch. This
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Exposure Adjusted Incidence Rate of AE During Open-label Treatment Epoch Per 100 Subject Years | Up to 128 weeks | This outcome measure was calculated dividing the number of adverse events (AEs) by the total patient exposure time and standardizing it per 100 patient-years. Exact Pearson-Clopper confidence intervals for single proportions were calculated to evaluate the precision of the estimated parameter. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients Discontinuing Open-label Treatment Epoch Due to AE | Up to 128 weeks | Participants discontinuing the Open-label Treatment Epoch due to adverse events (AEs) to evaluate the long-term tolerability of erenumab in patients with episodic migraine or chronic migraine. |
| Proportion of Patients Discontinuing Open-label Treatment Epoch Due to Non-AE Reasons | Up to 128 weeks | Participants discontinuing the Open-label Treatment Epoch due to non-AE reasons to evaluate the long-term tolerability of erenumab in patients with episodic migraine or chronic migraine. |
Countries
Germany
Participant flow
Recruitment details
Participants took part in 79 investigative sites in Germany.
Pre-assignment details
The screening period began once patients had signed the study informed consent. The Screening Epoch had a duration of 2 weeks. Eligible patients came from study CAMG334ADE01 (NCT03828539).
Participants by arm
| Arm | Count |
|---|---|
| Erenumab Erenumab dose could be adjusted from 70 mg to 140 mg or vice versa at the discretion of the physician at any scheduled study visit. | 701 |
| Total | 701 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 24 |
| Overall Study | Lost to Follow-up | 19 |
| Overall Study | New therapy for study indication | 9 |
| Overall Study | Physician Decision | 4 |
| Overall Study | Pregnancy | 9 |
| Overall Study | Protocol Deviation | 3 |
| Overall Study | Subject/guardian decision | 91 |
| Overall Study | Withdrawal of informed consent | 8 |
Baseline characteristics
| Characteristic | Erenumab |
|---|---|
| Age, Continuous | 41.8 years STANDARD_DEVIATION 12.3 |
| Race/Ethnicity, Customized Asian | 1 Participants |
| Race/Ethnicity, Customized Other | 4 Participants |
| Race/Ethnicity, Customized Unknown | 1 Participants |
| Race/Ethnicity, Customized White | 695 Participants |
| Sex: Female, Male Female | 608 Participants |
| Sex: Female, Male Male | 93 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 701 |
| other Total, other adverse events | 514 / 701 |
| serious Total, serious adverse events | 86 / 701 |
Outcome results
Primary
Exposure Adjusted Incidence Rate of AE During Open-label Treatment Epoch Per 100 Subject Years
This outcome measure was calculated dividing the number of adverse events (AEs) by the total patient exposure time and standardizing it per 100 patient-years. Exact Pearson-Clopper confidence intervals for single proportions were calculated to evaluate the precision of the estimated parameter.
Time frame: Up to 128 weeks
Population: Safety set (SAF) defined as all patients who received at least one dose of study treatment in the Open-label Treatment Epoch of this study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Erenumab | Exposure Adjusted Incidence Rate of AE During Open-label Treatment Epoch Per 100 Subject Years | 101.71 number of AEs per 100 patient-years |
Secondary
Proportion of Patients Discontinuing Open-label Treatment Epoch Due to AE
Participants discontinuing the Open-label Treatment Epoch due to adverse events (AEs) to evaluate the long-term tolerability of erenumab in patients with episodic migraine or chronic migraine.
Time frame: Up to 128 weeks
Population: Safety set (SAF) defined as all patients who received at least one dose of study treatment in the Open-label Treatment Epoch of this study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Erenumab | Proportion of Patients Discontinuing Open-label Treatment Epoch Due to AE | 29 Participants |
Secondary
Proportion of Patients Discontinuing Open-label Treatment Epoch Due to Non-AE Reasons
Participants discontinuing the Open-label Treatment Epoch due to non-AE reasons to evaluate the long-term tolerability of erenumab in patients with episodic migraine or chronic migraine.
Time frame: Up to 128 weeks
Population: Safety set (SAF) defined as all patients who received at least one dose of study treatment in the Open-label Treatment Epoch of this study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Erenumab | Proportion of Patients Discontinuing Open-label Treatment Epoch Due to Non-AE Reasons | 126 Participants |