An Open Label Trial of ALD403 (Eptinezumab) in Chronic Migraine (PREVAIL)
Primary Purpose
Migraine Disorder
Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
ALD403 (Eptinezumab)
Sponsored by
About this trial
This is an interventional prevention trial for Migraine Disorder
Eligibility Criteria
Inclusion Criteria:
- Males and females between 18 and 65 years of age, inclusive, who were diagnosed with migraines at ≤ 50 years of age, and have a history of chronic migraine for ≥ 12 months before screening.
Exclusion Criteria:
- Receipt of any monoclonal antibody treatment (within or outside a clinical trial) within 6 months before screening.
- Confounding and clinically significant pain syndromes (e.g. fibromyalgia, chronic low back pain, complex regional pain syndrome).
- Psychiatric conditions that are uncontrolled and/or untreated, including conditions that are not controlled for a minimum of 6 months prior to screening. Patients with a lifetime history of psychosis, mania, or dementia are excluded.
- History or diagnosis of complicated migraine (ICHD-III beta version, 20134), chronic tension-type headache, hypnic headache, cluster headache, hemicrania continua, new daily persistent headache, or sporadic and familial hemiplegic migraine.
Sites / Locations
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Massachusetts
- Research Site
- Research Site
- Research Site
- Massachusetts
- Research Site
- 02481
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
ALD403 (Eptinezumab) Dose Level 1
Arm Description
ALD403 (Eptinezumab) Dose Level 1 (IV)
Outcomes
Primary Outcome Measures
Number of Participants With Any Treatment Emergent Adverse Events (TEAEs)
Treatment emergent adverse events were defined as adverse events with start date and time on or after the date and time of the initial study drug infusion.
Number of Participants With a Clinically Significant Electrocardiogram
Overall investigator interpretation of participant electrocardiogram
Number of Participants With Any Clinically Significant Laboratory Values
Each of the laboratory values that were reported as abnormal and clinically significant and entered as adverse events in the database.
Number of Participants Experiencing Suicidal Ideation or Suicidal Behavior on Columbia-Suicide Severity Rating Scale (C-SSRS)
Baseline responses are collected at screening and assess suicidal ideation in the past 6 months. Post baseline reports the worst assessment of suicidal ideation since the last visit for all post baseline visits.
Number of Participants With Any Clinically Significant (CS) Changes in Vital Signs
Changes in vital signs that were considered clinically meaningful or clinically significant (CS) by the Investigator
Secondary Outcome Measures
Patient Global Impression of Change (PGIC) at Week 104
The PGIC includes a single question concerning the participant's impression of the change in their disease status since the start of the study. Seven responses are possible: Very much improved, much improved, minimally improved, no change, minimally worse, much worse, very much worse.
Change in Baseline of Short Form Health Survey (SF-36 v 2.0) Scale Scores
The SF-36 is a health survey consisting of 36 questions consisting of eight scaled scores to measure quality of life over the past 4 weeks (scale range: 0=worst to 100=best). Increases from baseline indicate improvement.
Health Related Quality of Life (EQ-5D-5L) at Week 12
The EQ-5D-5L is a descriptive health-related quality of life states consisting of 5 dimensions/questions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) each of which can take one of five responses. The responses record five levels of severity (no problems/slight problems/moderate problems/severe problems/extreme problems) within a particular EQ-5D dimension.
Change in Baseline of Headache Impact Test (HIT-6) Score
The HIT-6 measures the impact of headache on the participant's functional health and well-being in 6 domains: pain; role functioning (ability to carry out usual activities); social functioning; energy or fatigue; cognition; and emotional distress assess over the prior 12-week period. The total possible scores range from 36 (no impact) to 78 (worst impact). The change in baseline will be calculated from the average scores.
Change in Most Bothersome Symptom at Week 48
The Investigator verbally obtained the most bothersome symptom associated with the participant's migraine during the screening visit. The most bothersome symptom may include nausea, vomiting, sensitivity to light, sensitivity to sound, mental cloudiness, fatigue, pain with activity, mood changes, or other migraine related symptoms. Participants were asked to rate the improvement in this symptom from screening on a seven-point scale.
Change From Baseline of Migraine Disability Assessment (MIDAS) Total Score
The MIDAS questionnaire measures the effect headaches have on the participant's daily functioning. MIDAS is composed of five questions that ask about the participant's performance over the past 3 months. The response to each question is provided in number of days which are summed to determine the MIDAS total score and level of disability:
0-5, MIDAS Grade I, little or no disability; 6-10, MIDAS Grade II, mild disability; 11-20, MIDAS Grade III, moderate disability; 21+, MIDAS Grade IV, severe disability;
A higher value represents a worse outcome.
Development of Anti-ALD403 Antibody by Visit
Serum blood samples were taken at visits to test for the development of antibodies to ALD403, or anti-drug antibodies (ADA). Participants who tested positive for anti-ALD403 antibodies at the time of the last study visit were asked to provide up to 2 additional blood samples for immunogenicity testing at approximately 3 month intervals for up to 6 months.
Summary of Neutralizing Properties of Anti-ALD403 Antibodies by Visit
Any samples that were positive for anti-ALD403 antibody, there was additional testing to characterize the anti-ALD403 antibody for the potential to neutralize (NAb) ALD403 activity.
Full Information
NCT ID
NCT02985398
First Posted
December 5, 2016
Last Updated
April 10, 2020
Sponsor
Alder Biopharmaceuticals, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT02985398
Brief Title
An Open Label Trial of ALD403 (Eptinezumab) in Chronic Migraine
Acronym
PREVAIL
Official Title
An Open Label Phase 3 Trial to Evaluate the Safety of ALD403 Administered Intravenously in Patients With Chronic Migraines
Study Type
Interventional
2. Study Status
Record Verification Date
April 2020
Overall Recruitment Status
Completed
Study Start Date
December 2016 (Actual)
Primary Completion Date
April 2018 (Actual)
Study Completion Date
March 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Alder Biopharmaceuticals, Inc.
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
An evaluation of long term safety of repeat ALD403 doses in Chronic Migraine
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Migraine Disorder
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
128 (Actual)
8. Arms, Groups, and Interventions
Arm Title
ALD403 (Eptinezumab) Dose Level 1
Arm Type
Experimental
Arm Description
ALD403 (Eptinezumab) Dose Level 1 (IV)
Intervention Type
Biological
Intervention Name(s)
ALD403 (Eptinezumab)
Other Intervention Name(s)
Eptinezumab-jjmr, Vyepti
Primary Outcome Measure Information:
Title
Number of Participants With Any Treatment Emergent Adverse Events (TEAEs)
Description
Treatment emergent adverse events were defined as adverse events with start date and time on or after the date and time of the initial study drug infusion.
Time Frame
104 Weeks
Title
Number of Participants With a Clinically Significant Electrocardiogram
Description
Overall investigator interpretation of participant electrocardiogram
Time Frame
Baseline, Day 0 Postdose, Week 12, 24, 36, 48 60, 72 and 84 (Predose and Postdose), and Week 104
Title
Number of Participants With Any Clinically Significant Laboratory Values
Description
Each of the laboratory values that were reported as abnormal and clinically significant and entered as adverse events in the database.
Time Frame
104 Weeks
Title
Number of Participants Experiencing Suicidal Ideation or Suicidal Behavior on Columbia-Suicide Severity Rating Scale (C-SSRS)
Description
Baseline responses are collected at screening and assess suicidal ideation in the past 6 months. Post baseline reports the worst assessment of suicidal ideation since the last visit for all post baseline visits.
Time Frame
104 Weeks
Title
Number of Participants With Any Clinically Significant (CS) Changes in Vital Signs
Description
Changes in vital signs that were considered clinically meaningful or clinically significant (CS) by the Investigator
Time Frame
104 Weeks
Secondary Outcome Measure Information:
Title
Patient Global Impression of Change (PGIC) at Week 104
Description
The PGIC includes a single question concerning the participant's impression of the change in their disease status since the start of the study. Seven responses are possible: Very much improved, much improved, minimally improved, no change, minimally worse, much worse, very much worse.
Time Frame
Week 104
Title
Change in Baseline of Short Form Health Survey (SF-36 v 2.0) Scale Scores
Description
The SF-36 is a health survey consisting of 36 questions consisting of eight scaled scores to measure quality of life over the past 4 weeks (scale range: 0=worst to 100=best). Increases from baseline indicate improvement.
Time Frame
Baseline to Week 12
Title
Health Related Quality of Life (EQ-5D-5L) at Week 12
Description
The EQ-5D-5L is a descriptive health-related quality of life states consisting of 5 dimensions/questions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) each of which can take one of five responses. The responses record five levels of severity (no problems/slight problems/moderate problems/severe problems/extreme problems) within a particular EQ-5D dimension.
Time Frame
Week 12
Title
Change in Baseline of Headache Impact Test (HIT-6) Score
Description
The HIT-6 measures the impact of headache on the participant's functional health and well-being in 6 domains: pain; role functioning (ability to carry out usual activities); social functioning; energy or fatigue; cognition; and emotional distress assess over the prior 12-week period. The total possible scores range from 36 (no impact) to 78 (worst impact). The change in baseline will be calculated from the average scores.
Time Frame
Baseline, Week 1-4, Week 9-12
Title
Change in Most Bothersome Symptom at Week 48
Description
The Investigator verbally obtained the most bothersome symptom associated with the participant's migraine during the screening visit. The most bothersome symptom may include nausea, vomiting, sensitivity to light, sensitivity to sound, mental cloudiness, fatigue, pain with activity, mood changes, or other migraine related symptoms. Participants were asked to rate the improvement in this symptom from screening on a seven-point scale.
Time Frame
Baseline to Week 48
Title
Change From Baseline of Migraine Disability Assessment (MIDAS) Total Score
Description
The MIDAS questionnaire measures the effect headaches have on the participant's daily functioning. MIDAS is composed of five questions that ask about the participant's performance over the past 3 months. The response to each question is provided in number of days which are summed to determine the MIDAS total score and level of disability:
0-5, MIDAS Grade I, little or no disability; 6-10, MIDAS Grade II, mild disability; 11-20, MIDAS Grade III, moderate disability; 21+, MIDAS Grade IV, severe disability;
A higher value represents a worse outcome.
Time Frame
Baseline to Week 12
Title
Development of Anti-ALD403 Antibody by Visit
Description
Serum blood samples were taken at visits to test for the development of antibodies to ALD403, or anti-drug antibodies (ADA). Participants who tested positive for anti-ALD403 antibodies at the time of the last study visit were asked to provide up to 2 additional blood samples for immunogenicity testing at approximately 3 month intervals for up to 6 months.
Time Frame
Baseline, Week 2, 4, 8, 12, 24, 36, 48, 72 and 104
Title
Summary of Neutralizing Properties of Anti-ALD403 Antibodies by Visit
Description
Any samples that were positive for anti-ALD403 antibody, there was additional testing to characterize the anti-ALD403 antibody for the potential to neutralize (NAb) ALD403 activity.
Time Frame
Baseline, Week 2, 4, 8, 12, 24, 36, 48, 72 and 104
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Males and females between 18 and 65 years of age, inclusive, who were diagnosed with migraines at ≤ 50 years of age, and have a history of chronic migraine for ≥ 12 months before screening.
Exclusion Criteria:
Receipt of any monoclonal antibody treatment (within or outside a clinical trial) within 6 months before screening.
Confounding and clinically significant pain syndromes (e.g. fibromyalgia, chronic low back pain, complex regional pain syndrome).
Psychiatric conditions that are uncontrolled and/or untreated, including conditions that are not controlled for a minimum of 6 months prior to screening. Patients with a lifetime history of psychosis, mania, or dementia are excluded.
History or diagnosis of complicated migraine (ICHD-III beta version, 20134), chronic tension-type headache, hypnic headache, cluster headache, hemicrania continua, new daily persistent headache, or sporadic and familial hemiplegic migraine.
Facility Information:
Facility Name
Research Site
City
San Diego
State/Province
California
ZIP/Postal Code
92108
Country
United States
Facility Name
Research Site
City
Santa Monica
State/Province
California
ZIP/Postal Code
90404
Country
United States
Facility Name
Research Site
City
Colorado Springs
State/Province
Colorado
ZIP/Postal Code
80918
Country
United States
Facility Name
Research Site
City
Bradenton
State/Province
Florida
ZIP/Postal Code
34201
Country
United States
Facility Name
Research Site
City
DeLand
State/Province
Florida
ZIP/Postal Code
32720
Country
United States
Facility Name
Massachusetts
City
Miami
State/Province
Florida
ZIP/Postal Code
33125
Country
United States
Facility Name
Research Site
City
Tampa
State/Province
Florida
ZIP/Postal Code
33634
Country
United States
Facility Name
Research Site
City
Winter Haven
State/Province
Florida
ZIP/Postal Code
33880
Country
United States
Facility Name
Research Site
City
Prairie Village
State/Province
Kansas
ZIP/Postal Code
66206
Country
United States
Facility Name
Massachusetts
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02131
Country
United States
Facility Name
Research Site
City
North Attleboro
State/Province
Massachusetts
ZIP/Postal Code
02760
Country
United States
Facility Name
02481
City
Wellesley
State/Province
Massachusetts
ZIP/Postal Code
02481
Country
United States
Facility Name
Research Site
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55402
Country
United States
Facility Name
Research Site
City
Brooklyn
State/Province
New York
ZIP/Postal Code
11229
Country
United States
Facility Name
Research Site
City
Rochester
State/Province
New York
ZIP/Postal Code
14609
Country
United States
Facility Name
Research Site
City
Dayton
State/Province
Ohio
ZIP/Postal Code
45432
Country
United States
Facility Name
Research Site
City
Mount Pleasant
State/Province
South Carolina
ZIP/Postal Code
29464
Country
United States
Facility Name
Research Site
City
Chattanooga
State/Province
Tennessee
ZIP/Postal Code
37421
Country
United States
Facility Name
Research Site
City
Fort Worth
State/Province
Texas
ZIP/Postal Code
76104
Country
United States
Facility Name
Research Site
City
Bellevue
State/Province
Washington
ZIP/Postal Code
98007
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
35804294
Citation
Blumenfeld A, Ettrup A, Hirman J, Ebert B, Cady R. Long-term reductions in disease impact in patients with chronic migraine following preventive treatment with eptinezumab. BMC Neurol. 2022 Jul 8;22(1):251. doi: 10.1186/s12883-022-02774-3.
Results Reference
derived
PubMed Identifier
33781209
Citation
Smith TR, Spierings ELH, Cady R, Hirman J, Schaeffler B, Shen V, Sperling B, Brevig T, Josiassen MK, Brunner E, Honeywell L, Mehta L. Safety and tolerability of eptinezumab in patients with migraine: a pooled analysis of 5 clinical trials. J Headache Pain. 2021 Mar 30;22(1):16. doi: 10.1186/s10194-021-01227-5. Erratum In: J Headache Pain. 2021 May 25;22(1):46.
Results Reference
derived
PubMed Identifier
33740902
Citation
Kudrow D, Cady RK, Allan B, Pederson SM, Hirman J, Mehta LR, Schaeffler BA. Long-term safety and tolerability of eptinezumab in patients with chronic migraine: a 2-year, open-label, phase 3 trial. BMC Neurol. 2021 Mar 19;21(1):126. doi: 10.1186/s12883-021-02123-w.
Results Reference
derived
Learn more about this trial
An Open Label Trial of ALD403 (Eptinezumab) in Chronic Migraine
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