Trial Outcomes & Findings for Evaluation of ALD403 (Eptinezumab) in the Prevention of Chronic Migraine (NCT NCT02974153)
NCT ID: NCT02974153
Last Updated: 2020-06-09
Results Overview
Monthly migraine days are summarized in 28-day intervals, and averaged across Weeks 1-12
COMPLETED
PHASE3
1121 participants
Week 1-12
2020-06-09
Participant Flow
A total of 2263 participants signed the ICF, of which 1121 participants met the entry criteria and were randomized into the trial.
Participant milestones
| Measure |
300 mg ALD403
Participants were randomized to receive a single 300 mg IV infusion of ALD403 on Days 0 and 84 (Week 12).
|
100 mg ALD403
Participants were randomized to receive a single 100 mg IV infusion of ALD403 on Days 0 and 84 (Week 12).
|
Placebo
Participants were randomized to receive a single placebo IV infusion on Days 0 and 84 (Week 12).
|
|---|---|---|---|
|
Overall Study
STARTED
|
374
|
372
|
375
|
|
Overall Study
Participants Treated
|
350
|
356
|
366
|
|
Overall Study
COMPLETED
|
322
|
324
|
325
|
|
Overall Study
NOT COMPLETED
|
52
|
48
|
50
|
Reasons for withdrawal
| Measure |
300 mg ALD403
Participants were randomized to receive a single 300 mg IV infusion of ALD403 on Days 0 and 84 (Week 12).
|
100 mg ALD403
Participants were randomized to receive a single 100 mg IV infusion of ALD403 on Days 0 and 84 (Week 12).
|
Placebo
Participants were randomized to receive a single placebo IV infusion on Days 0 and 84 (Week 12).
|
|---|---|---|---|
|
Overall Study
Adverse Event
|
6
|
0
|
1
|
|
Overall Study
Lack of Efficacy
|
6
|
5
|
10
|
|
Overall Study
Lost to Follow-up
|
9
|
10
|
17
|
|
Overall Study
Physician Decision
|
0
|
2
|
1
|
|
Overall Study
Withdrawal by Subject
|
9
|
16
|
11
|
|
Overall Study
Study Burden
|
8
|
7
|
3
|
|
Overall Study
Other
|
14
|
8
|
7
|
Baseline Characteristics
Evaluation of ALD403 (Eptinezumab) in the Prevention of Chronic Migraine
Baseline characteristics by cohort
| Measure |
300 mg ALD403
n=350 Participants
Participants were randomized to receive a single 300 mg IV infusion of ALD403 on Days 0 and 84 (Week 12).
|
100 mg ALD403
n=356 Participants
Participants were randomized to receive a single 100 mg IV infusion of ALD403 on Days 0 and 84 (Week 12).
|
Placebo
n=366 Participants
Participants were randomized to receive a single placebo IV infusion on Days 0 and 84 (Week 12).
|
Total
n=1072 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
41.0 years
STANDARD_DEVIATION 10.36 • n=39 Participants
|
41.0 years
STANDARD_DEVIATION 11.72 • n=41 Participants
|
39.6 years
STANDARD_DEVIATION 11.28 • n=35 Participants
|
40.5 years
STANDARD_DEVIATION 11.15 • n=31 Participants
|
|
Sex: Female, Male
Female
|
314 Participants
n=39 Participants
|
307 Participants
n=41 Participants
|
325 Participants
n=35 Participants
|
946 Participants
n=31 Participants
|
|
Sex: Female, Male
Male
|
36 Participants
n=39 Participants
|
49 Participants
n=41 Participants
|
41 Participants
n=35 Participants
|
126 Participants
n=31 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
18 Participants
n=39 Participants
|
33 Participants
n=41 Participants
|
35 Participants
n=35 Participants
|
86 Participants
n=31 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
332 Participants
n=39 Participants
|
323 Participants
n=41 Participants
|
331 Participants
n=35 Participants
|
986 Participants
n=31 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=39 Participants
|
00 Participants
n=41 Participants
|
0 Participants
n=35 Participants
|
0 Participants
n=31 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=39 Participants
|
1 Participants
n=41 Participants
|
1 Participants
n=35 Participants
|
3 Participants
n=31 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=39 Participants
|
1 Participants
n=41 Participants
|
1 Participants
n=35 Participants
|
3 Participants
n=31 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
1 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
0 Participants
n=35 Participants
|
1 Participants
n=31 Participants
|
|
Race (NIH/OMB)
Black or African American
|
23 Participants
n=39 Participants
|
21 Participants
n=41 Participants
|
38 Participants
n=35 Participants
|
82 Participants
n=31 Participants
|
|
Race (NIH/OMB)
White
|
322 Participants
n=39 Participants
|
332 Participants
n=41 Participants
|
321 Participants
n=35 Participants
|
975 Participants
n=31 Participants
|
|
Race (NIH/OMB)
More than one race
|
2 Participants
n=39 Participants
|
1 Participants
n=41 Participants
|
4 Participants
n=35 Participants
|
7 Participants
n=31 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=39 Participants
|
0 Participants
n=41 Participants
|
1 Participants
n=35 Participants
|
1 Participants
n=31 Participants
|
|
Region of Enrollment
Hungary
|
3 participants
n=39 Participants
|
5 participants
n=41 Participants
|
3 participants
n=35 Participants
|
11 participants
n=31 Participants
|
|
Region of Enrollment
United States
|
195 participants
n=39 Participants
|
198 participants
n=41 Participants
|
232 participants
n=35 Participants
|
625 participants
n=31 Participants
|
|
Region of Enrollment
Czechia
|
12 participants
n=39 Participants
|
7 participants
n=41 Participants
|
8 participants
n=35 Participants
|
27 participants
n=31 Participants
|
|
Region of Enrollment
Ukraine
|
34 participants
n=39 Participants
|
43 participants
n=41 Participants
|
33 participants
n=35 Participants
|
110 participants
n=31 Participants
|
|
Region of Enrollment
United Kingdom
|
3 participants
n=39 Participants
|
4 participants
n=41 Participants
|
2 participants
n=35 Participants
|
9 participants
n=31 Participants
|
|
Region of Enrollment
Spain
|
18 participants
n=39 Participants
|
22 participants
n=41 Participants
|
18 participants
n=35 Participants
|
58 participants
n=31 Participants
|
|
Region of Enrollment
Russia
|
32 participants
n=39 Participants
|
27 participants
n=41 Participants
|
27 participants
n=35 Participants
|
86 participants
n=31 Participants
|
|
Region of Enrollment
Belgium
|
0 participants
n=39 Participants
|
0 participants
n=41 Participants
|
1 participants
n=35 Participants
|
1 participants
n=31 Participants
|
|
Region of Enrollment
Denmark
|
3 participants
n=39 Participants
|
2 participants
n=41 Participants
|
1 participants
n=35 Participants
|
6 participants
n=31 Participants
|
|
Region of Enrollment
Italy
|
7 participants
n=39 Participants
|
3 participants
n=41 Participants
|
5 participants
n=35 Participants
|
15 participants
n=31 Participants
|
|
Region of Enrollment
Georgia
|
36 participants
n=39 Participants
|
38 participants
n=41 Participants
|
23 participants
n=35 Participants
|
97 participants
n=31 Participants
|
|
Region of Enrollment
Slovakia
|
4 participants
n=39 Participants
|
5 participants
n=41 Participants
|
8 participants
n=35 Participants
|
17 participants
n=31 Participants
|
|
Region of Enrollment
Germany
|
3 participants
n=39 Participants
|
2 participants
n=41 Participants
|
5 participants
n=35 Participants
|
10 participants
n=31 Participants
|
|
Baseline Migraine Days
Less than 17 days per month
|
197 Participants
n=39 Participants
|
199 Participants
n=41 Participants
|
206 Participants
n=35 Participants
|
602 Participants
n=31 Participants
|
|
Baseline Migraine Days
Greater than or equal to 17 days per month
|
153 Participants
n=39 Participants
|
157 Participants
n=41 Participants
|
160 Participants
n=35 Participants
|
470 Participants
n=31 Participants
|
|
Medication overuse headache diagnosis
No
|
203 Participants
n=39 Participants
|
217 Participants
n=41 Participants
|
221 Participants
n=35 Participants
|
641 Participants
n=31 Participants
|
|
Medication overuse headache diagnosis
Yes
|
147 Participants
n=39 Participants
|
139 Participants
n=41 Participants
|
145 Participants
n=35 Participants
|
431 Participants
n=31 Participants
|
PRIMARY outcome
Timeframe: Week 1-12Population: Full Analysis Population - all randomized participants who received investigational product or placebo
Monthly migraine days are summarized in 28-day intervals, and averaged across Weeks 1-12
Outcome measures
| Measure |
300 mg ALD403
n=350 Participants
Participants received a single 300 mg IV infusion of ALD403 on Days 0 and 84 (Week 12).
|
100 mg ALD403
n=356 Participants
Participants received a single 100 mg IV infusion of ALD403 on Days 0 and 84 (Week 12).
|
Placebo
n=366 Participants
Participants received a single placebo IV infusion on Days 0 and 84 (Week 12).
|
|---|---|---|---|
|
Change From Baseline in Monthly Migraine Days
|
-8.2 Migraine Days
Interval -23.0 to 11.0
|
-7.7 Migraine Days
Interval -22.0 to 10.0
|
-5.6 Migraine Days
Interval -25.0 to 9.0
|
SECONDARY outcome
Timeframe: Week 1-12Population: Full Analysis Population - all randomized participants who received investigational product or placebo
Participants with an average reduction in migraine days of at least 75% over Weeks 1 to 12, as compared with baseline.
Outcome measures
| Measure |
300 mg ALD403
n=350 Participants
Participants received a single 300 mg IV infusion of ALD403 on Days 0 and 84 (Week 12).
|
100 mg ALD403
n=356 Participants
Participants received a single 100 mg IV infusion of ALD403 on Days 0 and 84 (Week 12).
|
Placebo
n=366 Participants
Participants received a single placebo IV infusion on Days 0 and 84 (Week 12).
|
|---|---|---|---|
|
75% Migraine Responder Rate
|
116 Participants
|
95 Participants
|
55 Participants
|
SECONDARY outcome
Timeframe: Week 1-4Population: Full Analysis Population - all randomized participants who received investigational product or placebo
Participants with an average reduction in migraine days of at least 75% over Weeks 1 to 4, as compared with baseline.
Outcome measures
| Measure |
300 mg ALD403
n=350 Participants
Participants received a single 300 mg IV infusion of ALD403 on Days 0 and 84 (Week 12).
|
100 mg ALD403
n=356 Participants
Participants received a single 100 mg IV infusion of ALD403 on Days 0 and 84 (Week 12).
|
Placebo
n=366 Participants
Participants received a single placebo IV infusion on Days 0 and 84 (Week 12).
|
|---|---|---|---|
|
75% Migraine Responder Rate - 4 Week
|
129 Participants
|
110 Participants
|
57 Participants
|
SECONDARY outcome
Timeframe: Week 1-12Population: Full Analysis Population - all randomized participants who received investigational product or placebo
Participants with an average reduction in migraine days of at least 50% over Weeks 1 to 12, as compared with baseline.
Outcome measures
| Measure |
300 mg ALD403
n=350 Participants
Participants received a single 300 mg IV infusion of ALD403 on Days 0 and 84 (Week 12).
|
100 mg ALD403
n=356 Participants
Participants received a single 100 mg IV infusion of ALD403 on Days 0 and 84 (Week 12).
|
Placebo
n=366 Participants
Participants received a single placebo IV infusion on Days 0 and 84 (Week 12).
|
|---|---|---|---|
|
50% Migraine Responder Rate
|
215 Participants
|
205 Participants
|
144 Participants
|
SECONDARY outcome
Timeframe: Day 1Population: Full Analysis Population - all randomized participants who received investigational product or placebo
The percentage of participants with a migraine on the day after dosing, where Day 0 is treatment Day and Day 1 is the day after dosing.
Outcome measures
| Measure |
300 mg ALD403
n=350 Participants
Participants received a single 300 mg IV infusion of ALD403 on Days 0 and 84 (Week 12).
|
100 mg ALD403
n=356 Participants
Participants received a single 100 mg IV infusion of ALD403 on Days 0 and 84 (Week 12).
|
Placebo
n=366 Participants
Participants received a single placebo IV infusion on Days 0 and 84 (Week 12).
|
|---|---|---|---|
|
Percentage of Participants With a Migraine on the Day After Dosing
|
27.8 Percentage of participants
|
28.6 Percentage of participants
|
42.3 Percentage of participants
|
SECONDARY outcome
Timeframe: Week 1-12Population: Full Analysis Population - all randomized participants who received investigational product or placebo
An acute medication migraine day was a day with any triptan or ergotamine use as recorded in the eDiary.
Outcome measures
| Measure |
300 mg ALD403
n=350 Participants
Participants received a single 300 mg IV infusion of ALD403 on Days 0 and 84 (Week 12).
|
100 mg ALD403
n=356 Participants
Participants received a single 100 mg IV infusion of ALD403 on Days 0 and 84 (Week 12).
|
Placebo
n=366 Participants
Participants received a single placebo IV infusion on Days 0 and 84 (Week 12).
|
|---|---|---|---|
|
Change in Monthly Acute Medication Days
|
-3.5 Acute Medication Migraine Days
Standard Deviation 4.62
|
-3.3 Acute Medication Migraine Days
Standard Deviation 4.89
|
-1.9 Acute Medication Migraine Days
Standard Deviation 4.18
|
SECONDARY outcome
Timeframe: Baseline to Week 12Population: Full Analysis Population - all randomized participants who received investigational product or placebo
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 assessed over the prior 12-week period. The total possible scores range from 36 (no impact) to 78 (worst impact).
Outcome measures
| Measure |
300 mg ALD403
n=350 Participants
Participants received a single 300 mg IV infusion of ALD403 on Days 0 and 84 (Week 12).
|
100 mg ALD403
n=356 Participants
Participants received a single 100 mg IV infusion of ALD403 on Days 0 and 84 (Week 12).
|
Placebo
n=366 Participants
Participants received a single placebo IV infusion on Days 0 and 84 (Week 12).
|
|---|---|---|---|
|
Change From Baseline of Headache Impact Test (HIT-6) Score
|
-7.3 score on a scale
Interval -40.0 to 10.0
|
-6.2 score on a scale
Interval -34.0 to 10.0
|
-4.5 score on a scale
Interval -32.0 to 15.0
|
SECONDARY outcome
Timeframe: Baseline to Week 4Population: Full Analysis Population - all randomized participants who received investigational product or placebo
The avarage change in percentage of participants with a migraine on any given day during baseline and the equivalent avarage rate over Weeks 1-4.
Outcome measures
| Measure |
300 mg ALD403
n=350 Participants
Participants received a single 300 mg IV infusion of ALD403 on Days 0 and 84 (Week 12).
|
100 mg ALD403
n=356 Participants
Participants received a single 100 mg IV infusion of ALD403 on Days 0 and 84 (Week 12).
|
Placebo
n=366 Participants
Participants received a single placebo IV infusion on Days 0 and 84 (Week 12).
|
|---|---|---|---|
|
Change in Migraine Prevalence From Baseline to Week 4
|
-29.8 percentage of participants with migraine
Interval -32.1 to -27.49
|
-27.1 percentage of participants with migraine
Interval -29.35 to -24.78
|
-18.8 percentage of participants with migraine
Interval -21.06 to -16.54
|
SECONDARY outcome
Timeframe: Week 1-12Population: Full Analysis Population - all randomized participants who received investigational product or placebo
Participants with an average reduction in headache days of at least 75% over Weeks 1 to 12, as compared with baseline.
Outcome measures
| Measure |
300 mg ALD403
n=350 Participants
Participants received a single 300 mg IV infusion of ALD403 on Days 0 and 84 (Week 12).
|
100 mg ALD403
n=356 Participants
Participants received a single 100 mg IV infusion of ALD403 on Days 0 and 84 (Week 12).
|
Placebo
n=366 Participants
Participants received a single placebo IV infusion on Days 0 and 84 (Week 12).
|
|---|---|---|---|
|
75% Headache Responder Rate
|
61 Participants
|
49 Participants
|
29 Participants
|
SECONDARY outcome
Timeframe: Week 1-12Population: Full Analysis Population - all randomized participants who received investigational product or placebo
Participants with an average reduction in headache days of at least 50% over Weeks 1 to 12, as compared with baseline.
Outcome measures
| Measure |
300 mg ALD403
n=350 Participants
Participants received a single 300 mg IV infusion of ALD403 on Days 0 and 84 (Week 12).
|
100 mg ALD403
n=356 Participants
Participants received a single 100 mg IV infusion of ALD403 on Days 0 and 84 (Week 12).
|
Placebo
n=366 Participants
Participants received a single placebo IV infusion on Days 0 and 84 (Week 12).
|
|---|---|---|---|
|
50% Headache Responder Rate
|
169 Participants
|
150 Participants
|
95 Participants
|
SECONDARY outcome
Timeframe: Week 1-12Population: Full Analysis Population - all randomized participants who received investigational product or placebo
For each 4-week period the 100% response is determined, and the result for a participant is the average rate across Weeks 1-12. If a participant has one 4-week period out of 3 with 100% response, they are included as 33%.
Outcome measures
| Measure |
300 mg ALD403
n=350 Participants
Participants received a single 300 mg IV infusion of ALD403 on Days 0 and 84 (Week 12).
|
100 mg ALD403
n=356 Participants
Participants received a single 100 mg IV infusion of ALD403 on Days 0 and 84 (Week 12).
|
Placebo
n=366 Participants
Participants received a single placebo IV infusion on Days 0 and 84 (Week 12).
|
|---|---|---|---|
|
100% Migraine Responder Rate
|
15.1 percent of participants
|
10.8 percent of participants
|
5.1 percent of participants
|
SECONDARY outcome
Timeframe: Week 1-12Population: Full Analysis Population - all randomized participants who received investigational product or placebo
For each 4-week period the 100% response is determined, and the result for a participant is the average rate across Weeks 1-12. If a participant has one 4-week period out of 3 with 100% response, they are included as 33%.
Outcome measures
| Measure |
300 mg ALD403
n=350 Participants
Participants received a single 300 mg IV infusion of ALD403 on Days 0 and 84 (Week 12).
|
100 mg ALD403
n=356 Participants
Participants received a single 100 mg IV infusion of ALD403 on Days 0 and 84 (Week 12).
|
Placebo
n=366 Participants
Participants received a single placebo IV infusion on Days 0 and 84 (Week 12).
|
|---|---|---|---|
|
100% Headache Responder Rate
|
3.8 Percent of participants
|
2.0 Percent of participants
|
1.5 Percent of participants
|
SECONDARY outcome
Timeframe: Week 13-24Population: Full Analysis Population - all randomized participants who received investigational product or placebo
Monthly migraine days are summarized in 28-day intervals, and averaged across Weeks 13-24.
Outcome measures
| Measure |
300 mg ALD403
n=350 Participants
Participants received a single 300 mg IV infusion of ALD403 on Days 0 and 84 (Week 12).
|
100 mg ALD403
n=356 Participants
Participants received a single 100 mg IV infusion of ALD403 on Days 0 and 84 (Week 12).
|
Placebo
n=366 Participants
Participants received a single placebo IV infusion on Days 0 and 84 (Week 12).
|
|---|---|---|---|
|
Change From Baseline in Monthly Migraine Days (Weeks 13-24)
|
-9.0 Migraine Days
Standard Deviation 6.72
|
-8.3 Migraine Days
Standard Deviation 7.03
|
-6.4 Migraine Days
Standard Deviation 7.16
|
SECONDARY outcome
Timeframe: Week 1-12Population: Full Analysis Population - all randomized participants who received investigational product or placebo
Monthly headache days are summarized in 28-day intervals, and averaged across Weeks 1-12.
Outcome measures
| Measure |
300 mg ALD403
n=350 Participants
Participants received a single 300 mg IV infusion of ALD403 on Days 0 and 84 (Week 12).
|
100 mg ALD403
n=356 Participants
Participants received a single 100 mg IV infusion of ALD403 on Days 0 and 84 (Week 12).
|
Placebo
n=366 Participants
Participants received a single placebo IV infusion on Days 0 and 84 (Week 12).
|
|---|---|---|---|
|
Change From Baseline in Monthly Headache Days (Weeks 1-12)
|
-8.8 Headache Days
Standard Deviation 6.10
|
-8.2 Headache Days
Standard Deviation 5.78
|
-6.4 Headache Days
Standard Deviation 5.99
|
SECONDARY outcome
Timeframe: 32 weeksPopulation: Full Analysis Population - all randomized participants who received investigational product or placebo
The time to first migraine after dosing based upon the migraine data entered into the eDiary
Outcome measures
| Measure |
300 mg ALD403
n=350 Participants
Participants received a single 300 mg IV infusion of ALD403 on Days 0 and 84 (Week 12).
|
100 mg ALD403
n=356 Participants
Participants received a single 100 mg IV infusion of ALD403 on Days 0 and 84 (Week 12).
|
Placebo
n=366 Participants
Participants received a single placebo IV infusion on Days 0 and 84 (Week 12).
|
|---|---|---|---|
|
Time to First Migraine After Dosing
|
4.0 days
Interval 1.0 to 11.0
|
4.0 days
Interval 1.0 to 9.0
|
2.0 days
Interval 1.0 to 5.0
|
SECONDARY outcome
Timeframe: Week 1-12Population: Full Analysis Population - all randomized participants who received investigational product or placebo
The percentage of migraines with acute medication usage. Participants with no migraine will be included with a rate of zero.
Outcome measures
| Measure |
300 mg ALD403
n=350 Participants
Participants received a single 300 mg IV infusion of ALD403 on Days 0 and 84 (Week 12).
|
100 mg ALD403
n=356 Participants
Participants received a single 100 mg IV infusion of ALD403 on Days 0 and 84 (Week 12).
|
Placebo
n=366 Participants
Participants received a single placebo IV infusion on Days 0 and 84 (Week 12).
|
|---|---|---|---|
|
Change From Baseline to Week 12 in Percentage of Migraines With Use of Acute Medication
|
-14.10 percentage of acute medication migraines
Standard Deviation 28.86
|
-9.79 percentage of acute medication migraines
Standard Deviation 26.78
|
-2.82 percentage of acute medication migraines
Standard Deviation 20.94
|
SECONDARY outcome
Timeframe: Week 1-12Population: Full Analysis Population - all randomized participants who received investigational product or placebo
The percentage of headaches with acute medication usage. Participants with no headaches will be included with a rate of zero.
Outcome measures
| Measure |
300 mg ALD403
n=350 Participants
Participants received a single 300 mg IV infusion of ALD403 on Days 0 and 84 (Week 12).
|
100 mg ALD403
n=356 Participants
Participants received a single 100 mg IV infusion of ALD403 on Days 0 and 84 (Week 12).
|
Placebo
n=366 Participants
Participants received a single placebo IV infusion on Days 0 and 84 (Week 12).
|
|---|---|---|---|
|
Change From Baseline to Week 12 in Percentage of Headaches With Use of Acute Medication
|
-7.46 percentage of acute medication headaches
Standard Deviation 23.32
|
-3.08 percentage of acute medication headaches
Standard Deviation 21.31
|
-0.16 percentage of acute medication headaches
Standard Deviation 19.12
|
SECONDARY outcome
Timeframe: Week 1-12Population: Full Analysis Population - all randomized participants who received investigational product or placebo
The percent change in frequency of migraine days from Weeks 1-12 was calculated as the number of migraine days within 4-week intervals that were then averaged up to Week 12. The difference of this estimate from baseline was calculated as the change from baseline in the frequency of migraine days over Weeks 1-12.
Outcome measures
| Measure |
300 mg ALD403
n=350 Participants
Participants received a single 300 mg IV infusion of ALD403 on Days 0 and 84 (Week 12).
|
100 mg ALD403
n=356 Participants
Participants received a single 100 mg IV infusion of ALD403 on Days 0 and 84 (Week 12).
|
Placebo
n=366 Participants
Participants received a single placebo IV infusion on Days 0 and 84 (Week 12).
|
|---|---|---|---|
|
Percent Change in Frequency of Migraine Days - Week 1-12
|
-53.5 percent change of migraine days
Standard Deviation 35.46
|
-48.6 percent change of migraine days
Standard Deviation 36.60
|
-34.5 percent change of migraine days
Standard Deviation 38.17
|
SECONDARY outcome
Timeframe: Week 1-12Population: Full Analysis Population - all randomized participants who received investigational product or placebo
The percent change in frequency of headache days from Weeks 1-12 was calculated as the number of headache days within 4-week intervals that were then averaged up to Week 12. The difference of this estimate from baseline was calculated as the change from baseline in the frequency of headache days over Weeks 1-12.
Outcome measures
| Measure |
300 mg ALD403
n=350 Participants
Participants received a single 300 mg IV infusion of ALD403 on Days 0 and 84 (Week 12).
|
100 mg ALD403
n=356 Participants
Participants received a single 100 mg IV infusion of ALD403 on Days 0 and 84 (Week 12).
|
Placebo
n=366 Participants
Participants received a single placebo IV infusion on Days 0 and 84 (Week 12).
|
|---|---|---|---|
|
Percent Change in Frequency of Headache Days - Week 1-12
|
-44.1 percent change of headache days
Standard Deviation 30.59
|
-41.2 percent change of headache days
Standard Deviation 29.20
|
-31.4 percent change of headache days
Standard Deviation 28.62
|
SECONDARY outcome
Timeframe: Week 1-12Population: Full Analysis Population - all randomized participants who received investigational product or placebo
The change from baseline in percentage of migraines that are classified as severe over Weeks 1-12.
Outcome measures
| Measure |
300 mg ALD403
n=350 Participants
Participants received a single 300 mg IV infusion of ALD403 on Days 0 and 84 (Week 12).
|
100 mg ALD403
n=356 Participants
Participants received a single 100 mg IV infusion of ALD403 on Days 0 and 84 (Week 12).
|
Placebo
n=366 Participants
Participants received a single placebo IV infusion on Days 0 and 84 (Week 12).
|
|---|---|---|---|
|
Change From Baseline in Percentage of Severe Migraines
|
-18.17 percentage of migraines scored "severe"
Standard Deviation 27.90
|
-16.39 percentage of migraines scored "severe"
Standard Deviation 26.17
|
-10.82 percentage of migraines scored "severe"
Standard Deviation 25.73
|
SECONDARY outcome
Timeframe: Week 1-12Population: Full Analysis Population - all randomized participants who received investigational product or placebo
The change from baseline in percentage of headaches that are classified as severe over Weeks 1-12.
Outcome measures
| Measure |
300 mg ALD403
n=350 Participants
Participants received a single 300 mg IV infusion of ALD403 on Days 0 and 84 (Week 12).
|
100 mg ALD403
n=356 Participants
Participants received a single 100 mg IV infusion of ALD403 on Days 0 and 84 (Week 12).
|
Placebo
n=366 Participants
Participants received a single placebo IV infusion on Days 0 and 84 (Week 12).
|
|---|---|---|---|
|
Change From Baseline in Percentage of Severe Headache
|
-14.00 percentage of headaches scored "severe"
Standard Deviation 22.50
|
-14.01 percentage of headaches scored "severe"
Standard Deviation 20.95
|
-9.12 percentage of headaches scored "severe"
Standard Deviation 22.12
|
SECONDARY outcome
Timeframe: Week 1-12Population: Full Analysis Population - all randomized participants who received investigational product or placebo
Migraine hours are the sum of migraines within 4 week intervals, and the average 4 week duration within 12 weeks.
Outcome measures
| Measure |
300 mg ALD403
n=350 Participants
Participants received a single 300 mg IV infusion of ALD403 on Days 0 and 84 (Week 12).
|
100 mg ALD403
n=356 Participants
Participants received a single 100 mg IV infusion of ALD403 on Days 0 and 84 (Week 12).
|
Placebo
n=366 Participants
Participants received a single placebo IV infusion on Days 0 and 84 (Week 12).
|
|---|---|---|---|
|
Change From Baseline in Monthly Migraine Hours, Weeks 1-12
|
-80.9 migraine hours
Standard Deviation 89.17
|
-75.2 migraine hours
Standard Deviation 90.40
|
-52.8 migraine hours
Standard Deviation 101.82
|
SECONDARY outcome
Timeframe: Week 1-12Population: Full Analysis Population - all randomized participants who received investigational product or placebo
Headache hours are the sum of the duration of headaches within 4 week intervals, and the average 4 week duration within 12 week intervals.
Outcome measures
| Measure |
300 mg ALD403
n=350 Participants
Participants received a single 300 mg IV infusion of ALD403 on Days 0 and 84 (Week 12).
|
100 mg ALD403
n=356 Participants
Participants received a single 100 mg IV infusion of ALD403 on Days 0 and 84 (Week 12).
|
Placebo
n=366 Participants
Participants received a single placebo IV infusion on Days 0 and 84 (Week 12).
|
|---|---|---|---|
|
Change From Baseline in Monthly Headache Hours, Weeks 1-12
|
-82.5 headache hours
Standard Deviation 88.85
|
-74.6 headache hours
Standard Deviation 84.57
|
-54.8 headache hours
Standard Deviation 97.15
|
SECONDARY outcome
Timeframe: 32 weeksPopulation: Full Analysis Population - all randomized participants who received investigational product or placebo
The number of participants with migraine-free intervals starting within the first 2 weeks of treatment. The longest migraine free interval for each participant is recorded.
Outcome measures
| Measure |
300 mg ALD403
n=350 Participants
Participants received a single 300 mg IV infusion of ALD403 on Days 0 and 84 (Week 12).
|
100 mg ALD403
n=356 Participants
Participants received a single 100 mg IV infusion of ALD403 on Days 0 and 84 (Week 12).
|
Placebo
n=366 Participants
Participants received a single placebo IV infusion on Days 0 and 84 (Week 12).
|
|---|---|---|---|
|
Duration of Migraine-Free Intervals
<= 7 days
|
132 Participants
|
146 Participants
|
226 Participants
|
|
Duration of Migraine-Free Intervals
8-14 days
|
86 Participants
|
95 Participants
|
75 Participants
|
|
Duration of Migraine-Free Intervals
15-21 days
|
38 Participants
|
42 Participants
|
23 Participants
|
|
Duration of Migraine-Free Intervals
>21 days
|
94 Participants
|
73 Participants
|
42 Participants
|
SECONDARY outcome
Timeframe: Baseline to Week 12Population: Full Analysis Population - all randomized participants who received investigational product or placebo
The SF-36 is a health survey containing 36 questions consisting of eight scaled scores to measure quality of life over the past 4 weeks. All scales are on a range of 0 to 100, with 0 being the worst and 100 being the best. Scales are reported separately. Increases from baseline indicate improvement.
Outcome measures
| Measure |
300 mg ALD403
n=338 Participants
Participants received a single 300 mg IV infusion of ALD403 on Days 0 and 84 (Week 12).
|
100 mg ALD403
n=343 Participants
Participants received a single 100 mg IV infusion of ALD403 on Days 0 and 84 (Week 12).
|
Placebo
n=343 Participants
Participants received a single placebo IV infusion on Days 0 and 84 (Week 12).
|
|---|---|---|---|
|
Change From Baseline of Short Form Health Survey (SF-36 v 2.0) Scale Scores
Physical Functioning
|
3.3 score on a scale
Standard Deviation 6.22
|
2.6 score on a scale
Standard Deviation 5.98
|
1.5 score on a scale
Standard Deviation 6.88
|
|
Change From Baseline of Short Form Health Survey (SF-36 v 2.0) Scale Scores
Role Physical
|
6.0 score on a scale
Standard Deviation 8.46
|
4.6 score on a scale
Standard Deviation 8.53
|
3.6 score on a scale
Standard Deviation 8.08
|
|
Change From Baseline of Short Form Health Survey (SF-36 v 2.0) Scale Scores
Bodily Pain
|
6.2 score on a scale
Standard Deviation 8.71
|
5.1 score on a scale
Standard Deviation 9.12
|
4.0 score on a scale
Standard Deviation 8.55
|
|
Change From Baseline of Short Form Health Survey (SF-36 v 2.0) Scale Scores
General Health
|
3.5 score on a scale
Standard Deviation 7.45
|
2.3 score on a scale
Standard Deviation 6.89
|
0.7 score on a scale
Standard Deviation 7.53
|
|
Change From Baseline of Short Form Health Survey (SF-36 v 2.0) Scale Scores
Vitality
|
4.5 score on a scale
Standard Deviation 9.02
|
4.2 score on a scale
Standard Deviation 8.84
|
2.3 score on a scale
Standard Deviation 8.23
|
SECONDARY outcome
Timeframe: Week 12Population: Full Analysis Population - all randomized participants who received investigational product or placebo. The Week 12 scores only include participants who completed the Week 12 visit.
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.
Outcome measures
| Measure |
300 mg ALD403
n=337 Participants
Participants received a single 300 mg IV infusion of ALD403 on Days 0 and 84 (Week 12).
|
100 mg ALD403
n=344 Participants
Participants received a single 100 mg IV infusion of ALD403 on Days 0 and 84 (Week 12).
|
Placebo
n=343 Participants
Participants received a single placebo IV infusion on Days 0 and 84 (Week 12).
|
|---|---|---|---|
|
Patient Global Impression of Change (PGIC) at Week 12
Much Improved
|
142 Participants
|
126 Participants
|
92 Participants
|
|
Patient Global Impression of Change (PGIC) at Week 12
Minimally Improved
|
68 Participants
|
82 Participants
|
85 Participants
|
|
Patient Global Impression of Change (PGIC) at Week 12
No Change
|
51 Participants
|
69 Participants
|
111 Participants
|
|
Patient Global Impression of Change (PGIC) at Week 12
Minimally Worse
|
3 Participants
|
10 Participants
|
16 Participants
|
|
Patient Global Impression of Change (PGIC) at Week 12
Very Much Improved
|
73 Participants
|
54 Participants
|
38 Participants
|
|
Patient Global Impression of Change (PGIC) at Week 12
Much Worse
|
0 Participants
|
2 Participants
|
1 Participants
|
|
Patient Global Impression of Change (PGIC) at Week 12
Very Much Worse
|
0 Participants
|
1 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Week 12Population: Full Analysis Population - all randomized participants who received investigational product or placebo. The Week 12 scores only include participants who completed the Week 12 visit.
The EQ-5D-5L is a descriptive system of 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.
Outcome measures
| Measure |
300 mg ALD403
n=338 Participants
Participants received a single 300 mg IV infusion of ALD403 on Days 0 and 84 (Week 12).
|
100 mg ALD403
n=344 Participants
Participants received a single 100 mg IV infusion of ALD403 on Days 0 and 84 (Week 12).
|
Placebo
n=343 Participants
Participants received a single placebo IV infusion on Days 0 and 84 (Week 12).
|
|---|---|---|---|
|
Health Related Quality of Life (EQ-5D-5L) at Week 12
Self-care · No problems
|
320 Participants
|
337 Participants
|
331 Participants
|
|
Health Related Quality of Life (EQ-5D-5L) at Week 12
Self-care · Moderate Problems
|
5 Participants
|
1 Participants
|
4 Participants
|
|
Health Related Quality of Life (EQ-5D-5L) at Week 12
Anxiety/Depression · No problems
|
220 Participants
|
227 Participants
|
219 Participants
|
|
Health Related Quality of Life (EQ-5D-5L) at Week 12
Anxiety/Depression · Moderate Problems
|
23 Participants
|
25 Participants
|
27 Participants
|
|
Health Related Quality of Life (EQ-5D-5L) at Week 12
Mobility · No problems
|
289 Participants
|
289 Participants
|
298 Participants
|
|
Health Related Quality of Life (EQ-5D-5L) at Week 12
Mobility · Slight Problems
|
41 Participants
|
41 Participants
|
37 Participants
|
|
Health Related Quality of Life (EQ-5D-5L) at Week 12
Mobility · Moderate Problems
|
8 Participants
|
13 Participants
|
6 Participants
|
|
Health Related Quality of Life (EQ-5D-5L) at Week 12
Mobility · Severe Problems
|
0 Participants
|
1 Participants
|
2 Participants
|
|
Health Related Quality of Life (EQ-5D-5L) at Week 12
Mobility · Extreme Problems
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Health Related Quality of Life (EQ-5D-5L) at Week 12
Self-care · Slight Problems
|
13 Participants
|
6 Participants
|
7 Participants
|
|
Health Related Quality of Life (EQ-5D-5L) at Week 12
Self-care · Severe Problems
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Health Related Quality of Life (EQ-5D-5L) at Week 12
Self-care · Extreme Problems
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Health Related Quality of Life (EQ-5D-5L) at Week 12
Usual Activities · No problems
|
227 Participants
|
233 Participants
|
241 Participants
|
|
Health Related Quality of Life (EQ-5D-5L) at Week 12
Usual Activities · Slight Problems
|
79 Participants
|
78 Participants
|
71 Participants
|
|
Health Related Quality of Life (EQ-5D-5L) at Week 12
Usual Activities · Moderate Problems
|
27 Participants
|
28 Participants
|
26 Participants
|
|
Health Related Quality of Life (EQ-5D-5L) at Week 12
Usual Activities · Severe Problems
|
5 Participants
|
5 Participants
|
4 Participants
|
|
Health Related Quality of Life (EQ-5D-5L) at Week 12
Usual Activities · Extreme Problems
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Health Related Quality of Life (EQ-5D-5L) at Week 12
Pain/Discomfort · No problems
|
122 Participants
|
121 Participants
|
130 Participants
|
|
Health Related Quality of Life (EQ-5D-5L) at Week 12
Pain/Discomfort · Slight Problems
|
140 Participants
|
127 Participants
|
120 Participants
|
|
Health Related Quality of Life (EQ-5D-5L) at Week 12
Pain/Discomfort · Moderate Problems
|
56 Participants
|
78 Participants
|
75 Participants
|
|
Health Related Quality of Life (EQ-5D-5L) at Week 12
Pain/Discomfort · Severe Problems
|
18 Participants
|
14 Participants
|
16 Participants
|
|
Health Related Quality of Life (EQ-5D-5L) at Week 12
Pain/Discomfort · Extreme Problems
|
2 Participants
|
4 Participants
|
2 Participants
|
|
Health Related Quality of Life (EQ-5D-5L) at Week 12
Anxiety/Depression · Slight Problems
|
91 Participants
|
87 Participants
|
91 Participants
|
|
Health Related Quality of Life (EQ-5D-5L) at Week 12
Anxiety/Depression · Severe Problems
|
4 Participants
|
5 Participants
|
5 Participants
|
|
Health Related Quality of Life (EQ-5D-5L) at Week 12
Anxiety/Depression · Extreme Problems
|
0 Participants
|
0 Participants
|
1 Participants
|
Adverse Events
300 mg ALD403
100 mg ALD403
Placebo
Serious adverse events
| Measure |
300 mg ALD403
n=350 participants at risk
Participants received a single 300 mg IV infusion of ALD403 on Days 0 and 84 (Week 12).
|
100 mg ALD403
n=356 participants at risk
Participants received a single 100 mg IV infusion of ALD403 on Days 0 and 84 (Week 12).
|
Placebo
n=366 participants at risk
Participants received a single placebo IV infusion on Days 0 and 84 (Week 12).
|
|---|---|---|---|
|
Gastrointestinal disorders
Gastric Ulcer
|
0.00%
0/350 • Baseline to Week 32 (end of study)
|
0.28%
1/356 • Baseline to Week 32 (end of study)
|
0.00%
0/366 • Baseline to Week 32 (end of study)
|
|
Gastrointestinal disorders
Haematemesis
|
0.00%
0/350 • Baseline to Week 32 (end of study)
|
0.28%
1/356 • Baseline to Week 32 (end of study)
|
0.00%
0/366 • Baseline to Week 32 (end of study)
|
|
Infections and infestations
Gastroenteritis
|
0.29%
1/350 • Baseline to Week 32 (end of study)
|
0.00%
0/356 • Baseline to Week 32 (end of study)
|
0.00%
0/366 • Baseline to Week 32 (end of study)
|
|
Injury, poisoning and procedural complications
Fall
|
0.29%
1/350 • Baseline to Week 32 (end of study)
|
0.00%
0/356 • Baseline to Week 32 (end of study)
|
0.00%
0/366 • Baseline to Week 32 (end of study)
|
|
Injury, poisoning and procedural complications
Spinal Compression Fracture
|
0.29%
1/350 • Baseline to Week 32 (end of study)
|
0.00%
0/356 • Baseline to Week 32 (end of study)
|
0.00%
0/366 • Baseline to Week 32 (end of study)
|
|
Injury, poisoning and procedural complications
Tibia Fracture
|
0.00%
0/350 • Baseline to Week 32 (end of study)
|
0.28%
1/356 • Baseline to Week 32 (end of study)
|
0.00%
0/366 • Baseline to Week 32 (end of study)
|
|
Nervous system disorders
Migraine
|
0.00%
0/350 • Baseline to Week 32 (end of study)
|
0.28%
1/356 • Baseline to Week 32 (end of study)
|
0.00%
0/366 • Baseline to Week 32 (end of study)
|
|
Nervous system disorders
Migraine With Aura
|
0.29%
1/350 • Baseline to Week 32 (end of study)
|
0.00%
0/356 • Baseline to Week 32 (end of study)
|
0.00%
0/366 • Baseline to Week 32 (end of study)
|
|
Nervous system disorders
Seizure
|
0.29%
1/350 • Baseline to Week 32 (end of study)
|
0.00%
0/356 • Baseline to Week 32 (end of study)
|
0.00%
0/366 • Baseline to Week 32 (end of study)
|
|
Nervous system disorders
Syncope
|
0.00%
0/350 • Baseline to Week 32 (end of study)
|
0.28%
1/356 • Baseline to Week 32 (end of study)
|
0.27%
1/366 • Baseline to Week 32 (end of study)
|
|
Psychiatric disorders
Depression Suicidal
|
0.00%
0/350 • Baseline to Week 32 (end of study)
|
0.28%
1/356 • Baseline to Week 32 (end of study)
|
0.00%
0/366 • Baseline to Week 32 (end of study)
|
|
Psychiatric disorders
Suicide Attempt
|
0.29%
1/350 • Baseline to Week 32 (end of study)
|
0.00%
0/356 • Baseline to Week 32 (end of study)
|
0.00%
0/366 • Baseline to Week 32 (end of study)
|
|
Renal and urinary disorders
Nephrolithiasis
|
0.00%
0/350 • Baseline to Week 32 (end of study)
|
0.00%
0/356 • Baseline to Week 32 (end of study)
|
0.27%
1/366 • Baseline to Week 32 (end of study)
|
|
Reproductive system and breast disorders
Menometrorrhagia
|
0.00%
0/350 • Baseline to Week 32 (end of study)
|
0.00%
0/356 • Baseline to Week 32 (end of study)
|
0.27%
1/366 • Baseline to Week 32 (end of study)
|
Other adverse events
| Measure |
300 mg ALD403
n=350 participants at risk
Participants received a single 300 mg IV infusion of ALD403 on Days 0 and 84 (Week 12).
|
100 mg ALD403
n=356 participants at risk
Participants received a single 100 mg IV infusion of ALD403 on Days 0 and 84 (Week 12).
|
Placebo
n=366 participants at risk
Participants received a single placebo IV infusion on Days 0 and 84 (Week 12).
|
|---|---|---|---|
|
Infections and infestations
Nasopharyngitis
|
9.4%
33/350 • Baseline to Week 32 (end of study)
|
5.3%
19/356 • Baseline to Week 32 (end of study)
|
6.0%
22/366 • Baseline to Week 32 (end of study)
|
|
Infections and infestations
Upper respiratory tract infection
|
5.4%
19/350 • Baseline to Week 32 (end of study)
|
4.2%
15/356 • Baseline to Week 32 (end of study)
|
5.5%
20/366 • Baseline to Week 32 (end of study)
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place