Trial Outcomes & Findings for A Study to Evaluate the Efficacy and Safety of Fremanezumab for Preventive Treatment of Migraine in Patients With Major Depressive Disorder (NCT NCT04041284)
NCT ID: NCT04041284
Last Updated: 2023-10-02
Results Overview
A migraine day was defined as when at least 1 of following situations occurred: A calendar day (0:00 to 23:59) demonstrating at least 4 consecutive hours of a headache meeting criteria for migraine with or without aura; a calendar day (0:00 to 23:59) demonstrating at least 4 consecutive hours of a headache meeting criteria for probable migraine (where only 1 migraine criterion was missing); a calendar day (0:00 to 23:59) demonstrating a headache of any duration that was treated with migraine-specific medications (triptans and ergot compounds); and a calendar day (00:00 to 23:59) that was immediately consecutive of any day fulfilling 3 criteria above, where participants report headache of any duration. Monthly averages were derived and normalized to 28 days equivalent by formula: (number of days of efficacy variable over 12 week period/number of days with assessments recorded in e-diary for 12 week period)\*28. Least square (LS) mean was calculated using analysis of covariance (ANCOVA).
COMPLETED
PHASE4
353 participants
Baseline (Day -28 to Day -1), up to Week 12
2023-10-02
Participant Flow
Of the 540 participants screened, 353 participants were enrolled/randomized.
Participant milestones
| Measure |
Placebo
Participants received placebo matched to fremanezumab subcutaneously (SC) during the 12-week double blind (DB) period and then continued into the open-label (OL) extension period in which all participants received a single quarterly dose of fremanezumab Dose 2 SC on Day 85.
|
Fremanezumab
Participants received monthly doses of fremanezumab Dose 1 SC during the 12-week DB period and then continued into the OL extension period in which all participants received a single quarterly dose of fremanezumab Dose 2 SC on Day 85.
|
|---|---|---|
|
DB Phase (12 Weeks)
STARTED
|
178
|
175
|
|
DB Phase (12 Weeks)
DB Safety Analysis Set
|
177
|
176
|
|
DB Phase (12 Weeks)
DB Modified Intent-to-treat (mITT) Analysis Set
|
178
|
175
|
|
DB Phase (12 Weeks)
COMPLETED
|
166
|
164
|
|
DB Phase (12 Weeks)
NOT COMPLETED
|
12
|
11
|
|
OL Phase (12 Weeks)
STARTED
|
166
|
164
|
|
OL Phase (12 Weeks)
OL Safety Analysis Set
|
165
|
165
|
|
OL Phase (12 Weeks)
OL mITT Analysis Set
|
165
|
161
|
|
OL Phase (12 Weeks)
COMPLETED
|
154
|
155
|
|
OL Phase (12 Weeks)
NOT COMPLETED
|
12
|
9
|
Reasons for withdrawal
| Measure |
Placebo
Participants received placebo matched to fremanezumab subcutaneously (SC) during the 12-week double blind (DB) period and then continued into the open-label (OL) extension period in which all participants received a single quarterly dose of fremanezumab Dose 2 SC on Day 85.
|
Fremanezumab
Participants received monthly doses of fremanezumab Dose 1 SC during the 12-week DB period and then continued into the OL extension period in which all participants received a single quarterly dose of fremanezumab Dose 2 SC on Day 85.
|
|---|---|---|
|
DB Phase (12 Weeks)
Adverse Event
|
0
|
3
|
|
DB Phase (12 Weeks)
Withdrawal by Subject
|
6
|
4
|
|
DB Phase (12 Weeks)
Protocol deviation
|
3
|
3
|
|
DB Phase (12 Weeks)
Lost to Follow-up
|
1
|
0
|
|
DB Phase (12 Weeks)
Lack of Efficacy
|
1
|
1
|
|
DB Phase (12 Weeks)
Other than specified
|
1
|
0
|
|
OL Phase (12 Weeks)
Withdrawal by Subject
|
5
|
5
|
|
OL Phase (12 Weeks)
Protocol deviation
|
0
|
1
|
|
OL Phase (12 Weeks)
Pregnancy
|
1
|
1
|
|
OL Phase (12 Weeks)
Other than specified
|
6
|
2
|
Baseline Characteristics
A Study to Evaluate the Efficacy and Safety of Fremanezumab for Preventive Treatment of Migraine in Patients With Major Depressive Disorder
Baseline characteristics by cohort
| Measure |
Placebo
n=178 Participants
Participants received placebo matched to fremanezumab SC during the 12-week DB period and then continued into the OL extension period in which all participants received a single quarterly dose of fremanezumab Dose 2 SC on Day 85.
|
Fremanezumab
n=175 Participants
Participants received monthly doses of fremanezumab Dose 1 SC during the 12-week DB period and then continued into the OL extension period in which all participants received a single quarterly dose of fremanezumab Dose 2 SC on Day 85.
|
Total
n=353 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
42.3 years
STANDARD_DEVIATION 12.64 • n=93 Participants
|
43.5 years
STANDARD_DEVIATION 11.94 • n=4 Participants
|
42.9 years
STANDARD_DEVIATION 12.30 • n=27 Participants
|
|
Sex: Female, Male
Female
|
156 Participants
n=93 Participants
|
154 Participants
n=4 Participants
|
310 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
22 Participants
n=93 Participants
|
21 Participants
n=4 Participants
|
43 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
6 Participants
n=93 Participants
|
5 Participants
n=4 Participants
|
11 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
171 Participants
n=93 Participants
|
170 Participants
n=4 Participants
|
341 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
2 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
2 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Black or African American
|
4 Participants
n=93 Participants
|
4 Participants
n=4 Participants
|
8 Participants
n=27 Participants
|
|
Race (NIH/OMB)
White
|
172 Participants
n=93 Participants
|
170 Participants
n=4 Participants
|
342 Participants
n=27 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
|
Number of migraine days
|
14.4 days
STANDARD_DEVIATION 6.15 • n=93 Participants
|
15.1 days
STANDARD_DEVIATION 6.41 • n=4 Participants
|
14.8 days
STANDARD_DEVIATION 6.28 • n=27 Participants
|
PRIMARY outcome
Timeframe: Baseline (Day -28 to Day -1), up to Week 12Population: DB mITT analysis set included all randomized participants who received at least 1 dose of study drug and had at least 10 days of postrandomization efficacy assessment on the primary endpoint.
A migraine day was defined as when at least 1 of following situations occurred: A calendar day (0:00 to 23:59) demonstrating at least 4 consecutive hours of a headache meeting criteria for migraine with or without aura; a calendar day (0:00 to 23:59) demonstrating at least 4 consecutive hours of a headache meeting criteria for probable migraine (where only 1 migraine criterion was missing); a calendar day (0:00 to 23:59) demonstrating a headache of any duration that was treated with migraine-specific medications (triptans and ergot compounds); and a calendar day (00:00 to 23:59) that was immediately consecutive of any day fulfilling 3 criteria above, where participants report headache of any duration. Monthly averages were derived and normalized to 28 days equivalent by formula: (number of days of efficacy variable over 12 week period/number of days with assessments recorded in e-diary for 12 week period)\*28. Least square (LS) mean was calculated using analysis of covariance (ANCOVA).
Outcome measures
| Measure |
Double-blind Phase: Placebo
n=178 Participants
Participants received placebo matched to fremanezumab SC during the 12-week DB period.
|
Double-blind Phase: Fremanezumab
n=175 Participants
Participants received monthly doses of fremanezumab Dose 1 SC during the 12-week DB period.
|
Open-label Phase: Placebo/Fremanezumab Dose 2
Participants received a single quarterly dose of fremanezumab Dose 2 SC on Day 85.
|
Open-label Phase: Fremanezumab Dose 1/Fremanezumab Dose 2
Participants received a single quarterly dose of fremanezumab Dose 2 SC on Day 85.
|
|---|---|---|---|---|
|
Change From Baseline in Monthly Average Number of Migraine Days During the 12-Week DB Treatment Phase After the First Dose of Study Drug
|
-2.9 days
Standard Error 0.49
|
-5.1 days
Standard Error 0.50
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 8Population: DB mITT analysis set included all randomized participants who received at least 1 dose of study drug and had at least 10 days of postrandomization efficacy assessment on the primary endpoint.
The HAM-D 17 is a list of 17 items used to determine a participant's level of depression. The HAM-D total score comprises a sum of the 17 individual item scores. 8 items scored in a range of 0 (none/absent) to 2 (severe symptom) include: Insomnia (early, middle, late), somatic symptoms (gastrointestinal and general), genital symptoms, loss of weight, and insight. The following 9 items are scored in a range of 0 (none/absent) to 4 (severe symptom): Agitation, depressed mood, feelings of guilt, suicide, work and activities, retardation, anxiety (psychic and somatic), and hypochondriasis. The HAM-D17 total score is calculated as the sum of the 17 individual symptom scores; the total score can range from 0 to 52. Higher HAM-D17 scores indicate more severe depression. LS mean was calculated using mixed-effects model for repeated measures (MMRM).
Outcome measures
| Measure |
Double-blind Phase: Placebo
n=178 Participants
Participants received placebo matched to fremanezumab SC during the 12-week DB period.
|
Double-blind Phase: Fremanezumab
n=175 Participants
Participants received monthly doses of fremanezumab Dose 1 SC during the 12-week DB period.
|
Open-label Phase: Placebo/Fremanezumab Dose 2
Participants received a single quarterly dose of fremanezumab Dose 2 SC on Day 85.
|
Open-label Phase: Fremanezumab Dose 1/Fremanezumab Dose 2
Participants received a single quarterly dose of fremanezumab Dose 2 SC on Day 85.
|
|---|---|---|---|---|
|
Change From Baseline in Hamilton Depression Rating Scale-17 (HAM-D 17) Items Total Score at Week 8
|
-4.6 units on a scale
Standard Error 0.54
|
-6.0 units on a scale
Standard Error 0.55
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day -28 to Day -1) up to Week 12Population: DB mITT analysis set included all randomized participants who received at least 1 dose of study drug and had at least 10 days of postrandomization efficacy assessment on the primary endpoint.
A migraine day was defined as when at least 1 of the following situations occurred: A calendar day (0:00 to 23:59) demonstrating at least 4 consecutive hours of a headache meeting criteria for migraine with or without aura; a calendar day (0:00 to 23:59) demonstrating at least 4 consecutive hours of a headache meeting criteria for probable migraine, a migraine subtype where only 1 migraine criterion was missing; a calendar day (0:00 to 23:59) demonstrating a headache of any duration that was treated with migraine-specific medications (triptans and ergot compounds); and a calendar day (00:00 to 23:59) that was immediately consecutive of any day fulfilling the 3 criteria above, where participants report headache of any duration. Monthly averages were derived and normalized to 28 days equivalent by formula: (number of days of efficacy variable over 12 week period/number of days with assessments recorded in e-diary for 12 week period)\*28.
Outcome measures
| Measure |
Double-blind Phase: Placebo
n=178 Participants
Participants received placebo matched to fremanezumab SC during the 12-week DB period.
|
Double-blind Phase: Fremanezumab
n=175 Participants
Participants received monthly doses of fremanezumab Dose 1 SC during the 12-week DB period.
|
Open-label Phase: Placebo/Fremanezumab Dose 2
Participants received a single quarterly dose of fremanezumab Dose 2 SC on Day 85.
|
Open-label Phase: Fremanezumab Dose 1/Fremanezumab Dose 2
Participants received a single quarterly dose of fremanezumab Dose 2 SC on Day 85.
|
|---|---|---|---|---|
|
Number of Participants With ≥50% Reduction in Monthly Average Number of Migraine Days During the 12 Weeks After the First Dose of Study Drug
|
24 Participants
|
57 Participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: DB mITT analysis set included all randomized participants who received at least 1 dose of study drug and had at least 10 days of postrandomization efficacy assessment on the primary endpoint.
The MSQoL version 2.1 is a 14-item questionnaire that assesses the impact of migraine and migraine treatment on a participant's quality of life during the previous 4 weeks. Each item is scored on a 6-point scale where: 1=none of the time to 6=all of the time. The MSQoL measures the degree to which performance of normal activities is limited by migraine (Role Function-Restrictive domain comprising 7 items; score range 7 to 42), the degree to which performance of normal activities is prevented by migraine (Role Function-Preventive domain comprising 4 items; score range 4 to 24), and the emotional effects of migraine (Emotional Function domain comprising 3 items; score range 3 to 18). Total raw scores for each domain is the sum of the final item value for all of the items in that domain. After the total raw score is computed for each domain, they are transformed to a 0-100 scale with higher scores indicating a better health-related quality of life. LS mean was calculated using MMRM.
Outcome measures
| Measure |
Double-blind Phase: Placebo
n=178 Participants
Participants received placebo matched to fremanezumab SC during the 12-week DB period.
|
Double-blind Phase: Fremanezumab
n=175 Participants
Participants received monthly doses of fremanezumab Dose 1 SC during the 12-week DB period.
|
Open-label Phase: Placebo/Fremanezumab Dose 2
Participants received a single quarterly dose of fremanezumab Dose 2 SC on Day 85.
|
Open-label Phase: Fremanezumab Dose 1/Fremanezumab Dose 2
Participants received a single quarterly dose of fremanezumab Dose 2 SC on Day 85.
|
|---|---|---|---|---|
|
Change From Baseline in Migraine-Specific Quality of Life (MSQoL) Questionnaire Role Function-Restrictive and Role Function-Preventive Domain Scores at Week 12
Restrictive score
|
15.9 units on a scale
Standard Error 2.00
|
27.2 units on a scale
Standard Error 2.04
|
—
|
—
|
|
Change From Baseline in Migraine-Specific Quality of Life (MSQoL) Questionnaire Role Function-Restrictive and Role Function-Preventive Domain Scores at Week 12
Preventive score
|
12.3 units on a scale
Standard Error 1.95
|
22.2 units on a scale
Standard Error 2.00
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Weeks 4, 8, and 12Population: DB mITT analysis set included all randomized participants who received at least 1 dose of study drug and had at least 10 days of postrandomization efficacy assessment on the primary endpoint.
The CGI-S is a short questionnaire filled out by the investigator that rates a participant's mental health from 1 (normal, not at all ill) to 7 (among the most extremely ill participants).
Outcome measures
| Measure |
Double-blind Phase: Placebo
n=178 Participants
Participants received placebo matched to fremanezumab SC during the 12-week DB period.
|
Double-blind Phase: Fremanezumab
n=175 Participants
Participants received monthly doses of fremanezumab Dose 1 SC during the 12-week DB period.
|
Open-label Phase: Placebo/Fremanezumab Dose 2
Participants received a single quarterly dose of fremanezumab Dose 2 SC on Day 85.
|
Open-label Phase: Fremanezumab Dose 1/Fremanezumab Dose 2
Participants received a single quarterly dose of fremanezumab Dose 2 SC on Day 85.
|
|---|---|---|---|---|
|
Change From Baseline in Clinical Global Impression - Severity (CGI-S) Scale Score at Weeks 4, 8, and 12
Change at Week 4
|
-0.4 units on a scale
Standard Error 0.10
|
-0.6 units on a scale
Standard Error 0.10
|
—
|
—
|
|
Change From Baseline in Clinical Global Impression - Severity (CGI-S) Scale Score at Weeks 4, 8, and 12
Change at Week 8
|
-0.6 units on a scale
Standard Error 0.10
|
-0.1 units on a scale
Standard Error 0.10
|
—
|
—
|
|
Change From Baseline in Clinical Global Impression - Severity (CGI-S) Scale Score at Weeks 4, 8, and 12
Change at Week 12
|
-0.8 units on a scale
Standard Error 0.10
|
-1.1 units on a scale
Standard Error 0.10
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: DB mITT analysis set included all randomized participants who received at least 1 dose of study drug and had at least 10 days of postrandomization efficacy assessment on the primary endpoint.
Migraine related disability was assessed using the HIT-6. The questionnaire measures the adverse impact of headache on social functioning, role functioning, vitality, cognitive functioning, and psychological distress. It also assesses headache severity. Each question was answered on the scale ranging with the following response options: 6 points (never), 8 points (rarely), 10 points (sometimes), 11 points (very often), and 13 points (always). The total score was obtained from summation of the 6 question points. The HIT-6 total score ranges between 36 and 78, with higher scores reflecting greater impact.
Outcome measures
| Measure |
Double-blind Phase: Placebo
n=178 Participants
Participants received placebo matched to fremanezumab SC during the 12-week DB period.
|
Double-blind Phase: Fremanezumab
n=175 Participants
Participants received monthly doses of fremanezumab Dose 1 SC during the 12-week DB period.
|
Open-label Phase: Placebo/Fremanezumab Dose 2
Participants received a single quarterly dose of fremanezumab Dose 2 SC on Day 85.
|
Open-label Phase: Fremanezumab Dose 1/Fremanezumab Dose 2
Participants received a single quarterly dose of fremanezumab Dose 2 SC on Day 85.
|
|---|---|---|---|---|
|
Change From Baseline in 6-Item Headache Impact Test (HIT-6) Disability Score at Week 12
|
-5.2 units on a scale
Standard Error 0.71
|
-8.8 units on a scale
Standard Error 0.73
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline up to Week 24Population: DB safety analysis set included all randomized participants who received at least 1 dose of study drug during the DB treatment period. OL safety analysis set included all participants who received at least 1 of dose of study drug during the OL treatment period.
An adverse event (AE) was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious AEs (SAEs) were defined as death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. AEs were considered TEAEs if onset occurred on or after the first dose date. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Outcome measures
| Measure |
Double-blind Phase: Placebo
n=177 Participants
Participants received placebo matched to fremanezumab SC during the 12-week DB period.
|
Double-blind Phase: Fremanezumab
n=176 Participants
Participants received monthly doses of fremanezumab Dose 1 SC during the 12-week DB period.
|
Open-label Phase: Placebo/Fremanezumab Dose 2
n=165 Participants
Participants received a single quarterly dose of fremanezumab Dose 2 SC on Day 85.
|
Open-label Phase: Fremanezumab Dose 1/Fremanezumab Dose 2
n=165 Participants
Participants received a single quarterly dose of fremanezumab Dose 2 SC on Day 85.
|
|---|---|---|---|---|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
|
48 Participants
|
70 Participants
|
31 Participants
|
29 Participants
|
SECONDARY outcome
Timeframe: Baseline up to Week 24Population: DB safety analysis set included all randomized participants who received at least 1 dose of study drug during the DB treatment period. OL safety analysis set included all participants who received at least 1 of dose of study drug during the OL treatment period. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.
Criteria for potentially clinically significant vital signs values: Pulse: ≥120 beats per minute (bpm) and increase from baseline of ≥15 bpm or ≤50 bpm and decrease from baseline of ≥15 bpm; Systolic blood pressure (SBP): ≥180 millimeters of mercury (mmHg) and increase from baseline of ≥20 mmHg or ≤90 mmHg and decrease from baseline of ≥20 mmHg; Diastolic blood pressure (DBP): ≥105 mmHg and increase from baseline of ≥15 mmHg or ≤50 mmHg and decrease from baseline of ≥15 mmHg; Respiratory rate: \<10 breaths per minute; and Body temperature: ≥38.3 degrees celsius (ºC) and change from baseline of ≥1.1ºC.
Outcome measures
| Measure |
Double-blind Phase: Placebo
n=174 Participants
Participants received placebo matched to fremanezumab SC during the 12-week DB period.
|
Double-blind Phase: Fremanezumab
n=173 Participants
Participants received monthly doses of fremanezumab Dose 1 SC during the 12-week DB period.
|
Open-label Phase: Placebo/Fremanezumab Dose 2
n=162 Participants
Participants received a single quarterly dose of fremanezumab Dose 2 SC on Day 85.
|
Open-label Phase: Fremanezumab Dose 1/Fremanezumab Dose 2
n=164 Participants
Participants received a single quarterly dose of fremanezumab Dose 2 SC on Day 85.
|
|---|---|---|---|---|
|
Number of Participants With Potentially Clinically Significant Abnormal Vital Signs Values
|
0 Participants
|
5 Participants
|
2 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: Baseline up to Week 24Population: DB safety analysis set included all randomized participants who received at least 1 dose of study drug during the DB treatment period. OL safety analysis set included all participants who received at least 1 of dose of study drug during the OL treatment period.
Physical examination included height, weight, general appearance; head, eyes, ears, nose, and throat; chest and lungs; heart; abdomen; musculoskeletal; skin; lymph nodes; and neurological. Clinical significance was per investigator's discretion.
Outcome measures
| Measure |
Double-blind Phase: Placebo
n=177 Participants
Participants received placebo matched to fremanezumab SC during the 12-week DB period.
|
Double-blind Phase: Fremanezumab
n=176 Participants
Participants received monthly doses of fremanezumab Dose 1 SC during the 12-week DB period.
|
Open-label Phase: Placebo/Fremanezumab Dose 2
n=165 Participants
Participants received a single quarterly dose of fremanezumab Dose 2 SC on Day 85.
|
Open-label Phase: Fremanezumab Dose 1/Fremanezumab Dose 2
n=165 Participants
Participants received a single quarterly dose of fremanezumab Dose 2 SC on Day 85.
|
|---|---|---|---|---|
|
Number of Participants With Clinically Significant Abnormal Physical Examination Findings
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline up to Week 24Population: DB safety analysis set included all randomized participants who received at least 1 dose of study drug during the DB treatment period. OL safety analysis set included all participants who received at least 1 of dose of study drug during the OL treatment period.
Outcome measures
| Measure |
Double-blind Phase: Placebo
n=177 Participants
Participants received placebo matched to fremanezumab SC during the 12-week DB period.
|
Double-blind Phase: Fremanezumab
n=176 Participants
Participants received monthly doses of fremanezumab Dose 1 SC during the 12-week DB period.
|
Open-label Phase: Placebo/Fremanezumab Dose 2
n=165 Participants
Participants received a single quarterly dose of fremanezumab Dose 2 SC on Day 85.
|
Open-label Phase: Fremanezumab Dose 1/Fremanezumab Dose 2
n=165 Participants
Participants received a single quarterly dose of fremanezumab Dose 2 SC on Day 85.
|
|---|---|---|---|---|
|
Number of Participants With Drug Hypersensitivity and Seasonal Allergy
Drug hypersensitivity
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Drug Hypersensitivity and Seasonal Allergy
Seasonal allergy
|
1 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline up to Week 24Population: DB safety analysis set included all randomized participants who received at least 1 dose of study drug during the DB treatment period. OL safety analysis set included all participants who received at least 1 of dose of study drug during the OL treatment period.
Concomitant medications included agents acting on the renin-angiotensin system, analgesics, antibacterials for systemic use, antihistamines for systemic use, anti-inflammatory and antirheumatic products, beta-blocking agents, drugs for acid related disorder, lipid modifying agents, mineral supplement, other gynecologicals, psychoanaleptics, psycholeptics, sex hormones and modulators of the genital system, thyroid therapy, vaccines, and vitamins.
Outcome measures
| Measure |
Double-blind Phase: Placebo
n=177 Participants
Participants received placebo matched to fremanezumab SC during the 12-week DB period.
|
Double-blind Phase: Fremanezumab
n=176 Participants
Participants received monthly doses of fremanezumab Dose 1 SC during the 12-week DB period.
|
Open-label Phase: Placebo/Fremanezumab Dose 2
n=165 Participants
Participants received a single quarterly dose of fremanezumab Dose 2 SC on Day 85.
|
Open-label Phase: Fremanezumab Dose 1/Fremanezumab Dose 2
n=165 Participants
Participants received a single quarterly dose of fremanezumab Dose 2 SC on Day 85.
|
|---|---|---|---|---|
|
Number of Participants Who Used Concomitant Medication
|
173 Participants
|
173 Participants
|
160 Participants
|
163 Participants
|
SECONDARY outcome
Timeframe: Baseline up to Week 24Population: DB safety analysis set included all randomized participants who received at least 1 dose of study drug during the DB treatment period. OL safety analysis set included all participants who received at least 1 of dose of study drug during the OL treatment period.
Concomitant medications for migraine/headache included analgesics, antiepileptics, muscle relaxants, anti-inflammatory and antirheumatic products, agents acting on the renin-angiotensin system, anesthetics, antianemic preparations, antibacterials for systemic use, antihistamines for systemic use, beta-blocking agents, lipid modifying agents, mineral supplement, other gynecologicals, psychoanaleptics, psycholeptics, sex hormones and modulators of the genital system, thyroid therapy, vaccines, vitamins etc.
Outcome measures
| Measure |
Double-blind Phase: Placebo
n=177 Participants
Participants received placebo matched to fremanezumab SC during the 12-week DB period.
|
Double-blind Phase: Fremanezumab
n=176 Participants
Participants received monthly doses of fremanezumab Dose 1 SC during the 12-week DB period.
|
Open-label Phase: Placebo/Fremanezumab Dose 2
n=165 Participants
Participants received a single quarterly dose of fremanezumab Dose 2 SC on Day 85.
|
Open-label Phase: Fremanezumab Dose 1/Fremanezumab Dose 2
n=165 Participants
Participants received a single quarterly dose of fremanezumab Dose 2 SC on Day 85.
|
|---|---|---|---|---|
|
Number of Participants Who Used Concomitant Medication for Migraine/Headache
|
170 Participants
|
169 Participants
|
156 Participants
|
160 Participants
|
SECONDARY outcome
Timeframe: Baseline up to Week 24Population: DB safety analysis set included all randomized participants who received at least 1 dose of study drug during the DB treatment period. OL safety analysis set included all participants who received at least 1 of dose of study drug during the OL treatment period.
Outcome measures
| Measure |
Double-blind Phase: Placebo
n=177 Participants
Participants received placebo matched to fremanezumab SC during the 12-week DB period.
|
Double-blind Phase: Fremanezumab
n=176 Participants
Participants received monthly doses of fremanezumab Dose 1 SC during the 12-week DB period.
|
Open-label Phase: Placebo/Fremanezumab Dose 2
n=165 Participants
Participants received a single quarterly dose of fremanezumab Dose 2 SC on Day 85.
|
Open-label Phase: Fremanezumab Dose 1/Fremanezumab Dose 2
n=165 Participants
Participants received a single quarterly dose of fremanezumab Dose 2 SC on Day 85.
|
|---|---|---|---|---|
|
Number of Participants Who Did Not Complete the Study Due to AE
|
0 Participants
|
3 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline, Weeks 4, 8, 12, and 24Population: DB safety analysis set included all randomized participants who received at least 1 dose of study drug during the DB treatment period. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure. 'Number analyzed' = participants evaluable at specified timepoint of the respective phase of the study.
C-SSRS included responses for Suicidal Ideation or Suicidal Behavior in 10 categories: 1=Wish to be dead; 2=Non-specific active suicidal thoughts; 3=Active suicidal ideation with any methods (not plan) without intent to act; 4=Active suicidal ideation with some intent to act, without specific plan; 5=Active suicidal ideation with specific plan and intent; 6=Preparatory acts or behavior; 7=Aborted attempt; 8=Interrupted attempt; 9=Non-fatal suicide attempt; and 10=Completed suicide. Participants who responded "Yes" to any category were considered Positive, participants who responded "No" for all categories were considered Negative, and participants who were evaluable but did not complete the questionnaire were considered Incomplete. A Positive response was considered as a worse outcome and the investigator determined if further evaluation was needed. Any Suicidal ideation or Suicidal Behavior events reported as TEAEs along with all other reported TEAEs are included in the AE module.
Outcome measures
| Measure |
Double-blind Phase: Placebo
n=177 Participants
Participants received placebo matched to fremanezumab SC during the 12-week DB period.
|
Double-blind Phase: Fremanezumab
n=176 Participants
Participants received monthly doses of fremanezumab Dose 1 SC during the 12-week DB period.
|
Open-label Phase: Placebo/Fremanezumab Dose 2
n=153 Participants
Participants received a single quarterly dose of fremanezumab Dose 2 SC on Day 85.
|
Open-label Phase: Fremanezumab Dose 1/Fremanezumab Dose 2
n=155 Participants
Participants received a single quarterly dose of fremanezumab Dose 2 SC on Day 85.
|
|---|---|---|---|---|
|
Number of Participants Reporting Any Suicidal Ideation or Suicidal Behavior According to the Columbia Suicide Severity Rating Scale (C-SSRS)
Baseline · Incomplete
|
0 Participants
|
0 Participants
|
—
|
—
|
|
Number of Participants Reporting Any Suicidal Ideation or Suicidal Behavior According to the Columbia Suicide Severity Rating Scale (C-SSRS)
Baseline · Negative
|
177 Participants
|
176 Participants
|
—
|
—
|
|
Number of Participants Reporting Any Suicidal Ideation or Suicidal Behavior According to the Columbia Suicide Severity Rating Scale (C-SSRS)
Baseline · Positive
|
0 Participants
|
0 Participants
|
—
|
—
|
|
Number of Participants Reporting Any Suicidal Ideation or Suicidal Behavior According to the Columbia Suicide Severity Rating Scale (C-SSRS)
Week 4 · Incomplete
|
1 Participants
|
0 Participants
|
—
|
—
|
|
Number of Participants Reporting Any Suicidal Ideation or Suicidal Behavior According to the Columbia Suicide Severity Rating Scale (C-SSRS)
Week 4 · Negative
|
168 Participants
|
168 Participants
|
—
|
—
|
|
Number of Participants Reporting Any Suicidal Ideation or Suicidal Behavior According to the Columbia Suicide Severity Rating Scale (C-SSRS)
Week 4 · Positive
|
0 Participants
|
1 Participants
|
—
|
—
|
|
Number of Participants Reporting Any Suicidal Ideation or Suicidal Behavior According to the Columbia Suicide Severity Rating Scale (C-SSRS)
Week 8 · Incomplete
|
0 Participants
|
0 Participants
|
—
|
—
|
|
Number of Participants Reporting Any Suicidal Ideation or Suicidal Behavior According to the Columbia Suicide Severity Rating Scale (C-SSRS)
Week 8 · Negative
|
170 Participants
|
164 Participants
|
—
|
—
|
|
Number of Participants Reporting Any Suicidal Ideation or Suicidal Behavior According to the Columbia Suicide Severity Rating Scale (C-SSRS)
Week 8 · Positive
|
0 Participants
|
0 Participants
|
—
|
—
|
|
Number of Participants Reporting Any Suicidal Ideation or Suicidal Behavior According to the Columbia Suicide Severity Rating Scale (C-SSRS)
Week 12 · Incomplete
|
0 Participants
|
0 Participants
|
—
|
—
|
|
Number of Participants Reporting Any Suicidal Ideation or Suicidal Behavior According to the Columbia Suicide Severity Rating Scale (C-SSRS)
Week 12 · Negative
|
165 Participants
|
163 Participants
|
—
|
—
|
|
Number of Participants Reporting Any Suicidal Ideation or Suicidal Behavior According to the Columbia Suicide Severity Rating Scale (C-SSRS)
Week 12 · Positive
|
0 Participants
|
0 Participants
|
—
|
—
|
|
Number of Participants Reporting Any Suicidal Ideation or Suicidal Behavior According to the Columbia Suicide Severity Rating Scale (C-SSRS)
Week 24 · Incomplete
|
—
|
—
|
0 Participants
|
0 Participants
|
|
Number of Participants Reporting Any Suicidal Ideation or Suicidal Behavior According to the Columbia Suicide Severity Rating Scale (C-SSRS)
Week 24 · Negative
|
—
|
—
|
152 Participants
|
153 Participants
|
|
Number of Participants Reporting Any Suicidal Ideation or Suicidal Behavior According to the Columbia Suicide Severity Rating Scale (C-SSRS)
Week 24 · Positive
|
—
|
—
|
1 Participants
|
2 Participants
|
Adverse Events
Double-blind Phase: Placebo
Double-blind Phase: Fremanezumab
Open-label Phase: Placebo/Fremanezumab Dose 2
Open-label Phase: Fremanezumab Dose 1/Fremanezumab Dose 2
Serious adverse events
| Measure |
Double-blind Phase: Placebo
n=177 participants at risk
Participants received placebo matched to fremanezumab SC during the 12-week DB period.
|
Double-blind Phase: Fremanezumab
n=176 participants at risk
Participants received monthly doses of fremanezumab Dose 1 SC during the 12-week DB period.
|
Open-label Phase: Placebo/Fremanezumab Dose 2
n=165 participants at risk
Participants received a single quarterly dose of fremanezumab Dose 2 SC on Day 85.
|
Open-label Phase: Fremanezumab Dose 1/Fremanezumab Dose 2
n=165 participants at risk
Participants received a single quarterly dose of fremanezumab Dose 2 SC on Day 85.
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Hiatus hernia
|
0.56%
1/177 • Number of events 1 • Baseline up to Week 24
DB safety analysis set included all randomized participants who received at least 1 dose of study drug during the DB treatment period. OL safety analysis set included all participants who received at least 1 of dose of study drug during the OL treatment period. One participant was randomized to Placebo and received placebo in the DB period but was summarized in the Fremanezumab treatment group in all safety summaries due to an error in recording treatment.
|
0.00%
0/176 • Baseline up to Week 24
DB safety analysis set included all randomized participants who received at least 1 dose of study drug during the DB treatment period. OL safety analysis set included all participants who received at least 1 of dose of study drug during the OL treatment period. One participant was randomized to Placebo and received placebo in the DB period but was summarized in the Fremanezumab treatment group in all safety summaries due to an error in recording treatment.
|
0.00%
0/165 • Baseline up to Week 24
DB safety analysis set included all randomized participants who received at least 1 dose of study drug during the DB treatment period. OL safety analysis set included all participants who received at least 1 of dose of study drug during the OL treatment period. One participant was randomized to Placebo and received placebo in the DB period but was summarized in the Fremanezumab treatment group in all safety summaries due to an error in recording treatment.
|
0.00%
0/165 • Baseline up to Week 24
DB safety analysis set included all randomized participants who received at least 1 dose of study drug during the DB treatment period. OL safety analysis set included all participants who received at least 1 of dose of study drug during the OL treatment period. One participant was randomized to Placebo and received placebo in the DB period but was summarized in the Fremanezumab treatment group in all safety summaries due to an error in recording treatment.
|
|
Hepatobiliary disorders
Cholecystitis acute
|
0.00%
0/177 • Baseline up to Week 24
DB safety analysis set included all randomized participants who received at least 1 dose of study drug during the DB treatment period. OL safety analysis set included all participants who received at least 1 of dose of study drug during the OL treatment period. One participant was randomized to Placebo and received placebo in the DB period but was summarized in the Fremanezumab treatment group in all safety summaries due to an error in recording treatment.
|
0.00%
0/176 • Baseline up to Week 24
DB safety analysis set included all randomized participants who received at least 1 dose of study drug during the DB treatment period. OL safety analysis set included all participants who received at least 1 of dose of study drug during the OL treatment period. One participant was randomized to Placebo and received placebo in the DB period but was summarized in the Fremanezumab treatment group in all safety summaries due to an error in recording treatment.
|
0.61%
1/165 • Number of events 1 • Baseline up to Week 24
DB safety analysis set included all randomized participants who received at least 1 dose of study drug during the DB treatment period. OL safety analysis set included all participants who received at least 1 of dose of study drug during the OL treatment period. One participant was randomized to Placebo and received placebo in the DB period but was summarized in the Fremanezumab treatment group in all safety summaries due to an error in recording treatment.
|
0.00%
0/165 • Baseline up to Week 24
DB safety analysis set included all randomized participants who received at least 1 dose of study drug during the DB treatment period. OL safety analysis set included all participants who received at least 1 of dose of study drug during the OL treatment period. One participant was randomized to Placebo and received placebo in the DB period but was summarized in the Fremanezumab treatment group in all safety summaries due to an error in recording treatment.
|
|
Infections and infestations
COVID-19
|
0.00%
0/177 • Baseline up to Week 24
DB safety analysis set included all randomized participants who received at least 1 dose of study drug during the DB treatment period. OL safety analysis set included all participants who received at least 1 of dose of study drug during the OL treatment period. One participant was randomized to Placebo and received placebo in the DB period but was summarized in the Fremanezumab treatment group in all safety summaries due to an error in recording treatment.
|
0.57%
1/176 • Number of events 1 • Baseline up to Week 24
DB safety analysis set included all randomized participants who received at least 1 dose of study drug during the DB treatment period. OL safety analysis set included all participants who received at least 1 of dose of study drug during the OL treatment period. One participant was randomized to Placebo and received placebo in the DB period but was summarized in the Fremanezumab treatment group in all safety summaries due to an error in recording treatment.
|
0.00%
0/165 • Baseline up to Week 24
DB safety analysis set included all randomized participants who received at least 1 dose of study drug during the DB treatment period. OL safety analysis set included all participants who received at least 1 of dose of study drug during the OL treatment period. One participant was randomized to Placebo and received placebo in the DB period but was summarized in the Fremanezumab treatment group in all safety summaries due to an error in recording treatment.
|
0.00%
0/165 • Baseline up to Week 24
DB safety analysis set included all randomized participants who received at least 1 dose of study drug during the DB treatment period. OL safety analysis set included all participants who received at least 1 of dose of study drug during the OL treatment period. One participant was randomized to Placebo and received placebo in the DB period but was summarized in the Fremanezumab treatment group in all safety summaries due to an error in recording treatment.
|
|
Investigations
C-reactive protein increased
|
0.00%
0/177 • Baseline up to Week 24
DB safety analysis set included all randomized participants who received at least 1 dose of study drug during the DB treatment period. OL safety analysis set included all participants who received at least 1 of dose of study drug during the OL treatment period. One participant was randomized to Placebo and received placebo in the DB period but was summarized in the Fremanezumab treatment group in all safety summaries due to an error in recording treatment.
|
0.57%
1/176 • Number of events 1 • Baseline up to Week 24
DB safety analysis set included all randomized participants who received at least 1 dose of study drug during the DB treatment period. OL safety analysis set included all participants who received at least 1 of dose of study drug during the OL treatment period. One participant was randomized to Placebo and received placebo in the DB period but was summarized in the Fremanezumab treatment group in all safety summaries due to an error in recording treatment.
|
0.00%
0/165 • Baseline up to Week 24
DB safety analysis set included all randomized participants who received at least 1 dose of study drug during the DB treatment period. OL safety analysis set included all participants who received at least 1 of dose of study drug during the OL treatment period. One participant was randomized to Placebo and received placebo in the DB period but was summarized in the Fremanezumab treatment group in all safety summaries due to an error in recording treatment.
|
0.00%
0/165 • Baseline up to Week 24
DB safety analysis set included all randomized participants who received at least 1 dose of study drug during the DB treatment period. OL safety analysis set included all participants who received at least 1 of dose of study drug during the OL treatment period. One participant was randomized to Placebo and received placebo in the DB period but was summarized in the Fremanezumab treatment group in all safety summaries due to an error in recording treatment.
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.00%
0/177 • Baseline up to Week 24
DB safety analysis set included all randomized participants who received at least 1 dose of study drug during the DB treatment period. OL safety analysis set included all participants who received at least 1 of dose of study drug during the OL treatment period. One participant was randomized to Placebo and received placebo in the DB period but was summarized in the Fremanezumab treatment group in all safety summaries due to an error in recording treatment.
|
0.00%
0/176 • Baseline up to Week 24
DB safety analysis set included all randomized participants who received at least 1 dose of study drug during the DB treatment period. OL safety analysis set included all participants who received at least 1 of dose of study drug during the OL treatment period. One participant was randomized to Placebo and received placebo in the DB period but was summarized in the Fremanezumab treatment group in all safety summaries due to an error in recording treatment.
|
0.61%
1/165 • Number of events 1 • Baseline up to Week 24
DB safety analysis set included all randomized participants who received at least 1 dose of study drug during the DB treatment period. OL safety analysis set included all participants who received at least 1 of dose of study drug during the OL treatment period. One participant was randomized to Placebo and received placebo in the DB period but was summarized in the Fremanezumab treatment group in all safety summaries due to an error in recording treatment.
|
0.00%
0/165 • Baseline up to Week 24
DB safety analysis set included all randomized participants who received at least 1 dose of study drug during the DB treatment period. OL safety analysis set included all participants who received at least 1 of dose of study drug during the OL treatment period. One participant was randomized to Placebo and received placebo in the DB period but was summarized in the Fremanezumab treatment group in all safety summaries due to an error in recording treatment.
|
|
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous
|
0.00%
0/177 • Baseline up to Week 24
DB safety analysis set included all randomized participants who received at least 1 dose of study drug during the DB treatment period. OL safety analysis set included all participants who received at least 1 of dose of study drug during the OL treatment period. One participant was randomized to Placebo and received placebo in the DB period but was summarized in the Fremanezumab treatment group in all safety summaries due to an error in recording treatment.
|
0.00%
0/176 • Baseline up to Week 24
DB safety analysis set included all randomized participants who received at least 1 dose of study drug during the DB treatment period. OL safety analysis set included all participants who received at least 1 of dose of study drug during the OL treatment period. One participant was randomized to Placebo and received placebo in the DB period but was summarized in the Fremanezumab treatment group in all safety summaries due to an error in recording treatment.
|
0.61%
1/165 • Number of events 1 • Baseline up to Week 24
DB safety analysis set included all randomized participants who received at least 1 dose of study drug during the DB treatment period. OL safety analysis set included all participants who received at least 1 of dose of study drug during the OL treatment period. One participant was randomized to Placebo and received placebo in the DB period but was summarized in the Fremanezumab treatment group in all safety summaries due to an error in recording treatment.
|
0.00%
0/165 • Baseline up to Week 24
DB safety analysis set included all randomized participants who received at least 1 dose of study drug during the DB treatment period. OL safety analysis set included all participants who received at least 1 of dose of study drug during the OL treatment period. One participant was randomized to Placebo and received placebo in the DB period but was summarized in the Fremanezumab treatment group in all safety summaries due to an error in recording treatment.
|
|
Psychiatric disorders
Depression
|
0.00%
0/177 • Baseline up to Week 24
DB safety analysis set included all randomized participants who received at least 1 dose of study drug during the DB treatment period. OL safety analysis set included all participants who received at least 1 of dose of study drug during the OL treatment period. One participant was randomized to Placebo and received placebo in the DB period but was summarized in the Fremanezumab treatment group in all safety summaries due to an error in recording treatment.
|
0.00%
0/176 • Baseline up to Week 24
DB safety analysis set included all randomized participants who received at least 1 dose of study drug during the DB treatment period. OL safety analysis set included all participants who received at least 1 of dose of study drug during the OL treatment period. One participant was randomized to Placebo and received placebo in the DB period but was summarized in the Fremanezumab treatment group in all safety summaries due to an error in recording treatment.
|
0.00%
0/165 • Baseline up to Week 24
DB safety analysis set included all randomized participants who received at least 1 dose of study drug during the DB treatment period. OL safety analysis set included all participants who received at least 1 of dose of study drug during the OL treatment period. One participant was randomized to Placebo and received placebo in the DB period but was summarized in the Fremanezumab treatment group in all safety summaries due to an error in recording treatment.
|
0.61%
1/165 • Number of events 1 • Baseline up to Week 24
DB safety analysis set included all randomized participants who received at least 1 dose of study drug during the DB treatment period. OL safety analysis set included all participants who received at least 1 of dose of study drug during the OL treatment period. One participant was randomized to Placebo and received placebo in the DB period but was summarized in the Fremanezumab treatment group in all safety summaries due to an error in recording treatment.
|
Other adverse events
Adverse event data not reported
Additional Information
Director, Clinical Research
Teva Branded Pharmaceutical Products, R&D Inc.
Results disclosure agreements
- Principal investigator is a sponsor employee Sponsor has the right 60 days before submission for publication to review/provide comments. If the Sponsor's review shows that potentially patentable subject matter would be disclosed, publication or public disclosure shall be delayed for up to 90 additional days in order for the Sponsor, or Sponsor's designees, to file the necessary patent applications. In multicenter trials, each PI will postpone single center publications until after disclosure or publication of multicenter data.
- Publication restrictions are in place
Restriction type: OTHER