Trial Outcomes & Findings for A Study to Test the Effectiveness and Safety of Fremanezumab on Participants With Fibromyalgia (NCT NCT03965091)

NCT ID: NCT03965091

Last Updated: 2023-03-30

Results Overview

The PI-NRS is an 11-point pain intensity numerical rating scale where 0=no pain and 10=worst possible pain; higher scores indicating more pain. Weekly average of the daily average PI-NRS pain score over the past 24 hours was derived using formula: Summation of non-missing efficacy variable in an analysis week divided by the number of days with non-missing efficacy variable in the analysis week. Baseline was defined as the last 14 days before the first dose of study drug.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

189 participants

Primary outcome timeframe

Baseline, Week 12

Results posted on

2023-03-30

Participant Flow

Participant milestones

Participant milestones
Measure
Placebo
Participants received placebo matched to fremanezumab subcutaneously (SC) on Days 1, 29, 57, and 85.
Fremanezumab Dose A
Participants received fremanezumab SC on Days 1, 29, and 57 and placebo matched to fremanezumab SC on Day 85.
Fremanezumab Dose B
Participants received fremanezumab SC on Days 1, 29, and 57 and placebo matched to fremanezumab SC on Day 85.
Overall Study
STARTED
64
62
63
Overall Study
Received at Least 1 Dose of Study Drug
64
62
63
Overall Study
COMPLETED
41
45
45
Overall Study
NOT COMPLETED
23
17
18

Reasons for withdrawal

Reasons for withdrawal
Measure
Placebo
Participants received placebo matched to fremanezumab subcutaneously (SC) on Days 1, 29, 57, and 85.
Fremanezumab Dose A
Participants received fremanezumab SC on Days 1, 29, and 57 and placebo matched to fremanezumab SC on Day 85.
Fremanezumab Dose B
Participants received fremanezumab SC on Days 1, 29, and 57 and placebo matched to fremanezumab SC on Day 85.
Overall Study
Adverse Event
0
2
3
Overall Study
Withdrawal by Subject
11
3
5
Overall Study
Non-compliance with study drug
0
0
1
Overall Study
Lost to Follow-up
1
1
1
Overall Study
Lack of Efficacy
2
0
0
Overall Study
Other than specified
9
11
8

Baseline Characteristics

A Study to Test the Effectiveness and Safety of Fremanezumab on Participants With Fibromyalgia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Placebo
n=64 Participants
Participants received placebo matched to fremanezumab SC on Days 1, 29, 57, and 85.
Fremanezumab Dose A
n=62 Participants
Participants received fremanezumab SC on Days 1, 29, and 57 and placebo matched to fremanezumab SC on Day 85.
Fremanezumab Dose B
n=63 Participants
Participants received fremanezumab SC on Days 1, 29, and 57 and placebo matched to fremanezumab SC on Day 85.
Total
n=189 Participants
Total of all reporting groups
Age, Continuous
51.4 years
STANDARD_DEVIATION 11.54 • n=5 Participants
52.3 years
STANDARD_DEVIATION 11.75 • n=7 Participants
52.2 years
STANDARD_DEVIATION 12.59 • n=5 Participants
51.9 years
STANDARD_DEVIATION 11.91 • n=4 Participants
Sex: Female, Male
Female
60 Participants
n=5 Participants
59 Participants
n=7 Participants
59 Participants
n=5 Participants
178 Participants
n=4 Participants
Sex: Female, Male
Male
4 Participants
n=5 Participants
3 Participants
n=7 Participants
4 Participants
n=5 Participants
11 Participants
n=4 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
6 Participants
n=5 Participants
9 Participants
n=7 Participants
7 Participants
n=5 Participants
22 Participants
n=4 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
58 Participants
n=5 Participants
53 Participants
n=7 Participants
55 Participants
n=5 Participants
166 Participants
n=4 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
0 Participants
n=7 Participants
1 Participants
n=5 Participants
1 Participants
n=4 Participants
Race/Ethnicity, Customized
Race · White
58 Participants
n=5 Participants
50 Participants
n=7 Participants
54 Participants
n=5 Participants
162 Participants
n=4 Participants
Race/Ethnicity, Customized
Race · Black or African American
5 Participants
n=5 Participants
9 Participants
n=7 Participants
5 Participants
n=5 Participants
19 Participants
n=4 Participants
Race/Ethnicity, Customized
Race · Asian
0 Participants
n=5 Participants
0 Participants
n=7 Participants
2 Participants
n=5 Participants
2 Participants
n=4 Participants
Race/Ethnicity, Customized
Race · American Indian or Alaska Native
0 Participants
n=5 Participants
1 Participants
n=7 Participants
1 Participants
n=5 Participants
2 Participants
n=4 Participants
Race/Ethnicity, Customized
Race · Other
1 Participants
n=5 Participants
2 Participants
n=7 Participants
1 Participants
n=5 Participants
4 Participants
n=4 Participants
Weekly Average of the Daily Average Pain Intensity-Numerical Rating Scale (PI-NRS) Score
5.6 units on a scale
STANDARD_DEVIATION 1.05 • n=5 Participants
5.8 units on a scale
STANDARD_DEVIATION 1.03 • n=7 Participants
6.0 units on a scale
STANDARD_DEVIATION 1.11 • n=5 Participants
5.8 units on a scale
STANDARD_DEVIATION 1.07 • n=4 Participants

PRIMARY outcome

Timeframe: Baseline, Week 12

Population: Modified intent-to-treat (mITT) analysis set included all randomized participants who received at least 1 dose of study drug and at least 1 postbaseline entry of daily average pain intensity using the PI-NRS. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.

The PI-NRS is an 11-point pain intensity numerical rating scale where 0=no pain and 10=worst possible pain; higher scores indicating more pain. Weekly average of the daily average PI-NRS pain score over the past 24 hours was derived using formula: Summation of non-missing efficacy variable in an analysis week divided by the number of days with non-missing efficacy variable in the analysis week. Baseline was defined as the last 14 days before the first dose of study drug.

Outcome measures

Outcome measures
Measure
Placebo
n=46 Participants
Participants received placebo matched to fremanezumab SC on Days 1, 29, 57, and 85.
Fremanezumab Dose A
n=52 Participants
Participants received fremanezumab SC on Days 1, 29, and 57 and placebo matched to fremanezumab SC on Day 85.
Fremanezumab Dose B
n=50 Participants
Participants received fremanezumab SC on Days 1, 29, and 57 and placebo matched to fremanezumab SC on Day 85.
Change From Baseline in the Weekly Average of the Daily Average Pain Intensity-Numerical Rating Scale (PI-NRS) Score Over the Past 24 Hours at Week 12
-1.5 units on a scale
Standard Deviation 1.79
-1.2 units on a scale
Standard Deviation 1.58
-1.3 units on a scale
Standard Deviation 1.61

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: mITT analysis set included all randomized participants who received at least 1 dose of study drug and at least 1 postbaseline entry of daily average pain intensity using the PI-NRS. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.

The FIQR is a commonly used instrument in the evaluation of fibromyalgia participants. It contains 21 questions in 3 domains: function (9 questions), overall impact (2 questions), and symptoms (10 questions). Questions are graded on a 0 to 10 numeric scale with 10 being the worst. All questions are framed in the context of the last 7 days. The sub-total score for each domain is the summation of scores in the domain. The function sub-total score ranges from 0 (better) to 90 (worst), with a lower score indicating better (higher) function; overall impact sub-total score ranges from 0 to 20, with a lower score indicating better (lower) impact; the symptoms sub-total score ranges from 0 to 100, with a lower score indicating a better (lower) level of symptoms. Baseline was defined as the last 14 days before the first dose of study drug.

Outcome measures

Outcome measures
Measure
Placebo
n=43 Participants
Participants received placebo matched to fremanezumab SC on Days 1, 29, 57, and 85.
Fremanezumab Dose A
n=45 Participants
Participants received fremanezumab SC on Days 1, 29, and 57 and placebo matched to fremanezumab SC on Day 85.
Fremanezumab Dose B
n=46 Participants
Participants received fremanezumab SC on Days 1, 29, and 57 and placebo matched to fremanezumab SC on Day 85.
Change From Baseline in the Individual Components of the Fibromyalgia Impact Questionnaire Revised (FIQR) Score: Symptom Subscore, Impact Subscore, and Functional Subscore at Week 12
Change at Week 12 in Symptoms Subscore
-9.1 units on a scale
Standard Deviation 13.99
-4.0 units on a scale
Standard Deviation 13.76
-8.1 units on a scale
Standard Deviation 15.19
Change From Baseline in the Individual Components of the Fibromyalgia Impact Questionnaire Revised (FIQR) Score: Symptom Subscore, Impact Subscore, and Functional Subscore at Week 12
Change at Week 12 in Impact Subscore
-2.0 units on a scale
Standard Deviation 4.60
-1.6 units on a scale
Standard Deviation 5.00
-2.2 units on a scale
Standard Deviation 4.27
Change From Baseline in the Individual Components of the Fibromyalgia Impact Questionnaire Revised (FIQR) Score: Symptom Subscore, Impact Subscore, and Functional Subscore at Week 12
Change at Week 12 in Functional Subscore
-9.5 units on a scale
Standard Deviation 16.26
-4.7 units on a scale
Standard Deviation 18.54
-6.7 units on a scale
Standard Deviation 13.35

SECONDARY outcome

Timeframe: Week 12

Population: mITT analysis set included all randomized participants who received at least 1 dose of study drug and at least 1 postbaseline entry of daily average pain intensity using the PI-NRS.

The PGIC scale evaluates all aspects of participants' health and assesses if there has been an improvement or decline in clinical status since the start of the study. Participants recorded responses to the PGIC scale at Week 12. Improvement was recorded on a 7-point scale, with 1 = very much improved, 2 = Much Improved, 3 = Minimally Improved, 4 = No Change, 5 = Minimally Worse, 6 = Much Worse, and 7 = Very Much Worse. Scale "much improved" or "very much improved" were considered improved.

Outcome measures

Outcome measures
Measure
Placebo
n=64 Participants
Participants received placebo matched to fremanezumab SC on Days 1, 29, 57, and 85.
Fremanezumab Dose A
n=62 Participants
Participants received fremanezumab SC on Days 1, 29, and 57 and placebo matched to fremanezumab SC on Day 85.
Fremanezumab Dose B
n=63 Participants
Participants received fremanezumab SC on Days 1, 29, and 57 and placebo matched to fremanezumab SC on Day 85.
Responder Rate of the Patient Global Impression of Change (PGIC) Rating: Number of Participants Who Were Much Improved or Very Much Improved at Week 12
14 Participants
12 Participants
11 Participants

SECONDARY outcome

Timeframe: Week 12

Population: mITT analysis set included all randomized participants who received at least 1 dose of study drug and at least 1 postbaseline entry of daily average pain intensity using the PI-NRS. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.

The PI-NRS is an 11-point pain intensity numerical rating scale where 0=no pain and 10=worst possible pain; higher scores indication more pain. Weekly average of the daily average PI-NRS pain score over the past 24 hours was derived using formula: Summation of non-missing efficacy variable in an analysis week divided by the number of days with non-missing efficacy variable in the analysis week.

Outcome measures

Outcome measures
Measure
Placebo
n=46 Participants
Participants received placebo matched to fremanezumab SC on Days 1, 29, 57, and 85.
Fremanezumab Dose A
n=52 Participants
Participants received fremanezumab SC on Days 1, 29, and 57 and placebo matched to fremanezumab SC on Day 85.
Fremanezumab Dose B
n=50 Participants
Participants received fremanezumab SC on Days 1, 29, and 57 and placebo matched to fremanezumab SC on Day 85.
Number of Participants Who Experienced ≥30% Reduction From Baseline in Weekly Average of Daily Average PI-NRS Score at Week 12
19 Participants
18 Participants
18 Participants

SECONDARY outcome

Timeframe: Week 12

Population: mITT analysis set included all randomized participants who received at least 1 dose of study drug and at least 1 postbaseline entry of daily average pain intensity using the PI-NRS. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.

The PI-NRS is an 11-point pain intensity numerical rating scale where 0=no pain and 10=worst possible pain; higher scores indication more pain. Weekly average of the daily average PI-NRS pain score over the past 24 hours was derived using formula: Summation of non-missing efficacy variable in an analysis week divided by the number of days with non-missing efficacy variable in the analysis week.

Outcome measures

Outcome measures
Measure
Placebo
n=46 Participants
Participants received placebo matched to fremanezumab SC on Days 1, 29, 57, and 85.
Fremanezumab Dose A
n=52 Participants
Participants received fremanezumab SC on Days 1, 29, and 57 and placebo matched to fremanezumab SC on Day 85.
Fremanezumab Dose B
n=50 Participants
Participants received fremanezumab SC on Days 1, 29, and 57 and placebo matched to fremanezumab SC on Day 85.
Number of Participants Who Experienced ≥50% Reduction From Baseline in Weekly Average of Daily Average PI-NRS Score at Week 12
11 Participants
6 Participants
8 Participants

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: mITT analysis set included all randomized participants who received at least 1 dose of study drug and at least 1 postbaseline entry of daily average pain intensity using the PI-NRS. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.

The PI-NRS is an 11-point pain intensity numerical rating scale where 0=no pain and 10=worst possible pain; higher scores indication more pain. Weekly average of the daily worst PI-NRS pain score over the past 24 hours was derived using formula: Summation of non-missing efficacy variable in an analysis week divided by the number of days with non-missing efficacy variable in the analysis week. Baseline was defined as the last 14 days before the first dose of study drug.

Outcome measures

Outcome measures
Measure
Placebo
n=46 Participants
Participants received placebo matched to fremanezumab SC on Days 1, 29, 57, and 85.
Fremanezumab Dose A
n=52 Participants
Participants received fremanezumab SC on Days 1, 29, and 57 and placebo matched to fremanezumab SC on Day 85.
Fremanezumab Dose B
n=50 Participants
Participants received fremanezumab SC on Days 1, 29, and 57 and placebo matched to fremanezumab SC on Day 85.
Change From Baseline in the Weekly Average of Daily Worst PI-NRS Score Over Past 24 Hours at Week 12
-1.6 units on a scale
Standard Deviation 2.00
-1.4 units on a scale
Standard Deviation 1.54
-1.3 units on a scale
Standard Deviation 1.80

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: mITT analysis set included all randomized participants who received at least 1 dose of study drug and at least 1 postbaseline entry of daily average pain intensity using the PI-NRS. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.

The PROMIS SF8a scale contains 8 items and assesses sleep disturbance over the past 7 days. One item assessing overall sleep quality use a scale of very poor, poor, fair, good, or very good. Other 7 items use a scale of not at all, a little bit, somewhat, quite a bit, or very much. Each item of the PROMIS sleep disturbance SF8a is on 5-point scales (1 to 5), with 1 for the lowest sleep disturbance and 5 for the highest sleep disturbance. The total score ranging from 8 (lowest sleep disturbance) to 40 (highest sleep disturbance) was calculated as the summation of 8 non-missing scores. T-score was calculated from the total raw score using the scoring table (PROMIS-Sleep Disturbance Scoring Manual) with a mean of 50 and a standard deviation of 10. Possible range for T-score is 30 to 80, with higher scores indicating greater severity of sleep impairment.

Outcome measures

Outcome measures
Measure
Placebo
n=43 Participants
Participants received placebo matched to fremanezumab SC on Days 1, 29, 57, and 85.
Fremanezumab Dose A
n=46 Participants
Participants received fremanezumab SC on Days 1, 29, and 57 and placebo matched to fremanezumab SC on Day 85.
Fremanezumab Dose B
n=42 Participants
Participants received fremanezumab SC on Days 1, 29, and 57 and placebo matched to fremanezumab SC on Day 85.
Change From Baseline in Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance Short Form (SF) 8a T-score at Week 12
-4.7 T-score
Standard Deviation 8.39
-2.6 T-score
Standard Deviation 8.31
-3.1 T-score
Standard Deviation 6.86

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: mITT analysis set included all randomized participants who received at least 1 dose of study drug and at least 1 postbaseline entry of daily average pain intensity using the PI-NRS. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.

The PROMIS physical function scale measures self-reported capability. This includes the functioning of one's upper extremities (dexterity), lower extremities (walking or mobility), and central regions (neck, back), as well as instrumental activities of daily living, such as running errands over the past 7 days. A single physical function capability score is obtained from a SF. The PROMIS physical function SF12a scale contains 12 items with 5-point scales (1 \[not at all\] to 5 \[very much\]) for each item with a total score ranging from 12 (poor physical function) to 60 (better physical function). A higher score indicates greater level of physical capability. Total raw score was calculated as the summation of 12 non-missing scores for participants who can walk 25 feet or summation of 6 non-missing scores for participants who cannot walk for 25 feet. The calculated total raw score was converted into scale score using the scoring tables (PROMIS-Physical Function Scoring Manual).

Outcome measures

Outcome measures
Measure
Placebo
n=43 Participants
Participants received placebo matched to fremanezumab SC on Days 1, 29, 57, and 85.
Fremanezumab Dose A
n=45 Participants
Participants received fremanezumab SC on Days 1, 29, and 57 and placebo matched to fremanezumab SC on Day 85.
Fremanezumab Dose B
n=46 Participants
Participants received fremanezumab SC on Days 1, 29, and 57 and placebo matched to fremanezumab SC on Day 85.
Change From Baseline in the PROMIS Physical Function SF 12a Scale Score at Week 12
1.8 units on a scale
Standard Deviation 3.67
0.7 units on a scale
Standard Deviation 4.28
1.0 units on a scale
Standard Deviation 3.59

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: mITT analysis set included all randomized participants who received at least 1 dose of study drug and at least 1 postbaseline entry of daily average pain intensity using the PI-NRS. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.

The PROMIS Fatigue SF8a contains 8 items with 5-point scales (1 \[never\] to 5 \[always\]) for each item over the past 7 days. The total raw score ranges from 8 (lowest level of fatigue) to 40 (highest level of fatigue) was calculated as the summation of 8 non-missing scores. T-score was calculated from the total raw score using the scoring table (PROMIS-Fatigue Scoring Manual) with a mean of 50 and a standard deviation of 10; scores higher than 50 indicate greater fatigue compared to the reference population.

Outcome measures

Outcome measures
Measure
Placebo
n=43 Participants
Participants received placebo matched to fremanezumab SC on Days 1, 29, 57, and 85.
Fremanezumab Dose A
n=45 Participants
Participants received fremanezumab SC on Days 1, 29, and 57 and placebo matched to fremanezumab SC on Day 85.
Fremanezumab Dose B
n=45 Participants
Participants received fremanezumab SC on Days 1, 29, and 57 and placebo matched to fremanezumab SC on Day 85.
Change From Baseline in the PROMIS Fatigue SF 8a T-Score at Week 12
-3.9 T-score
Standard Deviation 8.61
-3.3 T-score
Standard Deviation 6.92
-3.3 T-score
Standard Deviation 7.97

SECONDARY outcome

Timeframe: Baseline up to Week 16

Population: Safety analysis set included all randomized participants who received at least 1 dose of study drug.

An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse events (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. Any AE occurring on or after the first dose of study drug is considered a treatment-emergent AE (TEAE). A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.

Outcome measures

Outcome measures
Measure
Placebo
n=64 Participants
Participants received placebo matched to fremanezumab SC on Days 1, 29, 57, and 85.
Fremanezumab Dose A
n=62 Participants
Participants received fremanezumab SC on Days 1, 29, and 57 and placebo matched to fremanezumab SC on Day 85.
Fremanezumab Dose B
n=63 Participants
Participants received fremanezumab SC on Days 1, 29, and 57 and placebo matched to fremanezumab SC on Day 85.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
34 Participants
30 Participants
29 Participants

SECONDARY outcome

Timeframe: Baseline up to Week 16

Population: Safety analysis set included all randomized participants who received at least 1 dose of study drug. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.

Potentially clinically significant serum chemistry abnormalities included: Blood urea nitrogen ≥10.71 millimoles (mmol)/liter (L) and Gamma-glutamyl transpeptidase (GGT) ≥3 \* upper limit of normal (ULN).

Outcome measures

Outcome measures
Measure
Placebo
n=61 Participants
Participants received placebo matched to fremanezumab SC on Days 1, 29, 57, and 85.
Fremanezumab Dose A
n=60 Participants
Participants received fremanezumab SC on Days 1, 29, and 57 and placebo matched to fremanezumab SC on Day 85.
Fremanezumab Dose B
n=62 Participants
Participants received fremanezumab SC on Days 1, 29, and 57 and placebo matched to fremanezumab SC on Day 85.
Number of Participants With at Least 1 Potentially Clinically Significant Abnormal Serum Chemistry Value
2 Participants
2 Participants
1 Participants

SECONDARY outcome

Timeframe: Baseline up to Week 16

Population: Safety analysis set included all randomized participants who received at least 1 dose of study drug. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.

Potentially clinically significant hematological abnormalities included: White blood cells (WBCs) count ≤3.0 \* 10\^9/L; Hemoglobin ≤95 grams (g)/L in females; Hematocrit \<0.32 L/L in females; Platelets ≥700 \* 10\^9/L; and Eosinophils/Leukocytes ≥10%.

Outcome measures

Outcome measures
Measure
Placebo
n=61 Participants
Participants received placebo matched to fremanezumab SC on Days 1, 29, 57, and 85.
Fremanezumab Dose A
n=60 Participants
Participants received fremanezumab SC on Days 1, 29, and 57 and placebo matched to fremanezumab SC on Day 85.
Fremanezumab Dose B
n=62 Participants
Participants received fremanezumab SC on Days 1, 29, and 57 and placebo matched to fremanezumab SC on Day 85.
Number of Participants With at Least 1 Potentially Clinically Significant Abnormal Hematology Value
4 Participants
3 Participants
7 Participants

SECONDARY outcome

Timeframe: Baseline up to Week 16

Population: Safety analysis set included all randomized participants who received at least 1 dose of study drug.

Outcome measures

Outcome measures
Measure
Placebo
n=64 Participants
Participants received placebo matched to fremanezumab SC on Days 1, 29, 57, and 85.
Fremanezumab Dose A
n=62 Participants
Participants received fremanezumab SC on Days 1, 29, and 57 and placebo matched to fremanezumab SC on Day 85.
Fremanezumab Dose B
n=63 Participants
Participants received fremanezumab SC on Days 1, 29, and 57 and placebo matched to fremanezumab SC on Day 85.
Number of Participants With at Least 1 Potentially Clinically Significant Urinalysis Abnormalities
0 Participants
0 Participants
0 Participants

SECONDARY outcome

Timeframe: Baseline up to Week 16

Population: Safety analysis set included all randomized participants who received at least 1 dose of study drug. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.

Clinically significant vital signs abnormalities included: Systolic blood pressure (BP): ≤90 millimeters of mercury (mmHg) and decrease from baseline of 20 mm Hg; Diastolic BP: ≥105 mmHg and increase from baseline of ≥15 mmHg or ≤50 mmHg and decrease from baseline of ≥15 mmHg.

Outcome measures

Outcome measures
Measure
Placebo
n=62 Participants
Participants received placebo matched to fremanezumab SC on Days 1, 29, 57, and 85.
Fremanezumab Dose A
n=60 Participants
Participants received fremanezumab SC on Days 1, 29, and 57 and placebo matched to fremanezumab SC on Day 85.
Fremanezumab Dose B
n=62 Participants
Participants received fremanezumab SC on Days 1, 29, and 57 and placebo matched to fremanezumab SC on Day 85.
Number of Participants With at Least 1 Clinically Significant Abnormal Vital Signs Value
1 Participants
2 Participants
0 Participants

SECONDARY outcome

Timeframe: Baseline up to Week 16

Population: Safety analysis set included all randomized participants who received at least 1 dose of study drug.

Physical examination included: General appearance, HEENT (head, ears, eyes, nose, and throat examination), chest and lungs, heart, cardiovascular, abdomen, musculoskeletal, skin, lymph nodes, neurological, and extremities/back.

Outcome measures

Outcome measures
Measure
Placebo
n=64 Participants
Participants received placebo matched to fremanezumab SC on Days 1, 29, 57, and 85.
Fremanezumab Dose A
n=62 Participants
Participants received fremanezumab SC on Days 1, 29, and 57 and placebo matched to fremanezumab SC on Day 85.
Fremanezumab Dose B
n=63 Participants
Participants received fremanezumab SC on Days 1, 29, and 57 and placebo matched to fremanezumab SC on Day 85.
Number of Participants With at Least 1 Physical Examination Abnormal Finding
24 Participants
25 Participants
28 Participants

SECONDARY outcome

Timeframe: Baseline to Week 16

Population: Safety analysis set included all randomized participants who received at least 1 dose of study drug. Here, 'Overall number of participants analyzed' = participants with both baseline and postbaseline ECG value.

The number of participants with a difference (shift) from baseline in any of the following ECG parameters is reported by group: heart rate, PR interval, QRS interval, RR interval, QT interval corrected usingthe Fridericia formula (QTcF) and QT interval corrected using the Bazett's formula (QTcB). Shifts represented as Baseline - endpoint value (last observed post-baseline value).

Outcome measures

Outcome measures
Measure
Placebo
n=58 Participants
Participants received placebo matched to fremanezumab SC on Days 1, 29, 57, and 85.
Fremanezumab Dose A
n=55 Participants
Participants received fremanezumab SC on Days 1, 29, and 57 and placebo matched to fremanezumab SC on Day 85.
Fremanezumab Dose B
n=59 Participants
Participants received fremanezumab SC on Days 1, 29, and 57 and placebo matched to fremanezumab SC on Day 85.
Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters
Normal - Normal
39 Participants
36 Participants
34 Participants
Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters
Normal - Abnormal, not clinically significant
9 Participants
11 Participants
6 Participants
Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters
Normal - Abnormal, clinically significant
0 Participants
0 Participants
1 Participants
Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters
Abnormal - Normal
4 Participants
2 Participants
5 Participants
Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters
Abnormal - Abnormal, not clinically significant
6 Participants
6 Participants
12 Participants
Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters
Abnormal - Abnormal, clinically significant
0 Participants
0 Participants
1 Participants

SECONDARY outcome

Timeframe: Baseline up to Week 16

Population: Safety analysis set included all randomized participants who received at least 1 dose of study drug.

Injection site AEs included injection site pain, injection site erythema, injection site induration, injection site pruritus, injection site bruising, injection site nodule, injection site swelling, and injection site warmth.

Outcome measures

Outcome measures
Measure
Placebo
n=64 Participants
Participants received placebo matched to fremanezumab SC on Days 1, 29, 57, and 85.
Fremanezumab Dose A
n=62 Participants
Participants received fremanezumab SC on Days 1, 29, and 57 and placebo matched to fremanezumab SC on Day 85.
Fremanezumab Dose B
n=63 Participants
Participants received fremanezumab SC on Days 1, 29, and 57 and placebo matched to fremanezumab SC on Day 85.
Number of Participants With at Least 1 Injection Site AE
5 Participants
8 Participants
7 Participants

SECONDARY outcome

Timeframe: Baseline up to Week 16

Population: Safety analysis set included all randomized participants who received at least 1 dose of study drug.

Outcome measures

Outcome measures
Measure
Placebo
n=64 Participants
Participants received placebo matched to fremanezumab SC on Days 1, 29, 57, and 85.
Fremanezumab Dose A
n=62 Participants
Participants received fremanezumab SC on Days 1, 29, and 57 and placebo matched to fremanezumab SC on Day 85.
Fremanezumab Dose B
n=63 Participants
Participants received fremanezumab SC on Days 1, 29, and 57 and placebo matched to fremanezumab SC on Day 85.
Number of Participants With Hypersensitivity/Anaphylaxis Reactions
0 Participants
1 Participants
0 Participants

SECONDARY outcome

Timeframe: Baseline up to Week 16

Population: mITT analysis set included all randomized participants who received at least 1 dose of study drug and at least 1 postbaseline entry of daily average pain intensity using the PI-NRS. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure. There were no participants with evaluable data in the Fremanezumab Dose B arm.

Outcome measures

Outcome measures
Measure
Placebo
n=2 Participants
Participants received placebo matched to fremanezumab SC on Days 1, 29, 57, and 85.
Fremanezumab Dose A
n=1 Participants
Participants received fremanezumab SC on Days 1, 29, and 57 and placebo matched to fremanezumab SC on Day 85.
Fremanezumab Dose B
Participants received fremanezumab SC on Days 1, 29, and 57 and placebo matched to fremanezumab SC on Day 85.
Time to Withdrawal of Treatment Due to Lack of Efficacy
NA weeks
Due to small number of participants who withdrew treatment due to lack of efficacy, median and 95% confidence interval (CI) could not be calculated.
NA weeks
Due to small number of participants who withdrew treatment due to lack of efficacy, median and 95% CI could not be calculated.

SECONDARY outcome

Timeframe: Baseline up to Week 16

Population: mITT analysis set included all randomized participants who received at least 1 dose of study drug and at least 1 postbaseline entry of daily average pain intensity using the PI-NRS. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure. There were no participants with evaluable data in the Placebo arm.

Outcome measures

Outcome measures
Measure
Placebo
Participants received placebo matched to fremanezumab SC on Days 1, 29, 57, and 85.
Fremanezumab Dose A
n=2 Participants
Participants received fremanezumab SC on Days 1, 29, and 57 and placebo matched to fremanezumab SC on Day 85.
Fremanezumab Dose B
n=3 Participants
Participants received fremanezumab SC on Days 1, 29, and 57 and placebo matched to fremanezumab SC on Day 85.
Time to Withdrawal of Treatment Due to AEs
NA weeks
Due to small number of participants who withdrew treatment due to AEs, median and 95% CI could not be calculated.
NA weeks
Due to small number of participants who withdrew treatment due to AEs, median and 95% CI could not be calculated.

Adverse Events

Placebo

Serious events: 1 serious events
Other events: 8 other events
Deaths: 0 deaths

Fremanezumab Dose A

Serious events: 1 serious events
Other events: 14 other events
Deaths: 0 deaths

Fremanezumab Dose B

Serious events: 1 serious events
Other events: 10 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Placebo
n=64 participants at risk
Participants received placebo matched to fremanezumab SC on Days 1, 29, 57, and 85.
Fremanezumab Dose A
n=62 participants at risk
Participants received fremanezumab SC on Days 1, 29, and 57 and placebo matched to fremanezumab SC on Day 85.
Fremanezumab Dose B
n=63 participants at risk
Participants received fremanezumab SC on Days 1, 29, and 57 and placebo matched to fremanezumab SC on Day 85.
Cardiac disorders
Acute myocardial infarction
0.00%
0/64 • Baseline up to Week 16
Safety analysis set included all randomized participants who received at least 1 dose of study drug.
0.00%
0/62 • Baseline up to Week 16
Safety analysis set included all randomized participants who received at least 1 dose of study drug.
1.6%
1/63 • Number of events 1 • Baseline up to Week 16
Safety analysis set included all randomized participants who received at least 1 dose of study drug.
Infections and infestations
Sepsis
1.6%
1/64 • Number of events 1 • Baseline up to Week 16
Safety analysis set included all randomized participants who received at least 1 dose of study drug.
0.00%
0/62 • Baseline up to Week 16
Safety analysis set included all randomized participants who received at least 1 dose of study drug.
0.00%
0/63 • Baseline up to Week 16
Safety analysis set included all randomized participants who received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
0.00%
0/64 • Baseline up to Week 16
Safety analysis set included all randomized participants who received at least 1 dose of study drug.
1.6%
1/62 • Number of events 1 • Baseline up to Week 16
Safety analysis set included all randomized participants who received at least 1 dose of study drug.
0.00%
0/63 • Baseline up to Week 16
Safety analysis set included all randomized participants who received at least 1 dose of study drug.

Other adverse events

Other adverse events
Measure
Placebo
n=64 participants at risk
Participants received placebo matched to fremanezumab SC on Days 1, 29, 57, and 85.
Fremanezumab Dose A
n=62 participants at risk
Participants received fremanezumab SC on Days 1, 29, and 57 and placebo matched to fremanezumab SC on Day 85.
Fremanezumab Dose B
n=63 participants at risk
Participants received fremanezumab SC on Days 1, 29, and 57 and placebo matched to fremanezumab SC on Day 85.
Gastrointestinal disorders
Nausea
1.6%
1/64 • Number of events 2 • Baseline up to Week 16
Safety analysis set included all randomized participants who received at least 1 dose of study drug.
6.5%
4/62 • Number of events 4 • Baseline up to Week 16
Safety analysis set included all randomized participants who received at least 1 dose of study drug.
1.6%
1/63 • Number of events 1 • Baseline up to Week 16
Safety analysis set included all randomized participants who received at least 1 dose of study drug.
General disorders
Injection site erythema
4.7%
3/64 • Number of events 7 • Baseline up to Week 16
Safety analysis set included all randomized participants who received at least 1 dose of study drug.
9.7%
6/62 • Number of events 14 • Baseline up to Week 16
Safety analysis set included all randomized participants who received at least 1 dose of study drug.
4.8%
3/63 • Number of events 7 • Baseline up to Week 16
Safety analysis set included all randomized participants who received at least 1 dose of study drug.
General disorders
Injection site induration
1.6%
1/64 • Number of events 2 • Baseline up to Week 16
Safety analysis set included all randomized participants who received at least 1 dose of study drug.
1.6%
1/62 • Number of events 3 • Baseline up to Week 16
Safety analysis set included all randomized participants who received at least 1 dose of study drug.
7.9%
5/63 • Number of events 23 • Baseline up to Week 16
Safety analysis set included all randomized participants who received at least 1 dose of study drug.
General disorders
Injection site pain
6.2%
4/64 • Number of events 10 • Baseline up to Week 16
Safety analysis set included all randomized participants who received at least 1 dose of study drug.
4.8%
3/62 • Number of events 3 • Baseline up to Week 16
Safety analysis set included all randomized participants who received at least 1 dose of study drug.
3.2%
2/63 • Number of events 2 • Baseline up to Week 16
Safety analysis set included all randomized participants who received at least 1 dose of study drug.
Infections and infestations
Nasopharyngitis
3.1%
2/64 • Number of events 2 • Baseline up to Week 16
Safety analysis set included all randomized participants who received at least 1 dose of study drug.
6.5%
4/62 • Number of events 4 • Baseline up to Week 16
Safety analysis set included all randomized participants who received at least 1 dose of study drug.
1.6%
1/63 • Number of events 1 • Baseline up to Week 16
Safety analysis set included all randomized participants who received at least 1 dose of study drug.
Infections and infestations
Upper respiratory tract infection
1.6%
1/64 • Number of events 1 • Baseline up to Week 16
Safety analysis set included all randomized participants who received at least 1 dose of study drug.
6.5%
4/62 • Number of events 4 • Baseline up to Week 16
Safety analysis set included all randomized participants who received at least 1 dose of study drug.
3.2%
2/63 • Number of events 3 • Baseline up to Week 16
Safety analysis set included all randomized participants who received at least 1 dose of study drug.

Additional Information

Director, Clinical Research

Teva Branded Pharmaceutical Products, R&D Inc.

Phone: 888-483-8279

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