NCT03965091

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

Terminated Phase 2 Results posted Last updated 30 March 2023

What this trial tests

Phase 2 trial testing Fremanezumab in Fibromyalgia in 189 participants. Terminated before completion.

Timeline

31 July 2019

Primary endpoint
19 January 2022

19 January 2022

Quick facts

Lead sponsor	Teva Branded Pharmaceutical Products R&D, Inc.
Phase	Phase 2
Status	Terminated
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	189
Start date	31 July 2019
Primary completion	19 January 2022
Estimated completion	19 January 2022
Sites	49 locations across United States

Drugs / interventions tested

• Fremanezumab (FREMANEZUMAB) — full drug profile →
• Placebo

Conditions studied

• Fibromyalgia — all drugs for Fibromyalgia →

Sponsor

Teva Branded Pharmaceutical Products R&D, Inc. — full company profile →

Who can join

Adults 18 to 75, any sex, with Fibromyalgia. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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 Primary · Baseline, Week 12

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.

Group	Value	95% CI
Placebo	-1.5	± 1.79
Fremanezumab Dose A	-1.2	± 1.58
Fremanezumab Dose B	-1.3	± 1.61

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 Secondary · Baseline, Week 12

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

Change at Week 12 in Symptoms Subscore

Group	Value	95% CI
Placebo	-9.1	± 13.99
Fremanezumab Dose A	-4.0	± 13.76
Fremanezumab Dose B	-8.1	± 15.19

Change at Week 12 in Impact Subscore

Group	Value	95% CI
Placebo	-2.0	± 4.60
Fremanezumab Dose A	-1.6	± 5.00
Fremanezumab Dose B	-2.2	± 4.27

Change at Week 12 in Functional Subscore

Group	Value	95% CI
Placebo	-9.5	± 16.26
Fremanezumab Dose A	-4.7	± 18.54
Fremanezumab Dose B	-6.7	± 13.35

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 Secondary · Week 12

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.

Group	Value	95% CI
Placebo	14
Fremanezumab Dose A	12
Fremanezumab Dose B	11

Number of Participants Who Experienced ≥30% Reduction From Baseline in Weekly Average of Daily Average PI-NRS Score at Week 12 Secondary · Week 12

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.

Group	Value	95% CI
Placebo	19
Fremanezumab Dose A	18
Fremanezumab Dose B	18

Number of Participants Who Experienced ≥50% Reduction From Baseline in Weekly Average of Daily Average PI-NRS Score at Week 12 Secondary · Week 12

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.

Group	Value	95% CI
Placebo	11
Fremanezumab Dose A	6
Fremanezumab Dose B	8

Change From Baseline in the Weekly Average of Daily Worst PI-NRS Score Over Past 24 Hours at Week 12 Secondary · Baseline, Week 12

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.

Group	Value	95% CI
Placebo	-1.6	± 2.00
Fremanezumab Dose A	-1.4	± 1.54
Fremanezumab Dose B	-1.3	± 1.80

Change From Baseline in Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance Short Form (SF) 8a T-score at Week 12 Secondary · Baseline, Week 12

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 w

Group	Value	95% CI
Placebo	-4.7	± 8.39
Fremanezumab Dose A	-2.6	± 8.31
Fremanezumab Dose B	-3.1	± 6.86

Change From Baseline in the PROMIS Physical Function SF 12a Scale Score at Week 12 Secondary · Baseline, Week 12

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 functi

Group	Value	95% CI
Placebo	1.8	± 3.67
Fremanezumab Dose A	0.7	± 4.28
Fremanezumab Dose B	1.0	± 3.59

Change From Baseline in the PROMIS Fatigue SF 8a T-Score at Week 12 Secondary · Baseline, Week 12

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.

Group	Value	95% CI
Placebo	-3.9	± 8.61
Fremanezumab Dose A	-3.3	± 6.92
Fremanezumab Dose B	-3.3	± 7.97

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Secondary · Baseline up to Week 16

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 consi

Group	Value	95% CI
Placebo	34
Fremanezumab Dose A	30
Fremanezumab Dose B	29

Number of Participants With at Least 1 Potentially Clinically Significant Abnormal Serum Chemistry Value Secondary · Baseline up to Week 16

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).

Group	Value	95% CI
Placebo	2
Fremanezumab Dose A	2
Fremanezumab Dose B	1

Number of Participants With at Least 1 Potentially Clinically Significant Abnormal Hematology Value Secondary · Baseline up to Week 16

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%.

Group	Value	95% CI
Placebo	4
Fremanezumab Dose A	3
Fremanezumab Dose B	7

Adverse events — posted to ClinicalTrials.gov

Time frame: Baseline up to Week 16. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo

Serious: 1/64 (2%)

Deaths: 0/64

Fremanezumab Dose A

Serious: 1/62 (2%)

Deaths: 0/62

Fremanezumab Dose B

Serious: 1/63 (2%)

Deaths: 0/63

Serious adverse events (3 terms)

Reaction	System	Placebo	Fremanezumab Dose A	Fremanezumab Dose B
Acute myocardial infarction	Cardiac disorders	—	—	—
Sepsis	Infections and infestations	—	—	—
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	—	—	—

Other adverse events (6 terms — click to expand)

Reaction	System	Placebo	Fremanezumab Dose A	Fremanezumab Dose B
Injection site erythema	General disorders	—	—	—
Injection site induration	General disorders	—	—	—
Nausea	Gastrointestinal disorders	—	—	—
Injection site pain	General disorders	—	—	—
Nasopharyngitis	Infections and infestations	—	—	—
Upper respiratory tract infection	Infections and infestations	—	—	—

Most-reported serious reactions: Acute myocardial infarction, Sepsis, Pulmonary embolism.

Data from ClinicalTrials.gov NCT03965091 adverse events section.

Sponsor's own description

The primary objective of the study is to estimate the treatment effect of fremanezumab administered subcutaneously (SC) in reducing pain in adult participants with fibromyalgia (FM). A secondary objective is to evaluate the effect of fremanezumab on other efficacy measures, including pain, quality of life, sleep, fatigue, improvement in health, physical functioning, and mood. Another secondary objective is to evaluate the safety and tolerability of fremanezumab administered SC in adult participants with FM.

The total duration of participant participation in the study is planned to be 21 weeks, consisting of a screening period of up to 5 weeks (ranging from 17 to 35 days), and a double-blind treatment period of 16 weeks.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Fremanezumab: a disease-specific option for the preventive treatment of migraine, including difficult-to-treat migraine.
   Friedman DI, Cohen JM. · · 2020 · cited 7× · PMID 32832978 · DOI 10.1042/etls20200018