Facial Pain, Rhinosinusitis
Conditions
Brief summary
This is a phase IV randomized, double-blinded, placebo-controlled study to evaluate the efficacy of Erenumab in subjects with midfacial pain or pressure, without clinical or radiographic evidence of sinusitis.
Detailed description
Eligible participants are randomized to receive either Erenumab or placebo by subcutaneous injection once monthly for 6 months. Study duration is eight months which includes a 30 day screening/lead-in period and 6 monthly treatment visits followed by a follow-up visit one month following the last dose of study drug administration. Participants will be expected to score on a scale of 1 to 10 their symptoms of facial pain/pressure, nasal congestion, and rhinorrhea as well well as any rescue medicines taken for pain each day via a mobile app.
Interventions
DRUGErenumab Prefilled Syringe
140mg Erenumab, pre-filled syringe given by subcutaneous injection
OTHERPlacebo
Placebo, pre-filled syringe given by subcutaneous injection
Sponsors
Amgen
David Jang, M.D.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Adults 18 years of age and older presenting to Duke Head & Neck Surgery and Communications Sciences clinic for evaluation of rhinosinusitis and/or facial pain or pressure. 2. Symptoms are present at least 10 days a month for the last 3 months as reported by subject. 3. Symptoms must include midfacial pain or uncomfortable pressure (may be unilateral or bilateral), which is defined as pain in the regions overlying the maxillary, ethmoid, frontal sinuses either together or individually. 4. Nasal endoscopy in the last three months shows no signs of inflammation (i.e. thick drainage, polyps, watery edema in the middle meatus or spheno-ethmoid recess (mild edema permitted). 5. Sinus CT scan or MRI within 12 months of enrollment during a symptomatic period shows no more than scattered minimal mucosal edema or mucous retention cyst with patent infundibula bilaterally. For subjects with a CT scan more than 12 months old or just an MRI, a CT will be repeated for study purposes. For patients with CT scans less than 12 months old, a CT will be repeated for study purposes if the subject has changes in symptoms suggestive of sinusitis. 6. Ability to read/write English. 7. Has a smart phone, ipod or iPad touch for completion of the EMA on a daily basis.
Exclusion criteria
1. Hypersensitivity to erenumab or to any of the drug components (acetate, polysorbate, and sucrose). 2. Previous exposure to erenumab or any other CGRP inhibitor in the six months prior to treatment. 3. Allergy to latex. 4. Inability to differentiate facial pain from other headaches. 5. Non-English speaking or unable to provide written informed consent. 6. On a preventative migraine medication (see below) during the 30 day lead-in period: * Category 1: Divalproex sodium, sodium valproate * Category 2: Topiramate * Category 3: Beta blockers (for example: atenolol, bisoprolol, metoprolol, nadolol, ebivolol, pindolol, propranolol, timolol) * Category 4: Tricyclic antidepressants (for example: amitriptyline, nortriptyline, protriptyline) * Category 5: Serotonin-norepinephrine reuptake inhibitors (for example: venlafaxine, desvenlafaxine, duloxetine, milnacipran) * Category 6: Flunarizine, verapamil * Category 7: Lisinopril, candesartan 7. Received botulinum toxin (Botox) to the head and neck for migraines in the last four months. 8. More than one major open surgery of the nose or sinuses for sinonasal cancer. 9. History of uncontrolled or unstable blood pressure. 10. History of liver failure. 11. History of metastatic malignancy in the last five years or actively undergoing treatment for cancer. 12. Active seizure disorder or other significant neurological conditions other than migraine. 13. Myocardial infarction (MI), stroke, transient ischemic attack (TIA), unstable angina, or coronary artery bypass surgery or other revascularization procedure within 12 months prior to screening. 14. History or evidence of any other unstable or clinically significant medical condition that in the opinion of the sponsor-investigator/ Principal Investigator, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion. 15. Evidence of drug or alcohol abuse or dependence within 12 months prior to screening, based on medical records or patient self-report. 16. Pregnant or breastfeeding, or expecting to conceive during the study, including through 16 weeks after the last dose of investigational product or placebo 17. Female subject of childbearing potential who is unwilling to use an acceptable method of effective contraception during treatment with investigational product or placebo through 16 weeks after the last dose of investigational product. Female subjects not of childbearing potential are defined as any female who is post-menopausal by history, defined as: * Age ≥ 55 years with cessation of menses for 12 or more months, OR * Age \< 55 years but no spontaneous menses for at least 2 years, OR * Underwent bilateral oophorectomy, bilateral salpingectomy, or hysterectomy 18. Unlikely to be able to complete all protocol required study visits or procedures. 19. Currently receiving treatment in another investigational device or drug study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Mean Number of Days Per Month With Significant Mid-facial Pain or Pressure | Baseline, 1,3, and 6 months | Significant mid-facial pain or pressure defined as greater than 4/10 on scale of 1 to 10, measured by daily diary completion. Reported as the change from baseline to six months. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Physical Function as Measured by Migraine Functional Impact Questionnaire (MFIQ) | Baseline, 1, 3 and 6 months | The MFIQ is a 26-item self-report questionnaire, developed to measure the subjective impact of migraine on physical functioning (everyday activities and physical impairment), as well as social and emotional functioning in the past seven days. The MFIQ Physical Function subscale is scored on a scale of 0-100, with higher scores indicating a greater impact. Reported as the change from baseline to six months. |
| Change in Usual Activities as Measured by Migraine Functional Impact Questionnaire (MFIQ) | Baseline, 1, 3 and 6 months | The MFIQ is a 26-item self-report questionnaire, developed to measure the subjective impact of migraine on physical functioning (everyday activities and physical impairment), as well as social and emotional functioning in the past seven days. The MFIQ usual activities subscale is scored on a scale of 0-100, with higher scores indicating a greater impact. Reported as the change from baseline to six months. |
| Change in Social Function as Measured by Migraine Function Impact Questionnaire (MFIQ) | Baseline, 1, 3 and 6 months | The MFIQ is a 26-item self-report questionnaire, developed to measure the subjective impact of migraine on physical functioning (everyday activities and physical impairment), as well as social and emotional functioning in the past seven days. The MFIQ Social Function subscale is scored on a scale of 0-100, with higher scores indicating a greater impact. Reported as the change from baseline to six months. |
| Change in Emotional Function as Measured by Migraine Function Impact Questionnaire (MFIQ) | Baseline, 1, 3 and 6 months | The MFIQ is a 26-item self-report questionnaire, developed to measure the subjective impact of migraine on physical functioning (everyday activities and physical impairment), as well as social and emotional functioning in the past seven days. The MFIQ Emotional Function subscale is scored on a scale of 0-100, with higher scores indicating a greater impact. Reported as the change from baseline to six months. |
| Change in SNOT-22 (Sino-nasal Outcome Test) | Baseline, 1, 3 and 6 months | The SNOT-22 consists of 22 items, each rated from 0 (no problem at all) to 5 (worst possible symptom). SNOT-22 total scores range from 0 to 110, with higher SNOT-22 total scores indicating worse symptoms. Reported as the change from baseline to six months. |
| Change in Mean Number of Days Per Month With Significant Nasal Congestion | Baseline, 1, 3 and 6 months | Measured by daily diary completion via mobile app. Reported as the change from baseline to six months. |
| Change in Mean Number of Days Per Month With Significant Rhinorrhea | Baseline, 1, 3 and 6 months | Measured by daily diary completion via mobile app. Reported as the change from baseline to six months. |
| Change in Mean Number of Days of Rescue Medication Used Per Month | Baseline, 1, 3 and 6 months | Measured by daily diary completion via mobile app. Reported as the change from baseline to six months. |
| Change From Baseline in Mean Daily Pain Score | Baseline, 1, 3 and 6 months | Measured by daily diary completion via mobile app on a scale of 1-10, where 1=no pain and 10=intense pain. Reported as the change from baseline to six months. |
| Change in Overall Impact (Global) as Measured by Migraine Function Impact Questionnaire (MFIQ) | Baseline, 1, 3 and 6 months | The MFIQ is a 26-item self-report questionnaire, developed to measure the subjective impact of migraine on physical functioning (everyday activities and physical impairment), as well as social and emotional functioning in the past seven days. The MFIQ Overall Impact is scored on a scale of 0-100, with higher scores indicating a greater impact. Reported as the change from baseline to six months. |
Countries
United States
Participant flow
Pre-assignment details
Four participants withdrew prior to administration of injection.
Participants by arm
| Arm | Count |
|---|---|
| Erenumab 140mg Erenumab administered by subcutaneous injection (in the abdomen, thigh, or upper arm), once monthly for six months.
Erenumab Prefilled Syringe: 140mg Erenumab, pre-filled syringe given by subcutaneous injection | 13 |
| Placebo Placebo administered by subcutaneous injection (in the abdomen, thigh, or upper arm), once monthly for six months.
Placebo: Placebo, pre-filled syringe given by subcutaneous injection | 12 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 1 |
| Overall Study | Lack of Efficacy | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 2 |
Baseline characteristics
| Characteristic | Placebo | Total | Erenumab |
|---|---|---|---|
| Age, Continuous | 43.2 years STANDARD_DEVIATION 12.5 | 47.4 years STANDARD_DEVIATION 12.4 | 51.4 years STANDARD_DEVIATION 11.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants | 24 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 5 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 9 Participants | 19 Participants | 10 Participants |
| Region of Enrollment United States | 12 Participants | 25 Participants | 13 Participants |
| Sex: Female, Male Female | 10 Participants | 21 Participants | 11 Participants |
| Sex: Female, Male Male | 2 Participants | 4 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 12 |
| other Total, other adverse events | 7 / 13 | 6 / 12 |
| serious Total, serious adverse events | 2 / 13 | 0 / 12 |
Outcome results
Primary
Change in Mean Number of Days Per Month With Significant Mid-facial Pain or Pressure
Significant mid-facial pain or pressure defined as greater than 4/10 on scale of 1 to 10, measured by daily diary completion. Reported as the change from baseline to six months.
Time frame: Baseline, 1,3, and 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Erenumab | Change in Mean Number of Days Per Month With Significant Mid-facial Pain or Pressure | -6.0 days per month | Standard Deviation 6.9 |
| Placebo | Change in Mean Number of Days Per Month With Significant Mid-facial Pain or Pressure | -5.8 days per month | Standard Deviation 8 |
p-value: 0.96ANOVA
Secondary
Change From Baseline in Mean Daily Pain Score
Measured by daily diary completion via mobile app on a scale of 1-10, where 1=no pain and 10=intense pain. Reported as the change from baseline to six months.
Time frame: Baseline, 1, 3 and 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Erenumab | Change From Baseline in Mean Daily Pain Score | -0.9 score on a scale | Standard Deviation 1.1 |
| Placebo | Change From Baseline in Mean Daily Pain Score | -1.2 score on a scale | Standard Deviation 1.6 |
p-value: 0.85Wilcoxon (Mann-Whitney)
Secondary
Change in Emotional Function as Measured by Migraine Function Impact Questionnaire (MFIQ)
The MFIQ is a 26-item self-report questionnaire, developed to measure the subjective impact of migraine on physical functioning (everyday activities and physical impairment), as well as social and emotional functioning in the past seven days. The MFIQ Emotional Function subscale is scored on a scale of 0-100, with higher scores indicating a greater impact. Reported as the change from baseline to six months.
Time frame: Baseline, 1, 3 and 6 months
Population: Participants with data collected at both timepoints.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Erenumab | Change in Emotional Function as Measured by Migraine Function Impact Questionnaire (MFIQ) | 0.4 score on a scale | Standard Deviation 5.9 |
| Placebo | Change in Emotional Function as Measured by Migraine Function Impact Questionnaire (MFIQ) | -6.6 score on a scale | Standard Deviation 5.7 |
p-value: 0.02ANOVA
Secondary
Change in Mean Number of Days of Rescue Medication Used Per Month
Measured by daily diary completion via mobile app. Reported as the change from baseline to six months.
Time frame: Baseline, 1, 3 and 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Erenumab | Change in Mean Number of Days of Rescue Medication Used Per Month | -5.2 days per month | Standard Deviation 8.4 |
| Placebo | Change in Mean Number of Days of Rescue Medication Used Per Month | -2.1 days per month | Standard Deviation 3.8 |
p-value: 0.35Wilcoxon (Mann-Whitney)
Secondary
Change in Mean Number of Days Per Month With Significant Nasal Congestion
Measured by daily diary completion via mobile app. Reported as the change from baseline to six months.
Time frame: Baseline, 1, 3 and 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Erenumab | Change in Mean Number of Days Per Month With Significant Nasal Congestion | -3.2 days per month | Standard Deviation 6 |
| Placebo | Change in Mean Number of Days Per Month With Significant Nasal Congestion | -2.8 days per month | Standard Deviation 4.7 |
p-value: 0.83ANOVA
Secondary
Change in Mean Number of Days Per Month With Significant Rhinorrhea
Measured by daily diary completion via mobile app. Reported as the change from baseline to six months.
Time frame: Baseline, 1, 3 and 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Erenumab | Change in Mean Number of Days Per Month With Significant Rhinorrhea | -1.4 days per month | Standard Deviation 5.7 |
| Placebo | Change in Mean Number of Days Per Month With Significant Rhinorrhea | -1.8 days per month | Standard Deviation 4.8 |
p-value: 0.83ANOVA
Secondary
Change in Overall Impact (Global) as Measured by Migraine Function Impact Questionnaire (MFIQ)
The MFIQ is a 26-item self-report questionnaire, developed to measure the subjective impact of migraine on physical functioning (everyday activities and physical impairment), as well as social and emotional functioning in the past seven days. The MFIQ Overall Impact is scored on a scale of 0-100, with higher scores indicating a greater impact. Reported as the change from baseline to six months.
Time frame: Baseline, 1, 3 and 6 months
Population: Participants with data collected at both timepoints.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Erenumab | Change in Overall Impact (Global) as Measured by Migraine Function Impact Questionnaire (MFIQ) | 0.11 score on a scale | Standard Deviation 0.78 |
| Placebo | Change in Overall Impact (Global) as Measured by Migraine Function Impact Questionnaire (MFIQ) | -1.33 score on a scale | Standard Deviation 1 |
p-value: 0.0036ANOVA
Secondary
Change in Physical Function as Measured by Migraine Functional Impact Questionnaire (MFIQ)
The MFIQ is a 26-item self-report questionnaire, developed to measure the subjective impact of migraine on physical functioning (everyday activities and physical impairment), as well as social and emotional functioning in the past seven days. The MFIQ Physical Function subscale is scored on a scale of 0-100, with higher scores indicating a greater impact. Reported as the change from baseline to six months.
Time frame: Baseline, 1, 3 and 6 months
Population: Participants with data collected at both timepoints.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Erenumab | Change in Physical Function as Measured by Migraine Functional Impact Questionnaire (MFIQ) | -3.3 score on a scale | Standard Deviation 4.5 |
| Placebo | Change in Physical Function as Measured by Migraine Functional Impact Questionnaire (MFIQ) | -5.6 score on a scale | Standard Deviation 6.5 |
p-value: 0.06ANOVA
Secondary
Change in SNOT-22 (Sino-nasal Outcome Test)
The SNOT-22 consists of 22 items, each rated from 0 (no problem at all) to 5 (worst possible symptom). SNOT-22 total scores range from 0 to 110, with higher SNOT-22 total scores indicating worse symptoms. Reported as the change from baseline to six months.
Time frame: Baseline, 1, 3 and 6 months
Population: Participants with data collected at both timepoints.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Erenumab | Change in SNOT-22 (Sino-nasal Outcome Test) | -10.1 score on a scale | Standard Deviation 13.8 |
| Placebo | Change in SNOT-22 (Sino-nasal Outcome Test) | -23.3 score on a scale | Standard Deviation 25.2 |
p-value: 0.19ANOVA
Secondary
Change in Social Function as Measured by Migraine Function Impact Questionnaire (MFIQ)
The MFIQ is a 26-item self-report questionnaire, developed to measure the subjective impact of migraine on physical functioning (everyday activities and physical impairment), as well as social and emotional functioning in the past seven days. The MFIQ Social Function subscale is scored on a scale of 0-100, with higher scores indicating a greater impact. Reported as the change from baseline to six months.
Time frame: Baseline, 1, 3 and 6 months
Population: Participants with data collected at both timepoints.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Erenumab | Change in Social Function as Measured by Migraine Function Impact Questionnaire (MFIQ) | -1.0 score on a scale | Standard Deviation 3.6 |
| Placebo | Change in Social Function as Measured by Migraine Function Impact Questionnaire (MFIQ) | 5.7 score on a scale | Standard Deviation 13 |
p-value: 0.058ANOVA
Secondary
Change in Usual Activities as Measured by Migraine Functional Impact Questionnaire (MFIQ)
The MFIQ is a 26-item self-report questionnaire, developed to measure the subjective impact of migraine on physical functioning (everyday activities and physical impairment), as well as social and emotional functioning in the past seven days. The MFIQ usual activities subscale is scored on a scale of 0-100, with higher scores indicating a greater impact. Reported as the change from baseline to six months.
Time frame: Baseline, 1, 3 and 6 months
Population: Participants with data collected at both timepoints.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Erenumab | Change in Usual Activities as Measured by Migraine Functional Impact Questionnaire (MFIQ) | -2.1 score on a scale | Standard Deviation 4.4 |
| Placebo | Change in Usual Activities as Measured by Migraine Functional Impact Questionnaire (MFIQ) | -10.9 score on a scale | Standard Deviation 9.6 |
p-value: 0.08Wilcoxon (Mann-Whitney)