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Low enrollment rate
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| Name | Class |
|---|---|
| Amgen | INDUSTRY |
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Evaluate erenumab- aooe efficacy as a therapeutic approach, for the management of painful chronic temporomandibular disorders (TMD).
The study will be a randomized, double blind, placebo-controlled trial comparing erenumab-aooe vs Placebo.
A total of 60 patients (30 per each arm) aged 18-65 years old of either sex, and any race or ethnicity presenting chronic temporomandibular disorders (TMD), (meeting the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) for Clinical and Research Applications of chronic TMD (myalgia +/- arthralgia) will be randomly assigned in a 1:1 parallel, double-blind clinical trial, to receive either erenumab-aooe or placebo. Participants will attend 6 clinic visits (Visit 0-Visit 5) over a period of 21 weeks (20 +/- 1 weeks). Changes in pain intensity and other pain outcomes related to TMD will be assessed. Blood samples will be collected, and participants will need to keep a daily symptom diary and answer some other questionnaires.
Chronic TMD is a considerable burden and affects significantly the quality of life of the sufferer. For some patients, TMD has a tendency to remit or improve pain symptomatology over time but for others, TMD have the potential to become chronic and to lead to persistent dysfunction.
Different classes of medications from anti-inflammatories, muscle relaxants, anxiolytics, antidepressants, anticonvulsants and a β-blocker have indicated to be beneficial for some patients as well as in clinical studies, but tolerability and side effects may be present for some patients. Furthermore, the indications of these drugs are for other disorders, so it is unclear their mechanism of action in TMD pathophysiology. Currently there is no medication specifically indicated for the management of TMD based on its molecular pathophysiology. However, there is evidence showing that CGRP has a role in TMD pathophysiology. CGRP is a key molecule in migraine pathophysiology. Erenumab-aooe is the first antibody therapeutic targeting the CGRP and has shown efficacy, to be well tolerated and with a safety profile similar to placebo for the prevention of migraine. The scientific premise for this study is that inhibiting CGRP in chronic TMD will decrease pain, pain related outcomes and improve TMJ biomechanics (function) in a safe and well tolerated manner for this patient population.
Potential participants will be pre-screened at the Brotman Facial Pain clinic and the Oral and Maxillofacial Surgery Clinic both at the University of Maryland, School of Dentistry or by telephone; those willing to participate will be scheduled for a screening and baseline visit (Visit 0). During this visit potential participants will be evaluated for eligibility (meeting the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) for Clinical and Research Applications) of chronic TMD (myalgia +/- arthralgia) and written informed consent will be obtained.
The screening and baseline procedures include medical history review, clinical examinations, tests and administration of questionnaires. After screening, eligible participants will start Visit 0/Day 0 which is the start of the baseline period with a duration of 28 days/4 weeks. Instructions will be given for the completion of a Daily Symptom Diary (DSD) and other questionnaires at home or online. Participants who show 80% compliance with the DSD and who meet the pain score (inclusion criteria) during the baseline period, will be randomly assigned to one of two groups either the investigational drug or placebo and will be scheduled for Visit 1. Visit 1 can occur within 7 days/1 week after the baseline period (+/- 7 days).
The study drug is erenumab-aooe 70mg, SC injection. Participants will attend 6 clinic visits (Visit 0-Visit 5) over a period of 21 weeks (20 +/- 1 weeks) or 140 +/- 7 days. After randomization and on Visit 1 (Week 4/Day 28), the participant will receive the drug or placebo. This same treatment will be administered once a month for 3 months (3 cycles/12 weeks). It will be administered on Visit 1/Day 28/Week 4; Visit 2/Day 56/Week 8; and Visit 3/Day 84/week 12. On Visit 0 (baseline) and on Visit 1, Visit 2, Visit 3, Visit 4/Day 112/Week 16 and visit 5/Day 140/Week 20, visits will include review of compliance with inclusion criteria, medical history review, review and collection of any adverse event, clinical examinations, questionnaires, tests, blood sample collection on Baseline/Visit 0 and Visit 4; and instruction to complete the DSD and questionnaires.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Erenumab-aooe | Active Comparator | Erenumab-aooe 70 mg/ml. Subcutaneous injection. Administered once every 4 weeks/28 days at visit 1, visit 2 and visit 3 for a total of 3 cycles. Other Name: Aimovig® |
|
| Placebo | Placebo Comparator | Placebo. Subcutaneous injection.Administered once every 4 weeks/28 days at visit 1, visit 2 and visit 3 for a total of 3 cycles. Other name: Placebo |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Erenumab-Aooe 70 MG in 1 mL Prefilled Syringe | Drug | Administered once every 4 weeks/28 days at visit 1, visit 2 and visit 3 for a total of 3 cycles. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change of >= 30% Reduction in the Monthly Average Pain Score From Baseline to Visit 4, Compared to Placebo. | Assessment of the efficacy of erenumab-aooe in the proportion of participants that achieve >=30% reduction (Yes/no) in monthly average pain score from baseline to Visit 4 (the end of last monthly treatment cycle), compared to placebo. The daily pain intensity score will be measured on a 0-100 numeric rating scale (NRS) and reported in the Daily Symptom Diary (DSD). The monthly mean pain intensity score will be determined from baseline, Visit 1/Day 28/Week 4, Visit 2/Day 56/Week 8, Visit 3/Day 84/week 12 and Visit 4/Day 112/Week 16. | From Visit 0 (Baseline phase/study day 0) to Visit 4 (study day 112) |
| Measure | Description | Time Frame |
|---|---|---|
| Change of >= 50% Reduction in Monthly TMD Pain Days, Compared to Placebo. | Assessment of the efficacy of erenumab-aooe in the proportion of participants with at least a 50% reduction (Yes/No) in monthly TMD days from baseline to Visit 5 (follow up/final visit). Definition of TMD pain day: A TMD pain day was any calendar day in which the participant experienced pain, stiffness, soreness, tenderness, in the jaw or temple area or either side being brief or continuous; and/or pain with TMJ biomechanics (chewing, mouth opening or any jaw movement; and/or pain with jaw activities (yawning, kissing, talking); and/or pain with jaw habits (chewing gum, clenching, grinding). |
| Measure | Description | Time Frame |
|---|---|---|
| Change of Pro-inflammatory and Anti-inflammatory Cytokine Profiles (Th1/Th2) When Compared to Placebo. | Blood samples will be evaluated for the presence of proinflammatory and anti-inflammatory cytokines. | Visit 0 (Baseline/study day 0) and Visit 4/Week 16 (study day 112) |
Inclusion Criteria:
In order to be eligible to participate in this study, an individual must meet all of the following criteria:
Provide signed and dated informed consent form
Is between 18 and 65 years of age (inclusive; male or female and any race or ethnicity)
Meets diagnostic criteria for TMD: Myalgia with or without arthralgia
• The participant must meet 2 criteria relating: 1) reported pain, ache or tenderness in the face, jaw/mandible, pre-auricular area, inside the ear or temple that it is modified by TMJ biomechanics. 2) finding(s) of TMD myalgia according to the classification DC/TMD criteria.
Has experienced facial pain and/or pain with TMJ biomechanics for the last 3 months episodically or unremitting
Has experienced facial pain for at least 10 days of the last 30 days prior to Baseline Visit (Visit 0)
Prior to randomization, has been compliant 80% with the entries in the Daily Symptom Diary within the baseline period and reported an average pain level ≥30 on a numerical rating scale (0-100) in the DSD, or has experienced a pain level ≥30 on the same scale for at least 3 days in the week prior to Visit 1.
If taking a prescription medication daily for the management of pain (taken for at least 30 days before baseline), agrees to continue the daily use of the medication throughout the study at the same dosage.
If taking prescription medication, opioid medication or OTC medications as needed or episodically for the management of TMD pain agrees to discontinue its use prior to the Screening and Baseline Visit.
If taking OTC pain medications daily agrees to continue its daily use at the same dosage throughout the study.
• If a participant is taking an over-the-counter medication daily for management of other type of pain or for prophylaxis of myocardial infarction or stroke, the participant will be encouraged to continue the same usage of that medication throughout the study.
Agrees to not start any new prescription medication for the management of pain throughout the study
Agrees to not start any injection therapy for the management of TMD (trigger point injections, steroid injections, Botox) during the course of the study
Agrees to not use acupuncture for the management of pain during the course of the study
Agrees to not have Physical therapy for the management of TMD during the course of the study.
Agrees to not start intraoral appliance therapy during the course of the study. If the patient has used a nightguard for more than one month before the study, agrees to continue use it only at night.
Females of childbearing potential agree to use one of the following methods of contraception throughout the study: licensed hormonal method, intrauterine device, female or male condoms with contraceptive foam, abstinence, bilateral tubal ligation/occlusion, or vasectomy in partner (if postmenopausal, must not have menstruated for at least 12 consecutive months)
Willing and able to understand and comply with all study procedures and be available for the duration of the study
Exclusion Criteria:
Participants with a history of congestive heart failure, rheumatoid arthritis or uncontrolled diabetes.
Participants with serious hepatic, respiratory, hematologic or immunologic illnesses, an unstable cardiovascular disease, or any other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with trial participation or Erenumab or may interfere with the interpretation of trial results and, in the judgment of the investigator, would make the participant inappropriate for entry into this trial
Participants with high blood pressure, history of abnormal electrocardiograms, history of heart conductance defects, malignant disease, chronic constipation, IBSc or any other severe acute or chronic medical or psychiatric condition or laboratory finding that may increase the risk associated with trial participation with Erenumab
Participants with active malignancy of any type or a history a malignancy (with exception of participants with malignancy surgically removed with no evidence of recurrence within 5 years before enrollment.
History of facial trauma or orofacial or orthognathic surgery within the previous 6 months
Patients with dental pain
Patients with trigeminal neuralgia or other neuropathic pain in the craniofacial area
Patients with degenerative joint disease in the TMJs, rheumatoid arthritis or any systemic arthritis
Patients with chronic migraine with and w/o aura following the ICHD-3 criteria treated or not treated with medication
• Without excluding headache attributed to TMD
Participants currently taking or have previously taken Erenumab or other CGRP monoclonal antibody (mAmb) or currently taking a CGRP-Receptor antagonist (gepants) for migraine prevention. CGRP-Receptor antagonist (gepants) for acute use for migraine are allowed.
Patients with hypersensitivity to Erenumab
Patients who have received the Botox injection protocol in the masseters and/or Migraine protocol within 3 months prior screening and baseline visit.
Used injections for management of TMD (trigger point injections, steroid injections) within 2 weeks prior to the Screening and Baseline Visit
Has commenced a new daily prescription medication for the management of pain within 30 days prior to the Screening and Baseline Visit
Has commenced intraoral appliance therapy for the management of facial pain within 30 days prior to the Screening and Baseline Visit
Patient currently undergoing active orthodontic treatment (passive retainers are permitted)
Treatment for drug or alcohol abuse within the last year
Has been treated with another investigational drug or treatment within 30 days prior to the Screening and Baseline Visit
Patients sensitive to Latex
Patient is pregnant, planning to become pregnant or breastfeeding
Anything that, in the opinion of the investigator, would place the participant at increased risk or impede the participant's full compliance with or completion of the study.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Maryland, School of Dentistry, Brotman Facial Pain Clinic | Baltimore | Maryland | 21201 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24591846 | Background | Romero-Reyes M, Uyanik JM. Orofacial pain management: current perspectives. J Pain Res. 2014 Feb 21;7:99-115. doi: 10.2147/JPR.S37593. eCollection 2014. | |
| 21855814 | Background | Dworkin SF. Temporomandibular disorder (TMD) pain-related disability found related to depression, nonspecific physical symptoms, and pain duration at 3 international sites. J Evid Based Dent Pract. 2011 Sep;11(3):143-4. doi: 10.1016/j.jebdp.2011.06.002. No abstract available. |
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1 completed study; 1 withdrawn/dis-enrolled from study after visit 1 due to side effect (constipation); 1 dis-enrolled due to ineligibility in not meeting anymore inclusion criteria in visit 1. 1 dis-enrolled short after consent/enrollment due to medical history update; 1 dis-enrolled due to changes in medical history in visit 1.
3 participants completed only baseline phase. Baseline period consisted of 28 days/ 4 weeks prior randomization. Only two participants were assigned to arm/group.
Subjects recruited and pre-screened at the Brotman Facial Pain clinic, University of Maryland, School of Dentistry.
Enrollment period: 05/26/2022 to 08/02/2022 Total number of subjects prescreened: 20
April 1st, 2022 was the estimated study start date. 05/26/2022 was the date of the first participant enrolled.
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| ID | Title | Description |
|---|---|---|
| FG000 | Erenumab-aooe | Erenumab-aooe 70 mg/ml. Subcutaneous injection. Administered once every 4 weeks/28 days at visit 1, visit 2 and visit 3 for a total of 3 cycles. Other Name: Aimovig® Erenumab-Aooe 70 MG in 1 mL Prefilled Syringe: Administered once every 4 weeks/28 days at visit 1, visit 2 and visit 3 for a total of 3 cycles. |
| FG001 | Placebo | Placebo. Subcutaneous injection.Administered once every 4 weeks/28 days at visit 1, visit 2 and visit 3 for a total of 3 cycles. Other name: Placebo Placebo: Administered once every 4 weeks/28 days at visit 1, visit 2 and visit 3 for a total of 3 cycles. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Enrollees who completed baseline period and randomization
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| ID | Title | Description |
|---|---|---|
| BG000 | Erenumab-aooe | Erenumab-aooe 70 mg/ml. Subcutaneous injection. Administered once every 4 weeks/28 days at visit 1, visit 2 and visit 3 for a total of 3 cycles. Other Name: Aimovig® Erenumab-Aooe 70 MG in 1 mL Prefilled Syringe: Administered once every 4 weeks/28 days at visit 1, visit 2 and visit 3 for a total of 3 cycles. |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change of >= 30% Reduction in the Monthly Average Pain Score From Baseline to Visit 4, Compared to Placebo. | Assessment of the efficacy of erenumab-aooe in the proportion of participants that achieve >=30% reduction (Yes/no) in monthly average pain score from baseline to Visit 4 (the end of last monthly treatment cycle), compared to placebo. The daily pain intensity score will be measured on a 0-100 numeric rating scale (NRS) and reported in the Daily Symptom Diary (DSD). The monthly mean pain intensity score will be determined from baseline, Visit 1/Day 28/Week 4, Visit 2/Day 56/Week 8, Visit 3/Day 84/week 12 and Visit 4/Day 112/Week 16. | Only one subject randomly blinded assigned to placebo completed the study. Data were not collected to report. | Posted | From Visit 0 (Baseline phase/study day 0) to Visit 4 (study day 112) |
|
From the first dose of study drug/placebo up to 4 weeks after the last dose (a total of 16 weeks).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Erenumab-aooe | Erenumab-aooe 70 mg/ml. Subcutaneous injection. Administered once every 4 weeks/28 days at visit 1, visit 2 and visit 3 for a total of 3 cycles. Other Name: Aimovig® Erenumab-Aooe 70 MG in 1 mL Prefilled Syringe: Administered once every 4 weeks/28 days at visit 1, visit 2 and visit 3 for a total of 3 cycles. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Other | Gastrointestinal disorders | Systematic Assessment | Constipation |
Early termination due to low enrollment rate.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Marcela Romero Reyes | University of Maryland, School of Dentistry | 4107067168 | mromero@umaryland.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jan 16, 2024 | Mar 4, 2024 | Prot_SAP_001.pdf |
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| ID | Term |
|---|---|
| D013705 | Temporomandibular Joint Disorders |
| D017271 | Craniomandibular Disorders |
| D013706 | Temporomandibular Joint Dysfunction Syndrome |
| D009209 | Myofascial Pain Syndromes |
| D009057 | Stomatognathic Diseases |
| D009140 | Musculoskeletal Diseases |
| ID | Term |
|---|---|
| D008336 | Mandibular Diseases |
| D007571 | Jaw Diseases |
| D007592 | Joint Diseases |
| D009135 | Muscular Diseases |
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| ID | Term |
|---|---|
| C000605816 | erenumab |
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| Placebo | Drug | Administered once every 4 weeks/28 days at visit 1, visit 2 and visit 3 for a total of 3 cycles. |
|
| From Visit 0 (Baseline phase/study day 0) to Visit 5 (study day 140 +/- 7) |
| Change of >= 30% Reduction in the Monthly Average Pain Score Compared to Placebo From Baseline to Visit 5. | Assessment of the efficacy of erenumab-aooe in the proportion of participants who achieved a least 30% reduction in the monthly average daily pain score from baseline to Visit 5 (follow up and final study visit). The monthly mean pain intensity score will be determined from baseline, Visit 1/Day 28/Week 4, Visit 2/Day 56/Week 8, Visit 3/Day 84/week 12, Visit 4/Day 112/Week 16 and Visit 5/Day 140/Week 20. | From Visit 0 (Baseline phase/study day 0) to Visit 5 (Study day 140 +/- 7) |
| Change in Pressure Pain Threshold (PPT) Measurement in Muscles of Mastication (Temporalis Muscle) Compared to Placebo From Baseline to Visit 5. | Assessments of pressure stimuli will be performed in the temporalis muscle and averaged to obtain a single pressure pain threshold value (kPa) per site. This assessment will be performed bilaterally in each temporalis muscle. A higher value means a better outcome. | Visit 0 (baseline/study day 0) to Visit 5/Week 20 (Study day 140 +/- 7) |
| Change in Pressure Pain Threshold (PPT) Measurement in Muscles of Mastication (Masseter Muscle) Compared to Placebo From Baseline to Visit 5. | Assessments of pressure stimuli will be performed in the masseter muscle and averaged to obtain a single pressure pain threshold value (kPa) per site. This assessment will be performed bilaterally in each masseter muscle. A higher PPT value means a better outcome. | Visit 0 (baseline/study day 0) to Visit 5/Week 20 (Study day 140 +/- 7) |
| Change in Pressure Pain Threshold (PPT) Measurement in Upper Trapezius Muscle Compared to Placebo From Baseline to Visit 5. | Assessments of pressure stimuli will be performed in the upper trapezius muscle and averaged to obtain a single pressure pain threshold value (kPa) per site (R/L side). This assessment will be performed bilaterally. A higher PPT value means a better outcome. | Visit 0 (baseline/study day 0) to Visit 5/Week 20 (Study day 140 +/- 7) |
| Change in Pressure Pain Threshold (PPT) Measurement in the Temporomandibular Joint (TMJ) Compared to Placebo From Baseline to Visit 5. | Assessments of pressure stimuli will be performed in the TMJ and averaged to obtain a single pressure pain threshold value (kPa) per site. This assessment will be performed bilaterally. A higher PPT value means a better outcome. | Visit 0 (baseline/study day 0) to Visit 5/Week 20 (Study day 140 +/- 7) |
| Change in Pressure Pain Threshold (PPT) Measurement at the Lateral Epicondyle Compared to Placebo From Baseline to Visit 5. | Assessments of pressure stimuli will be applied bilaterally in the right and left lateral epicondyles and averaged to obtain a single pressure pain threshold value (kPa) per site. A higher PPT value means a better outcome. | Visit 0 (baseline/study day 0) to Visit 5/Week 20 (Study day 140 +/- 7) |
| Change in Maximum Unassisted Jaw Opening During Erenumab-aooe Treatment, After Treatment and Compared to Placebo. | Measured during TMD examination. A higher value means a better outcome | Visit 0 (baseline/study day 0) to Visit 5/Week 20 (Study day 140 +/- 7) |
| Change in Maximum Pain Free Opening During Erenumab-aooe Treatment, After Treatment and Compared to Placebo. | Measured during TMD examination. A higher value means a better outcome | Visit 0 (baseline/study day 0) to Visit 5/week 20 (Study day 140 +/- 7) |
| Change in Maximum Assisted/Active Opening During Erenumab-aooe Treatment, After Treatment and Compared to Placebo. | Measured during TMD examination. A higher value means a better outcome | Visit 0 (baseline/study day 0) to Visit 5/Week 20 (Study day 140 +/- 7) |
| Change in the Jaw Functional Limitation Scale (JFLS) Global Score During Erenumab-aooe Treatment, After Treatment and Compared to Placebo. | The JFLS is a 20-item instrument that measures limitations across 3 domains related to TMJ biomechanics: masticatory function, jaw opening (vertical mobility), and verbal and emotional expression. A degree of limitation is rated on a 0-10 scale from 0 ("no limitation") to 10 ("severe limitation") | Visit 0 (baseline/study day 0) to Visit 5/Week 20 (Study day 140 +/- 7) |
| Change in the Frequency of Oral Behaviors Evaluated by the Oral Behaviors Checklist (OBC) During Erenumab-aooe Treatment, After Treatment and Compared to Placebo. | The Oral Behaviors Checklist (OBC) evaluates parafunctional behaviors and generates a single scale representing the frequency of 21 activities such as clenching, chewing gum, and holding objects between teeth, yawning. | Visit 0 (baseline/study day 0) to Visit 5/Week 20 (Study day 140 +/- 7) |
| Change in Graded Chronic Pain Scale (GCPS) Outcomes During Erenumab-aooe Treatment, After Treatment and Compared to Placebo. | The GCPS includes 7 items and assesses 2 dimensions of pain, pain intensity and pain-related disability. A higher grade means a worse outcome. | Visit 0 (baseline/study day 0) to Visit 5/Week 20 (Study day 140 +/- 7) |
| Change in Impression of Overall Status Measured by the Patient Global Impression of Change (PGIC) During Erenumab-aooe Treatment, After Treatment and Compared to Placebo. | The PGIC measures change in participant's overall status on a scale ranging from 1 (very much improved) to 7 (very much worse). | Visit 0 (baseline/study day 0) to Visit 5/Week 20 (Study day 140 +/- 7) |
| Change in the Hospital Anxiety and Depression Scale (HADS). Anxiety and Depression Score Change During Erenumab-aooe Treatment, After Treatment and Compared to Placebo. | The HADS evaluates anxiety (7 items) and depression (7 items) with a 14-item instrument assessing symptoms on a 4-point scale rated from 0 "not at all" to 3 "very often indeed". Responses provide separate scores for anxiety and depression. A higher score means a worse outcome. | Visit 0 (baseline/study day 0) to Visit 5/Week 20 (Study day 140 +/- 7) |
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| 32259079 | Background | King CT, Gegg CV, Hu SN, Sen Lu H, Chan BM, Berry KA, Brankow DW, Boone TJ, Kezunovic N, Kelley MR, Shi L, Xu C. Discovery of the Migraine Prevention Therapeutic Aimovig (Erenumab), the First FDA-Approved Antibody against a G-Protein-Coupled Receptor. ACS Pharmacol Transl Sci. 2019 Sep 3;2(6):485-490. doi: 10.1021/acsptsci.9b00061. eCollection 2019 Dec 13. |
| 19751369 | Background | Goncalves DA, Bigal ME, Jales LC, Camparis CM, Speciali JG. Headache and symptoms of temporomandibular disorder: an epidemiological study. Headache. 2010 Feb;50(2):231-41. doi: 10.1111/j.1526-4610.2009.01511.x. Epub 2009 Sep 14. |
| 19704086 | Background | Goncalves DA, Speciali JG, Jales LC, Camparis CM, Bigal ME. Temporomandibular symptoms, migraine, and chronic daily headaches in the population. Neurology. 2009 Aug 25;73(8):645-6. doi: 10.1212/WNL.0b013e3181b389c2. No abstract available. |
| 32929719 | Background | Akerman S, Romero-Reyes M. Preclinical studies investigating the neural mechanisms involved in the co-morbidity of migraine and temporomandibular disorders: the role of CGRP. Br J Pharmacol. 2020 Dec;177(24):5555-5568. doi: 10.1111/bph.15263. Epub 2020 Oct 21. |
| 22145886 | Background | Cady RJ, Glenn JR, Smith KM, Durham PL. Calcitonin gene-related peptide promotes cellular changes in trigeminal neurons and glia implicated in peripheral and central sensitization. Mol Pain. 2011 Dec 6;7:94. doi: 10.1186/1744-8069-7-94. |
| 25981890 | Background | Romero-Reyes M, Pardi V, Akerman S. A potent and selective calcitonin gene-related peptide (CGRP) receptor antagonist, MK-8825, inhibits responses to nociceptive trigeminal activation: Role of CGRP in orofacial pain. Exp Neurol. 2015 Sep;271:95-103. doi: 10.1016/j.expneurol.2015.05.005. Epub 2015 May 14. |
| 28460892 | Background | Tepper S, Ashina M, Reuter U, Brandes JL, Dolezil D, Silberstein S, Winner P, Leonardi D, Mikol D, Lenz R. Safety and efficacy of erenumab for preventive treatment of chronic migraine: a randomised, double-blind, placebo-controlled phase 2 trial. Lancet Neurol. 2017 Jun;16(6):425-434. doi: 10.1016/S1474-4422(17)30083-2. Epub 2017 Apr 28. |
| 30793254 | Background | Lattanzi S, Brigo F, Trinka E, Vernieri F, Corradetti T, Dobran M, Silvestrini M. Erenumab for Preventive Treatment of Migraine: A Systematic Review and Meta-Analysis of Efficacy and Safety. Drugs. 2019 Mar;79(4):417-431. doi: 10.1007/s40265-019-01069-1. |
| 29984601 | Background | Ashina M, Tepper S, Brandes JL, Reuter U, Boudreau G, Dolezil D, Cheng S, Zhang F, Lenz R, Klatt J, Mikol DD. Efficacy and safety of erenumab (AMG334) in chronic migraine patients with prior preventive treatment failure: A subgroup analysis of a randomized, double-blind, placebo-controlled study. Cephalalgia. 2018 Sep;38(10):1611-1621. doi: 10.1177/0333102418788347. Epub 2018 Jul 8. |
| 30360965 | Background | Reuter U, Goadsby PJ, Lanteri-Minet M, Wen S, Hours-Zesiger P, Ferrari MD, Klatt J. Efficacy and tolerability of erenumab in patients with episodic migraine in whom two-to-four previous preventive treatments were unsuccessful: a randomised, double-blind, placebo-controlled, phase 3b study. Lancet. 2018 Nov 24;392(10161):2280-2287. doi: 10.1016/S0140-6736(18)32534-0. Epub 2018 Oct 22. |
| 32493206 | Background | Ashina H, Iljazi A, Al-Khazali HM, Eigenbrodt AK, Larsen EL, Andersen AM, Hansen KJ, Brauner KB, Morch-Jessen T, Chaudhry B, Antic S, Christensen CE, Ashina M, Amin FM, Schytz HW. Efficacy, tolerability, and safety of erenumab for the preventive treatment of persistent post-traumatic headache attributed to mild traumatic brain injury: an open-label study. J Headache Pain. 2020 Jun 3;21(1):62. doi: 10.1186/s10194-020-01136-z. |
| 24275219 | Background | Slade GD, Fillingim RB, Sanders AE, Bair E, Greenspan JD, Ohrbach R, Dubner R, Diatchenko L, Smith SB, Knott C, Maixner W. Summary of findings from the OPPERA prospective cohort study of incidence of first-onset temporomandibular disorder: implications and future directions. J Pain. 2013 Dec;14(12 Suppl):T116-24. doi: 10.1016/j.jpain.2013.09.010. |
| 2594394 | Background | Ohrbach R, Gale EN. Pressure pain thresholds, clinical assessment, and differential diagnosis: reliability and validity in patients with myogenic pain. Pain. 1989 Nov;39(2):157-169. doi: 10.1016/0304-3959(89)90003-1. |
| 18474055 | Background | Ohrbach R, Granger C, List T, Dworkin S. Preliminary development and validation of the Jaw Functional Limitation Scale. Community Dent Oral Epidemiol. 2008 Jun;36(3):228-36. doi: 10.1111/j.1600-0528.2007.00397.x. |
| 18780535 | Background | Ohrbach R, Larsson P, List T. The jaw functional limitation scale: development, reliability, and validity of 8-item and 20-item versions. J Orofac Pain. 2008 Summer;22(3):219-30. |
| 17190029 | Background | Markiewicz MR, Ohrbach R, McCall WD Jr. Oral behaviors checklist: reliability of performance in targeted waking-state behaviors. J Orofac Pain. 2006 Fall;20(4):306-16. |
| 20701668 | Background | Ohrbach R. Assessment and further development of RDC/TMD Axis II biobehavioural instruments: a research programme progress report. J Oral Rehabil. 2010 Oct;37(10):784-98. doi: 10.1111/j.1365-2842.2010.02144.x. Epub 2010 Aug 4. |
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| 6880820 | Background | Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand. 1983 Jun;67(6):361-70. doi: 10.1111/j.1600-0447.1983.tb09716.x. |
| Placebo |
Placebo. Subcutaneous injection.Administered once every 4 weeks/28 days at visit 1, visit 2 and visit 3 for a total of 3 cycles. Other name: Placebo Placebo: Administered once every 4 weeks/28 days at visit 1, visit 2 and visit 3 for a total of 3 cycles. |
| BG002 | Total | Total of all reporting groups |
| Participants |
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| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| OG001 | Placebo | Placebo. Subcutaneous injection.Administered once every 4 weeks/28 days at visit 1, visit 2 and visit 3 for a total of 3 cycles. Other name: Placebo Placebo: Administered once every 4 weeks/28 days at visit 1, visit 2 and visit 3 for a total of 3 cycles. Study terminated early-no outcome data available to analyze outcome measures to assess efficacy of study drug versus placebo. Only one subject randomly blinded assigned to placebo completed the study. |
|
| Secondary | Change of >= 50% Reduction in Monthly TMD Pain Days, Compared to Placebo. | Assessment of the efficacy of erenumab-aooe in the proportion of participants with at least a 50% reduction (Yes/No) in monthly TMD days from baseline to Visit 5 (follow up/final visit). Definition of TMD pain day: A TMD pain day was any calendar day in which the participant experienced pain, stiffness, soreness, tenderness, in the jaw or temple area or either side being brief or continuous; and/or pain with TMJ biomechanics (chewing, mouth opening or any jaw movement; and/or pain with jaw activities (yawning, kissing, talking); and/or pain with jaw habits (chewing gum, clenching, grinding). | Only one subject randomly blinded assigned to placebo completed the study. Data were not collected to report. | Posted | From Visit 0 (Baseline phase/study day 0) to Visit 5 (study day 140 +/- 7) |
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| Secondary | Change of >= 30% Reduction in the Monthly Average Pain Score Compared to Placebo From Baseline to Visit 5. | Assessment of the efficacy of erenumab-aooe in the proportion of participants who achieved a least 30% reduction in the monthly average daily pain score from baseline to Visit 5 (follow up and final study visit). The monthly mean pain intensity score will be determined from baseline, Visit 1/Day 28/Week 4, Visit 2/Day 56/Week 8, Visit 3/Day 84/week 12, Visit 4/Day 112/Week 16 and Visit 5/Day 140/Week 20. | Only one subject randomly blinded assigned to placebo completed the study. Data were not collected to report. | Posted | From Visit 0 (Baseline phase/study day 0) to Visit 5 (Study day 140 +/- 7) |
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| Secondary | Change in Pressure Pain Threshold (PPT) Measurement in Muscles of Mastication (Temporalis Muscle) Compared to Placebo From Baseline to Visit 5. | Assessments of pressure stimuli will be performed in the temporalis muscle and averaged to obtain a single pressure pain threshold value (kPa) per site. This assessment will be performed bilaterally in each temporalis muscle. A higher value means a better outcome. | Only one subject randomly blinded assigned to placebo completed the study. Data were not collected to report. | Posted | Visit 0 (baseline/study day 0) to Visit 5/Week 20 (Study day 140 +/- 7) |
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| Secondary | Change in Pressure Pain Threshold (PPT) Measurement in Muscles of Mastication (Masseter Muscle) Compared to Placebo From Baseline to Visit 5. | Assessments of pressure stimuli will be performed in the masseter muscle and averaged to obtain a single pressure pain threshold value (kPa) per site. This assessment will be performed bilaterally in each masseter muscle. A higher PPT value means a better outcome. | Only one subject randomly blinded assigned to placebo completed the study. Data were not collected to report. | Posted | Visit 0 (baseline/study day 0) to Visit 5/Week 20 (Study day 140 +/- 7) |
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| Secondary | Change in Pressure Pain Threshold (PPT) Measurement in Upper Trapezius Muscle Compared to Placebo From Baseline to Visit 5. | Assessments of pressure stimuli will be performed in the upper trapezius muscle and averaged to obtain a single pressure pain threshold value (kPa) per site (R/L side). This assessment will be performed bilaterally. A higher PPT value means a better outcome. | Only one subject randomly blinded assigned to placebo completed the study. Data were not collected to report. | Posted | Visit 0 (baseline/study day 0) to Visit 5/Week 20 (Study day 140 +/- 7) |
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| Secondary | Change in Pressure Pain Threshold (PPT) Measurement in the Temporomandibular Joint (TMJ) Compared to Placebo From Baseline to Visit 5. | Assessments of pressure stimuli will be performed in the TMJ and averaged to obtain a single pressure pain threshold value (kPa) per site. This assessment will be performed bilaterally. A higher PPT value means a better outcome. | Only one subject randomly blinded assigned to placebo completed the study. Data were not collected to report. | Posted | Visit 0 (baseline/study day 0) to Visit 5/Week 20 (Study day 140 +/- 7) |
|
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| Secondary | Change in Pressure Pain Threshold (PPT) Measurement at the Lateral Epicondyle Compared to Placebo From Baseline to Visit 5. | Assessments of pressure stimuli will be applied bilaterally in the right and left lateral epicondyles and averaged to obtain a single pressure pain threshold value (kPa) per site. A higher PPT value means a better outcome. | Only one subject randomly blinded assigned to placebo completed the study. Data were not collected to report. | Posted | Visit 0 (baseline/study day 0) to Visit 5/Week 20 (Study day 140 +/- 7) |
|
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| Secondary | Change in Maximum Unassisted Jaw Opening During Erenumab-aooe Treatment, After Treatment and Compared to Placebo. | Measured during TMD examination. A higher value means a better outcome | Only one subject randomly blinded assigned to placebo completed the study. Data were not collected to report. | Posted | Visit 0 (baseline/study day 0) to Visit 5/Week 20 (Study day 140 +/- 7) |
|
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| Secondary | Change in Maximum Pain Free Opening During Erenumab-aooe Treatment, After Treatment and Compared to Placebo. | Measured during TMD examination. A higher value means a better outcome | Only one subject randomly blinded assigned to placebo completed the study. Data were not collected to report. | Posted | Visit 0 (baseline/study day 0) to Visit 5/week 20 (Study day 140 +/- 7) |
|
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| Secondary | Change in Maximum Assisted/Active Opening During Erenumab-aooe Treatment, After Treatment and Compared to Placebo. | Measured during TMD examination. A higher value means a better outcome | Only one subject randomly blinded assigned to placebo completed the study. Data were not collected to report. | Posted | Visit 0 (baseline/study day 0) to Visit 5/Week 20 (Study day 140 +/- 7) |
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| Secondary | Change in the Jaw Functional Limitation Scale (JFLS) Global Score During Erenumab-aooe Treatment, After Treatment and Compared to Placebo. | The JFLS is a 20-item instrument that measures limitations across 3 domains related to TMJ biomechanics: masticatory function, jaw opening (vertical mobility), and verbal and emotional expression. A degree of limitation is rated on a 0-10 scale from 0 ("no limitation") to 10 ("severe limitation") | Only one subject randomly blinded assigned to placebo completed the study. Data were not collected to report. | Posted | Visit 0 (baseline/study day 0) to Visit 5/Week 20 (Study day 140 +/- 7) |
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| Secondary | Change in the Frequency of Oral Behaviors Evaluated by the Oral Behaviors Checklist (OBC) During Erenumab-aooe Treatment, After Treatment and Compared to Placebo. | The Oral Behaviors Checklist (OBC) evaluates parafunctional behaviors and generates a single scale representing the frequency of 21 activities such as clenching, chewing gum, and holding objects between teeth, yawning. | Only one subject randomly blinded assigned to placebo completed the study. Data were not collected to report. | Posted | Visit 0 (baseline/study day 0) to Visit 5/Week 20 (Study day 140 +/- 7) |
|
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| Secondary | Change in Graded Chronic Pain Scale (GCPS) Outcomes During Erenumab-aooe Treatment, After Treatment and Compared to Placebo. | The GCPS includes 7 items and assesses 2 dimensions of pain, pain intensity and pain-related disability. A higher grade means a worse outcome. | Only one subject randomly blinded assigned to placebo completed the study. Data were not collected to report. | Posted | Visit 0 (baseline/study day 0) to Visit 5/Week 20 (Study day 140 +/- 7) |
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| Secondary | Change in Impression of Overall Status Measured by the Patient Global Impression of Change (PGIC) During Erenumab-aooe Treatment, After Treatment and Compared to Placebo. | The PGIC measures change in participant's overall status on a scale ranging from 1 (very much improved) to 7 (very much worse). | Only one subject randomly blinded assigned to placebo completed the study. Data were not collected to report. | Posted | Visit 0 (baseline/study day 0) to Visit 5/Week 20 (Study day 140 +/- 7) |
|
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| Secondary | Change in the Hospital Anxiety and Depression Scale (HADS). Anxiety and Depression Score Change During Erenumab-aooe Treatment, After Treatment and Compared to Placebo. | The HADS evaluates anxiety (7 items) and depression (7 items) with a 14-item instrument assessing symptoms on a 4-point scale rated from 0 "not at all" to 3 "very often indeed". Responses provide separate scores for anxiety and depression. A higher score means a worse outcome. | Only one subject randomly blinded assigned to placebo completed the study. Data were not collected to report. | Posted | Visit 0 (baseline/study day 0) to Visit 5/Week 20 (Study day 140 +/- 7) |
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| Other Pre-specified | Change of Pro-inflammatory and Anti-inflammatory Cytokine Profiles (Th1/Th2) When Compared to Placebo. | Blood samples will be evaluated for the presence of proinflammatory and anti-inflammatory cytokines. | Only one subject randomly blinded assigned to placebo completed the study. Data were not collected to report. | Posted | Visit 0 (Baseline/study day 0) and Visit 4/Week 16 (study day 112) |
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| 0 |
| 1 |
| 0 |
| 1 |
| 1 |
| 1 |
| EG001 | Placebo | Placebo. Subcutaneous injection.Administered once every 4 weeks/28 days at visit 1, visit 2 and visit 3 for a total of 3 cycles. Other name: Placebo Placebo: Administered once every 4 weeks/28 days at visit 1, visit 2 and visit 3 for a total of 3 cycles. | 0 | 1 | 0 | 1 | 0 | 1 |
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