Safety and Efficacy of Erenumab-aooe in Patients With Temporomandibular Disorder

Study Overview
=================
Brief Summary
-----------------
The purpose of this proof of concept study is to evaluate the safety and efficacy of the off-label use of Aimovig® (EREN) in reducing Temporomandibular Disorder (TMD) pain compared to placebo.

Detailed Description
-----------------
This will be a 24-week, randomized, double-blinded, placebo-controlled, parallel group proof-of-concept study with two arms (active and placebo). The plan is to enroll 30 subjects. There will be a four-week screening period to identify subjects that meet the diagnostic criteria (DC/TMD) for myalgia, recommended by the International RDC/TMD Consortium Network and Orofacial Pain Special Interest Group. The Diagnostic Criteria for Temporomandibular Disorders Symptom Questionnaire and DC/TMD Examination Form will be used during Screening and Baseline visits to confirm the TMD diagnosis and determine whether subjects meet the inclusion/exclusion criteria. Subjects will attend a Screening visit followed by Baseline visit to randomize eligible subjects to active (EREN) or placebo (EREN-P). During the Baseline visit and Wks 4, 8, 12, and 16, subjects will receive treatment with either 140 mg of EREN or Placebo administered by subcutaneous injection. At Baseline and Wks 4, 8, 12, 16, 20, and 24 subjects will be instructed to complete the Brief Pain Inventory (BPI); PEG (Pain, Enjoyment, General Activity) Scale; pain mediation assessment; Patient Global Impression of Change (PGIC) (except for Baseline visit); Jaw Function Limitation Scale (JFLS); Patient Health Questionnaire (PHQ-4); and Somatic Symptom Scale (SSS-8). These visits will include review of continuance criteria and adverse event collection. At the Screening and Baseline visits the subjects will be instructed on how to use the PEG Scale and pain use assessment app, which will be downloaded on their smartphone, to provide a daily assessment of their pain intensity and interference with enjoyment and general activity (PEG) and their daily used of pain medications. Subjects who do not own a smartphone or are unwilling to use the app on a daily basis will only complete the PEG and pain medication assessment at the Baseline visit and all subsequent visits using the app onsite.

Official Title
-----------------
A Randomized, Double Blind, Placebo-Controlled Single Center Phase 2 Pilot Study to Assess the Safety and Efficacy of Off-label Subcutaneous Administration of Erenumab-aooe in Patients With Temporomandibular Disorder

Conditions
-----------------
Temporomandibular Disorder

Intervention / Treatment
-----------------
* Drug: Erenumab-aooe (EREN) 140 mg s.c. administered every four weeks for a total of five treatments
* Drug: Placebo (EREN-P) s.c. administered every four weeks for a total of five treatments


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects eligible for inclusion in the study must meet all of the following criteria: Signed the informed consent; Have pain-related TMD myalgia assessed by history and clinical examination as established by the DC/TMD; Age 18 years and younger than 60 years; Have a good knowledge of the English language; Able to understand and comply with the study requirements; Have had TMD myalgia for 6 months or longer; and If taking pain medications, the dose regimen must be stable for at least 4 weeks prior to the screening visit. Exclusion Criteria: Subjects meeting any of the following criteria are not eligible for inclusion: Lacking stable bilateral posterior occlusion; Currently uses a complete maxillary or mandibular prosthetic denture; Currently pregnant or plan to become pregnant; Breastfeeding or plan to breastfeed; Allergic to erenumab-aooe or any of the ingredients in Aimovig® (acetate, polysorbate 80, and sucrose); Allergic to rubber or latex; Currently undergoing TMD treatment elsewhere; Currently undergoing orthodontic treatment; Currently included in other experimental protocols within the last 30 days before enrollment; Having 11 or more headaches during the past 4 weeks; Having received massage, acupuncture or physical therapy treatment of the head, neck or shoulders during the previous 3 months; History of unstable or acute severe pain from another pain condition; History of traumatic brain injury; History of surgical treatment or recommended surgical treatment for TMD; History of ongoing, unresolved disability litigation; History of drug abuse; History of moderate to severe sleep apnea requiring CPAP or oral mandibular repositioning appliance; Anything that would place the subjects at increased risk or preclude the individual's full compliance with or completion of the study (e.g., medical condition, laboratory finding, physical exam finding logistical complication); and History of previously receiving erenumab-aooe or other anti-CGRP therapies, including anti-CGRP and anti-CGRP receptor monoclonal antibodies and small molecule CGRP receptor antagonists (gepants). History of chronic constipation and/or using medication associated with decreased gastrointestinal motility. History of hypertension or risk factors for hypertension.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 59 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm A<br>Arm A: erenumab-aooe (EREN) 140 mg s.c. administered every four weeks for a total of five treatments | Drug: Erenumab-aooe (EREN) 140 mg s.c. administered every four weeks for a total of five treatments<br>* Erenumab-aooe (EREN) 140 mg s.c. administered at baseline and weeks 4, 8, 12 and 16 for a total of five treatments<br>* Other names: Aimovig®;|
| Placebo Comparator: Arm B<br>Arm B: placebo (EREN-P) s.c. administered every four weeks for a total of five treatments | Drug: Placebo (EREN-P) s.c. administered every four weeks for a total of five treatments<br>* Placebo (EREN-P) s.c. administered at baseline and weeks 4, 8, 12 and 16 for a total of five treatments<br>* Other names: Placebo;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in mean between-group difference in pain using the Brief Pain Inventory | Assessment of the effects of Aimovig® (EREN) compared to placebo (EREN-P) based on the change in mean between-group difference in pain using the Brief Pain Inventory (BPI) 4-item pain severity/intensity scale: 0 (Better) - 10 (Worse). | From baseline visit through the week 20 visit. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in mean between-group difference in pain based on assessment of pain interference | Assessment of the effects of Aimovig® (EREN) compared to placebo (EREN-P) based on the change in mean between-group difference in pain interference scale: 0 (Better) - 10 (Worse). | From baseline visit through the week 20 visit and after 24 weeks (two months after the last treatment). | 
| Change in mean between-group difference in pain based on assessment of trajectory of pain improvement based on changes in daily reporting of pain | Assessment of the effects of Aimovig® (EREN) compared to placebo (EREN-P) based on the change in mean between-group difference in trajectory of pain improvement based on changes in daily reporting of pain scale: 0 (Better) - 10 (Worse). | From baseline visit through the week 20 visit and after 24 weeks (two months after the last treatment). | 
| Change in mean between-group difference in pain based on assessment of days of use of TMD pain specific medication | Assessment of the effects of Aimovig® (EREN) compared to placebo (EREN-P) based on the change in mean between-group difference in days of use of TMD pain specific medication (yes/no) | From baseline visit through the week 20 visit and after 24 weeks (two months after the last treatment). | 
| Change in mean between-group difference in pain based on assessment of global improvement in pain | Assessment of the effects of Aimovig® (EREN) compared to placebo (EREN-P) based on the change in mean between-group difference in global improvement in pain scale: 1 (Better) - 7 (Worse). | From week 4 through the week 20 visit and after 24 weeks (two months after the last treatment). | 
| Change in mean between-group difference in pain based on assessment of jaw function | Assessment of the effects of Aimovig® (EREN) compared to placebo (EREN-P) based on the change in mean between-group difference in jaw function scale: 0 (Better) - 10 (Worse). | From baseline visit through the week 20 visit and after 24 weeks (two months after the last treatment). | 
| Change in mean between-group difference in pain based on assessment depressive and anxiety symptoms | Assessment of the effects of Aimovig® (EREN) compared to placebo (EREN-P) based on the change in mean between-group difference in depressive and anxiety symptoms scale: 0 (Better) - 3 (Worse). | From baseline visit through the week 20 visit and after 24 weeks (two months after the last treatment). | 
| Change in mean between-group difference in pain based on assessment of somatic symptom severity, and safety and tolerance | Assessment of the effects of Aimovig® (EREN) compared to placebo (EREN-P) based on the change in mean between-group difference in somatic symptom severity scale: 0 (Better) - 4 (Worse). | From baseline visit through the week 20 visit and after 24 weeks (two months after the last treatment). | 
| Change in mean between-group difference in pain based on assessment of safety and tolerance | Assessment of the effects of Aimovig® (EREN) compared to placebo (EREN-P) based on the change in mean between-group difference in safety and tolerance scale: 0 (Better) - 10 (Worse). | From baseline visit through the week 20 visit and after 24 weeks (two months after the last treatment). |