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

NCT04884763 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 20-D-242CAMG334AUS01T
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Temporomandibular Disorder

Outcome Measures

Primary Outcomes (1)

• Brief Pain Inventory (BPI) Pain Severity at 20 Weeks

  Assessment of pain severity using the Brief Pain Inventory (BPI) 4-item pain severity scale at 20 weeks: 0 (Better) - 10 (Worse). Interim assessments were performed at 4, 8, 12 and 16 weeks and post-treatment at 24 weeks (secondary outcome).

  20 weeks.

Secondary Outcomes (15)

• Brief Pain Inventory (BPI) Pain Interference at 20 Weeks

  20 weeks

• Average Daily Reported Pain Scores at 20 Weeks

  20 weeks

• % of Days Taking Medication for Pain at 20 Weeks

  20 weeks

• Pain Improvement Using the Patient Global Impression of Change in Pain at 20 Weeks

  20 weeks

• Jaw Function Limitation Scale (JFLS-8) at 20 Weeks

  20 weeks

Study Arms (2)

Arm A

ACTIVE COMPARATOR

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

Arm B

PLACEBO COMPARATOR

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

Interventions

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 at baseline and weeks 4, 8, 12 and 16 for a total of five treatments

Also known as: Aimovig®

Arm A

Placebo (EREN-P) s.c. administered every four weeks for a total of five treatments DRUG

Placebo (EREN-P) s.c. administered at baseline and weeks 4, 8, 12 and 16 for a total of five treatments

Also known as: Placebo

Arm B

Eligibility Criteria

• Age: 18 Years - 59 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• Indiana University: lead
• Amgen: collaborator

Study Sites (1)

Indiana University School of Dentistry, Oral Health Research Institute

Indianapolis, Indiana, 46202, United States

Location

Related Publications (24)

• Ashina M, Goadsby PJ, Reuter U, Silberstein S, Dodick D, Rippon GA, Klatt J, Xue F, Chia V, Zhang F, Cheng S, Mikol DD. Long-term safety and tolerability of erenumab: Three-plus year results from a five-year open-label extension study in episodic migraine. Cephalalgia. 2019 Oct;39(11):1455-1464. doi: 10.1177/0333102419854082. Epub 2019 May 30.

  PMID: 31146544 BACKGROUND

• de Leeuw, R, Editor, Orofacial Pain: Guidelines for Assessment, Diagnosis, and Management, The American Academy of Orofacial Pain, Sixth Edition, Hanover Park, IL: Quintessence Publishing Co, Inc., 2018, 1-2

  BACKGROUND

• Edvinsson L. The CGRP Pathway in Migraine as a Viable Target for Therapies. Headache. 2018 May;58 Suppl 1:33-47. doi: 10.1111/head.13305.

  PMID: 29697153 BACKGROUND

• Goadsby PJ, Reuter U, Hallstrom Y, Broessner G, Bonner JH, Zhang F, Sapra S, Picard H, Mikol DD, Lenz RA. A Controlled Trial of Erenumab for Episodic Migraine. N Engl J Med. 2017 Nov 30;377(22):2123-2132. doi: 10.1056/NEJMoa1705848.

  PMID: 29171821 BACKGROUND

• Hargreaves R, Olesen J. Calcitonin Gene-Related Peptide Modulators - The History and Renaissance of a New Migraine Drug Class. Headache. 2019 Jun;59(6):951-970. doi: 10.1111/head.13510. Epub 2019 Apr 25.

  PMID: 31020659 BACKGROUND

• Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia. 2013 Jul;33(9):629-808. doi: 10.1177/0333102413485658. No abstract available.

  PMID: 23771276 BACKGROUND

• Julious SA. Sample size of 12 per group rule of thumb for a pilot study. Pharmaceutical statistics. 2005;4:287-291.

  BACKGROUND

• Kean J, Monahan PO, Kroenke K, Wu J, Yu Z, Stump TE, Krebs EE. Comparative Responsiveness of the PROMIS Pain Interference Short Forms, Brief Pain Inventory, PEG, and SF-36 Bodily Pain Subscale. Med Care. 2016 Apr;54(4):414-21. doi: 10.1097/MLR.0000000000000497.

  PMID: 26807536 BACKGROUND

• Krebs EE, Lorenz KA, Bair MJ, Damush TM, Wu J, Sutherland JM, Asch SM, Kroenke K. Development and initial validation of the PEG, a three-item scale assessing pain intensity and interference. J Gen Intern Med. 2009 Jun;24(6):733-8. doi: 10.1007/s11606-009-0981-1. Epub 2009 May 6.

  PMID: 19418100 BACKGROUND

• Kroenke K, Evans E, Weitlauf S, McCalley S, Porter B, Williams T, Baye F, Lourens SG, Matthias MS, Bair MJ. Comprehensive vs. Assisted Management of Mood and Pain Symptoms (CAMMPS) trial: Study design and sample characteristics. Contemp Clin Trials. 2018 Jan;64:179-187. doi: 10.1016/j.cct.2017.10.006. Epub 2017 Oct 12.

  PMID: 29031492 BACKGROUND

• Kroenke K, Krebs EE, Turk D, Von Korff M, Bair MJ, Allen KD, Sandbrink F, Cheville AL, DeBar L, Lorenz KA, Kerns RD. Core Outcome Measures for Chronic Musculoskeletal Pain Research: Recommendations from a Veterans Health Administration Work Group. Pain Med. 2019 Aug 1;20(8):1500-1508. doi: 10.1093/pm/pny279.

  PMID: 30615172 BACKGROUND

• Kroenke K, Spitzer RL, Williams JB, Lowe B. An ultra-brief screening scale for anxiety and depression: the PHQ-4. Psychosomatics. 2009 Nov-Dec;50(6):613-21. doi: 10.1176/appi.psy.50.6.613.

  PMID: 19996233 BACKGROUND

• Maixner W, Fillingim RB, Williams DA, Smith SB, Slade GD. Overlapping Chronic Pain Conditions: Implications for Diagnosis and Classification. J Pain. 2016 Sep;17(9 Suppl):T93-T107. doi: 10.1016/j.jpain.2016.06.002.

  PMID: 27586833 BACKGROUND

• Noseda R, Burstein R. Migraine pathophysiology: anatomy of the trigeminovascular pathway and associated neurological symptoms, cortical spreading depression, sensitization, and modulation of pain. Pain. 2013 Dec;154 Suppl 1:S44-53. doi: 10.1016/j.pain.2013.07.021. Epub 2013 Jul 25.

  PMID: 23891892 BACKGROUND

• Ohrbach, R, editor. Diagnostic Criteria for Temporomandibular Disorders Assessment Instruments. Version 15May2016. www.rdc-tmdinternational.org Accessed on 23Sep2019

  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.

  PMID: 18474055 BACKGROUND

• Popko L. Some Notes on Papyrus Ebers, Ancient Egyptian Treatments of Migraine, and a Crocodile on the Patient's Head. Bull Hist Med. 2018;92(2):352-366. doi: 10.1353/bhm.2018.0030.

  PMID: 29961718 BACKGROUND

• Schiffman E, Ohrbach R, Truelove E, Look J, Anderson G, Goulet JP, List T, Svensson P, Gonzalez Y, Lobbezoo F, Michelotti A, Brooks SL, Ceusters W, Drangsholt M, Ettlin D, Gaul C, Goldberg LJ, Haythornthwaite JA, Hollender L, Jensen R, John MT, De Laat A, de Leeuw R, Maixner W, van der Meulen M, Murray GM, Nixdorf DR, Palla S, Petersson A, Pionchon P, Smith B, Visscher CM, Zakrzewska J, Dworkin SF; International RDC/TMD Consortium Network, International association for Dental Research; Orofacial Pain Special Interest Group, International Association for the Study of Pain. Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) for Clinical and Research Applications: recommendations of the International RDC/TMD Consortium Network* and Orofacial Pain Special Interest Groupdagger. J Oral Facial Pain Headache. 2014 Winter;28(1):6-27. doi: 10.11607/jop.1151.

  PMID: 24482784 BACKGROUND

• Speciali JG, Dach F. Temporomandibular dysfunction and headache disorder. Headache. 2015 Feb;55 Suppl 1:72-83. doi: 10.1111/head.12515. Epub 2015 Feb 3.

  PMID: 25644695 BACKGROUND

• Tepper SJ. History and Review of anti-Calcitonin Gene-Related Peptide (CGRP) Therapies: From Translational Research to Treatment. Headache. 2018 Nov;58 Suppl 3:238-275. doi: 10.1111/head.13379. Epub 2018 Sep 22.

  PMID: 30242830 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.

  PMID: 28460892 BACKGROUND

• Toussaint A, Kroenke K, Baye F, Lourens S. Comparing the Patient Health Questionnaire - 15 and the Somatic Symptom Scale - 8 as measures of somatic symptom burden. J Psychosom Res. 2017 Oct;101:44-50. doi: 10.1016/j.jpsychores.2017.08.002. Epub 2017 Aug 2.

  PMID: 28867423 BACKGROUND

• Yuan H, Spare NM, Silberstein SD. Targeting CGRP for the Prevention of Migraine and Cluster Headache: A Narrative Review. Headache. 2019 Jul;59 Suppl 2:20-32. doi: 10.1111/head.13583.

  PMID: 31291020 BACKGROUND

• Avila HC, Kroenke K, Eckert GJ, Gossweiler AG, Galvez LDC, Zero DT. A randomized, double blind, placebo-controlled pilot study to assess the efficacy of erenumab in individuals with temporomandibular disorder. J Oral Facial Pain Headache. 2025 Jun;39(2):75-83. doi: 10.22514/jofph.2025.027. Epub 2025 Jun 12.

  PMID: 41070535 DERIVED

Related Links

• Highlights of Prescribing Information

MeSH Terms

Conditions

Temporomandibular Joint Disorders

Interventions

erenumab

Condition Hierarchy (Ancestors)

Craniomandibular Disorders; Mandibular Diseases; Jaw Diseases; Musculoskeletal Diseases; Joint Diseases; Muscular Diseases; Stomatognathic Diseases

Results Point of Contact

• Title: Dr. Domenick Zero
• Organization: Indiana University School of Dentistry

dzero@iu.edu

3179877507

Study Officials

• Domenick T Zero, DDS, MS

  Indiana University

  PRINCIPAL INVESTIGATOR

• Harold C Avila, DDS, MS

  Indiana University

  PRINCIPAL INVESTIGATOR

• Kurt Kroenke, MD, MACP

  Regenstrief Institute, Inc.

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Department of Biomedical and Applied Sciences

Study Record Dates

• First Submitted: May 4, 2021
• First Posted: May 13, 2021
• Study Start: November 15, 2021
• Primary Completion: January 4, 2024
• Study Completion: January 4, 2024
• Last Updated: August 19, 2025
• Results First Posted: August 19, 2025

Record last verified: 2025-07

Locations

US (1)