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

Temporomandibular Disorder Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04884763
• Other study ID #: 20-D-242
• Secondary ID: CAMG334AUS01T
• Status: Completed
• Phase: Phase 2
• Start date: November 15, 2021
• Est. completion date: January 19, 2024

Study information

• Verified date: January 2024
• Source: Indiana University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: January 19, 2024
• Est. primary completion date: January 4, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 59 Years

Eligibility

Inclusion Criteria:

Subjects eligible for inclusion in the study must meet all of the following criteria:

1. Signed the informed consent;

2. Have pain-related TMD myalgia assessed by history and clinical examination as established by the DC/TMD;

3. Age 18 years and younger than 60 years;

4. Have a good knowledge of the English language;

5. Able to understand and comply with the study requirements;

6. Have had TMD myalgia for 6 months or longer; and

7. 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:

1. Lacking stable bilateral posterior occlusion;

2. Currently uses a complete maxillary or mandibular prosthetic denture;

3. Currently pregnant or plan to become pregnant;

4. Breastfeeding or plan to breastfeed;

5. Allergic to erenumab-aooe or any of the ingredients in Aimovig® (acetate, polysorbate 80, and sucrose);

6. Allergic to rubber or latex;

7. Currently undergoing TMD treatment elsewhere;

8. Currently undergoing orthodontic treatment;

9. Currently included in other experimental protocols within the last 30 days before enrollment;

10. Having 11 or more headaches during the past 4 weeks;

11. Having received massage, acupuncture or physical therapy treatment of the head, neck or shoulders during the previous 3 months;

12. History of unstable or acute severe pain from another pain condition;

13. History of traumatic brain injury;

14. History of surgical treatment or recommended surgical treatment for TMD;

15. History of ongoing, unresolved disability litigation;

16. History of drug abuse;

17. History of moderate to severe sleep apnea requiring CPAP or oral mandibular repositioning appliance;

18. 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

19. 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).

20. History of chronic constipation and/or using medication associated with decreased gastrointestinal motility.

21. History of hypertension or risk factors for hypertension.

Related Conditions & MeSH terms

• Temporomandibular Disorder
• Temporomandibular Joint Disorders
• Temporomandibular Joint Dysfunction Syndrome

Intervention

Drug:
• Erenumab-aooe (EREN) 140 mg s.c. administered every four weeks for a total of five treatments
Erenumab-aooe (EREN) 140 mg s.c. administered at baseline and weeks 4, 8, 12 and 16 for a total of five treatments
• Placebo (EREN-P) s.c. administered every four weeks for a total of five treatments
Placebo (EREN-P) s.c. administered at baseline and weeks 4, 8, 12 and 16 for a total of five treatments

Locations

Country	Name	City	State
United States	Indiana University School of Dentistry, Oral Health Research Institute	Indianapolis	Indiana

Sponsors (2)

Lead Sponsor	Collaborator
Indiana University	Novartis Pharmaceuticals

Country where clinical trial is conducted

United States, 

References & Publications (23)

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. — View Citation

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

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 23 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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).
Secondary	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).
Secondary	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).
Secondary	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).
Secondary	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).
Secondary	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).
Secondary	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).
Secondary	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).

External Links

•   Facial Pain
•   Highlights of Prescribing Information