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

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ClinicalTrials.gov Identifier: NCT04884763
Recruitment Status : Not yet recruiting
First Posted : May 13, 2021
Last Update Posted : May 14, 2021
Sponsor:
Collaborator:
Novartis Pharmaceuticals
Information provided by (Responsible Party):
Domenick Zero, Indiana University

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.

Condition or disease Intervention/treatment Phase
Temporomandibular Disorder 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 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Estimated Study Start Date : May 2021
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : January 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Arm A
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
Erenumab-aooe (EREN) 140 mg s.c. administered at baseline and weeks 4, 8, 12 and 16 for a total of five treatments
Other Name: Aimovig®

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




Primary Outcome Measures :
  1. Change in mean between-group difference in pain using the Brief Pain Inventory [ Time Frame: From baseline visit through the week 20 visit. ]
    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).


Secondary Outcome Measures :
  1. Change in mean between-group difference in pain based on assessment of pain interference [ Time Frame: From baseline visit through the week 20 visit and after 24 weeks (two months after the last treatment). ]
    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).

  2. Change in mean between-group difference in pain based on assessment of trajectory of pain improvement based on changes in daily reporting of pain [ Time Frame: From baseline visit through the week 20 visit and after 24 weeks (two months after the last treatment). ]
    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).

  3. Change in mean between-group difference in pain based on assessment of days of use of TMD pain specific medication [ Time Frame: From baseline visit through the week 20 visit and after 24 weeks (two months after the last treatment). ]
    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)

  4. Change in mean between-group difference in pain based on assessment of global improvement in pain [ Time Frame: From week 4 through the week 20 visit and after 24 weeks (two months after the last treatment). ]
    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).

  5. Change in mean between-group difference in pain based on assessment of jaw function [ Time Frame: From baseline visit through the week 20 visit and after 24 weeks (two months after the last treatment). ]
    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).

  6. Change in mean between-group difference in pain based on assessment depressive and anxiety symptoms [ Time Frame: From baseline visit through the week 20 visit and after 24 weeks (two months after the last treatment). ]
    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).

  7. Change in mean between-group difference in pain based on assessment of somatic symptom severity, and safety and tolerance [ Time Frame: From baseline visit through the week 20 visit and after 24 weeks (two months after the last treatment). ]
    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).

  8. Change in mean between-group difference in pain based on assessment of safety and tolerance [ Time Frame: From baseline visit through the week 20 visit and after 24 weeks (two months after the last treatment). ]
    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).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 59 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04884763


Contacts
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Contact: Jennifer L Tran 317-274-3306 jelbruce@iu.edu

Locations
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United States, Indiana
Indiana University School of Dentistry, Oral Health Research Institute
Indianapolis, Indiana, United States, 46202
Sponsors and Collaborators
Indiana University
Novartis Pharmaceuticals
Investigators
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Principal Investigator: 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.
Additional Information:
Publications:
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
Julious SA. Sample size of 12 per group rule of thumb for a pilot study. Pharmaceutical statistics. 2005;4:287-291.
Ohrbach, R, editor. Diagnostic Criteria for Temporomandibular Disorders Assessment Instruments. Version 15May2016. www.rdc-tmdinternational.org Accessed on 23Sep2019
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 Group†. J Oral Facial Pain Headache. 2014 Winter;28(1):6-27. doi: 10.11607/jop.1151.

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Responsible Party: Domenick Zero, Professor, Department of Cariology, Operative Dentistry and Dental Public Health, Indiana University
ClinicalTrials.gov Identifier: NCT04884763    
Other Study ID Numbers: 20-D-242
CAMG334AUS01T ( Other Identifier: Novartis Investigator Initiated Trials (IITs) Program )
First Posted: May 13, 2021    Key Record Dates
Last Update Posted: May 14, 2021
Last Verified: May 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Temporomandibular Joint Disorders
Temporomandibular Joint Dysfunction Syndrome
Craniomandibular Disorders
Mandibular Diseases
Jaw Diseases
Musculoskeletal Diseases
Joint Diseases
Muscular Diseases
Stomatognathic Diseases
Myofascial Pain Syndromes
Erenumab
Calcitonin Gene-Related Peptide Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs