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

Primary Purpose

Temporomandibular Disorder

Status

Active

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Erenumab-aooe (EREN) 140 mg s.c. administered every four weeks for a total of five treatments

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

About this trial

This is an interventional treatment trial for Temporomandibular Disorder

Eligibility Criteria

18 Years - 59 Years (Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

Indiana University School of Dentistry, Oral Health Research Institute

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Arm A

Arm B

Arm Description

Arm A: erenumab-aooe (EREN) 140 mg s.c. administered every four weeks for a total of five treatments

Arm B: placebo (EREN-P) s.c. administered every four weeks for a total of five treatments

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

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).

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).

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)

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).

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).

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).

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).

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).

Full Information

NCT ID

NCT04884763

First Posted

May 4, 2021

Last Updated

August 18, 2023

Sponsor

Indiana University

Collaborators

Novartis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT04884763

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

November 15, 2021 (Actual)

Primary Completion Date

November 30, 2023 (Anticipated)

Study Completion Date

December 28, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Indiana University

Collaborators

Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Temporomandibular Disorder

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Arm A

Arm Type

Active Comparator

Arm Description

Arm A: erenumab-aooe (EREN) 140 mg s.c. administered every four weeks for a total of five treatments

Arm Title

Arm B

Arm Type

Placebo Comparator

Arm Description

Arm B: placebo (EREN-P) s.c. administered every four weeks for a total of five treatments

Intervention Type

Drug

Intervention Name(s)

Erenumab-aooe (EREN) 140 mg s.c. administered every four weeks for a total of five treatments

Other Intervention Name(s)

Aimovig®

Intervention Description

Erenumab-aooe (EREN) 140 mg s.c. administered at baseline and weeks 4, 8, 12 and 16 for a total of five treatments

Intervention Type

Drug

Intervention Name(s)

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

Other Intervention Name(s)

Placebo

Intervention Description

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

Primary Outcome Measure Information:

Title

Change in mean between-group difference in pain using the Brief Pain Inventory

Description

Time Frame

From baseline visit through the week 20 visit.

Secondary Outcome Measure Information:

Title

Change in mean between-group difference in pain based on assessment of pain interference

Description

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).

Time Frame

From baseline visit through the week 20 visit and after 24 weeks (two months after the last treatment).

Title

Change in mean between-group difference in pain based on assessment of trajectory of pain improvement based on changes in daily reporting of pain

Description

Time Frame

From baseline visit through the week 20 visit and after 24 weeks (two months after the last treatment).

Title

Change in mean between-group difference in pain based on assessment of days of use of TMD pain specific medication

Description

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)

Time Frame

From baseline visit through the week 20 visit and after 24 weeks (two months after the last treatment).

Title

Change in mean between-group difference in pain based on assessment of global improvement in pain

Description

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).

Time Frame

From week 4 through the week 20 visit and after 24 weeks (two months after the last treatment).

Title

Change in mean between-group difference in pain based on assessment of jaw function

Description

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).

Time Frame

From baseline visit through the week 20 visit and after 24 weeks (two months after the last treatment).

Title

Change in mean between-group difference in pain based on assessment depressive and anxiety symptoms

Description

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).

Time Frame

From baseline visit through the week 20 visit and after 24 weeks (two months after the last treatment).

Title

Change in mean between-group difference in pain based on assessment of somatic symptom severity, and safety and tolerance

Description

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).

Time Frame

From baseline visit through the week 20 visit and after 24 weeks (two months after the last treatment).

Title

Change in mean between-group difference in pain based on assessment of safety and tolerance

Description

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).

Time Frame

From baseline visit through the week 20 visit and after 24 weeks (two months after the last treatment).

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

59 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Domenick T Zero, DDS, MS

Organizational Affiliation

Indiana University

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Harold C Avila, DDS, MS

Organizational Affiliation

Indiana University

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Kurt Kroenke, MD, MACP

Organizational Affiliation

Regenstrief Institute, Inc.

Official's Role

Principal Investigator

Facility Information:

Facility Name

Indiana University School of Dentistry, Oral Health Research Institute

City

Indianapolis

State/Province

Indiana

ZIP/Postal Code

46202

Country

United States

12. IPD Sharing Statement

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Links:

URL

https://www.nidcr.nih.gov/research/data-statistics/facial-pain

Description

Facial Pain

URL

https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/761077s007lbl.pdf

Description

Highlights of Prescribing Information

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

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