Study of BOTOX Injections to Assess Change in Disease Symptoms in Adult Participants With Upper Limb Essential Tremor

A Phase 2 Multicenter, Randomized, Double-blind, Placebo-controlled Study of BOTOX® (Botulinum Toxin Type A) Purified Neurotoxin Complex for the Treatment of Upper Limb Essential Tremor

Upper limb essential tremor (UL ET) is a movement disorder characterized by postural and/or kinetic tremor. It can cause difficulty with everyday tasks such as writing, pouring, and eating, and patients also experience associated social embarrassment. This study will assess how safe and effective BOTOX is in treating UL ET. Adverse events and change in disease activity will be evaluated.

BOTOX is an investigational drug being developed for the treatment of UL ET. Participants are randomly assigned to 1 of the 4 groups, called treatment arms. Each group receives different treatment. There is 1 in 2 chance that participants will be assigned to placebo. Around 174 participants, aged 18 to 80 years with UL ET will be enrolled in approximately 40 sites in North America.

Participants will receive BOTOX or placebo injections in Cycle 1 and Cycle 2. In Cycle 3, participants will receive unilateral or bilateral BOTOX injections. Each cycle is 12 weeks.

There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.

Study Overview

• Status: Recruiting
• Conditions: Upper Limb Essential Tremor (UL ET)
• Intervention / Treatment: Biological: BOTOX; Drug: Placebo for BOTOX

• Study Type: Interventional
• Enrollment (Estimated): 174
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: ABBVIE CALL CENTER; Phone Number: 844-663-3742; Email: abbvieclinicaltrials@abbvie.com

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6T 1Z9
      • Recruiting
      • Vancouver Coastal Health Authority - University of British Columbia /ID# 240356
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3S 1N2
      • Recruiting
      • Centricity Research /ID# 240587
  • Ontario
    • Toronto, Ontario, Canada, M5T 2S8
      • Recruiting
      • Toronto Western Hospital /ID# 231587
  • Quebec
    • Montreal, Quebec, Canada, H4A 3T2
      • Recruiting
      • Genge Partners /ID# 251546
• United States
  • Alabama
    • Hoover, Alabama, United States, 35244-5700
      • Recruiting
      • Accel Research Sites - Neurology and Neurodiagnostics of Alabama, LLC /ID# 240472
  • Arizona
    • Phoenix, Arizona, United States, 85013-4407
      • Recruiting
      • Barrow Neurological Institute /ID# 231731
    • Tucson, Arizona, United States, 85724
      • Recruiting
      • University of Arizona /ID# 239781
  • California
    • Loma Linda, California, United States, 92354
      • Recruiting
      • Loma Linda University /ID# 230905
  • Colorado
    • Aurora, Colorado, United States, 80045-2527
      • Recruiting
      • University of Colorado - Anschutz Medical Campus /ID# 239869
  • Connecticut
    • Stamford, Connecticut, United States, 06905
      • Recruiting
      • New England Institute for Clinical Research /ID# 238404
  • Florida
    • Boca Raton, Florida, United States, 33486
      • Recruiting
      • Parkinson's Disease and Movement Disorders Center of Boca Raton /ID# 231677
    • Fernandina Beach, Florida, United States, 32034-4779
      • Recruiting
      • Coastal Clinical Research Specialists /ID# 240897
    • Jacksonville, Florida, United States, 32205-8275
      • Recruiting
      • Coastal Clinical Research Specialists /ID# 240471
    • Port Saint Lucie, Florida, United States, 34952-7539
      • Completed
      • CDC Research Institute LLC /ID# 242744
    • Winter Park, Florida, United States, 32792-6707
      • Recruiting
      • Charter Research - Winter Park /ID# 241568
  • Georgia
    • Atlanta, Georgia, United States, 30329-2206
      • Recruiting
      • Emory University / Emory Brain Health Center /ID# 231911
    • Decatur, Georgia, United States, 30030-2627
      • Completed
      • Accel Research Site-NeuroStudies /ID# 239881
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Recruiting
      • Univ Kansas Med Ctr /ID# 231166
    • Overland Park, Kansas, United States, 66211-1363
      • Recruiting
      • Kansas Institute of Research /ID# 231623
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Recruiting
      • Tufts Medical Center /ID# 239929
    • Burlington, Massachusetts, United States, 01805
      • Recruiting
      • Lahey Hospital and Medical Center /ID# 233232
  • Michigan
    • Jackson, Michigan, United States, 49201-1852
      • Completed
      • Henry Ford Health Medical Center - Jackson /ID# 231400
  • New York
    • Amherst, New York, United States, 14226
      • Recruiting
      • Dent Neurosciences Research Center, Inc. /ID# 255665
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27517-4400
      • Recruiting
      • UNC Hospitals Neurology Clinic - Chapel Hill /ID# 238857
    • Winston-Salem, North Carolina, United States, 27103-6984
      • Recruiting
      • Neurology - Triad /ID# 239806
    • Winston-Salem, North Carolina, United States, 27157-0001
      • Recruiting
      • Wake Forest Baptist Medical Center /ID# 233550
  • Ohio
    • Centerville, Ohio, United States, 45459-3811
      • Recruiting
      • Dayton Center for Neurological Disorders /ID# 233737
    • New Albany, Ohio, United States, 43054-8167
      • Recruiting
      • The Orthopedic Foundation /ID# 232234
  • Oregon
    • Portland, Oregon, United States, 97239-3011
      • Recruiting
      • Oregon Health & Science University /ID# 231581
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107-4414
      • Recruiting
      • Thomas Jefferson University /ID# 232614
    • Pittsburgh, Pennsylvania, United States, 15260
      • Recruiting
      • University of Pittsburgh MC /ID# 233735
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Recruiting
      • Medical University of South Carolina /ID# 233538
      • Contact: Site Coordinator
  • Texas
    • Dallas, Texas, United States, 75214
      • Recruiting
      • Texas Neurology /ID# 250428
    • Dallas, Texas, United States, 75390-7208
      • Recruiting
      • University of Texas Southwestern Medical Center /ID# 239770
    • Georgetown, Texas, United States, 78628-4126
      • Recruiting
      • Texas Movement Disorder Specialists, PLLC /ID# 242524
    • Houston, Texas, United States, 77030
      • Recruiting
      • Baylor College of Medicine /ID# 231624
    • San Antonio, Texas, United States, 78229-3901
      • Recruiting
      • Univ Texas HSC San Antonio /ID# 232615
  • Virginia
    • Falls Church, Virginia, United States, 22043-2367
      • Recruiting
      • Integrated Neurology Services - Falls Church /ID# 233545
  • Wisconsin
    • Greenfield, Wisconsin, United States, 53228-1321
      • Recruiting
      • Gamma Therapeutic Center /ID# 232547
    • Marshfield, Wisconsin, United States, 54449
      • Recruiting
      • Marshfield Clinic - Marshfield /ID# 233191

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of essential tremor in accordance with modified Tremor Investigation Group (TRIG) criteria as described in the protocol.
• TREDS-Revised Scale (1-4 scale, whole numbers) unilateral score of >= 3 for the Tremor Disability Scale (TREDS) on any of the 7 unilateral items; no more than a single item score of 1 among the 7 unilateral items in the dominant limb.
• TETRAS activities of daily living (ADL) (recorded on a 0-4 scale, whole numbers) minimum score of >= 3 on any of the 5 unilateral items; no more than a single item score of <=1 among the 5 unilateral items in the dominant limb.

• At least one of the following criteria must also be met:

  • TETRAS UL score (0-4 scale, with 0.5 increments) of > 2 in the dominant limb on at least one of the 3 maneuvers OR
  • TETRAS Archimedes spiral task score (0-4 scale, with 0.5 increments) of > 2 in the dominant limb

Exclusion Criteria:

• Any uncontrolled clinically significant medical condition other than the one under study.
• Any medical condition that may put the participant at increased risk with exposure to BOTOX Purified Neurotoxin Complex.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BOTOX/BOTOX Unilateral; Participants will receive BOTOX in Cycle 1 and Cycle 2 and unilateral BOTOX in Cycle 3	Biological: BOTOX; Intramuscular injection; Other Names: Botulinum Toxin Type A
Experimental: BOTOX/BOTOX Bilateral; Participants will receive BOTOX in Cycle 1 and Cycle 2 and bilateral BOTOX in Cycle 3	Biological: BOTOX; Intramuscular injection; Other Names: Botulinum Toxin Type A
Experimental: Placebo/BOTOX Unilateral; Participants will receive placebo in Cycle 1 and Cycle 2 followed by unilateral BOTOX in Cycle 3.	Biological: BOTOX; Intramuscular injection; Other Names: Botulinum Toxin Type A; Drug: Placebo for BOTOX; Intramuscular injection
Experimental: Placebo/BOTOX Bilateral; Participants will receive placebo in Cycle 1 and Cycle 2 followed by bilateral BOTOX in Cycle 3.	Biological: BOTOX; Intramuscular injection; Other Names: Botulinum Toxin Type A; Drug: Placebo for BOTOX; Intramuscular injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Tremor Disability Scale-Revised (TREDS-R) Total Score Across 7 Unilateral Items	Tremor Disability Scale-Revised (TREDS-R) is a scale to assess activities of daily living (ADL) through a self-questionnaire asking participants to rate how easy or difficult it is to perform a particular activity. The scale consists of 20 items with each item rated on a scale of 1 (able to do the activity without difficulty) to 4 (cannot do the activity by yourself). 7 items included in this subset will be: use a spoon to drink soup, hold a cup of tea, pour milk from a bottle or carton, dial a telephone, pick up your change in a shop, insert an electric plug into a socket, unlock your front door with a key.	Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in TETRAS Activity of Daily Living (TETRAS ADL) Total Score Across 5 Unilateral Items	TETRAS Activity of Daily Living (TETRAS ADL) is a clinical rating scale using the total score across 5 unilateral items of the analyzed 10-item TETRAS ADL, with each item's recorded scores of 0 and 1 (0-4 scale) combined into one category with a score of 1 for analysis on a 1-4 scale. The 5 tasks included in this subset will be feeding with a spoon, drinking from a glass, pouring, using keys, and writing.	Week 24
Change From Baseline in TETRAS Archimedes Spiral Score	Tremor Research Group Essential Tremor Rating Assessment Scale (TETRAS) Archimedes Spiral is an item of the TETRAS performance subscale that is designed to assess tremor severity. During this test, participants are instructed to draw an unbroken spiral which is then scored from 0 to 4, with 1 being tremor is "barely visible" and 4 being "figure not recognizable."	Week 24
Change From Baseline in TETRAS Handwriting Score	TETRAS Handwriting is an item of the TETRAS performance subscale that is designed to assess tremor severity. During this test, participants are instructed to write the standard sentence "This is a sample of my best handwriting" using the dominant hand only, which is then scored from 0 to 4 with 1 being tremor is "slight: untidy due to tremor that is barely visible" and 4 being "severe: completely illegible."	Week 24
Change From Baseline in Clinical Global Impression of Severity (CGI-S)	CGI-S is a single item used to measure the clinician's impression of the current severity of the patient's essential tremor. The measure uses a 5-point rating scale where "0 = none, 1 = mild, 2 = moderate, 3 = severe, and 4 = very severe."	Week 24
Change From Baseline in Patient Global Impression of Severity (PGI-S)	PGI-S is a single item used to measure the participant's impression of severity of their essential tremor symptoms. The measure uses a 5-point rating scale where 0 = none, 1 = mild, 2 = moderate, 3 = severe, and 4 = very severe.	Week 24
Change From Baseline in Essential Tremor Rating Assessment (TETRAS UL) Score	TETRAS Upper Limb (UL) Scale is an item of the TETRAS performance subscale that is designed to assess upper limb tremor during three maneuvers: forward horizontal reach posture, lateral "wing beating" posture, and finger-nose-finger testing. Each maneuver is scored from 0 to 4, with 1 indicating a tremor amplitude that is "barely visible" and 4 indicating a tremor amplitude that is >= 20 cm.	Week 24

Collaborators and Investigators

• Sponsor: AbbVie
• Investigators: Study Director: ABBVIE INC., AbbVie

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): April 12, 2022
• Primary Completion (Estimated): November 15, 2024
• Study Completion (Estimated): June 27, 2025

Study Registration Dates

• First Submitted: October 1, 2021
• First Submitted That Met QC Criteria: January 19, 2022
• First Posted (Actual): January 31, 2022

Study Record Updates

• Last Update Posted (Actual): March 21, 2024
• Last Update Submitted That Met QC Criteria: March 19, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Botulinum Toxin Type A; BOTOX; Upper Limb Essential Tremor; UL ET
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Movement Disorders; Dyskinesias; Tremor; Essential Tremor; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Cholinergic Agents; Membrane Transport Modulators; Acetylcholine Release Inhibitors; Neuromuscular Agents; Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA
• Other Study ID Numbers: M21-471; 2021-002191-39 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols and clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
• IPD Sharing Time Frame: For details on when studies are available for sharing, please refer to the link below.
• IPD Sharing Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Use Agreement (DUA). For more information on the process, or to submit a request, visit the following link.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• 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