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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Upper Limb Essential Tremor (UL ET)

Intervention / Treatment
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* Biological: BOTOX
* Drug: Placebo for BOTOX


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Upper Limb Essential Tremor, UL ET, BOTOX, Botulinum Toxin Type A