A Study to Investigate the Efficacy and Safety of NT 201 (Botulinum Toxin) Compared With Placebo for the Treatment of Adult Participants With Essential Tremor in the Arm

Prospective, Randomized, Double-blind, Placebo-controlled, Parallel-group Trial With an Open-label Period to Investigate the Efficacy and Safety of NT 201 in the Unilateral and Bilateral Treatment of Essential Tremor of the Upper Limb

The purpose of this study is to determine whether a single treatment with NT 201 (botulinum toxin) is superior to placebo (no medicine) for one-sided treatment of essential tremor in the motor-dominant arm (Unilateral Period). Participants will be assigned to the treatment groups by chance and neither the participants nor the research staff who interact with them will know the allocation.

The following treatment cycle will investigate the safety and tolerability of two-sided treatment with NT 201 (botulinum toxin) (Open Label Bilateral Period). All participants will receive NT 201 treatment.

Study Overview

• Status: Completed
• Conditions: Essential Tremor of the Upper Limb
• Intervention / Treatment: Drug: Placebo; Drug: NT 201

• Study Type: Interventional
• Enrollment (Actual): 78
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • London, Ontario, Canada, N6A 5A5
      • London Health Sciences Centre, Merz Investigational Site #0010087
• Poland
  • Krakow, Poland, 30-539
    • Specjalistyczne Gabinety, Merz Investigational Site #0480059
  • Lodz, Poland, 90-640
    • NeuroKlinika Gabinet Lekarski, Merz Investigational Site #0480101
  • Oświęcim, Poland, 32-600
    • Instytut Zdrowia Dr. Boczarska-Jedynak
  • Warsaw, Poland, 03-242
    • Mazowiecki Szpital Bródnowski, Merz Investigational Site #0480064
• United States
  • Florida
    • Tampa, Florida, United States, 33612
      • USF, Department of Neurology, Merz Investigational Site #0010020
  • Nebraska
    • Omaha, Nebraska, United States, 68131
      • University of Nebraska Medical Center, Merz Investigational Site #0010269
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Cleveland Clinic Lou Ruvo Center for Brain Health, Merz Investigational Site #0010457
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai Medical Center, Merz Investigational Site #0010191
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center, Neuroscience Institute, Merz Investigational Site #0010206
  • Texas
    • Houston, Texas, United States, 77030
      • Houston Methodist Neurological Institute, Merz Investigational Site #0010226
  • Virginia
    • McLean, Virginia, United States, 22101
      • Medstar Georgetown Neurology, Merz Investigational Site #0010231
  • Washington
    • Seattle, Washington, United States, 98195
      • UW Medical Center - Montlake, Merz Investigational Site #0010450
    • Spokane, Washington, United States, 99202
      • Selkirk Neurology, Merz Investigational Site #0010456

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

- Score of ≥ 2 (at least 1 cm tremor amplitude) in at least two out of three maneuvers of test item 4 (upper limb tremor) of the TETRAS performances scale confirmed by an independent TETRAS expert by means of video assessment.

Exclusion Criteria:

• History or presence of day-to-day fluctuations in ET which would jeopardize meaningful tremor assessment over time, e.g. severe tremor on one day and minimal or no tremor on another day.
• Other neurological signs, such as dystonia, ataxia, or parkinsonism, which in the judgment of the investigator could interfere with the ET diagnosis and/or assessment of ET in ULs.
• Tremor types other than ET

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NT 201 (IncobotulinumtoxinA, Xeomin); Unilateral Treatment Period (1 treatment cycle): subjects to receive unilateral intramuscular injection of NT 201 (130-165 units) into muscles of the motor-dominant upper limb. Open Label Bilateral Treatment Period (1 treatment cycle): subjects to receive bilateral intramuscular injection of NT 201 (130-165 units) into muscles of both upper limbs.	Drug: NT 201; Active ingredient: Clostridium Botulinum neurotoxin Type A free from complexing proteins. Solution for injection prepared by reconstitution of powder with 0.9% Sodium Chloride (NaCl).; Other Names: Xeomin; Botulinum toxin type A (150 kiloDalton), free from complexing proteins; IncobotulinumtoxinA; Incobotulinumtoxin A
Placebo Comparator: Placebo; Unilateral Treatment Period (1 treatment cycle): subjects to receive unilateral intramuscular placebo injection into muscles of the motor-dominant upper limb. Open Label Bilateral Treatment Period (1 treatment cycle): subjects to receive bilateral intramuscular injection of NT 201 (130-165 units per arm) into muscles of both upper limbs.	Drug: Placebo; Solution for injection prepared by reconstitution of powder with 0.9% Sodium Chloride (NaCl).; Drug: NT 201; Active ingredient: Clostridium Botulinum neurotoxin Type A free from complexing proteins. Solution for injection prepared by reconstitution of powder with 0.9% Sodium Chloride (NaCl).; Other Names: Xeomin; Botulinum toxin type A (150 kiloDalton), free from complexing proteins; IncobotulinumtoxinA; Incobotulinumtoxin A

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Unilateral Treatment Period: Change From Baseline to Week 6 in Maximum Tremor Amplitude of the Wrist	TremorTek kinematic analytic investigational device is combination of computer software and wearable movement sensors that allows to collect motion data when placed on individual's arm to quantify tremor in various muscle groups that impact shoulder, elbow, wrist. This assessment system was used to measure maximum angular tremor amplitude at wrist of injected limb (unit: degrees). Angular tremor amplitude was measure of tremor severity. Reduction of maximum angular tremor amplitude at wrist of injected limb represented tremor improvement.	Baseline up to Week 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Unilateral Treatment Period: Change From Baseline to Week 6 in the Essential Tremor Rating Assessment Scale (TETRAS) Performance Dominant Upper Limb (UL) Score as Assessed by Investigator	The TETRAS was a validated clinical scale for the assessment of essential tremor severity. The TETRAS performance subscale was utilized by the qualified investigators to assess the tremor severity. The TETRAS Performance dominant UL score included TETRAS Performance items 4 (including subitems a, b, c for 3 manoeuvres), 6 to 8 of dominant UL. Each individual item score ranged from 0 to 4. The performance dominant UL score ranged from 0 to 24. Higher scores indicated more severe tremor.	Baseline up to Week 6
Unilateral Treatment Period: Change From Baseline to Week 6 in the TETRAS Activities of Daily Living (ADL) UL Score	TETRAS ADL subscale was another component of TETRAS. ADL subscale of TETRAS was completed by study subjects through an interview procedure to assess impact of tremor on activities of daily living. TETRAS ADL UL score was the sum of eight ADL items (on UL tremor [items 2-9]). Items were rated on a 5-point response scale each ranged from 0 (normal status/impact) to 4 (severe status/impact). The ADL UL score ranged from 0 to 32. Higher scores indicated greater tremor severity.	Baseline up to Week 6
Unilateral Treatment Period: Change From Baseline to Week 6 in TETRAS ADL Functional Impact Score	TETRAS ADL Functional Impact score was the sum of the following three ADL items: occupational impairment (item 10), overall disability (item 11), and social impact (item 12) of ET. The items are rated on a 5-point response scale each ranged from 0 (normal status/impact) to 4 (severe status/impact). The ADL Functional Impact score ranged from 0 to 12. Higher scores indicated greater tremor severity.	Baseline up to Week 6
Bilateral Treatment Period: Change From Cycle 2 Baseline to Week 6 in TETRAS Performance Dominant UL Score	TETRAS was a validated clinical scale for the assessment of essential tremor severity. The TETRAS performance subscale was utilized by the qualified investigators to assess the tremor severity. The TETRAS Performance dominant UL score included TETRAS Performance items 4 ((including subitems a, b, c for 3 manoeuvres), 6 to 8 of dominant UL. Each individual item score ranged from 0 to 4. The performance dominant UL score ranged from 0 to 24. Higher scores indicated more severe tremor.	Baseline of Cycle 2 up to Week 6 (Cycle length = 12 weeks)
Bilateral Treatment Period: Change From Cycle 2 Baseline to Week 6 in TETRAS Performance Subscale Score	The TETRAS was a validated clinical scale for the assessment of essential tremor severity. The TETRAS performance subscale was utilized by the qualified investigators to assess the tremor severity. TETRAS performance subscale consisted of 9 items: head, face, and voice tremor (items 1-3), UL tremor of right and left UL (item 4) in three tasks (forward outstretched postural tremor, lateral "wing-beating" postural tremor, kinetic tremor), Archimedes spirals with both hands, handwriting with motor-dominant hand, and dot approximation task with both hands (items 6-8), and lower limb tremor and standing tremor (items 5 and 9). Each item was rated from 0 (no tremor) to 4 (severe tremor) with overall performance score of 0 to 64, calculated as the sum of subscale items. Higher scores indicated greater tremor severity.	Baseline of Cycle 2 up to Week 6 (Cycle length =12 weeks)
Bilateral Treatment Period: Change From Cycle 2 Baseline to Week 6 in TETRAS ADL UL Score	TETRAS ADL subscale was another component of TETRAS. ADL subscale of TETRAS was completed by study subjects through an interview procedure to assess impact of tremor on activities of daily living. TETRAS ADL UL score was the sum of eight ADL items on UL tremor (items 2-9). Items were rated on a 5-point response scale each ranged from 0 (normal status/impact) to 4 (severe status/impact). The ADL UL score ranged from 0 to 32. Higher scores indicated greater tremor severity.	Baseline of Cycle 2 up to Week 6 (Cycle length = 12 weeks)
Bilateral Treatment Period: Change From Cycle 2 Baseline to Week 6 in TETRAS ADL Functional Impact Score	TETRAS ADL Functional Impact score was the sum of the following three ADL items: occupational impairment (item 10), overall disability (item 11), and social impact (item 12) of ET. The items are rated on a 5-point response scale each ranged from 0 (normal status/impact) to 4 (severe status/impact). The ADL Functional Impact score ranged from 0 to 12. Higher scores indicated greater tremor severity.	Baseline of Cycle 2 up to Week 6 (Cycle length = 12 weeks)
Percentage of Subjects With At-least One Treatment Related Treatment-emergent Adverse Events (TEAEs)	An adverse event (AE) is any untoward medical occurrence in subject administered pharmaceutical product. TEAEs of unilateral treatment period (Cycle 1) = AEs from first injection up to injection in the bilateral treatment period (Week 24). TEAEs of bilateral treatment period (Cycle 2) = AEs from injection in bilateral treatment period up to end of study (Week 36).	Unilateral Treatment Period: From first injection in unilateral treatment period up to re-injection in Bilateral Treatment Period (Week 24); Bilateral Treatment Period: From re-injection in Bilateral Treatment Period at Week 24 up to end of study(Week 36)
Unilateral Treatment Period: Subject's Global Impression of Change Scale (GICS) Score of Motor-dominant UL at Week 6	The GICS was used to evaluate overall clinical impression of change after treatment by the subject. The response option was a common 9-point Likert scale ranged from -4 to +4, with the following values: +4 (very much improved); +3 (much improved); +2 (improved); +1 (minimally improved); 0 (no change); -1 (minimally worse); -2 (worse); -3 (much worse); -4 (very much worse). A higher score indicated improvements.	Week 6
Unilateral Treatment Period: Investigator's GICS Score of Motor-dominant UL at Week 6	The GICS was used to evaluate the overall clinical impression of change after treatment by the investigator. The response option was a common 9-point Likert scale ranged from -4 to +4, with the following values: +4 (very much improved); +3 (much improved); +2 (improved); +1 (minimally improved); 0 (no change); -1 (minimally worse); -2 (worse); -3 (much worse); -4 (very much worse). A higher score indicated improvements.	Week 6

Collaborators and Investigators

• Sponsor: Merz Pharmaceuticals GmbH
• Investigators: Study Director: Merz Medical Expert, Merz Pharmaceuticals GmbH

Study record dates

Study Major Dates

• Study Start (Actual): February 24, 2021
• Primary Completion (Actual): April 26, 2023
• Study Completion (Actual): November 21, 2023

Study Registration Dates

• First Submitted: February 19, 2021
• First Submitted That Met QC Criteria: February 19, 2021
• First Posted (Actual): February 23, 2021

Study Record Updates

• Last Update Posted (Actual): May 28, 2026
• Last Update Submitted That Met QC Criteria: May 11, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Movement Disorders; Dyskinesias; Tremor; Essential Tremor; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Hydrolases; Enzymes; Enzymes and Coenzymes; Botulinum Toxins; Metalloendopeptidases; Endopeptidases; Peptide Hydrolases; Metalloproteases; Bacterial Proteins; Bacterial Toxins; Toxins, Biological; Botulinum Toxins, Type A; incobotulinumtoxinA
• Other Study ID Numbers: M602011069; 2021-001988-24 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No