Essential Tremor of the Upper LimbPhase 2NCT04766723
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
A Phase 2 study testing NT 201 in people with Essential Tremor of the Upper Limb, run by Merz Pharmaceuticals GmbH at 14 sites in 3 countries.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Essential Tremor of the Upper Limb
- What is being tested?
- NT 201
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 78 participants
- Where
- 14 sitesin 3 countries
- Study dates
- 24 Feb 2021to 21 Nov 2023
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
14 sites in 3 countries.
14 sites in 3 countries
United States9 sites
Houston Methodist Neurological Institute, Merz Investigational Site #0010226
Houston, Texas, 77030
Cleveland Clinic Lou Ruvo Center for Brain Health, Merz Investigational Site #0010457
Las Vegas, Nevada, 89106
Medstar Georgetown Neurology, Merz Investigational Site #0010231
McLean, Virginia, 22101
Vanderbilt University Medical Center, Neuroscience Institute, Merz Investigational Site #0010206
Nashville, Tennessee, 37232
Mount Sinai Medical Center, Merz Investigational Site #0010191
New York, New York, 10029
University of Nebraska Medical Center, Merz Investigational Site #0010269
Omaha, Nebraska, 68131
UW Medical Center - Montlake, Merz Investigational Site #0010450
Seattle, Washington, 98195
Selkirk Neurology, Merz Investigational Site #0010456
Spokane, Washington, 99202
USF, Department of Neurology, Merz Investigational Site #0010020
Tampa, Florida, 33612
Poland4 sites
Specjalistyczne Gabinety, Merz Investigational Site #0480059
Krakow, 30-539
NeuroKlinika Gabinet Lekarski, Merz Investigational Site #0480101
Lodz, 90-640
Instytut Zdrowia Dr. Boczarska-Jedynak
Oświęcim, 32-600
Mazowiecki Szpital Bródnowski, Merz Investigational Site #0480064
Warsaw, 03-242
Canada1 site
London Health Sciences Centre, Merz Investigational Site #0010087
London, Ontario, N6A 5A5
About this study
Official title: 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.
- Conditions
- Essential Tremor of the Upper Limb
- Being tested
- NT 201, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NT 201Drug
Also called Incobotulinumtoxin A, IncobotulinumtoxinA, Xeomin, Botulinum toxin type A (150 kiloDalton), free from complexing proteins
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).
PlaceboDrug
Solution for injection prepared by reconstitution of powder with 0.9% Sodium Chloride (NaCl).
| Study group | Role | What they receive |
|---|---|---|
| NT 201 (IncobotulinumtoxinA, Xeomin) | Experimental | 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. Receives: Drug: NT 201 |
| Placebo | Placebo comparator | 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. Receives: Drug: NT 201; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline up to Week 6
Secondary outcomes (10)
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.
Measured: 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.
Measured: 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.
Measured: Baseline up to Week 6
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Feb 2021
- Study start24 Feb 2021
- Primary completion26 Apr 2023
- Study completion21 Nov 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Essential Tremor of the Upper LimbStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 78 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merz Pharmaceuticals GmbH
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Merz Medical Expert, Study director, Merz Pharmaceuticals GmbH
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04766723
- Sponsor's protocol ID
- M602011069
- Other IDs
- 2021-001988-24
- Status last verified
- May 2026
- First submitted
- 19 Feb 2021
- Last updated
- 28 May 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No