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An open-label, uncontrolled, single-arm study of NT 201 in patients with cervical dystonia

An open-label, uncontrolled, single-arm study of NT 201 in patients with cervical dystonia

30

A total of 30 patients (Group A: 27, Group B: 3) who had provided informed consent were enrolled and received the study drug. Group A included patients diagnosed with idiopathic cervical dystonia (CD). Group B comprised patients with tardive dyskinesia (cervical) or tardive CD. By the 48-week mark, 29 patients received up to seven multiple injections. One patient discontinued treatment after the third injection and did not receive the fourth injection. The reason for discontinuation was "withdrawn at patient's request". All 30 patients were included in both the FAS and safety population. All of the 30 patients included in the FAS were Japanese, of whom 20 (66.7%) were male and 10 (33.3%) were female. The duration of CD [mean (SD)] was 92.58 (123.9) months in Group A and 111.17 (31.0) months in Group B. Of the 27 patients in Group A, 7 (25.9%) were botulinum toxin-naive and 20 (74.1%) had previous botulinum toxin treatment, while all 3 (100%) patients in Group B had previous botulinum toxin treatment. In Group A, the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) total score [mean (SD)] of botulinum toxin-naive patients and those with previous botulinum toxin treatment was 47.07 (7.45) and 45.95 (11.32), respectively. In Group B, the TWSTRS total score [mean (SD)] was 45.75 (1.32). Based on TWSTRS severity score categories, in Group A, 8 (29.6%) patients had moderate (TWSTRS severity score: 16-21) CD and 19 (70.4%) exhibited severe (TWSTRS severity score: 22-35) CD, while in Group B, all 3 (100.0%) patients had severe CD. Overall, 22 (73.3%) patients had severe CD and 8 (26.7%) had moderate CD.

Number of patients enrolled: 30 patients Full analysis set (FAS): 30 patients Safety population: 30 patients

Adverse Events (AEs) were reported in 80.0% (24/30), and related AEs were observed 46.7% (14/30). Serious AEs were reported in 3.3% (1/30). The event was considered not related to the investigational drug. None of patients reported deaths or AEs leading to study discontinuation occurred, and all AEs were of mild to moderate severity. The most frequently reported AEs were dysphagia [33.3% (10/30)], followed by nasopharyngitis [23.3% (7/30)] and muscular weakness [20.0% (6/30)]. The most common related AE was dysphagia [33.3% (10/30)], followed by muscular weakness [20.0% (6/30)]. All cases of dysphagia resolved during the study period. No trend toward an increased incidence of AEs with increasing dose was observed. The incidence of AEs by dose group were 100.0% (1/1) at <120 U, 60.0% (6/10) at >=120 to <240 U, 44.4% (4/9) at >=240 to <300 U, 42.9% (3/7) at >=300 to <400 U, 66.7% (8/12) at >=400 to <500 U, and 68.8% (11/16) at 500 U. The incidence of AEs following the second injection: 55.6% (10/18) for >=6 to <8 weeks, 59.3% (16/27) for >=8 to <12 weeks, and 60.0% (6/10) for >=12 weeks. No apparent trend toward a higher incidence of AEs were observed in patients with shorter intervals (<8 weeks).

<Primary Endpoint> In Group A (n=27), the Least squares mean (LSM) (standard error) of the change in the TWSTRS total score from baseline to 4 weeks after the administration, the primary endpoint, was -11.0 (1.77) (95% CI: -14.6, -7.3). The upper limit of the 95% CI (-7.3) was below the pre-specified threshold of efficacy (-3.0); thus, the primary endpoint was achieved. <Secondary Endpoint> In Group A, the TWSTRS subscores for severity, disability, and pain at first injection baseline [mean (SD)] was 23.0 (3.2), 12.8 (4.7), 10.5 (4.3). The mean of change from the first injection baseline at Week 4 in the TWSTRS severity, disability, and pain score [mean (SD)] was -5.7 (5.4), -3.0 (2.7), -2.3 (4.2), respectively. The change from the first injection baseline at Week 4 in the CDIP-58 [mean (SD)], assessed by patients covering 8 domains -head and neck symptoms, pain and discomfort, upper extremity movement, gait, sleeping, irritability, mood, and psychosocial functioning- was -7.07 (11.5). In Group A, Patient Evaluation of Global Response (PEGR) score [mean (SD)] at the first injection was 0.7 (1.29). At baseline, subscale D of the Modified Tsui Scale [mean (SD)] in Group A accompanied by head tremor was 1.5 (1.0) (n=16), the mean of change from the first injection baseline at Week 4 in the subscale D of the Modified Tsui Scale [mean (SD)] was -0.4 (0.6).

This Phase III open-label, single-arm study in 30 Japanese patients with CD evaluated NT 201 over 48 weeks (<= 500 U; >= 6 week-intervals). The primary endpoint (LSM of change from baseline in TWSTRS total score to 4 weeks after the first injection) met pre-specified criteria, improvements were also seen in motor symptoms, ADL, pain, QOL, and head tremor. NT 201 demonstrated consistent improvements with repeated injections . No severe or serious AE occurred, and no new safety signals were identified.

July. 27, 2026

July. 15, 2026

https://www.mdpi.com/2035-8377/18/7/136

No

https://jrct.mhlw.go.jp/latest-detail/jRCT2031230690

Sasaki Yuzuru

Teijin Pharma Limited

2-1, Kasumigaseki 3-chome, Chiyoda-ku, Tokyo 100-8585, Japan

nt201c-ct@teijin.co.jp

Sasaki Yuzuru

Teijin Pharma Limited

2-1, Kasumigaseki 3-chome, Chiyoda-ku, Tokyo 100-8585, Japan

+81-80-8539-8088

nt201c-ct@teijin.co.jp

Complete

April. 16, 2024

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

treatment purpose

The investigator will select subjects for Group A who meet all of the following criteria (1) to (10).
(1) Patients whose written informed consent has been obtained before participating in this study
(2) Patients aged 18 to 75 years at the time of informed consent
(3) A clinical diagnosed of cervical dystonia
(4) TWSTRS - total score >= 20 at the screening test
(5) TWSTRS - severity score >= 10 at the screening test
(6) TWSTRS - disability score >= 3 at the screening test
(7) TWSTRS - pain score >= 1 at the screening test
(8)For patients treated with a botulinum toxin therapy for cervical dystonia: At least 10 weeks must have been passed between the last injection with botulinum toxin for cervical dystonia and the screening test (The screening test can be conducted on the same day of the next 10 weeks or later after the last injection)
(9)For patients treated with a botulinum toxin therapy for cervical dystonia: The effect of the most recent botulinum treatment has disappeared in terms of the TWSTRS score at the time of the screening test, and the investigator has determined that the next botulinum toxin injection is required
(10)For patients treated with a botulinum toxin therapy for cervical dystonia: The investigator has determined that the therapeutic effect of the botulinum toxin preparation has been obtained with the most recent injection

The investigator will select subjects for Group B who meet all of (1), (2), (4) to (10), and the following criteria (11).
(11) A clinical diagnosed of tardive torticollis

[Exclusion criteria applicable to Group A and Group B]
(1) Traumatic torticollis and congenital torticollis
(2) Patients who only have symptoms of anterocollis, or among patients with symptoms other than anterocollis, patients with a TWSTRS - severity score for anterocollis >= 2 at the screening test
(3) Patients with a history of deep brain stimulation therapy, intrathecal baclofen therapy, or surgical therapy for cervical dystonia (myotomy, selective peripheral nerve blockade, etc.)
(4) Marked limitation on passive range of cervical motion that suggests contractures or other malformations
(5) Patients with systemic neuromuscular junction disorders (myasthenia gravis, Lambert-Eaton syndrome, etc.), patients with amyotrophic lateral sclerosis
(6) Treatment with botulinum toxins for any injection other than cervical dystonia within 16 weeks prior to baseline
(The screening test can be conducted on the same day of the next 16 weeks or later after the last injection)
(7) Patients who have been judged by the investigator to have had primary or secondary non-responder due to previous injection of botulinum toxin preparations
(8) Patients for whom one or more weeks have not passed since the last administration of anticoagulants (heparin, warfarin, etc.) by the date of the screening test (antiplatelet drugs are permitted)
(The screening test can be conducted on the same day of the next week or later after the last administration)
(9) Dysphagia scale >= 3: sever, with swallowing difficulties and requiring a change in diet
(10) Patients who need to perform the applicable prohibited concomitant treatment after the date of the screening test and until the completion of main period (excluding observation period after main period) or the completion of the final termination visit
(11) Patients whose dosage or administration of the applicable concomitant restricted drug(s) was changed in the last one week before the screening test (the screening test can be conducted on the same day of the next week or later after changing the dosage or administration), or patients whose dosage or administration of the applicable concomitant restricted drug(s) needs to be changed until the completion of the main period (excluding observation period thereafter)

[Exclusion criteria applicable only to Group A]
(12) Patients with tardive torticollis
(13) Patients who only have symptoms of retrocollis, or among patients with symptoms other than retrocollis, patients with a TWSTRS - severity score for retrocollis >= 2 at the screening test

Both

Cervical Dystonia

The investigator administers NT 201 to the patient's affected muscle. Dosing period should be 42 weeks.

Change from baseline in the TWSTRS- Total score at 4 weeks after the first injection

(1) TWSTRS-total score
(Excluding change from baseline to 4 week)
(2) TWSTRS Severity Score, TWSTRS Disability Score, TWSTRS Pain Score
(3) Cervical Dystonia Impact Profile (CDIP-58)
(4) Patient Evaluation of Global Response (PEGR)
(5) Global Assessment of Efficacy by Investigator (GAEI)
(6) Modified Tsui scale sub scale D (head tremor evaluation)
(7) Pain Visual Analogue Scale (VAS)
(8) EQ-5D-5L
(9) Duration of treatment
(10) Time to Onset of Treatment Effect After Injection
(11) Time to Waning of Treatment Effect After Injection

+81-45-722-8655

Feb. 15, 2024

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