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

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

29

A total of 29 patients provided written informed consent and were enrolled in the study. None of them discontinued the study. Among these 29 patients, 26 received a fourth injection and 3 received a seventh injection. All 29 patients were included in the full analysis set (FAS) and in the safety population. All 29 patients were Japanese. The majority (26 [89.7%]) of the patients were women, and the mean (standard deviation [SD]) age was 64.6 (11.18) years. The mean (SD) duration of blepharospasm was 86.55 (87.39) months. Among the 29 patients, 23 (79.3%) had previously received botulinum toxin treatment for blepharospasm, with all 23 receiving onabotulinumtoxinA. The mean (SD) Jankovic Rating Scale (JRS) severity score at baseline was 3.24 (0.58). In total, 6 (20.7%) patients had a medical history, and the most common (>=2 patients) medical history was cataract and eyelid ptosis (2 patients each). A total of 27 (93.1%) patients had comorbidities, and the most common comorbidity was hypertension, which was reported in 8 (27.6%) patients. One (3.4%) patient had symptoms of blepharoptosis at baseline.

Number of patients enrolled: 29 patients Full analysis set (FAS): 29 patients Safety population: 29 patients

Throughout the study period, adverse events (AEs) and treatment-related AEs were observed in 19 (65.5%) and 7 (24.1%) patients, respectively, in the safety population. None of the patients reported serious AEs, serious treatment-related AEs, or AEs leading to death or study discontinuation, and all AEs were mild to moderate in severity. The most commonly reported AEs were nasopharyngitis (5 [17.2%] patients) and eyelid ptosis (4 [13.8%] patients). The most commonly reported treatment-related AE was eyelid ptosis, which was observed in 4 (13.8%) patients. All patients reporting treatment-related AEs recovered without sequelae and continued treatment with NT 201. The proportion of patients experiencing AEs decreased with the number of injections, from 37.9% during the first injection cycle to 30.8% during the fourth injection cycle, and further to 0.0% during the seventh injection cycle. No notable trends were observed in the incidence rates of AEs when patients were stratified by NT 201 dose (58.8% [10/17 patients] at <=50 U, 50.0% [7/14 patients] at >50 to <=75 U, and 44.4% [4/9 patients] at >75 to <=100 U) or dosing interval (36.4% [4/11 patients] at >=6 to <8 weeks, 38.1% [8/21 patients] at >=8 to <12 weeks, and 30.0% [6/20 patients] at >=12 weeks). Among the AEs of special interest (effects on distal muscles, hypersensitivity reactions, eye disorders, convulsive attacks, and injection site reactions), eye disorders (31.0% [9/29 patients]) and effects on distal muscles (24.1% [7/29 patients]) were the most commonly observed. There were no notable findings related to laboratory parameters or vital signs.

<Primary Endpoint> The least squares (LS) mean of change in the JRS severity score from baseline to 6 weeks after the first injection was -2.08 (95% confidence interval [CI]: -2.49, -1.66; mixed-effects model for repeated measures [MMRM] analysis). The results met the prespecified efficacy criteria (the upper limit of the 95% CI was below the threshold value of -0.59). Similar results were obtained in the sensitivity analysis. <Secondary Endpoints> At baseline (before the initiation of the first injection), the mean (SD) of the JRS severity score, JRS frequency score, and JRS total score was 3.24 (0.58), 2.72 (0.75), and 5.97 (1.21), respectively (n = 29 for all). The JRS severity score, frequency score, and total score exhibited a trend toward reduction from baseline up to 48 weeks with repeated NT 201 injections. The mean (SD) of change in the JRS severity score from baseline was -1.97 (0.865) at 3 weeks after the first injection (n = 29) and -2.11 (1.100) at 6 weeks after the first injection (n = 28). During subsequent injections, the change in the JRS severity score at 6 weeks (mean [SD]) ranged from -1.38 (1.261) to -2.00 (0.00). The JRS severity, frequency, and total scores showed a reduction (improvement) from the first injection baseline at all assessment points, indicating sustained efficacy of NT 201 with a maximum of 7 injection cycles. The mean (SD) Blepharospasm Disability Index (BSDI) score at baseline was 1.65 (0.90) (n = 17). The BSDI score showed a sustained decrease from baseline to 48 weeks with repeated NT 201 injections. The mean (SD) of change from baseline in the BSDI score was -0.43 (0.577) at 3 weeks after the first injection (n = 16) and -0.34 (0.466) at 6 weeks after the first injection (n = 17). During subsequent injections, the change in the BSDI score (mean [SD]) ranged from -0.15 (0.420) to -0.92 (0.118) at baseline and from -0.30 (0.398) to -1.06 (0.255) at 6 weeks. The BSDI score showed a reduction (improvement) from the first injection baseline at all assessment points. The mean (SD) Patient Evaluation of Global Response (PEGR) score was 2.0 (1.13) for the first injection cycle (n = 29). The PEGR score showed a trend toward a reduction (improvement) from the first injection baseline in patient-assessed blepharospasm symptoms throughout the study period. The score in the fast blinking test (mean [SD]) was 2.3 (0.8) at baseline (n = 29), 1.0 (0.9) at 3 weeks after the first injection (n = 29), and 0.7 (0.7) at 6 weeks after the first injection (n = 28). During subsequent injections, the fast blinking test score (mean [SD]) ranged from 1.0 (0.0) to 1.7 (1.0) at baseline and 0.9 (0.8) to 1.2 (0.9) at 6 weeks. The quality of blinking showed improvement from the first injection baseline at all assessment points with repeated NT 201 injections.

This open-label, multicenter, phase 3 study evaluated the efficacy and safety of NT 201 in Japanese patients with blepharospasm. 29 patients received repeated NT 201 injections at doses up to 100 U for 48 weeks. The primary endpoint, LS mean of change from baseline in the JRS severity score to 6 weeks after the first injection, met the prespecified efficacy criteria. Secondary endpoints supported sustained efficacy. No severe or serious AEs were reported. No new safety concerns were identified.

May. 08, 2026

Feb. 20, 2026

https://www.mdpi.com/2072-6651/18/2/109

No

https://jrct.mhlw.go.jp/latest-detail/jRCT2031230711

Hashizuka Masahiro

Teijin Pharma Limited

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

nt201b-ct@teijin.co.jp

Hashizuka Masahiro

Teijin Pharma Limited

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

+81-80-8304-6255

nt201b-ct@teijin.co.jp

Complete

May. 16, 2024

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

treatment purpose

Subjects must meet all of the following inclusion criteria.
(1) Written Informed consent obtained from subject before participating
(2) Age >= 18 years and =< 80 years at the time of informed consent
(3) A clinical diagnosis of blepharospasm
(4) Jankovic Rating Scale (JRS) severity score >= 2 at the screening visit
(5) Only for pretreated patients:
At least 10 weeks must have passed between the last injection with botulinum toxin for blepharospasm and the screening visit
(6) Only for pretreated patients:
Patients presenting with symptoms of blepharospasm and need for injection of botulinum toxin.

Subjects shall be excluded from this study if any of the following exclusion criteria.
(1) Psychotropic drugs induced blepharospasm
(2) The main symptom is apraxia of the eyelid opening
(3) Only for pretreated patients: No therapeutic response was observed with botulinum treatment for blepharospasm
(4) Treatment with botulism toxins for any injection other than blepharospasm (hemifacial spasm, cervical dystonia, cosmetics, etc.) within 16 weeks prior to the screening visit
(5) History of surgery for the treatment of dystonia including blepharospasm and myotomy surgery in the affected muscles
(6) Patients who have initiated, discontinued, or changed pharmaceuticals for the treatment of dystonia including blepharospasm within 12 weeks prior to screening visit
(7) Use any other investigational drugs/medical devices/products within 12 weeks prior to screening visit
(8) Patients who are planning to receive the prohibited concomitant medications from screening visit until the final visit
(9) Patients who are planning to start, discontinue or change the restricted concomitant medications by the end of the primary outcome measure from screening visit
(10) Myasthenia gravis, Lambert-Eaton syndrome, amyotrophic lateral sclerosis, or any other significant neuromuscular disease
(11) Infection in the area of the planned injection points or concerns about worsening systemic infection due to the local injection into the affected muscles
(12) Hypersensitivity to human serum albumin, sucrose, or Botulinum toxin A
(13) Pregnant women, patients who may be pregnant, patients who wish to become pregnant during the study period, or nursing mothers
(14) Women of childbearing potential who are unwilling or unable to use highly effective contraception from the date of informed consent until 16 weeks after the last injection of NT 201. [e.g., intrauterine device (IUD), intrauterine contraceptive system (IUS), oral contraceptives (low-dose pills), contraceptive surgery, or double barrier methods (e.g. condoms with spermicide, or condoms and pessaries) ]
(15) Severe or uncontrolled systemic diseases (e.g., cardiac, renal, pulmonary, hepatic, or gastrointestinal), malignant tumors, or known HIV infection in medical history
(16) Known or history of alcoholism or substance abuse
(17) Other than the above, patients judged by the investigator to be unsuitable for this study

Both

Blepharospasm

NT 201 is injected into the affected muscles. Dosing period should be 42 weeks.

Change from baseline in JRS severity score at 6 weeks after the first injection

(1) JRS (severity score, frequency score, total score)
(2) Blepharospasm Disability Index (BSDI)
(3) Patient Evaluation of Global Response (PEGR)
(4) EQ-5D-5L
(5) Blink test
(6) Time to onset of treatment effect after injection
(7) Time to waning of treatment effect after injection
(8) Duration of treatment interval
(9) Investigator's Global Assessment of Efficacy

+81-3-6779-8166

Feb. 22, 2024

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