Study of Abobotulinum Toxin Versus Neubotulinum Toxin Injection For Hemifacial Spasm in Thai Patients — DNHFS  

Hemifacial Spasm Clinical Trial

Official title: A 50-Week Prospective, Double-Blinded, Randomized, Cross-over Design in Multicenter Study of100 Unit of Abobotulinum Toxin Type A (Dysport®) Versus 33.33 Unit of Neubotulinum Toxin Type A (Neuronox®) Injection for Hemifacial Spasm in Thai Patients

Status Not yet recruiting

Clinical Trial Summary

A 50-Week Prospective, Double-Blinded, Randomized, Cross-over design in Multicenter Study of 100 unit of Abobotulinum Toxin Type A (Dysport®) versus 33.33 unit of Neubotulinum Toxin Type A (Neuronox®) Injection for Hemifacial Spasm in Thai Patients, designed gor comparing the effectiveness of Total intensity score after 4. 12. 16 and 24 weeks of treatment and to compare the long-term safety of the injections. Abobotulinum toxin A (Dysport *) dose 100 units compared ot neubotulinum toxin A injection (Neuronox / Neuronox®) dose 33.33 units. that it si non-inferiority (non-inferiority) ni the treatment of hemifacial spasm after administration of the drug ni the 0, 12" ,26", and 38" weeks ni the treatment of patients with hemi facial spasm, with a wash out period of 2 weeks between treatments. By proving the non-inferiority of Total intensity score at ,4 ,8 and12 week after treatment which calculated by severity score and duration of facial muscle spasm (hour per day)., as well as severity score and duration of functional impairment (hour per day) recorded for 4,8, and 21 weeks after each treatment between 33.33 unit of Neubotulinum Toxin Type A(Neuronox*) and 100 unit of Abobotulinum Toxin Type A (Dysport*)

Clinical Trial Description

There were two treatment arms in crossover designed study and the interest was on the comparison of total intensity score, duration of hemifcial spasm and duration of functional impairment in each pre- and post- treatment outcomes of (Dysport®) and (Neuronox®) , two pair-wised comparisons pre and post treatment after ,4- 8- and 12-week scale were carried out. For each of the pair-wise comparison, 2-sided p-value was used ot ensure that the overall Type I error-0.05. Beta error 80% (Multiple repeated analysis and general linear model may be analyses) in the efficacy of treatment. Two-sided exact p-values were reported in the efficacy analyses. Demographic and safety analyses were based on the summary of descriptive statistics.This study had a washout period of 2 weeks because there was a study on hemifacial spasm that Botulinum toxin A loses its effect before 12 weeks from a study of its action by Katalin Bihari and colleagues who found that Onabotulinumtoxin A (Botox®) has a duration of action in hemifacial spasm of 64.3 days compared to Abobotulinum toxin A (Dysport ®) has a duration of action ni hemifacial spasm of 41.8 days 5 (reference Bihari K. Safety, effectiveness, and duration of effect of Botox after switching from disport for blepharospasm, cervical dystonia and hemifacial spasm. Curr Med Res Opin 2005 Mar; 21(3):433-8). Another 5 studies as follows: Lolekha (2017) found that Onabotulinumtoxin A (Botox®) had a duration of action ni hemifacial spasm of 72.24 days. A, Yoshimura (1992) found that Onabotulinumtoxin A (Botox ®) has a duration of action in hemifacial spasm of 84 days. A, Rieder (2007) found that Onabotulinumtoxin A (Botox®) has a duration of action in hemifacial spasm of 71 days. A, Quagliato (2010) found that Onabotulinumtoxin A(Botox®) There is a duration of action in hemifacial spasm of 89.6 days. A and Kongsaengdao (2012) found that Neu-botulinumtoxin A (Neuronox®) / Abobotulinum Toxin A (Dysport®) had a clear measurement of the duration of action with a Patient diary that recorded symptoms for everyday. The duration of action in hemifacial spasm is 84 days, which has been shown to be no different from Neubotulinum toxin This study required a washout period in this study of 14 days, which si 98 days from the second injection ni V2, which si longer than the longest duration in the double blind randomized controll study. By Quagliato's (2010) which the effect ni hemifacial spasm lasting for 89.6 days.

Studies which not double blinded, randomized studies with a prospective trial design and clearly measured duration of action (Duration of effect from review or estimation or inference) cannot be used as a reference for this study due ot study bias.

Screening Period (-1 to 0 week):

At the screening visit and prior to performance of any study procedures, the investigators would explain the details of the study and the subject would have to sign on the written informed consent, exclusion criteria, and inclusion criteria.

Each subject who was willing to enrol into the study was asked about their medical history as well as their recent and current medications being taken.

Al enrolled subjects were asked to undertake an initial physical examination and had to satisty the criteria for the inclusion /exclusion before being enrolled into the study.

Al patients were asked to complete physical examination, HFS 30, AIMS, SF36, PHQ-9 and CES-D.

Laboratory blood (livers tests, haematology,) examinations, urine pregnancy test) were performed for safety reasons.

Double-Blind Treatment Period Inclusion visit: week -1-0 (V0-1)

After the screening period, al eligible subjects were entered into the treatment period and received either intramuscular injection of 33.33 unit of Neubotulinum Toxin Type A (0.3 ml) or 10 unit of Abobotulinum Toxin Type A. (0.3 ml) The injection was only performed after the subject was confirmed to be eligible against al the inclusion and exclusion criteria. The inclusion visit included the followings examination and tests before injection:

• physical and neurological examinations,

• vital signs,

• weight, urine pregnancy test (if suspected pregnancy or loss regular menstration), CBC, NIR laboratory test ni case of history of abnormal bleeding, HFS 30, AIMS, SF36, PHQ-9 and CES-D, Dispense Patient diary. Concomitant-treatment.

Folow up Visits V2, V3, V4, V5, V6 Visit 2 (V2) Al subject were asked ot complete physical examination, HFS 30, AIMS, SF36, PHQ-9 and CES-D and Patient diary wil be collected and dispense the new Patient diary before injection.

During of the visit, the investigator would conduct before injection:

• physical examination and neurological examination,

• monitoring of the vital signs,

• weight measurements,

• urine pregnancy test (if suspected pregnancy or loss regular menstration),

• Clinical global impression scale (CGIC-physician and patient),

• adverse events,

• Concomitant-treatment. after that, patient will receive either intramuscular injection of 100 unit of Abobotulinum Toxin Type A. (0.3 ml) or 33.33 unit of Neubotulinum Toxin Type A (0.3 ml) as same as Inclusion visit.

Visit 3 (V3) (performed after washout period 2 weeks ) Al subject were asked to complete physical examination, HFS 30, AIMS, SF36, PHQ-9, CGIC and CES-D and Patient diary wil be colected and dispense hte new Patient diary before injection.

During of the visit, the investigator would conduct before injection:

• physical examination and neurological examination,

• monitoring of the vital signs,

• weight measurements,

• urine pregnancy test (if suspected pregnancy or loss regular menstration),

• Clinical global impression scale (CGIC- physician and patient),

• adverse events,

• Concomitant-treatment. after that, patient will receive either intramuscular injection of 50 unit of Neubotulinum Toxin Type A (0.3 ml) or 250 unit of Abobotulinum Toxin Type A. (0.3 ml) by crossover trement with Inclusion visit and visit 2.

Visit 4(V4) All subject were asked to complete physical examination, HFS 30, AIMS, SF36, PHQ-9 and CES-D and Patient diary wil be collected and dispense the new Patient diary.

During of hte visit, the investigator would conduct before injection:

• physical examination and neurological examination,

• monitoring of the vital signs,

• weight measurements,

• urine pregnancy test (if suspected pregnancy or loss regular menstration),

• Clinical global impression scale (CGIC- physician and patient),

• adverse events, after that, patient will receive either intramuscular injection of 33.33 unit of Neubotulinum Toxin Type A(0.3 ml) or 10 unit of Abobotulinum Toxin Type A. (0.3 ml) as same as visit 3.

end Visit (V5) Al subject were asked to complete physical examination, HFS 30, AIMS, SF36, CGIC PHQ-9 and CES-D and Patient diary wil be collected

During of the visit, the investigator would conduct:

• physical examination and neurological examination,

• monitoring of the vital signs,

• weight measurements,

• urine pregnancy test (if suspected pregnancy or loss regular menstration),

• Clinical global impression scale (CGI - physician and patient),

• adverse events,

• Concomitant-treatment. after that patient may received either intramuscular injection of 100 unit of Abobotulinum Toxin Type A. (0.3 ml) or 33.33 unit of Neubotulinum Toxin Type A (0.3 ml) by re-emburstment from national policy.

NOTE: After 4 weeks of treatment of botulinum toxin A injection (weeks 4,16,24,30,42) there was a telephone call, interview, questionnaire HFS 30, AIMS, SF 36, CESD, PHQ9.

Safety folow up Visit (SFV, V6) Al subject were asked ot complete physical examination, by standard botulinum toxin clinic assessment.

During of the visit, the investigator would conduct:

• physical examination and neurological examination,

• monitoring of the vital signs,

• weight measurements,

• urine pregnancy test (if suspected pregnancy or loss regular menstration),, -Clinical global impression scale (CGIC- investigators and patient), adverse events,

• Concomitant-treatment, after that patient may received either 100 unit of Abobotulinum Toxin Type A. (0.3 ml) or 33.33 unit of Neubotulinum Toxin Type A (33.3 ml) by re- emburstment from national policy.

Study Population The study population consisted of male or female subjects, ages ranged between 18-80 years old, diagnosed with hemifacial spasm. These subjects were randomized ot receive 10 unit of Abobotulinum Toxin Type A(Dysport®) and 33.33 unit of Neubotulinum Toxin Type A(Neuronox®) injection in cross-over designed.

Study Duration The study duration was conducted over 62 weeks (-1 to 0 week for the screening period and four of 12-week interval for the double-blind cross over treatment period ( washout period 2 weeks between V2 and V3),and 12 week follow up period. ;

Related Conditions & MeSH terms

• Hemifacial Spasm
• Spasm

• NCT number: NCT04589364
• Study type: Interventional
• Source: Rajavithi Hospital
• Contact: subsai kongsaengdao, M.D.
• Phone: +66818180890
• Email: skhongsa@gmail.com
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: May 1, 2024
• Completion date: August 1, 2026