Effect and Safety of Local Injection of Botulinum Toxin Type B Against Digital Ulcer in Systemic Sclerosis

NCT03007004 | Completed Phase 2

• 1 other identifier: D2016017
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Efficacy and safety of local infusion of botulinum toxin type B in patients with systemic sclerosis (SSc) with digital ulcer is evaluated by a randomized, double-blind study.

Conditions

Systemic Sclerosis Patients With Digital Ulcers

Keywords

Systemic aclerosis; digital ulcer; botulinum toxin

Outcome Measures

Primary Outcomes (1)

• Percentage of subjects who completely lost index ulcer 8 weeks after administration

  The primary end point was the percentage of subjects with complete disappearance of index ulcer 8 weeks after administration. The index ulcer was defined as the largest DUs in the hand. The size of DU was measured as both the longest diameter of the ulcer and the diameter perpendicular to the center of the ulcer's diameter. Complete disappearance is defined as the disappearance of the area of the ulcer that has become epithelialized and covered by the epidermis from the periphery of the ulcer and continued coverage of the ulcer surface area that has been restored.

  8 weeks after administration

Secondary Outcomes (10)

• the percentage of subjects with complete disappearance of index ulcer at 4, 12, and 16 weeks after administration

  at 4, 12, and 16 weeks after administration

• the rate of change in the number of DUs per hand

  at 4, 8, 12, and 16 weeks after administration

• the number of newly formed DUs

  at 4, 8, 12, and 16 weeks after administration

• the number of newly formed DUs per hand

  at 4, 8, 12, and 16 weeks after administration

• the changes in RP severity were assessed using Raynaud's Condition Score [RCS]

  at 4, 8, 12, and 16 weeks after administration

Study Arms (2)

Botulinum toxin group

EXPERIMENTAL

400 units in one injection site（0.2mL） Total 2000 units（1.0mL） （For both hands total 4000 units; 2.0 mL）

Drug: Botulinum toxin type B (2500 units / vial)

Physiological saline (control drug) group

SHAM COMPARATOR

0.2mL in one injection site Total 1.0mL (For both hands total 2.0 mL)

Drug: Physiological saline

Interventions

Botulinum toxin type B (2500 units / vial) DRUG

BTX-B (E2014, Eisai, NerBloc®) was injected subcutaneously from the palmar side into seven locations around interphalangeal metacarpophalangeal joints, targeting the neurovascular bundles just proximal to the A1 pulley (the radial and ulnar sides of the first finger, the radial side of second finger, the ulnar side of the fifth finger and between the second to fifth fingers). Three locations between the second and third fingers, the third and fourth fingers, and the fourth and fifth fingers were injected with 400 U (0.2 ml) of BTX-B. In addition, the radial and ulnar sides of the first finger, the radial side of the second finger, and the ulnar side of the fifth finger were injected with half a dose of BTX-B (200 units; 0.1 ml). A total of 2000 U (1.0 ml) of BTX-B was injected into one hand. Injections were performed using a 30-gauge needle.

Also known as: BTX-B (E2014, Eisai, NerBloc®)

Botulinum toxin group

Physiological saline DRUG

Saline solution was injected subcutaneously from the palmar side into seven locations around interphalangeal metacarpophalangeal joints, targeting the neurovascular bundles just proximal to the A1 pulley (the radial and ulnar sides of the first finger, the radial side of second finger, the ulnar side of the fifth finger and between the second to fifth fingers). Three locations between the second and third fingers, the third and fourth fingers, and the fourth and fifth fingers were injected with saline (0.2 ml). In addition, the radial and ulnar sides of the first finger, the radial side of the second finger, and the ulnar side of the fifth finger were injected with half a dose of saline (0.1 ml). A total of 1.0 ml of saline was injected into one hand. Injections were performed using a 30-gauge needle.

Physiological saline (control drug) group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients diagnosed with SSc in diagnostic criteria (Appendix 1) by the American-European Rheumatology Association
• Patients who have Raynaud's phenomenon from consultation, inquiries, etc. judged by Clinical responsibility (sharing) doctor
• Patients with digital ulcer at acquiring consent The criteria for digital ulcers are as follows.
• It is a peripheral ulcer from the proximal interphalangeal joint and the thumb interphalangeal joint (including the interphalangeal joint).
• The continuity of coating by the epithelium has been lost and there is a depth that is visible to the eye. Incidentally, when exposed, cases covered with eschar or necrotic tissue are also included.
• If the exposure is not clearly recognized (crusted or covered with necrotic tissue), the investigational responsibility (shared) doctor can judge that the epidermis and the dermis are missing.
• It should not be the paronychia、crack、digital pitting scars.
• It should not be attached to the projection of the calcification.
• Size: The maximum diameter (major axis) is 0.5 cm or more.
• Bones, tendons and joints are not exposed.
• It is not accompanied by obvious infection findings.
• At the time of acquiring consent Patients over 18 years old
• Patients for whom consent has been obtained in writing on participation of this trial

You may not qualify if:

• Patients with Raynaud's phenomenon due to diseases other than SSc
• Patients with systemic neuromuscular junction disorder (myasthenia gravis, Lambert-Eaton syndrome, amyotrophic lateral sclerosis etc.)
• Patients with advanced respiratory dysfunction
• Patients with a history of hypersensitivity to components of botulinum toxin type B (botulinum toxin type B, human serum albumin, succinate buffer) or other botulinum toxin
• Patients who received botulinum toxin formulation within 4 months before study drug administration or who have continued efficacy of botulinum toxin at the time of administration of investigational drug even when administered more than 4 months ago
• Patients who received endothelin receptor antagonist within 60 days before study drug administration
• Patients who received the following medications within 14 days prior to study drug administration
• Argatroban hydrate injection
• Prostaglandin E1 Injection (eg alprostadil injection)

Sponsors & Collaborators

• Gunma University: lead

Study Sites (1)

Gunma University Graduate school of Medicine

Morishita, Gunma, 371-8511, Japan

Location

MeSH Terms

Conditions

digital ulcers

Interventions

rimabotulinumtoxinB; batrachotoxinin A 20-alpha-benzoate

Study Officials

• Sei-ichiro Motegi

  Gunma University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: December 28, 2016
• First Posted: December 30, 2016
• Study Start: December 12, 2016
• Primary Completion: May 14, 2019
• Study Completion: May 14, 2019
• Last Updated: May 14, 2020

Record last verified: 2020-05

Locations

JP (1)