A Study to Evaluate the Botulinum Toxin Type A for Injection(HengLi®) in Subjects With Post-stroke Upper Limb Spasticity

NCT02280083 | Completed Phase 3 DMC

• 1 other identifier: HengLi002
• Study Type: interventional
• Target: 180
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a multicenter, double-blind, randomized, placebo-controlled study designed to compare Botulinum Toxin Type A for Injection (HengLi®) with placebo on the efficacy and safety of treatment in post-stroke subjects with focal wrist, finger and in some cases, thumb spasticity. Approximately 180 subjects will be enrolled. The core period of the subjects will receive a single treatment session of intramuscular HengLi® 200U or 240U (if thumb spasticity is present) or placebo in a randomization ratio of 2:1. Research contains two parts: core phase and extension phase. In the core phase, subjects will finish 6 visits (12 weeks ) after initial injection. During the extension phase, subjects will accept two follow-up visit (6 weeks). Outcome measures include changes from baseline at every post injection visit as measured on the Modified Ashworth Scale (MAS), Disability Assessment Scale (DAS) and Global Assessment Scale(GAS). The primary efficacy endpoint is the change from baseline at week 6 for wrist flexor muscle tone as measured on the Modified Ashworth Scale. Safety parameters will also be measured including adverse events, vital signs (pulse and blood pressure) and clinical laboratory tests (haematology, serum chemistry and urinanalysis).

Conditions

Cerebrovascular Accident

Keywords

Spasticity, Post-Stroke; Botulinum toxin type A for Injection; upper limb spasticity

Outcome Measures

Primary Outcomes (1)

• Change From Baseline at Week 6 of Wrist Flexor Muscle Tone is calculated by the Modified Ashworth Scale (MAS)

  The investigator, physiotherapist, or occupational therapist extended the participant's wrist as quickly as possible to grade flexor muscle tone. The MAS wrist score was calculated by using the 6-point MAS (0, 1, 1+ \[regarded as 1.5\], 2, 3, and 4; 0=no increase in muscle tone; 4=affected part\[s\] rigid in flexion/extension). Change from Baseline at Week 6 was calculated as the value at Week 6 minus the value at Baseline.

  Baseline (Day 0) and Week 6

Secondary Outcomes (8)

• Area Under the Curve (AUC) for the Change From Baseline at Weeks 6 and 12 for MAS Wrist Score

  Baseline (Day 0), Week 6, and Week 12

• Change From Baseline at Weeks 1, 4, 8, 12, 16 and 18 for Wrist Flexor Muscle Tone are calculated by the MAS

  Baseline (Day 0) and Weeks 1, 4, 8, 12, 16 and 18

• Proportion of subjects Classified as Wrist Treatment Responders at All Post-injection Visits

  Weeks 1, 4, 6, 8, 12, 16 and 18

• Changes From Baseline at Week 1, 4, 6, 8, 12, 16 and 18 of Finger Flexor Muscle Tone are calculated by the MAS

  Baseline (Day 0) and Weeks 1, 4, 6, 8, 12, 16 and 18

• Changes From Baseline at Week 1, 4, 6, 8, 12, 16 and 18 of Thumb Flexor Muscle Tone are calculated by the MAS

  Baseline (Day 0) and Weeks 1, 4, 6, 8, 12, 16 and 18

Study Arms (2)

Botulinum Toxin Type A for Injection

EXPERIMENTAL

HengLi002(Botulinum Toxin Type A for Injection,also known as "HengLi®")

Drug: Botulinum Toxin Type A for Injection

placebo

PLACEBO COMPARATOR

excipient

Drug: placebo

Interventions

Botulinum Toxin Type A for Injection DRUG

HengLi002(Botulinum Toxin Type A for Injection,also known as "HengLi®")

Also known as: HengLi®

Botulinum Toxin Type A for Injection

placebo DRUG

placebo

placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥40kg in weight.
• Subjects voluntarily sign the informed consent.
• Subjects with upper limb spasticity who are at least 3 months post stroke and present with spasticity of both the wrist and fingers in the study limb.
• Both wrist flexor muscle tone and finger flexor muscle tone evaluation recorded 2 or greater individually as measured by MAS (0 to 4).
• At least one functional disability item (i.e., hygiene, dressing, pain, or cosmesis) evaluated 2 or greater by DAS (0 to 3).
• If using oral anti-spasticity medications, must be stable for at least 1 month prior to study enrolment.
• If taking any physical therapy or occupational therapy, must be stable on frequency, type, and intension for at least 1 month prior to study enrolment.
• In the opinion of the investigator, subject must clearly understand the intent of the study and be willing and able to comply with study instructions and complete the entire study.

You may not qualify if:

• Females who are pregnant, nursing, or planning a pregnancy during the study period, or females of childbearing potential, not using a reliable means of contraception.
• Known allergy or sensitivity to study medication or its components.
• Infection or dermatological condition at the injection sites.
• Significant inflammation in the study limb limiting joint movement.
• Unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, esophageal or gastric varices or persistent jaundice), cirrhosis, known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• History of or planned surgical intervention for spasticity of the study limb.
• Participation in another clinical study currently, or within the one months immediately prior to enrolment.
• Within six months prior to the study had received any treatment of patients with botulinum toxin of any serotype.
• Any medical condition that may put the subject at increased risk with exposure , including diagnosed myasthenia gravis, Eaton-Lambert syndrome, amyotrophic lateral sclerosis, or any other disorder that might have interfered with neuromuscular function.
• History of or planned treatment for spasticity with phenol or alcohol block in the study limb.
• Current treatment for spasticity with an intrathecal baclofen.
• QTc criteria: (either QTcb or QTcf, machine or manual overread, males or females); include the following details as appropriate: QTc≥450 millisecond (msec) or≥480msec for subjects with Bundle Branch Block-values based on either single electrocardiogram (ECG) values or triplicate ECG averaged QTc values obtained over a brief recording period.
• Liver function tests: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≥2xULN; alkaline phosphatase and bilirubin \>1.5xULN (isolated bilirubin \>1.5ULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).
• Concurrent use of aminoglycoside antibiotics or other agents that might interfere with neuromuscular function.
• Presence of clinically unstable severe cardiovascular, renal or respiratory disease.

Sponsors & Collaborators

• Lanzhou Institute of Biological Products Co., Ltd: lead

MeSH Terms

Conditions

Stroke; Muscle Spasticity

Interventions

Botulinum Toxins, Type A; Injections; Hengli BTX-A

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Muscular Diseases; Musculoskeletal Diseases; Muscle Hypertonia; Neuromuscular Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Botulinum Toxins; Metalloendopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Metalloproteases; Bacterial Proteins; Proteins; Amino Acids, Peptides, and Proteins; Bacterial Toxins; Toxins, Biological; Biological Factors; Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Xinhua Wan, archiater

  Peking Union Medical College Hospital

  STUDY DIRECTOR

• Shengyuan Yu, archiater

  The General Hospital of People's Liberation Army(301 hospital)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 29, 2014
• First Posted: October 31, 2014
• Study Start: July 1, 2014
• Primary Completion: February 1, 2016
• Study Completion: September 1, 2016
• Last Updated: September 26, 2016

Record last verified: 2016-09

Data Sharing

• IPD Sharing: Will not share