Dysport in Hallux Abducto Valgus (HAV) Phase IIa (DYSTANCE)

A Multiple-dose, Double-blind, Randomised, Placebo-controlled Study to Evaluate the Efficacy and Safety of Dysport for the Treatment of Pain Associated With Hallux Abducto Valgus

The purpose of this study is to investigate the efficacy and safety of treatment with multiple doses of Dysport in adults suffering from clinically significant pain associated with HAV who have not undergone surgery for their condition.

Study Overview

• Status: Completed
• Conditions: Hallux Abducto Valgus
• Intervention / Treatment: Biological: Botulinum toxin type A; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 186
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Jonesboro, Arkansas, United States, 72401
      • NEA Baptist Clinic
    • Little Rock, Arkansas, United States, 72212
      • Applied Research Center of Arkansas, Inc
  • California
    • Castro Valley, California, United States, 94546
      • Center for Clinical Research Inc.
    • Fresno, California, United States, 93710
      • Limb Preservation Platform, Inc.
    • Los Angeles, California, United States, 90057
      • Foot and Ankle Clinic
    • Los Angeles, California, United States, 90033
      • Southwestern Academic Limb Salvage Alliance
    • Santa Monica, California, United States, 90403
      • University Foot and Ankle Institute
  • Colorado
    • Thornton, Colorado, United States, 80229
      • Center for Spine and Orthopedics
  • Florida
    • Miami, Florida, United States, 33126
      • LCC Medical Research Institute
    • Orlando, Florida, United States, 32822
      • Conquest Research
    • South Miami, Florida, United States, 33301
      • Doctors Research Network
    • West Palm Beach, Florida, United States, 33406
      • Clinical research
  • Illinois
    • Belleville, Illinois, United States, 62226
      • Podiatry 1st
    • Des Plaines, Illinois, United States, 60016
      • Weil Foot & Ankle Institute
    • North Chicago, Illinois, United States, 60064
      • Rosalind Franklin Clinic
    • Springfield, Illinois, United States, 62704
      • Foot and Ankle Center of Illinois
  • Maryland
    • Pasadena, Maryland, United States, 21122
      • The Chesapeake Research Group
  • Missouri
    • Saint Louis, Missouri, United States, 63117
      • Dr. Allen M. Jacobs and Associates
  • Ohio
    • Youngstown, Ohio, United States, 22801
      • Ankle and Foot Care Centers
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73109
      • Medical Research International
  • Pennsylvania
    • Bryn Mawr, Pennsylvania, United States, 19010
      • Foot and Ankle Center
    • Harrisburg, Pennsylvania, United States, 17112
      • Harrisburg Foot and Ankle Center, INC
  • Texas
    • McAllen, Texas, United States, 78501
      • Futuro Clinical Trials, LLC
    • San Antonio, Texas, United States, 78229
      • Bio X Cell Research
    • Webster, Texas, United States, 77598
      • Texas Gulf Coast Medical Group
  • Utah
    • Salt Lake City, Utah, United States, 84117
      • Summit Foot & Ankle
  • Virginia
    • Harrisonburg, Virginia, United States, 22801
      • Harrisonburg Foot and Ankle Clinic
    • Suffolk, Virginia, United States, 23434
      • 1Foot 2Foot Centre for Foot and Ankle Care, PC
  • West Virginia
    • Salem, West Virginia, United States, 24153
      • Martinsville Research Institute, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Clinical diagnosis of HAV
• Painful HAV in the study foot at Baseline

Exclusion Criteria:

• Flat or square metatarsal head, metatarsus primus elevates, or severe cavus/planus in the study foot
• Other podiatric or orthopedic condition which would interfere with the evaluation of pain and/or function
• Medical history or clinical evidence of any vascular disease and/or diabetic condition

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dysport Dose 1; Intramuscular injection of Dysport on day 1 of double-blind period, followed by up to 2 open-label injections during open-label cycles, during approximately 36 weeks.	Biological: Botulinum toxin type A; Investigators will inject the reconstituted solution into foot muscles.; Other Names: AbobotulinumtoxinA (Dysport®); Clostridium botulinum toxin type A haemagglutinin complex (BTX-A-HAC)
Experimental: Dysport Dose 2; Intramuscular injection of Dysport on day 1 of double-blind period, followed by up to 2 open-label injections during open-label cycles, during approximately 36 weeks.	Biological: Botulinum toxin type A; Investigators will inject the reconstituted solution into foot muscles.; Other Names: AbobotulinumtoxinA (Dysport®); Clostridium botulinum toxin type A haemagglutinin complex (BTX-A-HAC)
Placebo Comparator: Placebo; Intramuscular injection of Placebo on day 1 of cycle 1 (double-blind period)	Drug: Placebo; Investigators will inject the reconstituted solution into foot muscles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Least Square (LS) Mean Change From Baseline in the Daily Numeric Pain Rating Scale (NPRS) Score at Week 8	The NPRS is a widely used and validated unidimensional measure of pain intensity in adults. Participants were asked to rate the intensity of their foot pain during physical activity (example, walking, standing or running) based on an 11-point scale ranging from 0 to 10, where 0 represents "no pain" and 10 represents "worst possible pain". Higher scores indicate a worse outcome. Daily pain intensities were recorded by the participant using an electronic diary (eDiary) for 7 consecutive days prior to each study visit. Baseline was defined as the daily NPRS score averaged over the 7 consecutive days prior to the Baseline visit (Day 1).	Baseline and Week 8 in the double-blind treatment period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
LS Mean Change From Baseline in the Daily NPRS Score at Weeks 4 and 12	The NPRS is a widely used and validated unidimensional measure of pain intensity in adults. Participants were asked to rate the intensity of their foot pain during physical activity (example, walking, standing or running) based on an 11-point scale ranging from 0 to 10, where 0 represents "no pain" and 10 represents "worst possible pain". Higher scores indicate a worse outcome. Daily pain intensities were recorded by the participant using an eDiary for 7 consecutive days prior to each study visit. Baseline was defined as the daily NPRS score averaged over the 7 consecutive days prior to the Baseline visit (Day 1).	Baseline and Weeks 4 and 12 in the double-blind treatment period
LS Mean Change From Baseline in the Daily Modified Foot Function Index (mFFI) Disability Subscale Score at Weeks 4, 8 and 12	The foot function index (FFI) was developed to assess foot-related pain, disability and activity limitations and later revised to include foot-related health and quality of life. A modified version of FFI specific to this study was used. The mFFI consists of a total of 21 items grouped into 3 subscales: pain (7 questions), disability (9 questions) and activity limitation (5 questions). The mFFI disability subscale is rated using numeric rating scale ranging from 0 to 10, where 0 represents "no difficulty" and 10 represents "so difficult unable to do". For each item, the participant was asked to record the number value which best corresponded to effect of the foot complaints. To obtain a subscale score, the item scores for a given subscale (i.e., pain, disability or activity limitation subscales) were totaled and divided by maximum total possible and then multiplied by 100. Each subscale score, as well as the total score, ranged from 0 to 100. Higher scores indicate a worse outcome.	Baseline and Weeks 4, 8 and 12 in the double-blind treatment period
LS Mean Change From Baseline in the Daily mFFI Pain Subscale Score at Weeks 4, 8 and 12	The FFI was developed to assess foot-related pain, disability and activity limitations and later revised to include foot-related health and quality of life. A modified version of the FFI specific to this study was used. The mFFI consists of a total of 21 items grouped into 3 subscales: pain (7 questions), disability (9 questions) and activity limitation (5 questions). The mFFI pain subscale is rated using numeric rating scale ranging from 0 to 10, where 0 represents "no pain" and 10 represents "worst pain imaginable". For each item, the participant was asked to record the number value which best corresponded to the effect of the foot complaints. To obtain a subscale score, the item scores for a given subscale (i.e., pain, disability or activity limitation subscales) were totaled and divided by the maximum total possible and then multiplied by 100. Each subscale score, as well as the total score, ranged from 0 to 100. Higher scores indicate a worse outcome.	Baseline and Weeks 4, 8 and 12 in the double-blind treatment period
LS Mean Change From Baseline in the Daily mFFI Total Score at Weeks 4, 8 and 12	The FFI was developed to assess foot-related pain, disability and activity limitations and later revised to include foot-related health and quality of life. A modified version of the FFI specific to this study was used. The mFFI consists of a total of 21 items grouped into three subscales: pain (7 questions), disability (9 questions) and activity limitation (5 questions). The mFFI items are rated using numeric rating scales ranging from 0 to 10, where 0 represents "no pain/no difficulty/none of the time" and 10 represents "worst pain imaginable/so difficult unable to do/all of the time" for pain, disability and activity limitation subscales, respectively. For each item, the participant was asked to record the number value which best corresponded to the effect of the foot complaints. To obtain a total score, the scores of all 3 subscales were totaled and divided by 3. Each subscale score, as well as the total score, ranged from 0 to 100. Higher scores indicate a worse outcome.	Baseline and Weeks 4, 8 and 12 in the double-blind treatment period
LS Mean Change From Baseline in the Daily mFFI Activity Limitation Subscale Score at Weeks 4, 8 and 12	The FFI was developed to assess foot-related pain, disability and activity limitations and later revised to include foot-related health and quality of life. A modified version of the FFI specific to this study was used. The mFFI consists of a total of 21 items grouped into 3 subscales: pain (7 questions), disability (9 questions) and activity limitation (5 questions). The mFFI activity limitation subscale is rated using numeric rating scale ranging from 0 to 10, where 0 represents "none of the time" and 10 represents "all of the time". For each item, the participant was asked to record the number value which best corresponded to the effect of the foot complaints. To obtain a subscale score, the item scores for a given subscale (i.e., pain, disability or activity limitation subscales) were totaled and divided by the maximum total possible and then multiplied by 100. Each subscale score, as well as the total score, ranged from 0 to 100. Higher scores indicate a worse outcome.	Baseline and Weeks 4, 8 and 12 in the double-blind treatment period
LS Mean Change From Baseline in HV Angle at Weeks 4, 8 and 12	The HV angle was measured directly on weight-bearing anteriorposterior radiographs, in which the X-ray beam was angled 15° towards the heel centered on the second tarsometatarsal joint with a source to image-receptor distance of 100 centimeters (cm).	Baseline and Weeks 4, 8 and 12 in the double-blind treatment period
LS Mean Change From Baseline in Intermetatarsal Angle at Weeks 4, 8 and 12	The intermetatarsal angle was measured directly on weight-bearing anteriorposterior radiographs, in which the X-ray beam was angled 15° towards the heel centered on the second tarsometatarsal joint with a source to image-receptor distance of 100 cm.	Baseline and Weeks 4, 8 and 12 in the double-blind treatment period
Median Time to Retreatment	Time to retreatment was calculated as ([Date of retreatment - previous injection date] + 1) / 7 (week). Time to retreatment was calculated for each cycle and the data presented here for the double-blind treatment period.	Up to 24 weeks in the double-blind treatment period
LS Mean Change From Baseline in Patient Global Impression of Severity (PGI-S) of Foot Pain Score at Weeks 4, 8 and 12	An assessment of PGI-S of foot pain was conducted by the participant using a 4-point Likert scale ranging from 0= no pain to 3= severe pain. Higher scores indicate a worse outcome. The PGI-S was assessed by the participant by answering the following question: "How severe was your foot pain while performing physical activities (example, standing, walking or running) over the past week?" (0=no pain; 1=mild pain; 2=moderate pain; 3=severe pain).	Baseline and Weeks 4, 8 and 12 in the double-blind treatment period
LS Mean Change From Baseline in PGI-S of Disability Score at Weeks 4, 8 and 12	An assessment of PGI-S of disability was conducted by the participant using a 4-point Likert scale ranging from 0= no disability to 3= severe disability. Higher scores indicate a worse outcome. The PGI-S was assessed by the participant by answering the following question: "How severe was your disability while performing physical activities (example, standing, walking or running) over the past week?" (0=no disability; 1=mild disability; 2=moderate disability; 3=severe disability).	Baseline and Weeks 4, 8 and 12 in the double-blind treatment period
LS Mean Patient Global Impression of Improvement (PGI-I) of Foot Pain Score at Weeks 4, 8 and 12	An assessment of PGI-I of foot pain was conducted by the participant using a 7-point Likert scale ranging from -3= very much worse to +3= very much improved. Higher scores indicate a better outcome. The PGI-I was assessed by the participant answering the following question: "Compared to your foot pain prior to the study treatment initiation, your foot pain while performing physical activities (example, standing, walking or running) now is: +3=very much improved; +2=much improved; +1=minimally improved; 0=no change; -1=minimally worse; -2=much worse; -3=very much worse".	Weeks 4, 8 and 12 in the double-blind treatment period
LS Mean PGI-I of Disability Score at Weeks 4, 8 and 12	An assessment of PGI-I of the participant's disability was conducted by the participant using a 7-point Likert scale ranging from -3= very much worse to +3= very much improved. Higher scores indicate a better outcome. The PGI-I was assessed by the participant answering the following question: "Compared to your disability prior to the study treatment initiation, your disability while performing physical activities (example, standing, walking or running) now is: +3=very much improved; +2=much improved; +1=minimally improved; 0=no change; -1=minimally worse; -2=much worse; -3=very much worse".	Weeks 4, 8 and 12 in the double-blind treatment period
Mean Change From Baseline in 36-Item Short Form Health Survey (SF-36) Score at Weeks 8 and 12	The SF-36 is a 36-item questionnaire which measures the extent to which physical health impacts an individual's functional ability and perceived wellbeing in mental, social, and physical aspects of life. The SF-36 has 8 subscales: physical function, role physical, bodily pain, global health, vitality, social function, role emotional and mental health. Each scale ranges from 0-100, where 0= lowest level of health and 100= highest level of health. Scores on these subscales can be aggregated into the physical component summary (physical function, role physical, bodily pain and global health) and mental component summary (mental health, vitality, social function and role emotional). Physical component summary score ranges from 0.65 to 80.73 and mental component summary score ranges from -8.81 to 81.65, where low score indicates lowest level of health and high score indicates highest level of health. Positive change from Baseline indicates an improvement in quality of life.	Baseline and Weeks 8 and 12 in the double-blind treatment period

Collaborators and Investigators

• Sponsor: Ipsen

Study record dates

Study Major Dates

• Study Start (Actual): June 19, 2018
• Primary Completion (Actual): December 17, 2019
• Study Completion (Actual): May 22, 2020

Study Registration Dates

• First Submitted: June 14, 2018
• First Submitted That Met QC Criteria: June 14, 2018
• First Posted (Actual): June 26, 2018

Study Record Updates

• Last Update Posted (Actual): July 2, 2021
• Last Update Submitted That Met QC Criteria: July 1, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Cholinergic Agents; Immunologic Factors; Membrane Transport Modulators; Acetylcholine Release Inhibitors; Neuromuscular Agents; Agglutinins; Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA; Hemagglutinins
• Other Study ID Numbers: D-FR-52120-237

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No