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NCT03569098: DYSTANCE

Dysport in Hallux Abducto Valgus (HAV) Phase IIa

Completed Phase 2 Results posted Last updated 2 July 2021
What this trial tests

Phase 2 trial testing Botulinum toxin type A in Hallux Abducto Valgus in 186 participants. Completed in 22 May 2020.

Timeline
19 June 2018
Primary endpoint
17 December 2019
22 May 2020

Quick facts

Lead sponsorIpsen
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposetreatment
Enrollment186
Start date19 June 2018
Primary completion17 December 2019
Estimated completion22 May 2020
Sites29 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Ipsen — full company profile →

Who can join

18 and older, any sex, with Hallux Abducto Valgus. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Least Square (LS) Mean Change From Baseline in the Daily Numeric Pain Rating Scale (NPRS) Score at Week 8 Primary · Baseline and Week 8 in the double-blind treatment period

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 d

GroupValue95% CI
Placebo-2.04-2.66 – -1.41
Dysport 300 U-1.71-2.33 – -1.10
Dysport 500 U-2.40-3.03 – -1.77
LS Mean Change From Baseline in the Daily NPRS Score at Weeks 4 and 12 Secondary · Baseline and Weeks 4 and 12 in the double-blind treatment period

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 Ba

Week 4
GroupValue95% CI
Placebo-1.68-2.26 – -1.11
Dysport 300 U-1.36-1.94 – -0.78
Dysport 500 U-1.85-2.45 – -1.25
Week 12
GroupValue95% CI
Placebo-1.72-2.35 – -1.09
Dysport 300 U-1.61-2.23 – -1.00
Dysport 500 U-2.42-3.06 – -1.78
LS Mean Change From Baseline in the Daily Modified Foot Function Index (mFFI) Disability Subscale Score at Weeks 4, 8 and 12 Secondary · Baseline and Weeks 4, 8 and 12 in the double-blind treatment period

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 t

Week 4
GroupValue95% CI
Placebo-17.95-23.06 – -12.84
Dysport 300 U-15.29-20.47 – -10.12
Dysport 500 U-16.87-22.27 – -11.48
Week 8
GroupValue95% CI
Placebo-22.44-28.00 – -16.87
Dysport 300 U-18.68-24.19 – -13.17
Dysport 500 U-21.26-27.05 – -15.48
Week 12
GroupValue95% CI
Placebo-17.21-23.11 – -11.31
Dysport 300 U-21.04-26.80 – -15.27
Dysport 500 U-21.50-27.61 – -15.39
LS Mean Change From Baseline in the Daily mFFI Pain Subscale Score at Weeks 4, 8 and 12 Secondary · Baseline and Weeks 4, 8 and 12 in the double-blind treatment period

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 be

Week 4
GroupValue95% CI
Placebo-17.97-23.23 – -12.70
Dysport 300 U-15.67-21.00 – -10.33
Dysport 500 U-19.30-24.86 – -13.73
Week 8
GroupValue95% CI
Placebo-22.30-28.15 – -16.45
Dysport 300 U-20.69-26.50 – -14.88
Dysport 500 U-24.58-30.67 – -18.49
Week 12
GroupValue95% CI
Placebo-18.94-25.05 – -12.83
Dysport 300 U-21.74-27.72 – -15.76
Dysport 500 U-24.30-30.64 – -17.96
LS Mean Change From Baseline in the Daily mFFI Total Score at Weeks 4, 8 and 12 Secondary · Baseline and Weeks 4, 8 and 12 in the double-blind treatment period

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 pa

Week 4
GroupValue95% CI
Placebo-14.87-18.98 – -10.75
Dysport 300 U-12.80-16.96 – -8.64
Dysport 500 U-15.10-19.45 – -10.76
Week 8
GroupValue95% CI
Placebo-18.82-23.32 – -14.32
Dysport 300 U-16.16-20.62 – -11.69
Dysport 500 U-18.79-23.48 – -14.11
Week 12
GroupValue95% CI
Placebo-15.65-20.48 – -10.82
Dysport 300 U-17.45-22.18 – -12.72
Dysport 500 U-18.89-23.90 – -13.88
LS Mean Change From Baseline in the Daily mFFI Activity Limitation Subscale Score at Weeks 4, 8 and 12 Secondary · Baseline and Weeks 4, 8 and 12 in the double-blind treatment period

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 num

Week 4
GroupValue95% CI
Placebo-9.02-12.08 – -5.96
Dysport 300 U-7.00-10.08 – -3.91
Dysport 500 U-9.03-12.28 – -5.79
Week 8
GroupValue95% CI
Placebo-12.12-15.52 – -8.71
Dysport 300 U-8.81-12.17 – -5.45
Dysport 500 U-10.62-14.17 – -7.07
Week 12
GroupValue95% CI
Placebo-11.09-14.79 – -7.40
Dysport 300 U-9.25-12.87 – -5.63
Dysport 500 U-10.84-14.69 – -6.99
LS Mean Change From Baseline in HV Angle at Weeks 4, 8 and 12 Secondary · Baseline and Weeks 4, 8 and 12 in the double-blind treatment period

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).

Week 4
GroupValue95% CI
Placebo-0.31-1.06 – 0.45
Dysport 300 U-0.25-0.99 – 0.49
Dysport 500 U-0.92-1.71 – -0.13
Week 8
GroupValue95% CI
Placebo-0.43-1.17 – 0.30
Dysport 300 U-0.67-1.40 – 0.05
Dysport 500 U-0.80-1.57 – -0.04
Week 12
GroupValue95% CI
Placebo0.30-0.44 – 1.05
Dysport 300 U-0.68-1.41 – 0.04
Dysport 500 U-0.45-1.22 – 0.33
LS Mean Change From Baseline in Intermetatarsal Angle at Weeks 4, 8 and 12 Secondary · Baseline and Weeks 4, 8 and 12 in the double-blind treatment period

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.

Week 4
GroupValue95% CI
Placebo0.06-0.34 – 0.46
Dysport 300 U0.400.01 – 0.79
Dysport 500 U0.16-0.25 – 0.58
Week 8
GroupValue95% CI
Placebo-0.02-0.41 – 0.36
Dysport 300 U0.490.11 – 0.87
Dysport 500 U0.450.05 – 0.85
Week 12
GroupValue95% CI
Placebo0.420.01 – 0.83
Dysport 300 U0.19-0.21 – 0.59
Dysport 500 U0.04-0.38 – 0.47
Median Time to Retreatment Secondary · Up to 24 weeks in the double-blind treatment period

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.

GroupValue95% CI
Placebo12.612 – 13
Dysport 300 U13.113 – 16
Dysport 500 U13.113 – 15
LS Mean Change From Baseline in Patient Global Impression of Severity (PGI-S) of Foot Pain Score at Weeks 4, 8 and 12 Secondary · Baseline and Weeks 4, 8 and 12 in the double-blind treatment period

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).

Week 4
GroupValue95% CI
Placebo-0.76-0.99 – -0.54
Dysport 300 U-0.56-0.80 – -0.32
Dysport 500 U-0.46-0.71 – -0.22
Week 8
GroupValue95% CI
Placebo-0.74-0.97 – -0.51
Dysport 300 U-0.64-0.88 – -0.39
Dysport 500 U-0.79-1.03 – -0.56
Week 12
GroupValue95% CI
Placebo-0.58-0.82 – -0.35
Dysport 300 U-0.59-0.82 – -0.36
Dysport 500 U-0.60-0.85 – -0.35
LS Mean Change From Baseline in PGI-S of Disability Score at Weeks 4, 8 and 12 Secondary · Baseline and Weeks 4, 8 and 12 in the double-blind treatment period

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).

Week 4
GroupValue95% CI
Placebo-0.47-0.70 – -0.25
Dysport 300 U-0.57-0.82 – -0.32
Dysport 500 U-0.42-0.68 – -0.16
Week 8
GroupValue95% CI
Placebo-0.54-0.80 – -0.28
Dysport 300 U-0.66-0.93 – -0.38
Dysport 500 U-0.68-0.94 – -0.42
Week 12
GroupValue95% CI
Placebo-0.55-0.80 – -0.31
Dysport 300 U-0.63-0.87 – -0.38
Dysport 500 U-0.67-0.93 – -0.40
LS Mean Patient Global Impression of Improvement (PGI-I) of Foot Pain Score at Weeks 4, 8 and 12 Secondary · Weeks 4, 8 and 12 in the double-blind treatment period

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".

Week 4
GroupValue95% CI
Placebo1.320.98 – 1.65
Dysport 300 U1.320.98 – 1.66
Dysport 500 U1.531.17 – 1.90
Week 8
GroupValue95% CI
Placebo1.300.94 – 1.67
Dysport 300 U1.361.00 – 1.73
Dysport 500 U1.320.96 – 1.69
Week 12
GroupValue95% CI
Placebo1.280.93 – 1.63
Dysport 300 U1.401.07 – 1.74
Dysport 500 U1.210.83 – 1.59

Adverse events — posted to ClinicalTrials.gov

Time frame: From first administration of study drug (Cycle 1 Day 1) up to end of the study, approximately 36 weeks.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Double-Blind Treatment Period (Cycle 1): Placebo
Serious: 0/61 (0%)
Deaths: 0/61
Double-Blind Treatment Period (Cycle 1): Dysport 300 U
Serious: 0/63 (0%)
Deaths: 0/63
Double-Blind Treatment Period (Cycle 1): Dysport 500 U
Serious: 1/56 (2%)
Deaths: 0/56
Open-Label Treatment Period (Cycle 2): Dysport 300 U
Serious: 1/146 (1%)
Deaths: 0/146
Open-Label Treatment Period (Cycle 3): Dysport 300 U
Serious: 0/8 (0%)
Deaths: 0/8
Open-Label Treatment Period (Cycle 3): Dysport 500 U
Serious: 1/56 (2%)
Deaths: 0/56

Serious adverse events (5 terms)

ReactionSystemDouble-Blind Treatment Per…Double-Blind Treatment Per…Double-Blind Treatment Per…Open-Label Treatment Perio…Open-Label Treatment Perio…Open-Label Treatment Perio…
Chronic myeloid leukaemiaNeoplasms benign, malignant and unspecified (incl cysts and polyps)
AphasiaNervous system disorders
Abdominal painGastrointestinal disorders
ConstipationGastrointestinal disorders
Colitis ischaemicGastrointestinal disorders
Other adverse events (3 terms — click to expand)

ReactionSystemDouble-Blind Treatment Per…Double-Blind Treatment Per…Double-Blind Treatment Per…Open-Label Treatment Perio…Open-Label Treatment Perio…Open-Label Treatment Perio…
Pain in extremityMusculoskeletal and connective tissue disorders
HyperkeratosisSkin and subcutaneous tissue disorders
Injection site painGeneral disorders

Most-reported serious reactions: Chronic myeloid leukaemia, Aphasia, Abdominal pain, Constipation, Colitis ischaemic.

Data from ClinicalTrials.gov NCT03569098 adverse events section.

Sponsor's own description

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.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Exploring the Relationship Between Clinical Presentation in Hallux Valgus and Response to AbobotulinumtoxinA Treatment.
    Baravarian B, DiDomenico LA, Volteau M, Armstrong DG, et al · · 2023 · cited 2× · PMID 36804286 · DOI 10.1053/j.jfas.2022.12.016
  2. Pain Reduction With AbobotulinumtoxinA for the Treatment of Hallux Valgus in Adult Participants: Results of a Randomized and Placebo-Controlled Phase 2 Trial.
    Armstrong DG, DiDomenico LA, Baravarian B, Parekh SG, et al · · 2023 · cited 1× · PMID 36335048 · DOI 10.1053/j.jfas.2022.07.002
  3. AbobotulinumtoxinA in the Management of Hallux Valgus in Adult Patients: Results of a Randomised And Placebo-Controlled Phase 2 Trial
    · 2020

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