A study to investigate DYSPORT® for the treatment of subjects with loss of bladder control and involuntary urination as a result of spinal cord injury or multiple sclerosis

• Register: EUCTR
• Last refreshed on: 25 November 2019
• Main ID: EUCTR2015-000507-44-BE
• Date of registration: 08/03/2016
• Prospective Registration: Yes
• Primary sponsor: Ipsen Innovation
• Public title: A study to investigate DYSPORT® for the treatment of subjects with loss of bladder control and involuntary urination as a result of spinal cord injury or multiple sclerosis
• Scientific title: A PHASE III, MULTICENTRE, RANDOMISED, DOUBLE BLIND, PARALLEL GROUP, PLACEBO CONTROLLED STUDY TO ASSESS THE EFFICACY AND SAFETY OF ONE OR MORE INTRADETRUSOR TREATMENTS OF 600 OR 800 UNITS OF DYSPORT® FOR THE TREATMENT OF URINARY INCONTINENCE IN SUBJECTS WITH NEUROGENIC DETRUSOR OVERACTIVITY DUE TO SPINAL CORD INJURY OR MULTIPLE SCLEROSIS
• Date of first enrolment: 31/03/2016
• Target sample size: 330
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-000507-44
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 4
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Belgium, Brazil, Chile, Colombia, France, Germany, Israel, Lithuania, Mexico, New Zealand, Peru, Russian Federation, Spain, Ukraine, United Kingdom

Contacts

• Name: Global Drug Development
• Affiliation: Ipsen Innovation

• Name: Global Drug Development
• Affiliation: Ipsen Innovation

Key inclusion & exclusion criteria

Inclusion criteria:
The following inclusion criteria will be assessed at the beginning of the Screening process:

1) Written informed consent prior to any study-related procedure.

2) Male or female, aged 18 to 80 years inclusive.

3) UI for at least 3 months prior to Screening as a result of NDO due to SCI or MS.

4) Subjects with SCI must have a stable neurological injury at T1 level or below which occurred at least 6 months prior to Screening.
OR
Subjects with MS must be clinically stable in the investigator’s opinion, with no exacerbation (relapse) of MS for at least 3 months prior to Screening.

5) Subjects in the non-urodynamic subset only, must have NDO (defined as the presence of involuntary detrusor contractions during the storage phase of urodynamic filling cystometry) on a historic urodynamic assessment performed in the 12 months prior to Screening
• If urodynamics are not performed in the 12 months prior to Screening or if results are not available, then a urodynamic filling cystometry assessment must be performed during Screening, per local practice (see inclusion criterion # 16).

6) Subjects must have had an inadequate response after at least 4 weeks of oral medications used in the treatment of NDO (e.g. anticholinergics, beta-3 agonists)and/or have intolerable side-effects.

7) Subjects who are to continue on concomitant oral medications for NDO during the study must be on a stable dose for at least 4 weeks prior to Screening.

8) Subjects who are to continue on concomitant oral medications for NDO during the study must be willing to continue on the same medications and doses during Screening and for at least 12 weeks following the first IMP administration.

9) Routinely performing CIC to ensure adequate bladder emptying (regularly performing CIC at a regimen of every 4–6 hours during waking hours, or more frequently). CIC regimen must be stable for at least 4 weeks prior to Screening (CIC may be performed by the subject or caregiver).

10) Subjects must be willing to continue on the same CIC regimen during Screening and for at least 12 weeks following the first IMP administration.

11) Female subjects of childbearing potential must have a negative pregnancy test result and be willing to use reliable contraceptive measures throughout study participation. Reliable forms of contraception include but are not limited to:
• hormonal contraceptives (e.g. oral, patch, injection)
• double barrier (e.g. male condom plus spermicide, or female diaphragm plus
spermicide)
• intrauterine device
• male partner has had a vasectomy
• total abstinence from intercourse with male partners (periodic abstinence is not
acceptable).
Female subjects meeting any of the following criteria are not considered to be of
childbearing potential:
• postmenopausal (=47 years of age and amenorrhoeic for at least 12 consecutive months)
• have been sterilised s
Exclusion criteria:
The following exclusion criteria will be assessed throughout the Screening process:

1) Any current condition (other than NDO) that may impact on bladder function, including but not limited to:
• predominant stress UI (rather than NDO-related incontinence)
• bladder stones
• current symptomatic urinary tract infection
• current active genitourinary infection, e.g. genital warts
• uterine prolapse
• cystocele
• rectocele.
Mild uterine prolapse, cystocele or rectocele that does not impact on bladder function
is not exclusionary.

2) Previous or current, tumour or malignancy affecting the spinal column or spinal cord, or any other nonstable cause of SCI.

3) Surgery less than 6 months prior to Screening for bladder stones.

4) Surgery less than 6 months prior to Screening for uterine prolapse, cystocele or rectocele.

5) Previous open surgery for NDO, e.g. augmentation cystoplasty.

6) Previous urethral stent placement or sphincterotomy.

7) Previous or current diagnosis of, or symptoms/signs/investigations suggestive of, significant urological or pelvic disease, including but not limited to:
• urinary tract malignancy (e.g. bladder, prostate, urethral or kidney cancer)
• hydronephrosis
• interstitial cystitis/bladder pain syndrome
• müllerian duct cysts
• radiation cystitis
• genitourinary tuberculosis.

8) Previous or current uninvestigated haematuria. Subjects with investigated haematuria may enter the study if significant urological/renal pathology has been ruled out to the satisfaction of the investigator.

9) Any condition that will prevent cystoscopic treatment administration or CIC usage e.g. urethral strictures.

10) Current indwelling bladder catheter, or removal of indwelling bladder catheter less than 4 weeks prior to Screening.

11) BTX-A treatment within 9 months prior to Screening for any urological condition
(e.g. detrusor or urethral sphincter treatments).

12) BTX-A treatment within 3 months prior to Screening for any non-urological condition.

13) Bladder instillation with any pharmacologic agent less than 3 months prior to
Screening.

14) Use of capsaicin or resiniferatoxin less than 6 months prior to Screening.

15) Any neuromodulation/electrostimulation usage for urinary symptoms/incontinence
within 4 weeks prior to Screening. Any implanted neuromodulation device must be switched off at least 4 weeks prior to Screening and must remain off throughout study participation.

16) Any concomitant therapy usage that, in the investigator’s opinion, would interfere with the evaluation of safety or efficacy of the IMP, and/or confound the study results.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Not possible to specify

Urinary incontinence caused by neurogenic detrusor overactivity due to either spinal cord injury or multiple sclerosis
MedDRA version: 20.1 Level: PT Classification code 10046543 Term: Urinary incontinence System Organ Class: 10038359 - Renal and urinary disorders

Intervention(s)

Trade Name: Dysport®
Product Name: Dysport®
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: CLOSTRIDIUM BOTULINUM TOXIN TYPE A
CAS Number: 93384-43-1
Current Sponsor code: 52120
Other descriptive name: BOTULINUM TOXIN A - HAEMAGGLUTININ COMPLEX
Concentration unit: U unit(s)
Concentration type: equal
Concentration number: 300-
Pharmaceutical form of the placebo: Powder for solution for injection
Route of administration of the placebo: Intravesical use

Trade Name: Dysport®
Product Name: Dysport®
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: CLOSTRIDIUM BOTULINUM TOXIN TYPE A
CAS Number: 93384-43-1
Current Sponsor code: 52120
Other descriptive name: BOTULINUM TOXIN A - HAEMAGGLUTININ COMPLEX
Concentration unit: U unit(s)
Concentration type: equal
Concentration number: 500-
Pharmaceutical form of the placebo: Powder for solution for injection
Route of administration of the placebo: Intravesical use

Primary Outcome(s)

Main Objective: • To assess the efficacy of two Dysport® doses (600 units (U) and 800 U), compared to placebo in reducing UI from Baseline to Week 6 following the first investigational medicinal product (IMP) administration.

Primary end point(s): • Mean change from study Baseline (assessed at Screening) to Week 6 after the first IMP administration in the weekly number of UI episodes:
• measured on a 7-day bladder diary.

Timepoint(s) of evaluation of this end point: Week 6

Secondary Objective: • To assess the efficacy of two Dysport® doses (600 U and 800 U), compared to placebo in improving bladder diary measures, urodynamic and patient-reported efficacy endpoints following the first IMP administration, including assessing duration of effect.

• To assess the efficacy of two Dysport® doses (600 U and 800 U) in improving bladder diary measures, urodynamic and patient-reported efficacy endpoints following retreatment IMP administrations, including assessing duration of effect.

• To assess the safety of two Dysport® doses (600 U and 800 U) for the treatment of UI due to NDO.

Secondary Outcome(s)

Secondary end point(s): Bladder diary measures:
• weekly number of UI episodes
• daily urinary frequency (total, spontaneous void only, CIC only)
• 24-hour voided volume (total, spontaneous void only, CIC only)
• volume per void (total, spontaneous void only, CIC only).

Urodynamic measures (urodynamic subset only):
• maximum cystometric capacity (MCC)
• maximum detrusor pressure (MDP) during storage
• volume at first involuntary detrusor contraction (Vol@1stIDC)
• maximum detrusor pressure at first involuntary detrusor contraction (PdetMax@1stIDC)
• end fill pressure (EFP)
• detrusor compliance (DC).

Patient-reported outcome questionnaires:
• incontinence quality of life (I-QoL) total summary score
• EuroQol 5-dimension 5-level (EQ-5D-5L)
• modified patient global impression - improvement (mPGI-I) score.

Proportion of subjects at post-treatment timepoints following the first and subsequent
treatments with:
• no episodes of UI (i.e. continence is achieved)
• UI response at several levels (i.e. =30% improvement, =50% improvement,
=75% improvement, etc.)
• no IDCs on urodynamic assessment (i.e. urodynamic cure is achieved)
(urodynamic subset only).

Duration of effect following the first and subsequent treatments measured by:
• time to request retreatment
• time to eligibility for retreatment
• time between treatments.

Timepoint(s) of evaluation of this end point: Refer to schedule of events in protocol

Secondary ID(s)

D-FR-52120-223

2015-000507-44-DE

Source(s) of Monetary Support

Ipsen Innovation

Ethics review

Status: Approved
Approval date:
Contact: