E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10064124 |
E.1.2 | Term | Cervical dystonia |
E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary study objectives will be assessed in terms of improvement of the subject’s CD at a pre-defined time point after treatment. The primary study objectives are to demonstrate the superiority of Dysport RU to placebo in terms of efficacy and to test the non-inferior efficacy of Dysport RU, when compared to Dysport, in CD subjects. In addition to testing for the primary study objectives, the superiority in terms of efficacy of Dysport versus placebo, will be assessed.
|
|
E.2.2 | Secondary objectives of the trial |
The secondary study objectives are the assessment of the short and long term clinical safety and efficacy of Dysport RU following repeated treatment cycles. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
All subjects must fulfil the following inclusion criteria to be eligible for the study:
(1) Provision of written informed consent prior to any study related procedures being carried out. In this study consent may be provided by the legal guardian or caregiver.
(2) Male or female of legal age of consent for each participating country (i.e. ≥18 years).
(3) Cervical Dystonia with at least 18 months duration since onset.
(4) Previously untreated with BTX-A or -B or if previously treated with BTX-A or -B, a minimum of 14 weeks since the last injection must have elapsed.
(5) Toronto Western Spasmodic Torticollis Rating Scale scores meeting the following criteria at baseline:
- TWSTRS - Total score ≥30.
- TWSTRS - Severity Sub-scale score ≥15.
- TWSTRS - Disability Sub-scale score ≥3.
- TWSTRS - Pain Sub-scale score ≥2. |
|
E.4 | Principal exclusion criteria |
Subjects will not be included in the study if any of the following are present/apply:
(1) Known hypersensitivity to BTX or related compounds, or any component in the study drug formulations (including cow milk protein).
(2) Pure anterocollis or pure retrocollis.
(3) In apparent remission from CD.
(4) Previous poor response as determined by standard practice at each site, (e.g. <20% improvement in TWSTRS total score from baseline to Week 4) to the last two BTX-A or -B treatments.
(5) A known requirement for fewer than 80 or more than 300 BOTOX® units injected into the neck muscles, fewer than 4,000 U or more than 12,500 U of BTX-B, or <250 U or >1000 U of Dysport.
(6) Subjects that are being treated with BTX-B due to lack of efficacy to BTX-A or have known neutralising antibodies to BTX-A.
(7) A requirement for BTX injection(s) into site(s) of the body other than the neck and unable to avoid such treatment(s) for the duration of the study.
(8) A known clinically significant underlying swallowing or respiratory abnormality which might be exacerbated by BTX treatment.
(9) Have sub-clinical or clinical evidence of marked defective neuromuscular transmission (e.g. myasthenia gravis) or persistent clinically significant neuromuscular weakness or a condition that would interfere with TWSTRS scoring.
(10) A total body weight less than 100 lbs (45.4 kg).
(11) Previous phenol or alcohol injections into the neck muscles.
(12) Previous myotomy or denervation surgery involving the neck or shoulder region.
(13) Cervical contracture that limits passive range of motion.
(14) Treatment with any drug that interferes either directly or indirectly with neuromuscular function (e.g. aminoglycoside antibiotics) within the last 30 days prior to study treatment.
(15) A current or expected requirement for concomitant medication that may interfere with the evaluation of study treatment (e.g. narcotics).
NOTE: muscle relaxants and benzodiazepines are permitted if the dosage has been stable for the 6 weeks prior to study treatment and is expected to remain at this stable dose until the Week 4 assessment. Every effort should be made to keep concomitant CD treatment constant throughout the study, however, changes in pain medication are acceptable if absolutely necessary according to clinical judgment.
(16) Any medical condition or laboratory finding that might compromise compliance with the objectives and procedures of this protocol or preclude the administration of BTX-A, as judged by the Investigator (including infection at the site for injection).
(17) In the opinion of the Investigator the subject is unable and/or unwilling to comply fully with the protocol and/or the study instructions.
(18) Was treated with any other IMP or device within the last 30 days before study entry.
(19) Is likely to require treatment during the study with drugs that are not permitted by the study protocol.
(20) Pregnancy or lactation: women of child-bearing potential must have a negative pre-study urine pregnancy test and subjects, or their partner, must agree to use adequate contraception (hormonal or barrier method of birth
control) prior to injection of study drug and for the duration of study participation. Non-childbearing potential is defined as post-menopausal for
at least 1 year, surgical sterilisation at least three months before entering screening, or hysterectomy.
(21) Previously treated in this study.
(22) Has a history of, or known current problems with alcohol or drug abuse, which in the opinion of the Investigator could interfere with the subject’s participation in the study. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in TWSTRS total score at the post-treatment cycle 1 Week 4 office visit. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Primary efficacy endpoint:
Change from baseline in TWSTRS total score at the post-treatment cycle 1 Week 4 office visit.
|
|
E.5.2 | Secondary end point(s) |
The secondary study objectives are the assessment of the short and long term clinical safety and efficacy of Dysport RU following repeated treatment cycles. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Week 4 visit:
Week 8 and Week 12 office visits.
The safety endpoints of the study are given below:
Day 1 and at each post-baseline visit after each treatment.
Week 4 office visit and at the end of the study/early withdrawal visit.
|
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
There is an open section as well as a blinded section to the trial. |
|
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 32 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Austria |
Canada |
Czech Republic |
Germany |
Hungary |
Poland |
Portugal |
Russian Federation |
Ukraine |
|
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
The end of the study is LPLV. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |