A Clinical Study to Investigate the Long-Term Safety and Effectiveness of Repeat Treatments of DaxibotulinumtoxinA for Injection in subjects with Isolated Cervical Dystonia (ASPEN-OLS)
- Conditions
- Cervical DystoniaMedDRA version: 21.0Level: LLTClassification code 10064124Term: Cervical dystoniaSystem Organ Class: 100000004859Therapeutic area: Diseases [C] - Nervous System Diseases [C10]
- Registration Number
- EUCTR2018-000447-11-IT
- Lead Sponsor
- Revance Therapeutics, Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 350
1.Adults, 18 to 80 years of age
2.Meets diagnostic criteria for isolated CD (idiopathic; dystonic symptoms localized to the head, neck, shoulder areas) with at least moderate severity at Baseline (Day 1), defined as a TWSTRS-total score of at least 20, with at least 15 on the TWSTRS-Severity subscale, at least 3 on the TWSTRS-Disability subscale, and at least 1 on the TWSTRS-Pain subscale (minimum TWSTRS subscale criteria applicable only to subjects not previously enrolled in Study Protocol 1720302)
3.Subjects who were previously enrolled in Study Protocol 1720302, and completed the study, including:
a)Those with no reduction or have an increase from baseline in the average TWSTRS-total score at Weeks 4 and 6 (i.e., no improvement or worsened disease status), and the investigator agreed that there was a need for retreatment based on the subject’s symptoms and neurologic exam findings
b)Those who benefited from study treatment and completed follow up study visits up to the time point of when their TWSTRS-total score reached/exceeded their target TWSTRS score
c)Those who benefited from study treatment but subsequently experienced significant recurrence of CD symptoms (e.g. pain) during the study before their TWSTRS-total score reached their target TWSTRS score and requested retreatment, which the investigator determined was warranted based on the subject’s symptoms and neurologic exam findings
d)Those who completed study visits up to Week 36 and their TWSTRS-total score never reached their target TWSTRS score and they never requested another treatment. The investigator determined that these subjects can be followed in the OLS until their TWSTRS-total score is the same or higher than their target TWSTRS score or until they request retreatment, which the investigator determined is clinically indicated
4.De novo subjects (not previously enrolled in Study Protocol 1720302):
a)Naïve to BoNT treatment
b)BoNT treatment-experienced; if previously treated with BoNTA, the subject must have demonstrated a clinically meaningful response to the last BoNTA treatment based on the clinical judgment of the investigator
5.Written Inforrned Consent incuding authorization to release health information
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 245
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 105
1. Cervical dystonia attributable to an underlying etiology, (e.g., traumatic torticollis or tardive torticollis)
2. Predominant retrocollis or anterocollis CD
3. Significant dystonia in other body areas, or is currently being treated with botulinum toxin (BoNT) for dystonia in areas other than those associated with isolated CD
4. Severe dysphagia (Grade 3 or 4 on the Dysphagia Severity Scale) at Screening or Baseline (prior to study treatment)
5. Any neuromuscular neurological conditions that may place the subject at increased risk of morbidity with exposure to BoNT, including peripheral motor neuropathic diseases (e.g., amyotrophic lateral sclerosis and motor neuropathy, and neuromuscular junctional disorders such as Lambert-Eaton syndrome and myasthenia gravis)
6. Previous treatment with any BoNT product for any condition within the 14 weeks prior to Screening (applicable only to de novo subj.)
7. Botulinum neurotoxin treatment-experienced subjects who had suboptimal or no treatment response to the most recent BoNTA injection for CD, as determined by the PI; or history of primary or secondary non-response to BoNTA injections, known to have neutralizing antibodies to BoNTA; or have a history of botulinum toxin type B (rimabotulinumtoxinA [Myobloc/Neurobloc]) injection for CD due to non-response or suboptimal response to BoNTA (applicable only to de novo subjects)
8. Botulinum neurotoxin treatment-experienced subjects who had suboptimal or no treatment response to the most recent BoNTA injection for CD, as determined by the investigator, or history of primary or secondary non-response to BoNTA injections, known to have neutralizing antibodies to BoNTA, or have a history of botulinum toxin type B injection for CD due to non-response or suboptimal response to BoNTA
9. Use of deep brain stimulation, or intrathecal baclofen for dystonia
10. Subj. on oral medications for focal dystonia or neuroleptics for psychiatric conditions, who have not been stable on their regimen for at least 4 weeks prior to Screening
11. Neurological abnormalities in the neck other than CD
12. Previous neck surgery, phenol injection to the neck muscles, myotomy or denervation surgery in the neck/shoulder region
13. Profound atrophy of cervical muscul. or cervical contractures or cervical spinal deformity leading to marked limitat. on passive range of motion
14. Use of aminoglycoside antibiotics, polymyxins, lincosamides or other agents that might interfere with neuromuscular transmission within 14 days prior to Screen.
15. Women of child bearing potential, who have a positive pregn. test at Screen., or do not agree to use an effective method of birth control during the course of the study
16. Female, who is pregnant or nursing
17. Screen. 12-lead ECG with exclusionary conduction criteria of corrected QT interval: QTcF interval > 450 msec (males) or > 470 msec (females), heart block, or ventricular tachycardia
18. History of severe (stage 3) chronic obstructive pulmon. disease, or unstable pulmon. disease within 30 days prior to Screening
19. History of chronic or recurrent hypokalemia, or serum potassium < 2.5 mEq/L or mmol/L on chemistry at Screen.
20. History of congestive heart failure, (New York Heart Association Class III or IV), Torsade de Pointe (TdP), and/or Long QT Syndrome,
21. Participants in an investigational drug or device study within the last 30 days prior to Screen. except for prot. 1720302
22. Active skin infections at the injection sites which w
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: - To evaluate the long-term safety of multiple continuous treatments of DAXI for injection<br>- To assess immunogenicity to BoNTA and RTP004 after multiple treatments of DAXI for injection;Primary end point(s): - The dose- and cycle-specific incidence of drug-related AEs<br>- The dose- and cycle-specific incidence of study drug discontinuation due to drug-related AEs<br>- The dose and cycle-specific incidence of treatment-emergent immunogenicity;Timepoint(s) of evaluation of this end point: It will be assessed at weeks 4 and 6;Secondary Objective: - To evaluate the long-term efficacy of multiple continuous treatments of DAXI for injection<br>- To establish the inter-treatment time interval or duration of effect<br>- To evaluate changes in symptom burden, daily activities, and psychosocial functioning after multiple continuous treatments of DAXI for injection
- Secondary Outcome Measures
Name Time Method Timepoint(s) of evaluation of this end point: It will be assessed at week 6;Secondary end point(s): - Inter-treatment time interval or duration of effect<br>- The dose- and cycle-specific average of the change in the TWSTRS-total score at Weeks 4 and 6 of each treatment cycle<br>- Percentage of subjects with at least moderate” (a 2-point) improvement on CGIC at Week 4 or Week 6 of the treatment cycle<br>- Percentage of subjects with at least moderate” (a 2-point) improvement on PGIC at Week 4 or Week 6 of the treatment cycle<br>- Changes in quality of life measures based on the CDIP-58