Assessment of Long-term Clinical Response to BoNT in Cervical Dystonia (RELY-CD)

• ClinicalTrials.gov Identifier: NCT05884528
• Recruitment Status: Recruiting
• First Posted: June 1, 2023
• Last Update Posted: May 20, 2024
• Sponsor: Merz Therapeutics GmbH
• Collaborator: Heinrich-Heine University, Duesseldorf
• Information provided by (Responsible Party): Merz Pharmaceuticals GmbH ( Merz Therapeutics GmbH )

Tracking Information

• First Submitted Date: May 8, 2023
• First Posted Date: June 1, 2023
• Last Update Posted Date: May 20, 2024
• Actual Study Start Date: July 8, 2023
• Estimated Primary Completion Date: May 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 22, 2023)

Percentage of patients with a clinically meaningful change in dose-effect at year 7 compared to reference year 2 between complex-free and complex-containing BoNT/A monotherapy [ Time Frame: Year 2 and year 7 ]

Dose-effect is a change in treatment response following dose adjustment.

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures (submitted: May 22, 2023): Clinical meaningfulness of change in efficacy from baseline (first visit on record) at each visit in years 2, 5, 7, 10 in all treatment groups [ Time Frame: Baseline (first visit on record), years 2, 5, 7, and 10 ]
• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: May 22, 2023)

• Incidence of frequent AEs overall and in patients with altered dose-effect [ Time Frame: Years 2, 5,7, and 10 ]
• Health-related quality of life measured by the EQ-5D [ Time Frame: Years 2, 5,7, and 10 ]
• Health-related quality of life measured by the SF-36 [ Time Frame: Years 2, 5,7, and 10 ]
• Health-related quality of life measured by the CDQ24 [ Time Frame: Years 2, 5,7, and 10 ]
• Sub-analysis of all outcome measures in switcher population (patients treated with more than one BoNT/A formulation) [ Time Frame: Years 2, 5,7, and 10 ]

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: Assessment of Long-term Clinical Response to BoNT in Cervical Dystonia
• Official Title: Assessment of Long-term Clinical Response to BoNT in Cervical Dystonia - Real-world Evidence of LongevitY of Botulinum Toxin in Cervical Dystonia

Brief Summary

The goal of this retrospective, international, multi-center chart abstraction is to learn about the long-term impact of product-specific immunogenicity-related factors in different botulinum neurotoxin type A formulations in patients suffering from cervical dystonia. The main question it aims to answer is:

Do complex-containing (CC) botulinum toxin formulations impact the long-term clinical outcome in cervical dystonia patients compared to a complex-free (CF) formulation?

Researchers will compare differences observed in years 2 and 7 between two toxin groups, i.e., botulinum neurotoxins type A containing complexing proteins (CC) and without complexing proteins (CF).

Detailed Description

Botulinum neurotoxin type A (BoNT/A) is first-line treatment in patients suffering from cervical dystonia. Effect of BoNT/A is temporary and must be repeated to maintain clinical effect. As for all biologics, repeated treatment bears the risk of activating an immune response due to the immunogenic nature of foreign proteins. Clinical signs of a potential immune response are reduced, or loss of efficacy, decreased duration of effect, and the need of a dose increase to maintain effect. Due to the different degree of purity and protein content, it is reasonable to assume that commercial BoNT/A formulations differ in immunogenic properties.

Pivotal clinical trials and monocentric real-world studies demonstrated an increased incidence of neutralizing antibodies (NAbs) and NAb-associated partial or complete secondary non-response. However, the clinical relevance of potential immunogenicity-related mechanisms has not been demonstrated in a larger multicentric cohort in a real-world setting. This chart abstraction is designed to address this gap.

• Study Type: Observational
• Study Design: Observational Model: Case-Control; Time Perspective: Retrospective
• Target Follow-Up Duration: Not Provided
• Biospecimen: Not Provided
• Sampling Method: Non-Probability Sample
• Study Population: The study population will comprise of patients with a diagnosis of cervical dystonia who received regular BoNT/A injections for symptomatic treatment of the disease. The sub-populations consist of long-term patients treated with only ever one BoNT/A formulation (monotherapy) or 2 BoNT/A formulations (switcher).
• Condition: Cervical Dystonia

Intervention

• Biological: CC BoNT/A
  Complex-containing BotulinumtoxinA (BoNT/A) formulations
  Other Names:

  • onabotulinumtoxinA
  • abobotulinumtoxinA
• Biological: CF BoNT/A
  Complex-free BotulinumtoxinA (BoNT/A) formulation
  Other Names:

  • incobotulinumtoxinA
  • NT 201
  • Botulinum toxin type A (150 kiloDalton), free from complexing proteins
• Biological: CF to CC BoNT/A
  Switch from complex-free to complex-containing BoNT/A formulations
  Other Names:

  • incobotulinumtoxinA
  • onabotulinumtoxinA
  • abobotulinumtoxinA
• Biological: CC to CF BoNT/A
  Switch from complex-containing to complex-free BoNT/A formulations
  Other Names:

  • onabotulinumtoxinA
  • abobotulinumtoxinA
  • incobotulinumtoxinA

Study Groups/Cohorts

• Complex-free BoNT/A formulation
  Patients exclusively treated with the complex-free (CF) formulation (incobotulinumtoxinA). A maximum of 328 patients will be enrolled in this group.
  Intervention: Biological: CF BoNT/A
• Complex-containing BoNT/A formulations
  Patients exclusively treated with a single complex-containing (CC) formulation (onabotulinumtoxinA or abobotulinumtoxinA). A maximum of 328 patients will be enrolled in this group.
  Intervention: Biological: CC BoNT/A
• Switcher CF to CC BoNT/A formulations
  The CF to CC switcher group includes all patients that were switched from a CF to a CC BoNT/A formulation. If more than one switch occurred, the first switch determines the group. Both switcher groups will in sum not exceed 325 patients.
  Intervention: Biological: CF to CC BoNT/A
• Switcher CC to CF BoNT/A formulations
  The CC to CF switcher group includes all patients that were switched from a CC to a CF BoNT/A formulation. If more than one switch occurred, the first switch determines the group. Both switcher groups will in sum not exceed 325 patients.
  Intervention: Biological: CC to CF BoNT/A

Publications *

• Ware JE Jr, Kosinski M, Gandek B, Aaronson NK, Apolone G, Bech P, Brazier J, Bullinger M, Kaasa S, Leplege A, Prieto L, Sullivan M. The factor structure of the SF-36 Health Survey in 10 countries: results from the IQOLA Project. International Quality of Life Assessment. J Clin Epidemiol. 1998 Nov;51(11):1159-65. doi: 10.1016/s0895-4356(98)00107-3.
• Albanese A, Bhatia K, Bressman SB, Delong MR, Fahn S, Fung VS, Hallett M, Jankovic J, Jinnah HA, Klein C, Lang AE, Mink JW, Teller JK. Phenomenology and classification of dystonia: a consensus update. Mov Disord. 2013 Jun 15;28(7):863-73. doi: 10.1002/mds.25475. Epub 2013 May 6.
• Albrecht P, Jansen A, Lee JI, Moll M, Ringelstein M, Rosenthal D, Bigalke H, Aktas O, Hartung HP, Hefter H. High prevalence of neutralizing antibodies after long-term botulinum neurotoxin therapy. Neurology. 2019 Jan 1;92(1):e48-e54. doi: 10.1212/WNL.0000000000006688. Epub 2018 Nov 21. Erratum In: Neurology. 2022 Feb 22;98(8):341.
• Carr WW, Jain N, Sublett JW. Immunogenicity of Botulinum Toxin Formulations: Potential Therapeutic Implications. Adv Ther. 2021 Oct;38(10):5046-5064. doi: 10.1007/s12325-021-01882-9. Epub 2021 Sep 13.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: May 22, 2023): 981
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: May 2024
• Estimated Primary Completion Date: May 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

• Clinical diagnosis of cervical dystonia
• Adults (m/f) 18-64 years of age at start of BoNT/A treatment
• Patient's written informed consent if required by local and/or national law.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 64 Years (Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Benjamin Waeschle; +496915030; benjamin.waeschle@uni-duesseldorf.de

Contact: Public Disclosure Manager; +496915030; clinicaltrials@merz.de

• Listed Location Countries: Germany

Administrative Information

• NCT Number: NCT05884528
• Other Study ID Numbers: M602011073
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Merz Pharmaceuticals GmbH ( Merz Therapeutics GmbH )
• Original Responsible Party: Same as current
• Current Study Sponsor: Merz Therapeutics GmbH
• Original Study Sponsor: Same as current
• Collaborators: Heinrich-Heine University, Duesseldorf

Investigators

• Study Director: Merz Medical Expert; Merz Therapeutics

• PRS Account: Merz Pharmaceuticals GmbH
• Verification Date: May 2024