Assessment of Long-term Clinical Response to BoNT in Cervical Dystonia

Cervical Dystonia Clinical Trial

— RELY-CD  

Official title:

Assessment of Long-term Clinical Response to BoNT in Cervical Dystonia - Real-world Evidence of LongevitY of Botulinum Toxin in Cervical Dystonia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05884528
• Other study ID #: M602011073
• Status: Recruiting
• Start date: July 8, 2023
• Est. completion date: July 2024

Study information

• Verified date: June 2024
• Source: Merz Pharmaceuticals GmbH
• Contact: Benjamin Waeschle
• Phone: +496915030
• Email: benjamin.waeschle[@]uni-duesseldorf.de
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 981
• Est. completion date: July 2024
• Est. primary completion date: May 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 64 Years

Eligibility

• 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.

Related Conditions & MeSH terms

• Cervical Dystonia
• Dystonia
• Dystonic Disorders
• Torticollis

Intervention

Biological:
• CC BoNT/A
Complex-containing BotulinumtoxinA (BoNT/A) formulations
• CF BoNT/A
Complex-free BotulinumtoxinA (BoNT/A) formulation
• CF to CC BoNT/A
Switch from complex-free to complex-containing BoNT/A formulations
• CC to CF BoNT/A
Switch from complex-containing to complex-free BoNT/A formulations

Locations

Country	Name	City	State
Germany	Düsseldorf University Hospital	Düsseldorf	North Rhine-Westphalia

Sponsors (2)

Lead Sponsor	Collaborator
Merz Therapeutics GmbH	Heinrich-Heine University, Duesseldorf

Country where clinical trial is conducted

Germany, 

References & Publications (4)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Incidence of frequent AEs overall and in patients with altered dose-effect		Years 2, 5,7, and 10
Other	Health-related quality of life measured by the EQ-5D		Years 2, 5,7, and 10
Other	Health-related quality of life measured by the SF-36		Years 2, 5,7, and 10
Other	Health-related quality of life measured by the CDQ24		Years 2, 5,7, and 10
Other	Sub-analysis of all outcome measures in switcher population (patients treated with more than one BoNT/A formulation)		Years 2, 5,7, and 10
Primary	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	Dose-effect is a change in treatment response following dose adjustment.	Year 2 and year 7
Secondary	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		Baseline (first visit on record), years 2, 5, 7, and 10