Clinical trial NCT05884528: 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
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Cervical Dystonia
Keywords: spasmodic torticollis, focal dystonia
Lead sponsor: Merz Pharmaceuticals GmbH
Sponsor class: INDUSTRY
Collaborators: name: Heinrich-Heine University, Duesseldorf
First posted: 2023-06-01
Enrollment: 270
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: RETROSPECTIVE
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).

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.

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.

Primary outcomes:
measure: 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
timeFrame: Year 2 and year 7
Secondary outcomes:
measure: 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
timeFrame: Baseline (first visit on record), years 2, 5, 7, and 10
Other outcomes:
measure: Incidence of frequent AEs overall and in patients with altered dose-effect
timeFrame: Years 2, 5,7, and 10
measure: Health-related quality of life measured by the EQ-5D
timeFrame: Years 2, 5,7, and 10
measure: Health-related quality of life measured by the SF-36
timeFrame: Years 2, 5,7, and 10
measure: Health-related quality of life measured by the CDQ24
timeFrame: Years 2, 5,7, and 10
measure: Sub-analysis of all outcome measures in switcher population (patients treated with more than one BoNT/A formulation)
timeFrame: Years 2, 5,7, and 10
Locations:
city: Düsseldorf
country: Germany
facility: Düsseldorf University Hospital
state: North Rhine-Westphalia
Study officials:
affiliation: Merz Therapeutics
name: Merz Medical Expert
role: STUDY_DIRECTOR
References:
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.
citation: 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.
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.
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.