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

Completed

• Conditions: Cervical Dystonia
• Interventions: Biological: CF to CC BoNT/A; Biological: CF BoNT/A; Biological: CC to CF BoNT/A; Biological: CC BoNT/A

• Registration Number: NCT05884528
• Lead Sponsor: Merz Therapeutics GmbH

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 Timeline

• Study First Submitted: 2023-05-08
• Study First Submitted QC: 2023-05-22
• Study First Posted: 2023-06-01
• Study Start: 2023-07-08
• Primary Completion: 2024-05-31
• Study Completion: 2024-07-31
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-20
• Last Update Posted: 2024-08-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 270

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Switcher CF to CC BoNT/A formulations	CF to CC BoNT/A	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.
Complex-free BoNT/A formulation	CF BoNT/A	Patients exclusively treated with the complex-free (CF) formulation (incobotulinumtoxinA). A maximum of 328 patients will be enrolled in this group.
Switcher CC to CF BoNT/A formulations	CC to CF BoNT/A	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.
Complex-containing BoNT/A formulations	CC BoNT/A	Patients exclusively treated with a single complex-containing (CC) formulation (onabotulinumtoxinA or abobotulinumtoxinA). A maximum of 328 patients will be enrolled in this group.

Primary Outcome Measures

Name	Time	Method
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	Year 2 and year 7	Dose-effect is a change in treatment response following dose adjustment.

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

Düsseldorf University Hospital; 🇩🇪 Düsseldorf, North Rhine-Westphalia, Germany