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| Name | Class |
|---|---|
| Heinrich-Heine University, Duesseldorf | OTHER |
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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).
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
| |
| 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. |
| |
| 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. |
| |
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CC BoNT/A | Biological | Complex-containing BotulinumtoxinA (BoNT/A) formulations |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of frequent AEs overall and in patients with altered dose-effect | Years 2, 5,7, and 10 | |
| Health-related quality of life measured by the EQ-5D | Years 2, 5,7, and 10 | |
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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).
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| Name | Affiliation | Role |
|---|---|---|
| Merz Medical Expert | Merz Therapeutics | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Düsseldorf University Hospital | Düsseldorf | North Rhine-Westphalia | 40255 | Germany |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 9817133 | Background | 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. | |
| 23649720 |
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| ID | Term |
|---|---|
| D014103 | Torticollis |
| D020821 | Dystonic Disorders |
| ID | Term |
|---|---|
| D004421 | Dystonia |
| D020820 | Dyskinesias |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
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| ID | Term |
|---|---|
| D019274 | Botulinum Toxins, Type A |
| C542869 | abobotulinumtoxinA |
| C545476 | incobotulinumtoxinA |
| ID | Term |
|---|---|
| D001905 | Botulinum Toxins |
| D008666 | Metalloendopeptidases |
| D010450 | Endopeptidases |
| D010447 | Peptide Hydrolases |
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| CF BoNT/A | Biological | Complex-free BotulinumtoxinA (BoNT/A) formulation |
|
|
| CF to CC BoNT/A | Biological | Switch from complex-free to complex-containing BoNT/A formulations |
|
|
| CC to CF BoNT/A | Biological | Switch from complex-containing to complex-free BoNT/A formulations |
|
|
| Health-related quality of life measured by the SF-36 |
| Years 2, 5,7, and 10 |
| Health-related quality of life measured by the CDQ24 | Years 2, 5,7, and 10 |
| Sub-analysis of all outcome measures in switcher population (patients treated with more than one BoNT/A formulation) | Years 2, 5,7, and 10 |
| 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. |
| 30464031 | Background | 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. |
| 34515975 | Background | 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. |
| D013568 |
| Pathological Conditions, Signs and Symptoms |
| D009069 | Movement Disorders |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D006867 |
| Hydrolases |
| D004798 | Enzymes |
| D045762 | Enzymes and Coenzymes |
| D045726 | Metalloproteases |
| D001426 | Bacterial Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D001427 | Bacterial Toxins |
| D014118 | Toxins, Biological |
| D001685 | Biological Factors |