Efficacy and safety of secukinumab in patients with giant cell arteritis: study protocol for a randomized, parallel group, double-blind, placebo-controlled phase II trial
Abstract Background One key pathological finding in giant cell arteritis (GCA) is the presence of interferon-gamma and interleukin (IL)-17 producing T helper (Th) 1 and Th17 cells in affected arteries. There is anecdotal evidence of successful induction and maintenance of remission with the monoclon...
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| Format: | Article |
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BMC
2021-08-01
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| Series: | Trials |
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| Online Access: | https://doi.org/10.1186/s13063-021-05520-1 |
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| author | Nils Venhoff Wolfgang A. Schmidt Peter Lamprecht Hans-Peter Tony Christine App Christian Sieder Carolin Legeler Claudia Jentzsch Jens Thiel |
| author_facet | Nils Venhoff Wolfgang A. Schmidt Peter Lamprecht Hans-Peter Tony Christine App Christian Sieder Carolin Legeler Claudia Jentzsch Jens Thiel |
| author_sort | Nils Venhoff |
| collection | DOAJ |
| description | Abstract Background One key pathological finding in giant cell arteritis (GCA) is the presence of interferon-gamma and interleukin (IL)-17 producing T helper (Th) 1 and Th17 cells in affected arteries. There is anecdotal evidence of successful induction and maintenance of remission with the monoclonal anti-IL-17A antibody secukinumab. Inhibition of IL-17A could therefore represent a potential new therapeutic option for the treatment of GCA. Methods This is a randomized, parallel-group, double-blind, placebo-controlled, multi-center, phase II study in which patients, treating physicians, and the associated clinical staff as well as the sponsor clinical team are blinded. It is designed to evaluate efficacy and safety of secukinumab compared to placebo in combination with an open-label prednisolone taper regimen. Patients included are naïve to biological therapy and have newly diagnosed or relapsing GCA. Fifty patients are randomly assigned in a 1:1 ratio to receive either 300 mg secukinumab or placebo subcutaneously at baseline, weeks 1, 2 and 3, and every 4 weeks from week 4. Patients in both treatment arms receive a 26-week prednisolone taper regimen. The study consists of a maximum 6-week screening period, a 52-week treatment period (including the 26-week tapering), and an 8-week safety follow-up, with primary and secondary endpoint assessments at week 28. Patients who do not achieve remission by week 12 experience a flare after remission or cannot adhere to the prednisolone tapering will enter the escape arm and receive prednisolone at a dose determined by the investigator’s clinical judgment. The blinded treatment is continued. Two optional imaging sub-studies are included (ultrasound and contrast-media enhanced magnetic resonance angiography [MRA]) to assess vessel wall inflammation and occlusion before and after treatment. The primary endpoint is the proportion of patients in sustained remission until week 28 in the secukinumab group compared to the proportion of patients in the placebo group. A Bayesian approach is applied. Discussion The trial design allows the first placebo-controlled data collection on the efficacy and safety of secukinumab in patients with GCA. Trial registration ClinicalTrials.gov NCT03765788 . Registration on 5 December 2018, prospective registration, EudraCT number 2018-002610-12; clinical trial protocol number CAIN457ADE11C. |
| first_indexed | 2024-12-22T10:53:37Z |
| format | Article |
| id | doaj.art-f4928bfde2514182945142901f3a3fe2 |
| institution | Directory Open Access Journal |
| issn | 1745-6215 |
| language | English |
| last_indexed | 2024-12-22T10:53:37Z |
| publishDate | 2021-08-01 |
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| series | Trials |
| spelling | doaj.art-f4928bfde2514182945142901f3a3fe22022-12-21T18:28:41ZengBMCTrials1745-62152021-08-0122111510.1186/s13063-021-05520-1Efficacy and safety of secukinumab in patients with giant cell arteritis: study protocol for a randomized, parallel group, double-blind, placebo-controlled phase II trialNils Venhoff0Wolfgang A. Schmidt1Peter Lamprecht2Hans-Peter Tony3Christine App4Christian Sieder5Carolin Legeler6Claudia Jentzsch7Jens Thiel8Department Innere Medizin, Klinik für Rheumatologie und Klinische Immunologie, Vaskulitiszentrum Freiburg, Universitätsklinikum FreiburgImmanuel Krankenhaus Berlin, Klinik für Innere Medizin, Abteilung Rheumatologie und Klinische Immunologie in Berlin-BuchUniversität zu Lübeck, Klinik für Rheumatologie und klinische ImmunologieMedizinische Klinik II, Universitätsklinik, Rheumatology/ImmunologyDepartment of Immunology, Hepatology & Dermatology, Novartis Pharma GmbHDepartment of Immunology, Hepatology & Dermatology, Novartis Pharma GmbHDepartment of Immunology, Hepatology & Dermatology, Novartis Pharma GmbHNovartis Pharma AGDepartment Innere Medizin, Klinik für Rheumatologie und Klinische Immunologie, Vaskulitiszentrum Freiburg, Universitätsklinikum FreiburgAbstract Background One key pathological finding in giant cell arteritis (GCA) is the presence of interferon-gamma and interleukin (IL)-17 producing T helper (Th) 1 and Th17 cells in affected arteries. There is anecdotal evidence of successful induction and maintenance of remission with the monoclonal anti-IL-17A antibody secukinumab. Inhibition of IL-17A could therefore represent a potential new therapeutic option for the treatment of GCA. Methods This is a randomized, parallel-group, double-blind, placebo-controlled, multi-center, phase II study in which patients, treating physicians, and the associated clinical staff as well as the sponsor clinical team are blinded. It is designed to evaluate efficacy and safety of secukinumab compared to placebo in combination with an open-label prednisolone taper regimen. Patients included are naïve to biological therapy and have newly diagnosed or relapsing GCA. Fifty patients are randomly assigned in a 1:1 ratio to receive either 300 mg secukinumab or placebo subcutaneously at baseline, weeks 1, 2 and 3, and every 4 weeks from week 4. Patients in both treatment arms receive a 26-week prednisolone taper regimen. The study consists of a maximum 6-week screening period, a 52-week treatment period (including the 26-week tapering), and an 8-week safety follow-up, with primary and secondary endpoint assessments at week 28. Patients who do not achieve remission by week 12 experience a flare after remission or cannot adhere to the prednisolone tapering will enter the escape arm and receive prednisolone at a dose determined by the investigator’s clinical judgment. The blinded treatment is continued. Two optional imaging sub-studies are included (ultrasound and contrast-media enhanced magnetic resonance angiography [MRA]) to assess vessel wall inflammation and occlusion before and after treatment. The primary endpoint is the proportion of patients in sustained remission until week 28 in the secukinumab group compared to the proportion of patients in the placebo group. A Bayesian approach is applied. Discussion The trial design allows the first placebo-controlled data collection on the efficacy and safety of secukinumab in patients with GCA. Trial registration ClinicalTrials.gov NCT03765788 . Registration on 5 December 2018, prospective registration, EudraCT number 2018-002610-12; clinical trial protocol number CAIN457ADE11C.https://doi.org/10.1186/s13063-021-05520-1Giant cell arteritisSecukinumabPhase II trialPlaceboDouble-blind |
| spellingShingle | Nils Venhoff Wolfgang A. Schmidt Peter Lamprecht Hans-Peter Tony Christine App Christian Sieder Carolin Legeler Claudia Jentzsch Jens Thiel Efficacy and safety of secukinumab in patients with giant cell arteritis: study protocol for a randomized, parallel group, double-blind, placebo-controlled phase II trial Trials Giant cell arteritis Secukinumab Phase II trial Placebo Double-blind |
| title | Efficacy and safety of secukinumab in patients with giant cell arteritis: study protocol for a randomized, parallel group, double-blind, placebo-controlled phase II trial |
| title_full | Efficacy and safety of secukinumab in patients with giant cell arteritis: study protocol for a randomized, parallel group, double-blind, placebo-controlled phase II trial |
| title_fullStr | Efficacy and safety of secukinumab in patients with giant cell arteritis: study protocol for a randomized, parallel group, double-blind, placebo-controlled phase II trial |
| title_full_unstemmed | Efficacy and safety of secukinumab in patients with giant cell arteritis: study protocol for a randomized, parallel group, double-blind, placebo-controlled phase II trial |
| title_short | Efficacy and safety of secukinumab in patients with giant cell arteritis: study protocol for a randomized, parallel group, double-blind, placebo-controlled phase II trial |
| title_sort | efficacy and safety of secukinumab in patients with giant cell arteritis study protocol for a randomized parallel group double blind placebo controlled phase ii trial |
| topic | Giant cell arteritis Secukinumab Phase II trial Placebo Double-blind |
| url | https://doi.org/10.1186/s13063-021-05520-1 |
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