A Placebo-controlled Phase 2 Trial to Investigate the Safety and Efficacy of Secukinumab in Giant Cell Arteritis

NCT03765788 | Completed Phase 2 Results DMC

• 2 other identifiers: CAIN457ADE11C2018-002610-12
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 11

Brief Summary

This study was designed to evaluate the efficacy and safety of secukinumab compared to placebo to maintain disease remission up to 28 weeks including corticosteroid tapering, as well as up to 1 year (52 weeks) in patients with newly diagnosed or relapsing giant cell arteritis (GCA) who were naïve to biological therapy.

Conditions

Giant Cell Arteritis

Keywords

GCA; ain457; Secukinumab; Subcutaneous; Vessel Inflammation; corticosteroid tapering; newly diagnosed or relapsing giant cell arteritis; prednisolone taper regimen; "escape"

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants in Sustained Remission Until Week 28

  Remission was defined as the absence of flare. Sustained remission was defined as the absence of flare until Week 28 and in adherence to the protocol prednisolone taper regimen. Flare was determined by the investigator and was defined as the recurrence after remission of signs or symptoms of Giant Cell Arteritis (GCA) and/or erythrocyte sedimentation rate (ESR) greater than or equal to (\>/=) 30 millimeters per hour (mm/hr) and/or C-reactive Protein (CRP) (\>/=10.0 mg/L) attributable to GCA. Patients were classified as non-responders if they did not achieve remission within 12 weeks of Baseline (remission referred to the absence of flare), were in the "escape arm" (this referred to patients entering escape between Baseline and Week 28), prematurely discontinued study treatment prior to Week 28 (absence of flare was checked prior to study treatment administration), did not have information to evaluate sustained remission response until Week 28.

  Until week 28

Secondary Outcomes (12)

• Percentage of Participants in Remission at Week 12

  Week 12

• Time to First GCA Flare After Clinical Remission

  Up to Week 52 (included)

• Total Cumulative Prednisolone Dose Over 28 Weeks and 52 Weeks

  from Baseline to week 28, from baseline to week 52 weeks

• Percentage of Participants With GCA Who Had Sustained Remission Until Week 52

  Until Week 52

• Number of Participants on Prednisolone Dose ≤ 5mg/Day

  Week 19, Week 28, Week 52

Study Arms (2)

Secukinumab

EXPERIMENTAL

Participants received secukinumab at a dose of 300 milligrams (mg) as subcutaneous (s.c.) injection at Baseline, Week 1,2,3,4 and then every 4 weeks thereafter through to week 48 along with a 26-week prednisolone tapering regimen.

Drug: Secukinumab 300 mg, s.c.; Drug: Prednisolone

Placebo

PLACEBO COMPARATOR

Participants received placebo as subcutaneous (s.c.) injection at Baseline, Week 1,2,3,4 and then every 4 weeks thereafter through to week 48 along with a 26-week prednisolone tapering regimen.

Drug: Prednisolone; Drug: Placebo

Interventions

Secukinumab 300 mg, s.c. DRUG

Secukinumab 300 mg was administered by subcutaneous (s.c.) injections using 1 mL pre-filled syringes (PFSs) throughout the study.

Also known as: AIN457

Secukinumab

Prednisolone DRUG

Prednisolone was provided as tablets (1 mg, 5 mg, 10 mg, 20 mg tablets) for daily administration as tapered regimen from a dose of 25 mg to 60 mg at Baseline to 1 mg at Week 26 (last dose)

Placebo; Secukinumab

Placebo DRUG

Placebo 300 mg was administered by subcutaneous (s.c.) injections using 1 mL pre-filled syringes (PFSs) throughout the study.

Placebo

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of GCA classified according to the following criteria:
• Age at onset of disease ≥ 50 years.
• History of ESR ≥ 30 mm/hr or CRP ≥ 10 mg/L.
• Unequivocal cranial symptoms of GCA (new-onset localized headache, scalp or temporal artery tenderness, ischemia-related vision loss, or otherwise unexplained mouth or jaw pain upon mastication) AND/OR symptoms of polymyalgia rheumatica (PMR) defined as shoulder and/or hip girdle pain associated with inflammatory morning stiffness
• Temporal artery biopsy revealing features of GCA AND/OR
• evidence of large-vessel vasculitis by angiography or cross-sectional imaging study such as magnetic resonance angiography (MRA), computed tomography angiography (CTA), positron emission tomography-computed tomography (PET CT), or ultrasound
• Active disease as defined by the presence of signs and symptoms of GCA (cranial or PMR) and elevated ESR ≥ 30 mm/hr, or CRP ≥ 10 mg/L, attributed to active GCA within 6 weeks of Baseline.
• Prednisolone dose of 25-60 mg/day at Baseline.

You may not qualify if:

• Previous exposure to secukinumab or other biologic drug directly targeting Interleukin(IL)-17 or IL-17 receptor.
• Patients treated with any cell-depleting therapies including but not limited to anti-CD20 or investigational agents (e.g. anti-CD3, anti-CD4, anti-CD5 or anti-CD19).
• Patients who have previously been treated with any biologic agent including but not limited to tocilizumab, sirukumab, abatacept, or tumor necrosis factor alpha (TNFα) inhibitors (infliximab, adalimumab, etanercept, certolizumab, golimumab).
• Patients who have previously been treated with tofacitinib or baricitinib.
• Patients treated with i.v. immunoglobulins or plasmapheresis within 8 weeks prior to Baseline.
• Patients treated with cyclophosphamide, tacrolimus or everolimus within 6 months prior to Baseline.
• Patients treated with hydroxychloroquine, cyclosporine A, azathioprine, sulfasalazine or mycophenolate mofetil within 4 weeks of Baseline.
• Patients treated with leflunomide within 8 weeks of Baseline unless a cholestyramine washout has been performed in which case the patient must be treated within 4 weeks of Baseline.
• Patients treated with an alkylating agent except for cyclophosphamide as mentioned above.
• Patients requiring systemic chronic glucocorticoid therapy for any other reason than GCA.
• Chronic systemic glucocorticoid therapy over the last 4 years or longer; or inability, in the opinion of the investigator, to withdraw glucocorticoid therapy through protocol-defined taper regimen due to suspected or established adrenal insufficiency.
• Patients requiring chronic (i.e. not occasional "prn") high potency opioid analgesics for pain management.
• Active ongoing inflammatory diseases or underlying metabolic, hematologic, renal, hepatic, pulmonary, neurologic, endocrine, cardiac, infectious or gastrointestinal conditions, which in the opinion of the investigator immunosuppressed the patient and/or places the patient at unacceptable risk for participation in an immunomodulatory therapy.
• History of renal trauma, glomerulonephritis, or patients with one kidney only, or a serum creatinine level exceeding 1.8 mg/dL (159.12 μmol/L).
• Screening total white blood cell (WBC) count \< 3000/μL, or platelets \< 100 000/μL or neutrophils \< 1500/μL or hemoglobin \< 8.3 g/dL (83 g/L).

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (11)

Novartis Investigative Site

Berlin, 13125, Germany

Location

Novartis Investigative Site

Cologne, 50937, Germany

Location

Novartis Investigative Site

Dresden, 01067, Germany

Location

Novartis Investigative Site

Erlangen, 91054, Germany

Location

Novartis Investigative Site

Freiburg im Breisgau, 79106, Germany

Location

Novartis Investigative Site

Germering, 82110, Germany

Location

Novartis Investigative Site

Herne, 44649, Germany

Location

Novartis Investigative Site

Ludwigshafen, 67063, Germany

Location

Novartis Investigative Site

Lübeck, 23538, Germany

Location

Novartis Investigative Site

Trier, 54292, Germany

Location

Novartis Investigative Site

Würzburg, 97080, Germany

Location

Related Publications (2)

• Venhoff N, Schmidt WA, Bergner R, Rech J, Unger L, Tony HP, Finzel S, Andreica I, Kofler DM, Weiner SM, Lamprecht P, Schulze-Koops H, App C, Pournara E, Mendelson MH, Sieder C, Maricos M, Thiel J. Safety and efficacy of secukinumab in patients with giant cell arteritis (TitAIN): a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Rheumatol. 2023 Jun;5(6):e341-e350. doi: 10.1016/S2665-9913(23)00101-7.

  PMID: 38251601 DERIVED

• Venhoff N, Schmidt WA, Lamprecht P, Tony HP, App C, Sieder C, Legeler C, Jentzsch C, Thiel J. 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. 2021 Aug 17;22(1):543. doi: 10.1186/s13063-021-05520-1.

  PMID: 34404463 DERIVED

Related Links

• Clinical\_Trials\_Results\_Word\_Form-CAIN457ADE11C.docx attachment has been refreshed from the Clinical Trials Results Word Form template. Data may be populated from the following (as available) : Study (70.0), Protocol (4.22), Results(0.22)
• A Plain Language Trial Summary is available on novctrd.com

MeSH Terms

Conditions

Giant Cell Arteritis

Interventions

secukinumab; Prednisolone

Condition Hierarchy (Ancestors)

Vasculitis, Central Nervous System; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Arteritis; Vasculitis; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 3, 2018
• First Posted: December 5, 2018
• Study Start: January 30, 2019
• Primary Completion: June 8, 2021
• Study Completion: June 8, 2021
• Last Updated: August 21, 2023
• Results First Posted: April 26, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will share

Locations

DE (11)