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

• Register: ClinicalTrials.gov
• Last refreshed on: 28 August 2023
• Main ID: NCT03765788
• Date of registration: 03/12/2018
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharmaceuticals
• Public title: A Placebo-controlled Phase 2 Trial to Investigate the Safety and Efficacy of Secukinumab in Giant Cell Arteritis TitAIN
• Scientific title: A Randomized, Parallel-group, Double-blind, Placebo-controlled, Multicenter Phase 2 Trial to Investigate the Safety and Efficacy of Secukinumab (AIN457) in Patients With Giant Cell Arteritis (TitAIN)
• Date of first enrolment: January 30, 2019
• Target sample size: 52
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/ct2/show/NCT03765788
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 2

Countries of recruitment

Germany

Contacts

• Name: Novartis Pharmaceuticals
• Affiliation: Novartis Pharmaceuticals

Key inclusion & exclusion criteria

Inclusion Criteria:

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

Patients with new onset GCA or relapsing GCA (Definition new onset: diagnosis of GCA within
6 weeks of Baseline Visit; Definition relapsing GCA: diagnosis of GCA (in accordance with
inclusion criterion no. 4) > 6 weeks before Baseline Visit and in the meantime achieved
remission (absence of signs and symptoms attributable to GCA and normalization of ESR (< 30
mm/hr) and CRP (<10.0mg/L) included) including previous treatment with = 25 mg/day
prednisolone equivalent for = 2 weeks.)

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.

Exclusion Criteria:

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 (TNFa) 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).

Major ischemic event, unrelated to GCA, within 12 weeks of screening.

Known infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C at
screening or randomization.

Life vaccinations within 6 weeks prior to Baseline or planned vaccination during study
participation until 12 weeks after last study treatment administration.



Age minimum: 50 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Giant Cell Arteritis

Intervention(s)

Drug: Prednisolone

Drug: Placebo

Drug: Secukinumab 300 mg, s.c.

Primary Outcome(s)

Percentage of Participants in Sustained Remission Until Week 28 [Time Frame: Until week 28]

Secondary Outcome(s)

Number of Participants on Prednisolone Dose = 5mg/Day [Time Frame: Week 19, Week 28, Week 52]

Patients Global Assessment (PGA) of Disease Activity: Change From Baseline Via Visual Analogue Scale (VAS) [Time Frame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 36, 44 & 52]

Change From Baseline in FACIT-Fatigue Scale [Time Frame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 36, 44 & 52]

Physicians Global Assessment (PhGA) of Disease Activity: Change From Baseline Score Via Visual Analogue Scale (VAS) [Time Frame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 36, 44 & 52]

Change From Baseline in EQ-5D-5L (EuroQol 5D) Questionnaire [Time Frame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 36, 44 & 52]

Change From Baseline in Short-Form (SF)-36 Questionnaire [Time Frame: Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 36, 44 & 52]

Percentage of Participants With GCA Who Had Sustained Remission Until Week 52 [Time Frame: Until Week 52]

Total Cumulative Prednisolone Dose Over 28 Weeks and 52 Weeks [Time Frame: from Baseline to week 28, from baseline to week 52 weeks]

Change From Baseline in C-Reactive Protein (CRP) Level [Time Frame: Baseline, Week 28, Week 52]

Change From Baseline in Erythrocyte Sedimentation Rate (ESR) [Time Frame: Baseline, Week 28, Week 52]

Percentage of Participants in Remission at Week 12 [Time Frame: Week 12]

Time to First GCA Flare After Clinical Remission [Time Frame: Up to Week 52 (included)]

Secondary ID(s)

CAIN457ADE11C

2018-002610-12

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 26/04/2023
• URL: https://clinicaltrials.gov/ct2/show/results/NCT03765788