Study in patients with giant cell arteritis to assess efficacy of secukinumab compared to placebo

• Register: EUCTR
• Last refreshed on: 21 July 2021
• Main ID: EUCTR2018-002610-12-DE
• Date of registration: 23/08/2018
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma GmbH
• Public title: Study in patients with giant cell arteritis to assess efficacy of secukinumab compared to placebo
• 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) - TitAIN
• Date of first enrolment: 06/12/2018
• Target sample size: 50
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2018-002610-12
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Germany

Contacts

• Name: Medizinischer Infoservice (MCC)
• Affiliation: Novartis Pharma GmbH

• Name: Medizinischer Infoservice (MCC)
• Affiliation: Novartis Pharma GmbH

Key inclusion & exclusion criteria

Inclusion criteria:
Patients eligible for inclusion in this study must meet all of the following criteria:
1. Signed informed consent must be obtained prior to participation in the study.
2. Patient must be able to understand and communicate with the investigator and comply with the requirements of the study.
3. Male or non-pregnant, non-lactating female patients at least 50 years of age.
4. 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.
5. 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 (< 10.0 mg/L) included) including previous treatment with = 25 mg/day prednisolone equivalent for = 2 weeks.
6. 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.
7. Prednisolone dose of 25-60 mg/day at Baseline.
8. Patients taking methotrexate (MTX) = 25 mg/week are allowed to continue their medication provided they have taken it for at least 3 months and are on a stable dose for at least 4 weeks prior to randomization and if they are on a stable folic acid treatment before randomization.

Other protocol-defined inclusion criteria may apply.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 25
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 25

Exclusion criteria:
Patients who fulfill any of the following criteria are not eligible for inclusion:
1. Pregnant or nursing (lactating) women where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test.
2. Women of childbearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during dosing of study treatment and for a minimum of 20 weeks after the last dose of secukinumab.
3. Previous exposure to secukinumab or other biologic drug directly targeting IL-17 or IL-17 receptor.
4. 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).
5. 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).
6. Patients who have previously been treated with tofacitinib or baricitinib.
7. Patients treated with i.v. immunoglobulins or plasmapheresis within 8 weeks prior to Baseline.
8. Patients treated with cyclophosphamide, tacrolimus or everolimus within 6 months prior to Baseline.
9. Patients treated with hydroxychloroquine, cyclosporine A, azathioprine, sulfasalazine or mycophenolate mofetil within 4 weeks of Baseline.
10. 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.
11. Patients treated with an alkylating agent except for cyclophosphamide as mentioned above.
12. Patients requiring systemic chronic glucocorticoid therapy for any other reason than GCA.
13. 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.
14. Patients requiring chronic (i.e. not occasional “prn”) high potency opioid analgesics for pain management.
15. Patients treated with any investigational agent within 4 weeks or within 5 half-lives of the drug (whichever is longer) prior to Baseline.
16. Contraindication or hypersensitivity to secukinumab.
17. Active ongoing inflammatory diseases other than GCA that might confound the evaluation of the benefit of secukinumab therapy.
18. 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 immunocomprises the patient and/or places the patient at unacceptable risk for participation in an immunomodulatory therapy.
19. Significant medical problems or diseases, including but not limited to the following: uncontrolled hypertension (= 160/95 mmHg), congestive heart failure (New York Heart Association (NYHA) status of class III or IV) and uncontrolled diabetes.
20. History of clinically significant liver disease or liver injury as indicated by abnormal liver function tests (LFTs) such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) or serum bilirubin.
21. History of renal trauma, glomerulonephritis, or patients with one kidney only, o

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Giant Cell Arteritis
MedDRA version: 23.1 Level: PT Classification code 10018250 Term: Giant cell arteritis System Organ Class: 10047065 - Vascular disorders

Therapeutic area: Body processes [G] - Immune system processes [G12]

Intervention(s)

Trade Name: Cosentyx
Product Name: Secukinumab
Product Code: AIN457
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: SECUKINUMAB
CAS Number: 1229022-83-6
Current Sponsor code: AIN457
Other descriptive name: SECUKINUMAB
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-
Pharmaceutical form of the placebo: Solution for injection in pre-filled syringe
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Secondary Objective: To evaluate the efficacy of secukinumab in combination with a 26-week prednisolone taper regimen vs. placebo in patients with GCA measured by:
• Remission rate at Week 12
• Time to first flare after remission
• Cumulative corticosteroid dose up to Week 28 and 52
• Patients in sustained remission up to Week 52
• Proportion of patients on prednisolone dose = 5mg/day at Week 19/28/52
• Changes from baseline in disease activity and quality of life measures at Week 4, 8, 12, 16, 20, 24, 28, 36, 44 and 52 for the following:
- Physician’s global assessment (PhGA) visual analog scale (VAS)
- Patient reported outcomes (PROs): Patient global assessment (PGA) VAS; Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-Fatigue); Short form 36 (SF36); EuroQoL 5D (EQ-5D)
Laboratory parameters (Baseline vs. Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52): CRP; ESR
To evaluate the safety/tolerability and immunogenicity of secukinumab

Main Objective: To demonstrate the efficacy of secukinumab compared to placebo, in combination with a 26-week prednisolone taper regimen, based on the proportion of patients with GCA who have sustained remission until week 28.

Timepoint(s) of evaluation of this end point: Week 28

Primary end point(s): Proportion of GCA patients in sustained remission at Week 28.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52

Secondary end point(s): - Efficacy
• Remission rate at Week 12
• Time to first flare after remission
• Cumulative corticosteroid dose up to Week 28 and 52
• Patients in sustained remission up to Week 52
• Proportion of patients on prednisolone dose = 5mg/day at Week 19/28/52
• Changes from baseline in disease activity and quality of life measures at Week 4, 8, 12, 16, 20, 24, 28, 36, 44 and 52 for the following:
- Physician’s global assessment (PhGA) visual analog scale (VAS)
- Patient reported outcomes (PROs): Patient global assessment (PGA) VAS; Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-Fatigue); Short form 36 (SF36); EuroQoL 5D (EQ-5D)
- Laboratory parameters (Baseline vs. Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52): CRP; ESR
- Safety/tolerability and immunogenicity of secukinumab

Secondary ID(s)

CAIN457ADE11C

Source(s) of Monetary Support

Novartis Pharma GmbH

Ethics review

Status: Approved
Approval date: 06/12/2018
Contact: