Phase III Study of Efficacy and Safety of Secukinumab Versus Placebo, in Combination With Glucocorticoid Taper Regimen, in Patients With Giant Cell Arteritis (GCA)

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04930094

Collaborator

(none)

240

Enrollment

Locations

Arms

Anticipated Duration (Months)

2.9

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a phase III study of efficacy and safety of secukinumab versus placebo, in combination with glucocorticoid taper regimen, in patients with giant cell arteritis (GCA)

Condition or Disease	Intervention/Treatment	Phase
Giant Cell Arteritis (GCA)	Biological: Secukinumab 300 mg Other: Placebo	Phase 3

Detailed Description

Randomized, parallel-group, double-blind, placebo-controlled, multi-center, Phase III study to evaluate the efficacy of secukinumab in combination with a 26-week prednisone taper regimen compared to pllacebo in combination with a 52-week prednisone taper regimen

Study Design

Study Type:

Interventional

Anticipated Enrollment :

240 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Masking Description:

Double Blind

Primary Purpose:

Treatment

Official Title:

A Randomized, Parallel Group, Double Blind, Placebo Controlled Multicenter Phase III Trial to Investigate the Efficacy and Safety of Secukinumab 300 mg Administered Subcutaneously Versus Placebo, in Combination With Glucocorticoid Taper Regimen, in Patients With Giant Cell Arteritis (GCA)

Actual Study Start Date :

Oct 6, 2021

Anticipated Primary Completion Date :

May 13, 2024

Anticipated Study Completion Date :

Jul 7, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Secukinumab 300 mg AIN457	Biological: Secukinumab 300 mg Secukinumab 300 mg Other Names: AIN457
Placebo Comparator: Placebo Placebo	Other: Placebo Placebo Other Names: Placebo Comparator

Arm

Intervention/Treatment

Experimental: Secukinumab 300 mg

AIN457

Biological: Secukinumab 300 mg

Secukinumab 300 mg

Other Names:

AIN457

Placebo Comparator: Placebo

Placebo

Other: Placebo

Placebo

Other Names:

Placebo Comparator

Outcome Measures

Primary Outcome Measures

Number of participants with sustained remission [52 weeks]
Primary objective is to determine whether the efficacy of secukinumab 300 mg s.c. in combination with a 26-week GC taper regimen is superior to placebo in combination with a 52-week glucocorticoids (GC) taper regimen in participants with giant cell arteritis (GCA) based on sustained remission at Week 52

Secondary Outcome Measures

Number of participants with clinical failure [12 weeks]
remission not achieved
Change in SF-36 score (PCS) [52 weeks]
Scores for each domain range from 0 to 100, with a higher score defining a more favorable health state
Change in GlucocorticoidToxicity Index (GTI) [52 weeks]
Change in Glucocorticoid Toxicity Index (GTI) as measured by the Agggregate Imrovement Score (AIS)
Change in FACIT-Fatigue Score [52 weeks]
The Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) is a 40-item measure that assesses self-reported fatigue and its impact upon daily activities and function. It was developed in the mid-1990's to meet a growing demand for more precise evaluation of fatigue associated with anemia in cancer patients. It is a subset of the longer (47-item) Functional Assessment of Cancer Therapy - Anemia (FACT-An), which includes the 27-item FACT-G and a 20-item subscale addressing additional concerns associated with the anemia of cancer and its treatment. This 20-item subscale, referred to as the anemia subscale, is comprised of 13 items that assess fatigue and its impact (the FACIT-Fatigue), and 7 additional symptoms associated with anemia (e.g., shortness of breath; headache).
Change in EQ-5D score [52 weeks]
The EQ-5D is an index value for health status. The EQ-5D self-reported questionnaire includes a visual analog scale (VAS), which records the respondent's self-rated health status on a graduated (0-100) scale, with higher scores for higher HRQoL
Cumulative GC dose [52 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Signed informed consent must be obtained prior to participation in the study.
Patient must be able to understand and communicate with the investigator and comply with the requirements of the study.
Male or non-pregnant, non-lactating female patients at least 50 years of age.
Diagnosis of GCA based on meeting all of the following criteria:
Age at onset of disease ≥ 50 years.
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) and/or symptoms of limb ischemia (claudication).
Temporal artery biopsy (TAB) revealing features of GCA and/or cross-sectional imaging study such as ultrasound (e.g. cranial or axillary), MRA, CTA, or PET-CT with evidence of vasculitis.
Active disease as defined by meeting both of the following within 6 weeks of Baseline:
Presence of signs or symptoms of GCA
Elevated erythrocyte sedimentation rate (ESR) ≥ 30 mm/hr or C-reactive protein (CRP) ≥ 10 mg/L attributed to active GCA or active GCA on TAB or imaging study
Patients to meet definition of new-onset GCA or relapsing GCA:
Definition of new-onset GCA: diagnosis of GCA within 6 weeks of Baseline visit
Definition relapsing GCA: diagnosis of GCA > 6 weeks before Baseline visit and patient has experienced recurrence of active disease following the institution of a treatment.
Patients must be eligible to receive prednisone (or equivalent) 20 mg-60 mg daily at Baseline.
Patients taking MTX (≤ 25 mg/week) are allowed to continue their medication provided they have taken it for at least 3 months, are on a stable dose for at least 4 weeks prior to randomization, and if they are on stable folic acid treatment before randomization

Exclusion Criteria:

Previous exposure to secukinumab or other biologic drug directly targeting IL-17 or IL-17 receptor.
Patients treated with any cell-depleting therapies.
Previous participation in clinical trial for GCA.
Patients who have been treated with inhibitors directly targeting IL-1, or IL-1 receptor, IL-12 and IL-23, or abatacept within 4 weeks or within 5 half-lives of the drug (whichever is longer) prior to Baseline.
Treatment with tocilizumab, other IL-6/IL6-R inhibitor or JAK inhibitor within 12 weeks or within 5 half-lives of the drug (whichever is longer) prior to Baseline, or if patient did not respond to or experienced a relapse during treatment any time before Baseline.
Any treatment received for GCA other than GCs and patient did not respond to treatment or experienced a relapse during treatment any time before Baseline.
Patients treated with i.v. immunoglobulins or plasmapheresis within 8 weeks prior to Baseline.
Patients treated with cyclophosphamide, tacrolimus, everolimus, hydroxychloroquine, cyclosporine A, azathioprine, sulfasalazine, mycophenolate mofetil within 6 months prior to 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 within 5 years prior to Baseline, unless specified in other exclusion criteria.
Patients requiring systemic chronic glucocorticoid therapy for any other reason than GCA.
Receipt of > 100 mg daily intravenous methylprednisolone pulse therapy within 6 weeks prior to Baseline.
Patients requiring chronic (i.e., not occasional "prn") high potency opioid analgesics for pain management.
Patients treated with any investigational agent within 4 weeks or within 5 half-lives of the drug (whichever is longer) prior to Baseline.
Contraindication or hypersensitivity to secukinumab.
Active ongoing inflammatory diseases other than GCA that might confound the evaluation of the benefit of secukinumab therapy, including inflammatory bowel disease or uveitis.
Major ischemic event (e.g. myocardial infarction, stroke, etc.) or transient ischemic attack (TIA) (except ischemia-related vision loss), related or unrelated to GCA, within 12 weeks of screening.
Confirmed diagnosis of any primary form of systemic vasculitis, other than GCA.
Any other biologics within 4 weeks or within 5 half-lives of the drug (whichever is longer) prior to Baseline.
Active ongoing diseases which in the opinion of the investigator immunocompromises the patient and/or places the patient at unacceptable risk for treatment with immunomodulatory therapy.
Active systemic infections during the last 2 weeks (exception: common cold) prior to randomization.
History of ongoing, chronic or recurrent infectious disease or evidence of tuberculosis infection as defined by a positive QuantiFERON TB- Gold Plus test. Patients with a positive test may participate in the study if further work up (according to local practice/guidelines) establishes conclusively that the patient has no evidence of active tuberculosis. If presence of latent tuberculosis is established then treatment according to local country guidelines must be initiated prior to randomization.
Live vaccinations within 6 weeks prior to Baseline or planned vaccination during study participation until 12 weeks after last study treatment administration.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Fontana	California	United States	92335
2	Novartis Investigative Site	Irvine	California	United States	92604
3	Novartis Investigative Site	Los Angeles	California	United States	90048
4	Novartis Investigative Site	Plantation	Florida	United States	33324
5	Novartis Investigative Site	Iowa City	Iowa	United States	52242
6	Novartis Investigative Site	Hopkinsville	Kentucky	United States	42240
7	Novartis Investigative Site	Hagerstown	Maryland	United States	21740
8	Novartis Investigative Site	Boston	Massachusetts	United States	02114
9	Novartis Investigative Site	Detroit	Michigan	United States	48202
10	Novartis Investigative Site	Saint Clair Shores	Michigan	United States	48081
11	Novartis Investigative Site	Jackson	Tennessee	United States	38305
12	Novartis Investigative Site	Grapevine	Texas	United States	76051
13	Novartis Investigative Site	Spring	Texas	United States	77382
14	Novartis Investigative Site	Ciudad Autonoma de Bs As	Buenos Aires	Argentina	C1119ACN
15	Novartis Investigative Site	Capital Federal		Argentina	C1023AAB
16	Novartis Investigative Site	Liverpool	New South Wales	Australia	2170
17	Novartis Investigative Site	Southport	Queensland	Australia	4215
18	Novartis Investigative Site	Hobart	Tasmania	Australia	7000
19	Novartis Investigative Site	Malvern East	Victoria	Australia	3145
20	Novartis Investigative Site	Murdoch	Western Australia	Australia	6150
21	Novartis Investigative Site	Leuven		Belgium	3000
22	Novartis Investigative Site	Liege		Belgium	4000
23	Novartis Investigative Site	Pleven		Bulgaria	5800
24	Novartis Investigative Site	Plovdiv		Bulgaria	4000
25	Novartis Investigative Site	Plovdiv		Bulgaria	4002
26	Novartis Investigative Site	Sofia		Bulgaria	1413
27	Novartis Investigative Site	Sherbrooke	Quebec	Canada	J1G 2E8
28	Novartis Investigative Site	Trois-Rivieres	Quebec	Canada	G8Z1Y2
29	Novartis Investigative Site	Brno Bohunice		Czechia	625 00
30	Novartis Investigative Site	Uherske Hradiste		Czechia	686 01
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32	Novartis Investigative Site	Esbjerg		Denmark	DK-6700
33	Novartis Investigative Site	Tallinn		Estonia	10138
34	Novartis Investigative Site	Tartu		Estonia	50406
35	Novartis Investigative Site	Kuopio		Finland	70100
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37	Novartis Investigative Site	Dijon		France	21000
38	Novartis Investigative Site	Le Mans		France	72037
39	Novartis Investigative Site	Nantes Cedex 1		France	44093
40	Novartis Investigative Site	Paris		France	75014
41	Novartis Investigative Site	Strasbourg		France	67000
42	Novartis Investigative Site	Bad Bramstedt		Germany	24576
43	Novartis Investigative Site	Berlin		Germany	13125
44	Novartis Investigative Site	Bonn		Germany	53105
45	Novartis Investigative Site	Dresden		Germany	01067
46	Novartis Investigative Site	Dresden		Germany	01307
47	Novartis Investigative Site	Erlangen		Germany	91054
48	Novartis Investigative Site	Freiburg		Germany	79106
49	Novartis Investigative Site	Herne		Germany	44649
50	Novartis Investigative Site	Ludwigshafen		Germany	D-67063
51	Novartis Investigative Site	Wuerzburg		Germany	97080
52	Novartis Investigative Site	Guatemala City		Guatemala	01010
53	Novartis Investigative Site	Guatemala City		Guatemala	01011
54	Novartis Investigative Site	Guatemala		Guatemala	01010
55	Novartis Investigative Site	Debrecen		Hungary	4032
56	Novartis Investigative Site	Pecs		Hungary	7623
57	Novartis Investigative Site	Szeged		Hungary	6720
58	Novartis Investigative Site	Firenze	FI	Italy	50139
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60	Novartis Investigative Site	Siena	SI	Italy	53100
61	Novartis Investigative Site	Bydgoszcz		Poland	85 168
62	Novartis Investigative Site	Krakow		Poland	30 002
63	Novartis Investigative Site	Wroclaw		Poland	53-224
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79	Novartis Investigative Site	Zurich		Switzerland	8091
80	Novartis Investigative Site	Pendik	Istanbul	Turkey	34899
81	Novartis Investigative Site	Ankara		Turkey	06100
82	Novartis Investigative Site	Antalya		Turkey	07070
83	Novartis Investigative Site	Sivas		Turkey	58140
84	Novartis Investigative Site	Newcastle Upon Tyne		United Kingdom	NE7 7DN