Secukinumab in Tumor Necrosis Factor (TNF) - Inadequate Response (IR) Psoriasis Participants. (SIGNATURE)

Novartis

Status and phase: Completed; Phase 3

Conditions: Psoriasis

Treatments: Biological: Secukinumab (AIN457)

Study type: Interventional

Funder types: Industry

Identifiers

NCT01961609

CAIN457AGB01

Details and patient eligibility

About

This study was designed to prove and quantify the hypothesis that secukinumab is effective, safe and well tolerated in the treatment of moderate to severe chronic plaque-type psoriasis in patients who are inadequate responders to anti-TNFα therapy in a United Kingdom (UK) and Republic of Ireland) specific population.

Full description

There is no clear evidence or guidelines on appropriate treatment once a patient with moderate/severe psoriasis has failed to respond to anti-TNFα therapy, whether a single anti-TNFα therapy failure or multiple anti-TNFα therapy failures.

Numerous double-blind, double-dummy, randomised, parallel-group, active and placebo controlled studies have already been designed and run for the Phase III secukinumab clinical development program, in accordance with Health Authorities guidelines and feedback, including Food and Drug Administration (FDA) and European Medicines Agency (EMA). None of these specifically studied patients who have failed to respond to anti-TNFα therapy as defined by National Institute for Health and Care Excellence (NICE) guidelines.

Therefore, this study utilises a pragmatic, open-label, non-comparator design, which has been shown to be appropriate in similar studies looking at anti-TNFα therapy in patients failing on other therapies (Papp et al. 2012; Strober et al. 2011), to answer the question of whether secukinumab is an appropriate choice in patients who have failed to respond to anti-TNFα therapy (TNF-IR) per NICE definitions, whether a single anti-TNFα therapy failure or multiple anti-TNFα therapy failures.

Enrollment: 235 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

1. Written informed consent must be obtained before any assessment is performed

2. Aged at least 18 years at screening

3. Chronic plaque-type psoriasis diagnosed for at least 6 months prior to screening

4. Moderate to severe disease severity:

   • PASI ≥10 and
   • DLQI >10

5. Failed to respond to systemic therapies including cyclosporine and/or methotrexate and/or PUVA (or is intolerant and/or has a contraindication to these)

6. Previously treated with at least one anti-TNFα for moderate or severe psoriasis but is a primary or secondary non-responder

7. Able to communicate well with the investigator, to understand and comply with the requirements of the study.

Key Exclusion Criteria:

1. Forms of psoriasis other than chronic plaque-type (e.g., pustular, erythrodermic and guttate psoriasis)
2. Drug-induced psoriasis (i.e., new onset or current exacerbation from beta-blockers, calcium channel inhibitors or lithium)
3. Ongoing use of prohibited psoriasis treatments (e.g., topical or systemic corticosteroids (CS), UV therapy). Washout periods detailed in the protocol must be adhered to.
4. Ongoing use of other non-psoriasis prohibited treatments. Washout periods detailed in the protocol have to be adhered to. All other prior non-psoriasis concomitant treatments must be on a stable dose for at least four weeks before initiation of study drug.
5. Previous exposure to secukinumab or any other biologic drug directly targeting IL-17 or the IL-17 receptor
6. 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 hCG laboratory test (> 5 mIU/mL)
7. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant unless they use 2 (two) effective forms of contraception during the study and for 16 weeks after stopping treatment.
8. Men with a female partner of child bearing potential defined as all women physiologically capable of becoming pregnant unless they use 1 (one) effective form of contraception during the study and for 16 weeks after stopping treatment.
9. Active systemic infections during the last two weeks (exception: common cold) prior to initiation of study drug and any infections that reoccur on a regular basis; investigator discretion should be used regarding patients who have travelled or recently resided in areas of endemic mycoses, such as histoplasmosis, coccidioidomycosis or blastomycosis and for patients with underlying conditions that may predispose them to infection, such as advanced or poorly controlled diabetes
10. History of an ongoing, chronic or recurrent infectious disease, or evidence of tuberculosis infection as defined by a positive QuantiFERON TB-Gold test (QFT) at screening. Patients with a positive QFT test may participate in the study if further work up establishes conclusively that the patient has no evidence of active tuberculosis. If presence of latent tuberculosis is established, then treatment must have been initiated and maintained according to UK guidelines.
11. Known infection with HIV, hepatitis B or hepatitis C at screening or at initiation of study drug.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

235 participants in 2 patient groups

Secukinumab (AIN457) 300 mg

Experimental group

Description:

Participants self-administered 300 mg secukinumab loading dose subcutaneously at Day 0 (initiation of study drug) and at weeks 1, 2, 3 \& 4, and then every 4 weeks. Following the Primary Endpoint at 16 weeks, participants meeting the NICE criteria of adequate response were eligible to continue on study treatment for a further 32 weeks. Participants not meeting this NICE criterion returned to routine treatment under the care of their usual Clinical Team. Following assessment at week 48, participants meeting the NICE criteria of adequate response were eligible to continue on study treatment for a further 24 weeks. Participants not meeting this NICE criterion returned to routine treatment under the care of their usual Clinical Team.

Treatment:

Biological: Secukinumab (AIN457)

Secukinumab (AIN457) 150 mg

Experimental group

Description:

Participants self-administered secukinumab 150 mg loading dose subcutaneously at Day 0 (initiation of study drug), weeks 1, 2, 3 \& 4 and then every 4 weeks. Following the Primary Endpoint at 16 weeks, participants meeting the NICE criteria of adequate response were eligible to continue on study treatment for a further 32 weeks at the 150mg dose. Participants not achieving the NICE criteria at the Primary Endpoint were up titrated to 300mg. Following assessment at week 48, participants meeting the NICE criteria of adequate response were eligible to continue on study treatment for a further 24 weeks at the 150mg dose. Participants not achieving the NICE criteria at 48 weeks on the 150mg dose were up titrated to 300mg.

Treatment:

Biological: Secukinumab (AIN457)