Study to Demonstrate the Efficacy, Safety and Tolerability of Intravenous Secukinumab up to 52 Weeks in Subjects With Active Psoriatic Arthritis (INVIGORATE 2)

Novartis

Status and phase: Completed; Phase 3

Conditions: Psoriatic Arthritis

Treatments: Drug: Placebo; Drug: AIN457 6 mg/kg i.v.; Drug: AIN457 3 mg/kg

Study type: Interventional

Funder types: Industry

Identifiers

NCT04209205

CAIN457P12302

Details and patient eligibility

About

The purpose of this study was to provide up to 52 weeks of efficacy, safety and tolerability data to support registration of intravenous (i.v.) secukinumab (Initial dose of 6 mg/kg at Baseline (BSL) followed thereafter with 3 mg/kg administered every four weeks) in patients with active psoriatic arthritis (PsA) despite current or previous Non-steroidal anti-inflammatory drugs (NSAIDs), Disease-modifying antirheumatic drugs (DMARDs) and/or anti-tumor necrosis factor (TNF) therapy.

Full description

This multicenter study used a randomized, double-blind, placebo-controlled, parallel-group design. A screening (SCR) period running up to 10 weeks before randomization was used to assess subject eligibility followed by a treatment period of 52 weeks.

At baseline, 381 patients with active psoriatic arthritis were randomized to one of the two treatment groups in a 1:1 randomization:

Group 1: Approximately 190 patients with active psoriatic arthritis; These patients received secukinumab 6 mg/kg i.v. at BSL, followed by the administration of secukinumab 3 mg/kg i.v. every four weeks starting at Week 4.

Group 2: Approximately 190 patients with active psoriatic arthritis; These patients received i.v. placebo at BSL and at Weeks 4, 8, and 12, followed by the administration of secukinumab 3 mg/kg i.v. every four weeks starting at Week 16.

Study consisted of 4 periods: a screening period (up to 10 weeks), treatment period 1 (total duration of 16 weeks) and treatment period 2 (total duration of 36 weeks) followed by a safety follow up period of 8 weeks after the end of treatment visit (i.e., Week 52).

Primary endpoint analysis will be performed with Week 16 data (last patient completing Treatment period 1 (Week 16). Long-term efficacy and safety assessments will be performed up to Week 52.

Enrollment: 381 patients

Sex: All

Ages: 18 to 100 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Patients eligible for inclusion in this study had to fulfill all of the following criteria:

• Diagnosis of PsA classified by CASPAR criteria and with symptoms for at least 6 months with moderate to severe PsA who must have at Baseline ≥3 tender joints out of 78 and ≥3 swollen out of 76 (dactylitis of a digit counts as one joint each)
• Rheumatoid factor and anti-CCP antibodies negative at screening
• Diagnosis of active plaque psoriasis or nail changes consistent with psoriasis or documented history of plaque psoriasis
• Subjects with PsA should have taken NSAIDs for at least 4 weeks prior to randomization with inadequate control of symptoms or at least one dose if stopped due to intolerance to NSAIDs
• Subjects taking corticosteroids must be on a stable dose of ≤10 mg/day prednisone or equivalent for at least 2 weeks before randomization and should remain on a stable dose up to Week 16
• Subjects taking MTX (≤ 25 mg/week) are allowed to continue their medication if the dose is stable for at least 4 weeks before randomization and should remain on a stable dose up to Week 52.

Patients fulfilling any of the following criteria are not eligible for inclusion in this study:

• Chest X-ray or chest MRI with evidence of ongoing infectious or malignant process, obtained within 3 months prior to screening and evaluated by a qualified physician
• Subjects taking high potency opioid analgesics (e.g. methadone, hydromorphone, morphine)
• Previous exposure to secukinumab or other biologic drug directly targeting IL-17 or IL-17 receptor
• Ongoing use of prohibited psoriasis treatments / medications (e.g., topical corticosteroids, UV therapy) at randomization. The following wash-out periods need to be observed:
• Oral or topical retinoids- 4 weeks
• Photochemotherapy (e.g. PUVA)- 4 weeks
• Phototherapy (UVA or UVB)- 2 weeks
• Topical skin treatments (except in face, eyes, scalp and genital area during screening, only corticosteroids with mild to moderate potency)- 2 weeks
• Any intramuscular or intravenous corticosteroid treatment within 4 weeks before randomization.
• Any therapy by intra-articular injections (e.g. corticosteroid) within 4 weeks before randomization.
• Subjects who have previously been treated with more than 3 different TNF inhibitors (investigational or approved).
• Subjects who have ever received biologic immunomodulating agents, investigational or approved except for those targeting TNFα.
• Previous treatment with any cell-depleting therapies including but not limited to anti-CD20 or investigational agents (e.g., CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti-CD19)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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381 participants in 2 patient groups, including a placebo group

AIN457 6 mg/kg - 3 mg/kg i.v.

Experimental group

Description:

AIN457 6 mg/kg i.v. infusion at baseline, followed by AIN457 3 mg/kg i.v. infusion every 4 weeks starting at Week 4 through Week 48 (exposure through Week 52).

Treatment:

Drug: AIN457 3 mg/kg

Drug: AIN457 6 mg/kg i.v.

Placebo

Placebo Comparator group

Description:

Matching placebo from baseline to Week 16 and switch to AIN457 3mg/kg i.v. infusion every 4 weeks through Week 48 (exposure through Week 52).

Treatment:

Drug: Placebo