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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01752634
Other study ID # CAIN457F2312
Secondary ID 2012-004439-22
Status Completed
Phase Phase 3
First received
Last updated
Start date April 14, 2013
Est. completion date January 9, 2019

Study information

Verified date April 2020
Source Novartis
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This study was to provide 24 - 52 week efficacy, safety and tolerability data to support the registration of the secukinumab (AIN457) prefilled syringe (PFS) for subcutaneous self administration in subjects with active PsA despite current or previous NSAID, DMARD and/or anti-TNFα therapy. An additional 4 years of long-term efficacy and safety data were collected during the post Week 52 period of the study.


Description:

At baseline (BSL), subjects whose eligibility was confirmed were randomized to one of the following four treatment groups.

- 75 mg secukinumab

- 150 mg secukinumab

- 300 mg secukinumab

- Placebo At Week 16, all subjects were classified as responders (≥ 20% improvement from BSL in both tender and swollen joint counts) or non-responders.

Subjects who were randomized to a secukinumab treatment group at baseline were targeted to remain on the same dose for the entire trial.

Subjects who were randomized to placebo at baseline were re-randomized at Week 16 as follows:

Placebo non-responders received secukinumab 150 mg s.c. or 300 mg s.c. (1:1) every 4 weeks, starting after the efficacy assessments at Week 16.

Placebo responders continued to receive placebo at Week 16 and Week 20 and received secukinumab 150 mg s.c. or 300 mg s.c. (1:1) every 4 weeks, starting after the efficacy assessments at Week 24.

This was a double-blind, double-dummy, randomized treatment trial until week 52 analysis was completed and open label afterwards.

An amendment to the study protocol (after all patients were in the trial for 2-3 years) introduced changes whereby patients previously treated with secukinumab 75 mg s.c. could change to receive 150 mg s.c. or 300 mg s.c., and patients previously treated with secukinumab 150 mg s.c. could change to receive 300 mg s.c., as deemed appropriate by the investigators.


Recruitment information / eligibility

Status Completed
Enrollment 397
Est. completion date January 9, 2019
Est. primary completion date May 12, 2014
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria:Patients eligible for inclusion in this study have 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 24

- 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.

Exclusion Criteria: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, scalp and genital area during screening, only corticosteroids with mild to moderate potency) 2 weeks

- Subjects who have ever received biologic immunomodulating agents except for those targeting TNFa, investigational or approved

- Previous treatment with any cell-depleting therapies including but not limited to anti-CD20, investigational agents (e.g., CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti-CD19)

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Secukinumab (AIN457)
Secukinumab (AIN457)
Placebo
Placebo PFS for s.c. administration.

Locations

Country Name City State
Australia Novartis Investigative Site Hobart Tasmania
Australia Novartis Investigative Site Kogarah New South Wales
Australia Novartis Investigative Site Malvern East Victoria
Australia Novartis Investigative Site Maroochydore Queensland
Belgium Novartis Investigative Site Genk
Belgium Novartis Investigative Site Hasselt
Belgium Novartis Investigative Site Leuven
Canada Novartis Investigative Site Pointe-Claire Quebec
Canada Novartis Investigative Site Quebec
Canada Novartis Investigative Site Sainte-Foy Quebec
Canada Novartis Investigative Site Trois-Rivieres Quebec
Canada Novartis Investigative Site Waterloo Ontario
Canada Novartis Investigative Site Winnipeg Manitoba
Czechia Novartis Investigative Site Bruntal Czech Republic
Czechia Novartis Investigative Site Pardubice Czech Republic
Czechia Novartis Investigative Site Prague 2
Czechia Novartis Investigative Site Uherske Hradiste
Germany Novartis Investigative Site Aachen
Germany Novartis Investigative Site Berlin
Germany Novartis Investigative Site Erlangen
Germany Novartis Investigative Site Erlangen
Germany Novartis Investigative Site Germering
Germany Novartis Investigative Site Hamburg
Germany Novartis Investigative Site Herne
Germany Novartis Investigative Site Wuerzburg
Germany Novartis Investigative Site Zerbst
Poland Novartis Investigative Site Lodz
Poland Novartis Investigative Site Poznan
Poland Novartis Investigative Site Poznan
Poland Novartis Investigative Site Warszawa
Poland Novartis Investigative Site Warszawa
Poland Novartis Investigative Site Wroclaw
Puerto Rico Novartis Investigative Site Ponce
Russian Federation Novartis Investigative Site Chelyabinsk
Russian Federation Novartis Investigative Site Ekaterinburg
Russian Federation Novartis Investigative Site Kazan
Russian Federation Novartis Investigative Site Moscow
Russian Federation Novartis Investigative Site Petrozavodsk
Russian Federation Novartis Investigative Site Rostov on Don
Russian Federation Novartis Investigative Site Sestroretsk
Russian Federation Novartis Investigative Site St Petersburg
Russian Federation Novartis Investigative Site Yaroslavl
Thailand Novartis Investigative Site Bangkok
United Kingdom Novartis Investigative Site Blackpool
United Kingdom Novartis Investigative Site Cambridge
United Kingdom Novartis Investigative Site Cannock Staffordshire
United Kingdom Novartis Investigative Site Dudley West Midlands
United Kingdom Novartis Investigative Site Glasgow
United Kingdom Novartis Investigative Site Guildford Surrey
United Kingdom Novartis Investigative Site Leeds West Yorkshire
United Kingdom Novartis Investigative Site London
United Kingdom Novartis Investigative Site London
United Kingdom Novartis Investigative Site London England
United Kingdom Novartis Investigative Site Salford Manchester
United Kingdom Novartis Investigative Site Southampton
United States Novartis Investigative Site Asheville North Carolina
United States Novartis Investigative Site Aventura Florida
United States Novartis Investigative Site Charleston South Carolina
United States Novartis Investigative Site Charlotte North Carolina
United States Novartis Investigative Site Columbia South Carolina
United States Novartis Investigative Site Duncansville Pennsylvania
United States Novartis Investigative Site Freehold New Jersey
United States Novartis Investigative Site Greenville South Carolina
United States Novartis Investigative Site League City Texas
United States Novartis Investigative Site Lincoln Nebraska
United States Novartis Investigative Site Mesquite Texas
United States Novartis Investigative Site Oklahoma City Oklahoma
United States Novartis Investigative Site Oklahoma City Oklahoma
United States Novartis Investigative Site Omaha Nebraska
United States Novartis Investigative Site Palm Harbor Florida
United States Novartis Investigative Site Peoria Arizona
United States Novartis Investigative Site Sarasota Florida
United States Novartis Investigative Site Syracuse New York
United States Novartis Investigative Site Tamarac Florida
United States Novartis Investigative Site Tampa Florida
United States Novartis Investigative Site Zephyrhills Florida

Sponsors (1)

Lead Sponsor Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  Czechia,  Germany,  Poland,  Puerto Rico,  Russian Federation,  Thailand,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary Number of Participants Achieving American College of Rheumatology 20 (ACR20) Response Criteria ACR20 response was defined as having a positive clinical response to treatment (individual improvement) in disease activity if the participant had at least 20% improvement in tender 68-joint count, swollen 66-joint count and at least 3 of the following 5 measures: patient's assessment of RA pain, patient's global assessment of disease activity, physician's global assessment of disease activity, subject self-assessed disability (Health Assessment Questionnaire [HAQ-DI] score), and/or acute phase reactant (high sensitivity c-reactive protein (hsCRP) or erythrocyte sedimentation rate (ESR).
For subjects with early escape at Week 16 or had missing values at Week 24 or discontinued prior to Week 24, their ACR20 was set to nonresponse at Week 24. This applied for all treatment regimens in order to minimize bias. The Placebo arm was analyzed as one group, irrespective of the re-randomization, as assessments made under the re-randomized active treatment were not included in this analysis.
Week 24
Secondary Number of Participants Achieving a PASI75 Response in the Subgroup of Subjects Who Have =3% Skin Involvement With Psoriasis PASI is a combined assessment of a lesion severity and affected area into a single score: 0 (no disease) to 72 (maximal disease). The body is divided into 4 areas for scoring (head, arms, trunk, legs; each area is scored by itself and scores are combined for a final PASI. For each area, percent of skin involved is estimated: 0 (0%) to 6 (90-100%), and severity is estimated by clinical signs, erythema, induration and desquamation; scale 0 (none) to 4 (maximum). Final PASI = sum of severity parameters for each area * area score weight of section (head: 0.1, arms: 0.2, body: 0.3, legs: 0.4). PASI 75 response was defined as participants achieving >= 75% improvement from baseline. For subjects with early escape at Week 16 or had missing values at Week 24 or discontinued prior to Week 24, their value was set to nonresponse at Week 24. This applied for all treatment regimens in order to minimize bias. Week 24
Secondary Number of Participants Achieving a PASI90 Response in the Subgroup of Subjects Who Have =3% Skin Involvement With Psoriasis PASI is a combined assessment of a lesion severity and affected area into a single score: 0 (no disease) to 72 (maximal disease). The body is divided into 4 areas for scoring (head, arms, trunk, legs; each area is scored by itself and scores are combined for a final PASI. For each area, percent of skin involved is estimated: 0 (0%) to 6 (90-100%), and severity is estimated by clinical signs, erythema, induration and desquamation; scale 0 (none) to 4 (maximum). Final PASI = sum of severity parameters for each area * area score weight of section (head: 0.1, arms: 0.2, body: 0.3, legs: 0.4). PASI 90 response was defined as participants achieving >= 90% improvement from baseline. For subjects with early escape at Week 16 or had missing values at Week 24 or discontinued prior to Week 24, their value was set to nonresponse at Week 24. This applied for all treatment regimens in order to minimize bias. Week 24
Secondary Change From Baseline in DAS28-CRP The DAS28 is a measure of disease activity based on Swollen and Tender Joint Counts, ESR or CRP and the Patient Global Assessment. A DAS28 score > 5.1 implies active disease, = 3.2 low disease activity, and < 2.6 remission. The score can range from 0 - 9.4. The data collected after the patient switched to secukinumab were treated as missing for placebo patients and were analyzed using a mixed-effects repeated measures model. For secukinumab patients, the actual values were used in the analysis.
The Placebo arm was analyzed as one group, irrespective of the re-randomization, as assessments made under the re-randomized active treatment were not included in this analysis.
Baseline, Week 24
Secondary Change From Baseline in SF36-Physical Component Score The SF-36 is an instrument to measure health-related quality of life among healthy patients and patients with acute and chronic conditions.
Score range is from 0 (no problems) to 100 (unable to perform the activity). SF-36 is a 36 item questionnaire which measures Quality of Life across eight domains, which are both physically and emotionally based. Two overall summary scores, the Physical Component Summary (PCS) and Mental Component Summary (MCS) can be computed. In this study, SF-36 PCS was used.
The Placebo arm was analyzed as one group, irrespective of the re-randomization, as assessments made under the re-randomized active treatment were not included in this analysis.
Baseline, Week 24
Secondary Change From Baseline in Stanford Health Assessment Questionnaire Disability Index (HAQ-DI) The HAQ-DI assesses a subject's level of functional ability and includes questions of fine movements of the upper extremity, locomotor activities of the lower extremity, and activities that involve both upper and lower extremities. There are 20 questions in 8 categories of functioning including dressing, rising, eating, walking, hygiene, reach, grip and usual activities. The stem of each item asks 'Over the past week, "are you able to..." perform a particular task'. Each item is scored on a 4 point scale from 0 - 3, representing normal, no difficulty (0), some difficulty (1), much difficulty (2) and unable to do (3). The disability index score is calculated as the mean of the available category scores, ranging from 0 to 3. A negative change from baseline indicates improvement. The Placebo arm was analyzed as one group, irrespective of the re-randomization, as assessments made under the re-randomized active treatment were not included in this analysis. Baseline, Week 24
Secondary Number of Participants Achieving American College of Rheumatology 50 (ACR50) Response Criteria ACR20 response was defined as having a positive clinical response to treatment (individual improvement) in disease activity if the participant had at least 50% improvement in tender 68-joint count, swollen 66-joint count and at least 3 of the following 5 measures: patient's assessment of RA pain, patient's global assessment of disease activity, physician's global assessment of disease activity, subject self-assessed disability (Health Assessment Questionnaire [HAQ-DI] score), and/or acute phase reactant (high sensitivity c-reactive protein (hsCRP) or erythrocyte sedimentation rate (ESR). For subjects with early escape at Week 16 or had missing values at Week 24 or discontinued prior to Week 24, their ACR20 was set to nonresponse at Week 24. This applied for all treatment regimens in order to minimize bias. The Placebo arm was analyzed as one group, irrespective of the re-randomization, as assessments made under the re-randomized active treatment were not included in this analysis. Week 24
Secondary Number of Participants With Dactylitis in the Subset of Subjects Who Had Dactylitis at Baseline Resolution of dactylitis was evaluated in the subset of patients who had disease activity at baseline. In this analysis, a lower percentage is desirable and resolution is defined as complete absence of the symptom. For subjects with early escape at Week 16 or had missing values at Week 24 or discontinued prior to Week 24, their assessment was set to nonresponse at Week 24 (presence of dactylitis). This applied for all treatment regimens in order to minimize bias. The Placebo arm was analyzed as one group, irrespective of the re-randomization, as assessments made under the re-randomized active treatment were not included in this analysis. Week 24
Secondary Number of Participants With Enthesitis in the Subset of Subjects Who Had Enthesitis at Baseline Resolution of enthesitis was evaluated in the subset of patients who had disease activity at baseline. In this analysis, a lower percentage is desirable and resolution is defined as complete absence of the symptom. For subjects with early escape at Week 16 or had missing values at Week 24 or discontinued prior to Week 24, their assessment was set to nonresponse at Week 24 (presence of enthesitis). This applied for all treatment regimens in order to minimize bias. The Placebo arm was analyzed as one group, irrespective of the re-randomization, as assessments made under the re-randomized active treatment were not included in this analysis. Week 24
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