4 Year Extension Study of Efficacy and Safety of Secukinumab in Patients With Moderate to Severe Chronic Plaque-type Psoriasis

• ClinicalTrials.gov Identifier: NCT01640951
• Recruitment Status: Completed
• First Posted: July 16, 2012
• Results First Posted: May 25, 2018
• Last Update Posted: May 25, 2018
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Study Description

Brief Summary:

CAIN457A2304E1 was an extension study to two phase III studies, CAIN457A2304 and CAIN457A2307 (core studies). This extension study planned to collect up to four years of long-term safety, tolerability and efficacy data of secukinumab in both the fixed interval regimen and the retreatment at start of relapse regimen. All subjects who completed the full study treatment period (52 weeks) in the cores studies CAIN457A2304 and CAIN457A2307 were eligible to participate in this extension study. In this extension study, the prefilled syringe (PFS) liquid formulation of secukinumab was used.

Condition or disease	Intervention/treatment	Phase
Moderate to Severe Chronic Plaque-Type Psoriasis	Drug: AIN457 150 mg; Drug: AIN457 300 mg; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 675 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Double-blind and Open Label, 4 Year Extension Study of Subcutaneous Secukinumab in Prefilled Syringes, Assessing Long-term Safety, Tolerability and Efficacy in Subjects With Moderate to Severe Chronic Plaque-type Psoriasis Treated With Either a Fixed Dose Regimen or on a Retreatment at Start of Relapse Regimen
• Actual Study Start Date: September 16, 2012
• Actual Primary Completion Date: May 4, 2017
• Actual Study Completion Date: May 4, 2017

Arms and Interventions

Arm	Intervention/treatment
Experimental: AIN457 150 mg - Fixed Interval (FI); 1 s.c. Secukinumab 150 mg Pre-filled seringue (PFS) injection + 1 s.c. Placebo (PBO) Secukinumab PFS injection every 4 weeks	Drug: AIN457 150 mg; (1 injection per dose) and placebo to Secukinumab 150 mg; Other Name: Secukinumab 150 mg; Drug: Placebo
Experimental: AIN457 150 mg - Start of relapse (SoR); Start of relapse: 1 s.c. Secukinumab 150 mg PFS injection + 1 s.c. PBO Secukinumab PFS injection every 4 weeks Otherwise: 2 s.c. PBO Secukinumab PFS injections every 4 weeks	Drug: AIN457 150 mg; (1 injection per dose) and placebo to Secukinumab 150 mg; Other Name: Secukinumab 150 mg; Drug: Placebo
Experimental: AIN457 300 mg - Fixed Interval (FI); 2 s.c. Secukinumab 150 mg PFS injections every 4 weeks	Drug: AIN457 300 mg; Secukinumab 150 mg (2 injections per dose); Other Name: Secukinumab 300 mg
Experimental: AIN457 300 mg - Start of Relapse (SoR); Start of relapse: 2 s.c. Secukinumab 150 mg PFS injection every 4 weeks Otherwise: 2 s.c. PBO Secukinumab PFS injections every 4 weeks	Drug: AIN457 300 mg; Secukinumab 150 mg (2 injections per dose); Other Name: Secukinumab 300 mg; Drug: Placebo
Experimental: AIN457 300 mg - Open Label (OL); Open Label - Secukinumab 300mg every 4 weeks	Drug: AIN457 300 mg; Secukinumab 150 mg (2 injections per dose); Other Name: Secukinumab 300 mg

Outcome Measures

Primary Outcome Measures :

1. Long-term Safety and Tolerability of Secukinumab [ Time Frame: Week 268 ]
   Analysis of absolute and relative frequencies for treatment emergent Adverse Event (AE), Serious Adverse Event (SAE) and Deaths by primary System Organ Class (SOC)

Secondary Outcome Measures :

1. Percentage of Participants Achieving Psoriasis Area and Severity Index (PASI) Score of 75 at Weeks 52, 104, 156, 208 and 260 [ Time Frame: Week 52, Week 104, Week 156, Week 208, Week 260 ]
   PASI: Combined assessment of lesion severity and affected area into a single score: 0 (no disease) to 72 (maximal disease). Body is divided into 4 areas for scoring (head, arms, trunk, legs; each area is scored by itself and scores are combined for 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)
2. Percentage of Participants Achieving Psoriasis Area and Severity Index (PASI) Scores of 50, 90 and 100 Over Time at Weeks 52, 104, 156, 208 and 260 [ Time Frame: Week 52, Week 104, Week 156, Week 208, Week 260 ]
   PASI: Combined assessment of lesion severity and affected area into a single score: 0 (no disease) to 72 (maximal disease). Body is divided into 4 areas for scoring (head, arms, trunk, legs; each area is scored by itself and scores are combined for 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)
3. Percent Change From Baseline in Psoriasis Area and Severity Index (PASI) Score at Weeks 52, 104, 156, 208 and 260 [ Time Frame: Baseline, Week 52, Week 104, Week 156, Week 208, Week 260 ]
   PASI: Combined assessment of lesion severity and affected area into a single score: 0 (no disease) to 72 (maximal disease). Body is divided into 4 areas for scoring (head, arms, trunk, legs; each area is scored by itself and scores are combined for 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)
4. Percentage of Participants Achieving Investigator's Global Assessment Modified 2011 (IGA) 2011 Score of 0 or 1 Over Time at Weeks 52, 104, 156, 208 and 260 [ Time Frame: Week 52, Week 104, Week 156, Week 208, Week 260 ]
   The IGA mod 2011 is a static scale, i.e., it refers exclusively to the participant's disease state at the time of the assessments and does not attempt a comparison to any of the participant's previous disease states at prior visits. The score ranges from 0 (clear) to 4 (severe). The score 0 is clear, 1 is almost clear, 2 is mild, 3 is moderate, and 4 is severe.
5. Percentage Change From Baseline in Dermatology Life Quality Index (DLQI©) Response at Weeks 52, 104, 156, 208 and 260 [ Time Frame: Baseline, Week 52, Week 104, Week 156, Week 208, Week 260 ]
   The DLQI is a quality of life measure used in the psoriatic The 10-item questionnaire has a score range of 0 (best) to 30 (worst) with higher scores indicating poor quality of life. The instrument contains six functional scales (i.e., symptoms and feeling, daily activities, leisure, work and school, personal relationships, treatment). Each item has 4 response categories, ranging from 0 (not at all) to 3 (very much). "Not relevant" is also a valid response and is scored as 0. The DLQI total score is a sum of the 10 questions
6. Percentage of Participants With Dermatology Life Quality Index (DLQI©) Response (DLQI 0 or 1) Over Time at Weeks 52, 104, 156, 208 and 260 [ Time Frame: Week 52, Week 104, Week 156, Week 208, Week 260 ]
   The DLQI is a quality of life measure used in the psoriatic The 10-item questionnaire has a score range of 0 (best) to 30 (worst) with higher scores indicating poor quality of life. The instrument contains six functional scales (i.e., symptoms and feeling, daily activities, leisure, work and school, personal relationships, treatment). Each item has 4 response categories, ranging from 0 (not at all) to 3 (very much). "Not relevant" is also a valid response and is scored as 0. The DLQI total score is a sum of the 10 questions
7. EuroQOL 5-Dimension Health Status Questionnaire (EQ-5D©) Score and Percent Change From Baseline at Weeks 52, 104 and 156 [ Time Frame: Baseline, Week 52, Week 104, Week 156 ]
   ED-5Q: Participant rated questionnaire to assess health related quality of life in terms of a single utility score. Five domains are assessed mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) each with three possible score: 1 indicates no problems, better state of health; 3 indicates worst state of health (example "confined to bed") A visual analog scale (VAS) assesses the health status from 0 (worst possible health state) to 100 (best possible health state)
8. Number of Participants With Treatment Emergent Anti-drug Antibodies (ADA) [ Time Frame: Week 268 ]
   The development of anti-secunimubab anti-bodies will decrease a participant's ability to respond to secukinumab treatment.
9. Percentage of Patients With Experiencing a Relapse [ Time Frame: Week 260 ]

   Relapse is defined as greater than 50% loss of the maximal PASI improvement from baseline.

   PASI is a combined assessment of lesion severity and affected area into a single score: 0 (no disease) to 72 (maximal disease). Body is divided into 4 areas for scoring (head, arms, trunk, legs; each area is scored by itself and scores are combined for 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). A negative mean percentage change indicates improvement.

10. Percentage of Patients With Experiencing a Rebound [ Time Frame: Up to Week 264 (8 weeks post last dose) ]

    Rebound of disease is defined as a worsening of PASI of > 125% of the value at baseline (core study), or new pustular, erythrodermic or more inflammatory psoriasis occurring within 8 weeks of stopping therapy (i.e., if this definition was fulfilled at more than 8 weeks after last study treatment administration, this was defined as rebound like event).

    PASI is a combined assessment of lesion severity and affected area into a single score: 0 (no disease) to 72 (maximal disease). Body is divided into 4 areas for scoring (head, arms, trunk, legs; each area is scored by itself and scores are combined for 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). A negative mean percentage change indicates improvement.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Subjects must be able to understand and communicate with the investigator and comply with the requirements of the study and must give a written, signed and dated informed consent before any study related activity is performed. Where relevant, a legal representative will also sign the informed consent according to local laws and regulations.
2. Subjects who complete Week 52 of study CAIN457A2304 or complete Week 40 of study CAIN457A2307
3. Subjects expected to benefit from participation in the extension study, as assessed by the subject and investigator

Exclusion Criteria:

1. A protocol deviation in the core studies which according to the investigator will prevent the meaningful analysis of the extension study for the individual subject
2. Ongoing use of prohibited psoriasis or non-psoriasis treatments. Time period from last use of prohibited treatments in the core study to first dose of study drug in this extension study.
3. Subjects expected to be exposed to an undue safety risk if participating in the trial
4. Current severe progressive or uncontrolled disease which in the judgment of the investigator renders the subject unsuitable for the trial
5. Plans for administration of live vaccines during the study period
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 (>10 mIU/mL).

Contacts and Locations

  Show 111 Study Locations

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

  Study Documents (Full-Text)

Documents provided by Novartis ( Novartis Pharmaceuticals ):

Study Protocol  [PDF] April 29, 2015

Statistical Analysis Plan  [PDF] April 11, 2018

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Bissonnette R, Luger T, Thaçi D, Toth D, Messina I, You R, Guana A, Fox T, Papavassilis C, Gilloteau I, Mrowietz U. Secukinumab sustains good efficacy and favourable safety in moderate-to-severe psoriasis after up to 3 years of treatment: results from a double-blind extension study. Br J Dermatol. 2017 Oct;177(4):1033-1042. doi: 10.1111/bjd.15706. Epub 2017 Sep 4.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01640951 History of Changes
• Other Study ID Numbers: CAIN457A2304E1; 2012-000985-39 ( EudraCT Number )
• First Posted: July 16, 2012
• Results First Posted: May 25, 2018
• Last Update Posted: May 25, 2018
• Last Verified: April 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

Psoriasis; Plaque; Inflammatory skin disease; Scaly patches; AIN457; Secukinumab; Moderate to Severe Plaque-type Psoriasis

Additional relevant MeSH terms:

Psoriasis; Skin Diseases, Papulosquamous; Skin Diseases; Antibodies, Monoclonal; Immunologic Factors; Physiological Effects of Drugs