Extension Study of Secukinumab Prefilled Syringes in Subjects With Moderate to Severe Chronic Plaque-type Psoriasis Completing Preceding Psoriasis Phase III Studies With Secukinumab

Study Overview
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Brief Summary
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This was an extension study of secukinumab prefilled syringes in subjects with moderate to severe chronic plaque-type psoriasis completing preceding psoriasis phase III studies with secukinumab. Subjects on secukinumab at the end of treatment period in phase III studies (e.g., ongoing CAIN457A2302 and CAIN457A2303 and potentially other secukinumab phase III studies) were eligible to join this extension study. This extension study was planned to collect an additional 2 years of long-term efficacy, safety, and tolerability data of secukinumab in either continuous or interrupted therapy (randomized withdrawal period) in subjects showing at least partial response to secukinumab and completing treatment period on secukinumab in previous phase III studies. In this extension study, the prefilled syringe (PFS) liquid formulation of secukinumab were used.

Official Title
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A Multicenter, Double-blind, Randomized Withdrawal Extension Study of Subcutaneous Secukinumab in Prefilled Syringes to Demonstrate Long-term Efficacy, Safety, and Tolerability up to 4 Years in Subjects With Moderate to Severe Chronic Plaque-type Psoriasis Completing Preceding Psoriasis Phase III Studies With Secukinumab

Conditions
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Moderate to Severe Plaque-type Psoriasis

Intervention / Treatment
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* Drug: Secukinumab (AIN457)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Completed the full study treatment period of 52 weeks in preceding phase III studies, and have been receiving secukinumab treatment during the maintenance phase of the preceding phase III studies, and show at least a partial response (PASI 50 or better) at Week 52 of the preceding phase III studies. Written informed consent form. Key Exclusion Criteria: A protocol deviation in either of the preceding phase III studies which according to the investigator prevented the meaningful analysis of the extension study for the individual subject. Ongoing use of prohibited psoriasis or non-psoriasis treatments. 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). Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unwilling to use effective contraception during the study and for 16 weeks after stopping treatment.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: PASI 75 Responders<br>PASI 75 responders participated in randomized withdrawal. Subjects who were PASI 75 responders at Week 52 visit of the core studies (e.g.CAIN457A2302 or CAIN457A2303) and have been on secukinumab s.c. 150 mg or 300 mg in core studies were randomized to continue same s.c. doses of secukinumab in PFS or receive placebo every 4 weeks up to Week 152 or until relapse. Participants on first full relapse received loading dose followed by routine dosing with secukinumab s.c. 150 mg or 300 mg regimen. | Drug: Secukinumab (AIN457)<br>* Secukinumab is a new type of psoriasis medication called a human monoclonal antibody. Monoclonal antibodies are proteins that recognize and bind to unique proteins that your body produces. Secukinumab binds and reduces the activity of a cytokine (a messenger protein in the body) called Interleukin 17 (IL-17). IL-17 is believed to be partly responsible for inflammation (pain, swelling, redness). Researchers believe that IL-17 causes symptoms of plaque-type psoriasis like plaques and scales. A product that targets IL-17 therefore may help to relieve these symptoms and conditions.<br>Drug: Placebo<br>* Placebo<br>|
| Experimental: Partial responders<br>Partial responders were not randomized. Subjects who were partial responders at Week 52 visit in core studies (e.g.CAIN457A2302 or CAIN457A2303) and have been on secukinumab s.c. 150 mg or 300 mg in core studies did not participate in the randomized withdrawal. These subjects continued same treatment s.c. dose in PFS (secukinumab s.c. 150 mg or 300 mg) as they were receiving at the time of completing the maintenance period (Week 52) in the core studies. | Drug: Secukinumab (AIN457)<br>* Secukinumab is a new type of psoriasis medication called a human monoclonal antibody. Monoclonal antibodies are proteins that recognize and bind to unique proteins that your body produces. Secukinumab binds and reduces the activity of a cytokine (a messenger protein in the body) called Interleukin 17 (IL-17). IL-17 is believed to be partly responsible for inflammation (pain, swelling, redness). Researchers believe that IL-17 causes symptoms of plaque-type psoriasis like plaques and scales. A product that targets IL-17 therefore may help to relieve these symptoms and conditions.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of Participants With Loss of Psoriasis Area and Severity Index (PASI) 75 Response up to Week 68 | The primary variable was the cumulative rate of patients who lost PASI 75 response up to Week 68 (time=0 being defined as Week 52). Loss of PASI 75 response was analyzed by means of a survival analysis defining loss of PASI 75 response as failure. The term cumulative rate corresponded to 1 minus the survival function within this survival analysis, and the cumulative rate and the survival functions were dependent on time t. PASI 75 response: patients achieving ≥ 75% improvement (reduction) in PASI score compared to baseline of the core study were defined as PASI 75 responders. | At week 68 (16 weeks after week 52) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With PASI 50, PASI 75, PASI 90, PASI 100 and IGA Mod 2011 0 or 1 (Observed Data) - Randomized Withdrawal Period | Psoriasis Area and Severity Index (PASI) 75 responder at week 52. Patients in the placebo groups were not evaluable after re-treatment with Secukinumab. PASI 75 Responders: patients with a PASI 75 response (patients achieving ≥75% improvement [reduction] in PASI score compared to baseline of the core study). PASI 50 response: patients achieving ≥ 50% improvement (reduction) in PASI score compared to baseline of the core study were defined as PASI 50 responders. PASI 90 response: patients achieving ≥ 90% improvement (reduction) in PASI score compared to baseline of the core study were defined as PASI 90 responders. PASI 100 response/remission: complete clearing of psoriasis (PASI=0) | Week 52, 104, and 156 | 
| Number of Participants With PASI 50, PASI 75, PASI 90, and PASI 100 (Observed Data) - Entire Study Period | Psoriasis Area and Severity Index (PASI) scoring system: The average degree of severity of each sign in each of the four body regions was assigned a score of 0-4. The area covered by lesions on each body region was estimated as a percentage of the total area of that particular body region. | Week 52, Week 104, Week 156, week 208, week 260 | 
| Percent Change From Baseline for PASI Score Over Time (Observed Data) - Randomized Withdrawal Period | The improvement (decrease from baseline) in PASI total scores observed at Week 52. Perc. change = 100 x Abs. change /Base. (Abs. change = Post - Base) For each post-baseline visit only patients with a value at both baseline and the respective post-baseline visit are included. | Week 52, 104, and 156 | 
| Percent Change From Baseline for PASI Score Over Time (Observed Data) - Entire Study Period | Perc. change = 100 x Abs. change /Base. (Abs. change = Post - Base) For each post-baseline visit only patients with a value at both baseline and the respective post-baseline visit are included. | Week 52, Week 104, Week 156, week 208, week 260 | 
| Number of Participants in Each IGA Mod 2011 Category (Observed Data)- Randomized Withdrawal Period | Investigator Global Assessment (IGA) mod 2011; scale from 0 - 4. Score 0: Clear (No signs of psoriasis. Post-inflammatory hyperpigmentation could be Present). Score 1: Almost clear (Normal to pink coloration of lesions; no thickening; no to minimal focal scaling), Score 2: Mild (Pink to light red coloration; just detectable to mild thickening; predominantly fine scaling). Score 3: Moderate (Dull bright red, clearly distinguishable erythema; clearly distinguishable to moderate thickening; moderate scaling). Score 4: Severe (Bright to deep dark red coloration; severe thickening with hard edges; severe /coarse scaling covering almost all or all lesions). Patients in the placebo groups were not evaluable after re-treatment with Secukinumab | Week 52 (baseline), 104, and 156 | 
| Number of Participants in Each IGA Mod 2011 Category (Observed Data) - Entire Study Period | Investigator's Global Assessment (IGA) mod 2011; scale from 0 - 4. Score 0= clear (no signs of psoriasis) Score 1 = almost clear no to minimal local scaling) Score 2 = mild (predominantly fine scaling) Score 3 = moderate (moderate scaling) Score 4 = severe (severe/coarse scaling covering almost all or all lesions) | Week 52, Week 104, Week 156, week 208, week 260 | 
| Number of Participants With IGA Mod 2011 0/1 Response (Observed Data) - Entire Study Period | Investigator's Global Assessment (IGA) mod 2011 0/1. Score 0= clear (no signs of psoriasis) Score 1 = almost clear no to minimal local scaling) Score 2 = mild (predominantly fine scaling) Score 3 = moderate (moderate scaling) Score 4 = severe (severe/coarse scaling covering almost all or all lesions) Based on this scale, a patient was considered as IGA mod 2011 0/1 responder if the patient achieved a score of 0 or 1 and improved by at least 2 points on the IGA scale compared to baseline. | Week 52, Week 104, Week 156, week 208, week 260 | 
| Percent of Participants With Loss of IGA Mod 2011 0 or 1 Response Over Time for Subjects With IGA Mod 2011 0 or 1 Response at Week 52 - Randomized Withdrawal Period | Summary for loss of IGA mod 2011 0 or 1 response over time for patients with response at Week 52. time = 0 refers to Week 52 | Week 68 | 
| Percent of Participants With PASI 75 Response - Treatment Period for Re-treated After Relapse | PASI 75 response since reinitiating treatment after relapse. time = 0 refers to Week 52 | up to week 260 | 
| Percent of Participants With IGA Mod 0 or 1 Response - Treatment Period for Re-treated After Relapse | IGA mod 2011 0 or 1 response since reinitiating treatment after relapse for subjects with IGA 0 or 1 response at week 52 and not have IGA 0 or 1 response at relapse. time = 0 refers to Week 52 | up to week 260 | 
| Percent pf Participants With Relapse Over Time - Randomized Withdrawal Period | Time 0 = week 52 | up to week 156 | 
| Percent of Participants With Relapse After Last Injection | Relapse: when the achieved maximal PASI improvement from baseline of core study was reduced by >50%. Time 0 = week 52 | up to week 16 | 
| Percent of Participants With Rebound After Last Injection | Rebound: PASI increases to > 125% of baseline (where baseline is the PASI at the randomization of the core study) or presence of new pustular psoriasis, new erythrodermic psoriasis or more inflammatory psoriasis occurring within 8 Weeks of stopping therapy (after the last dose of study treatment received). Rebound like event (RLE) was defined as increase of PASI of > 125% from baseline value or occurrence of new pustular, new erythrodermic or more inflammatory psoriasis any time after stopping therapy (last treatment administered) up to Week 68. Rebound was evaluated for the patients randomized to the placebo groups in the extension study; hence these patients received the last dose of secukinumab during the core studies. | up to week 68 | 
| Number of Participants With Dermatology Life Quality Index Response (DLQI 0 or 1) - Randomized Withdrawal Period (Observed Data) | Dermatology Life Quality Index (DLQI) scores range from 0 to 30. Lower absolute scores on DLQI indicate better/improved health-related quality-of life impairment. | Week 52 (baseline), 64, 76, 88, 104, 116, 128, 140, and 156 | 
| Number of Participants With Dermatology Life Quality Index Response (DLQI 0 or 1) - Entire Treatment Period | Dermatology Life Quality Index (DLQI) scores range from 0 to 30. Lower absolute scores on DLQI indicate better/improved health-related quality-of life impairment. | Week 52 (baseline), 64, 76, 88, 104, 116, 128, 140, and 156 | 
| EQ-5D Health State Assessment (Observed Value) - Randomized Withdrawal Period | EQ-5D: EuroQOL 5-Dimension Health Status Questionnaire. The EQ-5D© is a generic instrument to assess each patient's health status. It provides a simple descriptive profile and a single index value for health status. The EQ visual analog scale records the respondent's self-rated health on a vertical scale where the endpoints are labeled 'Best imaginable health state' and 'Worst imaginable health state'. This information can be used as a quantitative measure of health outcome as judged by the individual respondents. | Week 52 (baseline), 64, 76, 88, 104, 116, 128, 140, and 156 | 
| EQ-5D Health State Assessment (Observed Value) - Entire Study Period | EQ-5D: EuroQOL 5-Dimension Health Status Questionnaire. The EQ-5D© is a generic instrument to assess each patient's health status. It provides a simple descriptive profile and a single index value for health status. The EQ visual analog scale records the respondent's self-rated health on a vertical scale where the endpoints are labeled 'Best imaginable health state' and 'Worst imaginable health state'. This information can be used as a quantitative measure of health outcome as judged by the individual respondents. | week 64, 76, 88, 104, 116, 128, 140, and 156 | 
| Clinical Laboratory Evaluation - Hematology Parameters: Incidence Rate for Participants With Clinically CTCAE - Randomized Withdrawal Period | CTCAE: common terminology criteria for adverse events. A subject with multiple variable measurements is counted only once under the worst condition. LLN = lower limit of normal. IR=incidence rate per 100 subject years | Week 52-156 | 
| Clinical Laboratory Evaluation: Number of Participants With Clinically CTCAE - Entire Study Period | CTCAE: common terminology criteria for adverse events. A subject with multiple variable measurements is counted only once under the worst condition. LLN = lower limit of normal. | approximately 4 years | 
| Electrocardiogram: Incidence of Participants With ECG Test Results - Randomized Withdrawal Period | QTcB: QT interval corrected using Bazett's formula QTcF: QT interval corrected using Fridericia's formula A patient with multiple variable measurements is counted only once under the worst condition. IR=incidence rate per 100 subject years. | Week 52 - 156 | 
| Electrocardiogram: Number of Participants With ECG Test Results - Entire Treatment Period | QTcB: QT interval corrected using Bazett's formula QTcF: QT interval corrected using Fridericia's formula A patient with multiple variable measurements is counted only once under the worst condition. | Approximately 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Psoriasis, inflammatory skin disease, scaly patches, secukinumab (AIN457), Psoriasis Area and Severity Index (PASI), Investigator Global Assessment (IGA) mod 2011