Extension Study of Secukinumab Prefilled Syringes in Subjects With Moderate to Severe Chronic Plaque-type Psoriasis Completing Preceding Psoriasis Phase III Studies With Secukinumab
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| ClinicalTrials.gov Identifier: NCT01544595 |
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Recruitment Status :
Completed
First Posted : March 6, 2012
Results First Posted : December 20, 2018
Last Update Posted : December 20, 2018
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Moderate to Severe Plaque-type Psoriasis | Drug: Secukinumab (AIN457) Drug: Placebo | Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 1147 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Double (Participant, Investigator) |
| Primary Purpose: | Treatment |
| Official Title: | 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 |
| Actual Study Start Date : | June 19, 2012 |
| Actual Primary Completion Date : | June 26, 2017 |
| Actual Study Completion Date : | June 26, 2017 |
| Arm | Intervention/treatment |
|---|---|
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Placebo Comparator: PASI 75 Responders
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.
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Drug: Secukinumab (AIN457)
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. Drug: Placebo Placebo |
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Experimental: Partial responders
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.
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Drug: Secukinumab (AIN457)
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. |
- Percent of Participants With Loss of Psoriasis Area and Severity Index (PASI) 75 Response up to Week 68 [ Time Frame: At week 68 (16 weeks after week 52) ]
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.
- Number of Participants With PASI 50, PASI 75, PASI 90, PASI 100 and IGA Mod 2011 0 or 1 (Observed Data) - Randomized Withdrawal Period [ Time Frame: Week 52, 104, and 156 ]
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)
- Number of Participants With PASI 50, PASI 75, PASI 90, and PASI 100 (Observed Data) - Entire Study Period [ Time Frame: Week 52, Week 104, Week 156, week 208, week 260 ]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.
- Percent Change From Baseline for PASI Score Over Time (Observed Data) - Randomized Withdrawal Period [ Time Frame: Week 52, 104, and 156 ]
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.
- Percent Change From Baseline for PASI Score Over Time (Observed Data) - Entire Study Period [ Time Frame: Week 52, Week 104, Week 156, week 208, week 260 ]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.
- Number of Participants in Each IGA Mod 2011 Category (Observed Data)- Randomized Withdrawal Period [ Time Frame: Week 52 (baseline), 104, and 156 ]
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
- Number of Participants in Each IGA Mod 2011 Category (Observed Data) - Entire Study Period [ Time Frame: Week 52, Week 104, Week 156, week 208, week 260 ]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)
- Number of Participants With IGA Mod 2011 0/1 Response (Observed Data) - Entire Study Period [ Time Frame: Week 52, Week 104, Week 156, week 208, week 260 ]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.
- 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 [ Time Frame: Week 68 ]
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
- Percent of Participants With PASI 75 Response - Treatment Period for Re-treated After Relapse [ Time Frame: up to week 260 ]PASI 75 response since reinitiating treatment after relapse. time = 0 refers to Week 52
- Percent of Participants With IGA Mod 0 or 1 Response - Treatment Period for Re-treated After Relapse [ Time Frame: up to week 260 ]
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
- Percent pf Participants With Relapse Over Time - Randomized Withdrawal Period [ Time Frame: up to week 156 ]Time 0 = week 52
- Percent of Participants With Relapse After Last Injection [ Time Frame: up to week 16 ]
Relapse: when the achieved maximal PASI improvement from baseline of core study was reduced by >50%.
Time 0 = week 52
- Percent of Participants With Rebound After Last Injection [ Time Frame: up to week 68 ]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.
- Number of Participants With Dermatology Life Quality Index Response (DLQI 0 or 1) - Randomized Withdrawal Period (Observed Data) [ Time Frame: Week 52 (baseline), 64, 76, 88, 104, 116, 128, 140, and 156 ]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.
- Number of Participants With Dermatology Life Quality Index Response (DLQI 0 or 1) - Entire Treatment Period [ Time Frame: Week 52 (baseline), 64, 76, 88, 104, 116, 128, 140, and 156 ]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.
- EQ-5D Health State Assessment (Observed Value) - Randomized Withdrawal Period [ Time Frame: Week 52 (baseline), 64, 76, 88, 104, 116, 128, 140, and 156 ]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.
- EQ-5D Health State Assessment (Observed Value) - Entire Study Period [ Time Frame: week 64, 76, 88, 104, 116, 128, 140, and 156 ]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.
- Clinical Laboratory Evaluation - Hematology Parameters: Incidence Rate for Participants With Clinically CTCAE - Randomized Withdrawal Period [ Time Frame: Week 52-156 ]
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
- Clinical Laboratory Evaluation: Number of Participants With Clinically CTCAE - Entire Study Period [ Time Frame: approximately 4 years ]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.
- Electrocardiogram: Incidence of Participants With ECG Test Results - Randomized Withdrawal Period [ Time Frame: Week 52 - 156 ]
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.
- Electrocardiogram: Number of Participants With ECG Test Results - Entire Treatment Period [ Time Frame: Approximately 4 years ]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.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01544595
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| Study Director: | Novartis Pharmaceuticals | Novartis Pharmaceuticals |
Documents provided by Novartis ( Novartis Pharmaceuticals ):
| Responsible Party: | Novartis Pharmaceuticals |
| ClinicalTrials.gov Identifier: | NCT01544595 |
| Other Study ID Numbers: |
CAIN457A2302E1 2012-000533-39 |
| First Posted: | March 6, 2012 Key Record Dates |
| Results First Posted: | December 20, 2018 |
| Last Update Posted: | December 20, 2018 |
| Last Verified: | November 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 |
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