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

Moderate to Severe Plaque-type Psoriasis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01544595
• Other study ID #: CAIN457A2302E1
• Secondary ID: 2012-000533-39
• Status: Completed
• Phase: Phase 3
• Start date: June 19, 2012
• Est. completion date: June 26, 2017

Study information

• Verified date: November 2018
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1147
• Est. completion date: June 26, 2017
• Est. primary completion date: June 26, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Moderate to Severe Plaque-type Psoriasis
• Psoriasis

Intervention

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.
• Placebo
Placebo

Locations

Country	Name	City	State
Argentina	Novartis Investigative Site	Buenos Aires
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Mendoza
Australia	Novartis Investigative Site	Carlton	Victoria
Australia	Novartis Investigative Site	East Melbourne	Victoria
Australia	Novartis Investigative Site	Kogarah	New South Wales
Australia	Novartis Investigative Site	Woolloongabba	Queensland
Belgium	Novartis Investigative Site	Bruxelles
Belgium	Novartis Investigative Site	Gent
Belgium	Novartis Investigative Site	Liege
Canada	Novartis Investigative Site	Edmonton	Alberta
Canada	Novartis Investigative Site	Halifax	Nova Scotia
Canada	Novartis Investigative Site	Hamilton	Ontario
Canada	Novartis Investigative Site	Markham	Ontario
Canada	Novartis Investigative Site	Moncton	New Brunswick
Canada	Novartis Investigative Site	Montreal	Quebec
Canada	Novartis Investigative Site	Peterborough	Ontario
Canada	Novartis Investigative Site	Richmond Hil	Ontario
Canada	Novartis Investigative Site	Sainte-Foy	Quebec
Canada	Novartis Investigative Site	Surrey	British Columbia
Canada	Novartis Investigative Site	Vancouver	British Columbia
Canada	Novartis Investigative Site	Waterloo	Ontario
Colombia	Novartis Investigative Site	Barranquilla	Atlantico
Colombia	Novartis Investigative Site	Barranquilla
Colombia	Novartis Investigative Site	Bogota
Estonia	Novartis Investigative Site	Tallinn
Estonia	Novartis Investigative Site	Tallinn
Estonia	Novartis Investigative Site	Tartu
Finland	Novartis Investigative Site	Helsinki
France	Novartis Investigative Site	Bordeaux Cedex
France	Novartis Investigative Site	Marseille Cedex 9
France	Novartis Investigative Site	Martigues
France	Novartis Investigative Site	Nice Cedex 3
France	Novartis Investigative Site	Paris Cedex 10	Cedex 10
France	Novartis Investigative Site	Reims
France	Novartis Investigative Site	Toulouse Cedex
Germany	Novartis Investigative Site	Augsburg
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Bielefeld
Germany	Novartis Investigative Site	Bochum
Germany	Novartis Investigative Site	Bochum
Germany	Novartis Investigative Site	Bonn
Germany	Novartis Investigative Site	Darmstadt
Germany	Novartis Investigative Site	Dresden
Germany	Novartis Investigative Site	Erfurt
Germany	Novartis Investigative Site	Erlangen
Germany	Novartis Investigative Site	Essen
Germany	Novartis Investigative Site	Frankfurt
Germany	Novartis Investigative Site	Gera
Germany	Novartis Investigative Site	Goettingen
Germany	Novartis Investigative Site	Greifswald
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Hanau
Germany	Novartis Investigative Site	Heidelberg
Germany	Novartis Investigative Site	Kiel
Germany	Novartis Investigative Site	Koeln	Nordrhein-Westfalen
Germany	Novartis Investigative Site	Krefeld
Germany	Novartis Investigative Site	Muenchen
Germany	Novartis Investigative Site	Muenster
Germany	Novartis Investigative Site	Osnabrueck
Germany	Novartis Investigative Site	Plauen
Germany	Novartis Investigative Site	Recklinghausen
Germany	Novartis Investigative Site	Schwerin
Germany	Novartis Investigative Site	Tuebingen
Germany	Novartis Investigative Site	Wuppertal
Guatemala	Novartis Investigative Site	Guatemala City
Guatemala	Novartis Investigative Site	Guatemala City
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Debrecen
Hungary	Novartis Investigative Site	Kaposvar
Hungary	Novartis Investigative Site	Miskolc
Hungary	Novartis Investigative Site	Szeged
Hungary	Novartis Investigative Site	Szombathely
Iceland	Novartis Investigative Site	Kopavogur
Israel	Novartis Investigative Site	Afula
Israel	Novartis Investigative Site	Petach Tikva
Israel	Novartis Investigative Site	Ramat Gan
Italy	Novartis Investigative Site	Catania	CT
Italy	Novartis Investigative Site	Modena	MO
Japan	Novartis Investigative Site	Asahikawa-city	Hokkaido
Japan	Novartis Investigative Site	Bunkyo ku	Tokyo
Japan	Novartis Investigative Site	Chiyoda-ku	Tokyo
Japan	Novartis Investigative Site	Fukuoka-city	Fukuoka
Japan	Novartis Investigative Site	Inashiki-gun	Ibaraki
Japan	Novartis Investigative Site	Isehara-city	Kanagawa
Japan	Novartis Investigative Site	Kawasaki-city	Kanagawa
Japan	Novartis Investigative Site	Kobe-City	Hyogo
Japan	Novartis Investigative Site	Kurume city	Fukuoka
Japan	Novartis Investigative Site	Kyoto-city	Kyoto
Japan	Novartis Investigative Site	Maebashi city	Gunma
Japan	Novartis Investigative Site	Minato-ku	Tokyo
Japan	Novartis Investigative Site	Nagoya-city	Aichi
Japan	Novartis Investigative Site	Sagamihara-city	Kanagawa
Japan	Novartis Investigative Site	Sapporo-city	Hokkaido
Japan	Novartis Investigative Site	Shinagawa-ku	Tokyo
Japan	Novartis Investigative Site	Shinjuku-ku	Tokyo
Japan	Novartis Investigative Site	Shinjuku-ku	Tokyo
Korea, Republic of	Novartis Investigative Site	Busan
Korea, Republic of	Novartis Investigative Site	Daejeon	Korea
Korea, Republic of	Novartis Investigative Site	Gwangju
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul	Korea
Korea, Republic of	Novartis Investigative Site	Seoul	Korea
Korea, Republic of	Novartis Investigative Site	Seoul	Seocho-gu
Latvia	Novartis Investigative Site	Daugavpils	LVA
Latvia	Novartis Investigative Site	Riga
Latvia	Novartis Investigative Site	Riga
Latvia	Novartis Investigative Site	Ventspils	LVA
Lithuania	Novartis Investigative Site	Kaunas	LTU
Lithuania	Novartis Investigative Site	Klaipeda	LTU
Lithuania	Novartis Investigative Site	Vilnius
Lithuania	Novartis Investigative Site	Vilnius
Poland	Novartis Investigative Site	Lodz
Poland	Novartis Investigative Site	Lodz
Poland	Novartis Investigative Site	Poznan
Poland	Novartis Investigative Site	Wroclaw
Romania	Novartis Investigative Site	Bucuresti
Singapore	Novartis Investigative Site	Singapore
Spain	Novartis Investigative Site	Barcelona
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Sabadell	Barcelona
Spain	Novartis Investigative Site	Santa Coloma De Gramanet	Cataluña
Spain	Novartis Investigative Site	Valencia	Comunidad Valenciana
Sweden	Novartis Investigative Site	Malmo
Sweden	Novartis Investigative Site	Uppsala
Taiwan	Novartis Investigative Site	Hsin Chu
Taiwan	Novartis Investigative Site	Taichung
Taiwan	Novartis Investigative Site	Taipei
United Kingdom	Novartis Investigative Site	Dudley	West Midlands
United Kingdom	Novartis Investigative Site	Harrogate
United Kingdom	Novartis Investigative Site	London	England
United Kingdom	Novartis Investigative Site	Nuneaton
United Kingdom	Novartis Investigative Site	Plymouth	Devon
United Kingdom	Novartis Investigative Site	Salford	Manchester
United Kingdom	Novartis Investigative Site	Yeovil	Somerset
United States	Novartis Investigative Site	Ann Arbor	Michigan
United States	Novartis Investigative Site	Austin	Texas
United States	Novartis Investigative Site	Birmingham	Alabama
United States	Novartis Investigative Site	Birmingham	Alabama
United States	Novartis Investigative Site	Charleston	South Carolina
United States	Novartis Investigative Site	Colorado Springs	Colorado
United States	Novartis Investigative Site	Dallas	Texas
United States	Novartis Investigative Site	Dallas	Texas
United States	Novartis Investigative Site	Duncansville	Pennsylvania
United States	Novartis Investigative Site	High Point	North Carolina
United States	Novartis Investigative Site	Houston	Texas
United States	Novartis Investigative Site	Indianapolis	Indiana
United States	Novartis Investigative Site	Johnston	Rhode Island
United States	Novartis Investigative Site	Kingsport	Tennessee
United States	Novartis Investigative Site	Los Angeles	California
United States	Novartis Investigative Site	Louisville	Kentucky
United States	Novartis Investigative Site	Louisville	Kentucky
United States	Novartis Investigative Site	Nashville	Tennessee
United States	Novartis Investigative Site	New York	New York
United States	Novartis Investigative Site	Norfolk	Virginia
United States	Novartis Investigative Site	Oceanside	California
United States	Novartis Investigative Site	Omaha	Nebraska
United States	Novartis Investigative Site	Oregon City	Oregon
United States	Novartis Investigative Site	Pasadena	California
United States	Novartis Investigative Site	Philadelphia	Pennsylvania
United States	Novartis Investigative Site	Phoenix	Arizona
United States	Novartis Investigative Site	Phoenix	Arizona
United States	Novartis Investigative Site	Portland	Oregon
United States	Novartis Investigative Site	Portland	Oregon
United States	Novartis Investigative Site	Rochester	New York
United States	Novartis Investigative Site	Salt Lake City	Utah
United States	Novartis Investigative Site	San Antonio	Texas
United States	Novartis Investigative Site	San Diego	California
United States	Novartis Investigative Site	San Diego	California
United States	Novartis Investigative Site	Snellville	Georgia
United States	Novartis Investigative Site	Topeka	Kansas
United States	Novartis Investigative Site	Warren	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Canada,  Colombia,  Estonia,  Finland,  France,  Germany,  Guatemala,  Hungary,  Iceland,  Israel,  Italy,  Japan,  Korea, Republic of,  Latvia,  Lithuania,  Poland,  Romania,  Singapore,  Spain,  Sweden,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Percent pf Participants With Relapse Over Time - Randomized Withdrawal Period	Time 0 = week 52	up to week 156
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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