First Study of Secukinumab in Pre-filled Syringes in Subjects With Chronic Plaque-type Psoriasis: Response at 12 Weeks

Moderate to Severe Plaque-type Psoriasis Clinical Trial

— FEATURE  

Official title:

A Randomized, Double-blind, Placebo Controlled, Multicenter Study of Subcutaneous Secukinumab in Prefilled Syringes to Demonstrate Efficacy After Twelve Weeks of Treatment, and to Assess the Safety, Tolerability, Usability and Long-term Efficacy in Subjects With Chronic Plaque-type Psoriasis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01555125
• Other study ID #: CAIN457A2308
• Secondary ID: 2011-006057-28
• Status: Completed
• Phase: Phase 3
• Start date: May 8, 2012
• Est. completion date: October 24, 2016

Study information

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

Clinical Trial Summary

The purpose of this study is to demonstrate efficacy of secukinumab at Week 12 based on PASI and IGA response rates versus placebo in subjects with moderate to severe chronic plaque-type psoriasis.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 177
• Est. completion date: October 24, 2016
• Est. primary completion date: October 24, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion criteria:

• Moderate and severe plaque-type psoriasis diagnosed for at least 6 months.

• Severity of psoriasis disease meeting all of the following three criteria:

Psoriasis Area and Severity Index (PASI) score of 12 or greater, Investigator's Global Assessment (IGA) score of 3 or greater, Total body surface area (BSA) affected of 10% or greater.

-Inadequate control by prior use of topical treatment, phototherapy and/or systemic therapy.

Exclusion criteria:

• Current forms of psoriasis other than chronic plaque-type psoriasis (for example, pustular, erythrodermic, guttate).

• Current drug-induced psoriasis.

• Previous use of secukinumab or any drug that targets IL-17 or IL-17 receptor.

• Significant medical problems such as uncontrolled hypertension, congestive heart failure or a condition that significantly immunocompromises the subject.

• Hematological abnormalities.

• History of an ongoing, chronic or recurrent infectious disease, or evidence of untreated tuberculosis.

• History of lymphoproliferative disease or history of malignancy of any organ system within the past 5 years.

• Pregnant or nursing (lactating) women. Other protocol-defined inclusion/exclusion criteria may apply

Related Conditions & MeSH terms

• Moderate to Severe Plaque-type Psoriasis
• Psoriasis

Intervention

Drug:
• secukinumab 150 mg
After the data base lock of week 52 data has been performed, subjects will receive secukinumab 150 mg treatment as open label for the remainder of the extension treatment period
• secukinumab 300 mg
After the data base lock of week 52 data has been performed, subjects will receive secukinumab 300 mg treatment as open label for the remainder of the extension treatment period
• placebo
Subjects who were on placebo at Week 52 cannot continue in the extension treatment period

Locations

Country	Name	City	State
Canada	Novartis Investigative Site	Hamilton	Ontario
Canada	Novartis Investigative Site	North Bay	Ontario
Canada	Novartis Investigative Site	Quebec
Canada	Novartis Investigative Site	Waterloo	Ontario
Estonia	Novartis Investigative Site	Tallinn
Estonia	Novartis Investigative Site	Tartu
France	Novartis Investigative Site	Martigues
France	Novartis Investigative Site	Nice Cedex 3
France	Novartis Investigative Site	Rouen
France	Novartis Investigative Site	Toulouse Cedex
Germany	Novartis Investigative Site	Gera
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Leipzig
Germany	Novartis Investigative Site	Osnabrueck
Germany	Novartis Investigative Site	Regensburg	Bavaria
United States	Novartis Investigative Site	Atlanta	Georgia
United States	Novartis Investigative Site	Austin	Texas
United States	Novartis Investigative Site	Birmingham	Alabama
United States	Novartis Investigative Site	Boston	Massachusetts
United States	Novartis Investigative Site	Bryan	Texas
United States	Novartis Investigative Site	Charleston	South Carolina
United States	Novartis Investigative Site	Fridley	Minnesota
United States	Novartis Investigative Site	Glendale	Arizona
United States	Novartis Investigative Site	Goodlettsville	Tennessee
United States	Novartis Investigative Site	Hot Springs	Arkansas
United States	Novartis Investigative Site	Houston	Texas
United States	Novartis Investigative Site	Lake Oswego	Oregon
United States	Novartis Investigative Site	Los Angeles	California
United States	Novartis Investigative Site	Mobile	Alabama
United States	Novartis Investigative Site	Newnan	Georgia
United States	Novartis Investigative Site	Omaha	Nebraska
United States	Novartis Investigative Site	Portland	Oregon
United States	Novartis Investigative Site	Skokie	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Canada,  Estonia,  France,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Efficacy of Secukinumab Compared to Placebo in Subjects With Moderate to Severe Chronic Plaque-type Psoriasis at Week 12 Measure: PASI 75 (Psoriasis Area and Severity Index) Response.	A 75% reduction in the Psoriasis Area and Severity Index (PASI) score (PASI 75) is the current benchmark of primary endpoints for most clinical trials of psoriasis	12 weeks
Primary	Efficacy of Secukinumab Compared to Placebo in Subjects With Moderate to Severe Chronic Plaque-type Psoriasis Measure:IGA (Investigator's Global Assessment) With a 0 or 1 Response at Week 12	The IGA scale has been developed based on a previous version of the scale used in secukinumab phase II studies in collaboration with health authorities, in particular the FDA. The explanations/descriptions of the points on the scale have been improved to ensure appropriate differentiation between the points. The IGA used in this study is static, i.e. it refers exclusively to the subject's disease state at the time of the assessments, and does not attempt a comparison with any of the subject's previous disease states, whether at baseline or at a previous visit. IGA has a scale of 0-4 with the lower scores correlating to better performance. A score of 0= clear skin, 1= almost clear skin, 2=mild, 3=moderate,4=severe	12 weeks
Secondary	Absolute Change From Baseline in Self Injection Assessment Questionnaire (SIAQ) Domain Scores at Week 12	The three domains of the POST SIAQ are feelings about injections, self-image, self-confidence, injection-site reactions, ease of use, and satisfaction with self-injection. The SIAQ items are scored on a semantic Likert-type scale where lower numbers indicate a worse experience. Domain scores range from 0 to 10. Subjects self-injecting at this visit completed this SIAQ questionnaire. The POST-SIAQ is taken after the injection at that visit.	Week 12
Secondary	Absolute Change From Baseline in Self-Injection Assessment Questionnaire (SIAQ) Domain Scores at Week 48	The three domains of the POST SIAQ are feelings about injections, self-image, self-confidence, injection-site reactions, ease of use, and satisfaction with self-injection. The SIAQ items are scored on a semantic Likert-type scale where lower numbers indicate a worse experience. Domain scores range from 0 to 10. Subjects self-injecting at this visit completed this SIAQ questionnaire. The POST-SIAQ is taken after the injection at that visit.	Baseline, week 48
Secondary	Number of Subjects With Potential Use Related Hazards at Week 1	To assess potential use-related hazards with the secukinumab PFS for the subject	Week 1
Secondary	Percentage of Subjects With Successful Self Administration of Study Drug at Week 1	To assess the subject's ability to follow instructions for use with the secukinumab PFS	Week 1
Secondary	Percent of Responders With Psoriasis Area and Severity Index (PASI) Equal to or Greater Than 50, PASI 75, PASI 90, PASI 100, (Induction) With Non-responder Imputation	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). PASI 50, 75, 90 and 100 were defined as participants achieving = 50%, 75%, 90% or 100% improvement from baseline.	Week 12
Secondary	Percent of Responders With Psoriasis Area and Severity Index (PASI) Equal to or Greater Than 50, PASI 75, PASI 90, PASI 100, (Maintenance; Observed Data)	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). PASI 50, 75, 90 and 100 were defined as participants achieving = 50%, 75%, 90% or 100% improvement from baseline.	Week 52
Secondary	Percent of Responders With Investigator's Global Assessment (IGA) Mod 2011 Score of 0 or 1, (Maintenance; Observed Data)	The IGA mod 2011 scale is static, i.e. it referred exclusively to the participant's disease at the time of the assessment, and did not compare with any of the participant's previous disease states at previous visits. The scores are: 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate and 4 = severe.	Week 52
Secondary	Absolute Change From Baseline for PASI Score at Week 12, (Induction)	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:01, arms:0.2 body:0.3 legs:0.4)	Week 12
Secondary	Absolute Change From Baseline for PASI Score Over Time up to Week 52, (Maintenance; Observed Data)	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:01, arms:0.2 body:0.3 legs:0.4)	Week 52
Secondary	Number of Participants in Each Investigator's Global Assessment (IGA) Mod 2011 Category at Week 12, (Induction)	The IGA mod 2011 category scale is static, i.e. it referred exclusively to the participant's disease at the time of the assessment, and did not compare with any of the participant's previous disease states at previous visits. The scores are: 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate and 4 = severe	Week 12
Secondary	Percentage of Participants in Each Investigator's Global Assessment (IGA) Mod 2011 Category Over Time up to Week 52, (Maintenance; Observed Data)	The IGA mod 2011 category scale is static, i.e. it referred exclusively to the participant's disease at the time of the assessment, and did not compare with any of the participant's previous disease states at previous visits. The scores are: 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate and 4 = severe.	Week 52
Secondary	Change From Baseline in EQ-5D at Week 12 (Induction)	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)	Week 12
Secondary	Change From Baseline in EuroQOL 5-Dimension Health Status Questionnaire (EQ-5D) Over Time up to Week 52, (Maintenance)	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)	Week 52
Secondary	Median Percentage Change From Baseline in Dermatology Life Quality Index (DLQI) Total Score, (Induction)	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. This result was reflected in the percentage change from baseline at Week 12, higher reductions (improvements) in DLQI scores (median treatment difference).	Baseline and week 12
Secondary	Median Percentage Change From Baseline in Dermatology Life Quality Index (DLQI) Score Over Time up to Week 52, (Maintenance)	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. This result was reflected in the percentage change from baseline at Week 12, higher reductions (improvements) in DLQI scores (median treatment difference).	Baseline and week 52
Secondary	Percentage of Participants Achieving a DLQI Score of 0 or 1 at Week 12, (Induction)	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	Week 12
Secondary	Percentage of Participants Achieving a DLQI Score of 0 or 1 Over Time up to Week 52, (Maintenance)	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	Week 52
Secondary	Number of Responders With PASI Equal to or Greater Than 50, PASI 75, PASI 90, PASI 100 After Week 52	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). PASI 50, 75, 90 and 100 were defined as participants achieving = 50%, 75%, 90% or 100% improvement from baseline.	Week 172
Secondary	Absolute Change From Baseline for PASI Score After Week 52, (Observed Data)	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:01, arms:0.2 body:0.3 legs:0.4)	Week 172
Secondary	Number of Participants in Each IGA Mod 2011 Category After Week 52 (Observed Data)	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	Week 172
Secondary	Number of Participants Developing Treatment Emergent Anti-secukinumab Antibodies, Immunogenicity	The development of anti-secunimubab anti-bodies will decrease a participant's ability to respond to secukinumab treatment. The number of participants developing anti-secukinumab anti-bodies was measured from Baseline to 8 weeks after last treatment	Baseline and at Week 12, 24, 52, 100, 148, and 196, 204