Study to Evaluate the Safety and Efficacy of Secukinumab 300 mg and 150 mg in Adult Patients With Active Psoriatic Arthritis (PsA) After 16 Weeks of Treatment Compared to Placebo

Psoriatic Arthritis Clinical Trial

Official title:

A Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study to Evaluate the Safety and Efficacy of Secukinumab 300 mg and 150 mg in Adult Patients With Active Psoriatic Arthritis After 16 Weeks of Treatment Compared to Placebo and to Assess the Safety, Tolerability and Efficacy up to 52 Weeks

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02798211
• Other study ID #: CAIN457FUS01
• Status: Completed
• Phase: Phase 4
• Start date: June 27, 2016
• Est. completion date: December 5, 2018

Study information

• Verified date: October 2021
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To demonstrate that the efficacy of secukinumab 300 mg at Week 16 was superior to placebo in adult patients with active PsA based on the proportion of patients achieving an American College of Rheumatology 20 (ACR20) response.

Description:

Treatment Period 1 was defined as the period from Randomization through Week 16 (prior to the Week 16 dose). At the start of placebo-controlled Treatment Period 1, patients were randomized via Interactive Response Technology (IRT) in a 2:2:1 ratio to 1 of 3 treatment groups. Group 1- Secukinumab 300 mg: secukinumab 300 mg (2 s.c. injections of the 150-mg dose) once weekly for 5 weeks (at Baseline, Weeks 1, 2, 3, and 4), followed by dosing every 4 weeks. Group 2- Secukinumab 150 mg: secukinumab 150 mg (1 s.c. injection of the 150-mg dose and 1 s.c. injection of placebo) once weekly for 5 weeks (at Baseline, Weeks 1, 2, 3, and 4), followed by dosing every 4 weeks. Group 3- Placebo: placebo (2 s.c. injections of 150 mg secukinumab placebo per dose) once per week for 5 weeks (at Baseline, Weeks 1, 2, 3, and 4), followed by dosing every 4 weeks. At each study treatment visit 2 s.c. injections in the form of prefilled syringes (PFS) were administered. This was necessary to maintain the blind, as secukinumab in PFS is available in either 1.0 mL (150 mg) or 2 x 1.0 mL (300 mg). Placebo to secukinumab was also available in 1.0 mL to match the active drug. Rescue medication was not allowed before completion of Week 16 assessments. Treatment Period 2 patients receiving secukinumab 300 mg (Group 1) continued to receive the same dose up to Week 48. At Weeks 16, 28, and 40 patients on secukinumab 150 mg (Group 2) were classified as responders (≥20% improvement from BL in both tender and swollen joint counts) or nonresponders. - At Weeks 16, 28, and 40 patients on secukinumab 150 mg (Group 2) who were responders continued to receive secukinumab 150 mg (1.0 mL) plus placebo (1.0 mL) every 4 weeks until next evaluation of responder status at Weeks 28 or 40. - Patients who did not meet the responder criteria at Week 16, 28, or 40 started receiving secukinumab 300 mg s.c. every 4 weeks and continued this dose up to Week 48. - Patients on placebo (Group 3) regardless of their responder status started receiving secukinumab 300 mg s.c. every 4 weeks from Week 16 up to Week 48.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 258
• Est. completion date: December 5, 2018
• Est. primary completion date: December 5, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Male or non-pregnant, non-lactating female patients at least 18 years of age
• Diagnosis of PsA classified by CASPAR criteria and with symptoms for at least 6 months with moderate to severe PsA who must have at Baseline =3 tender joints out of 78 and =3 swollen out of 76 (dactylitis of a digit counts as one joint each)
• Rheumatoid factor and/or anti-CCP antibodies negative at screening
• A target skin psoriatic lesion and a PASI score of 1 or greater

Exclusion Criteria:

• Chest X-ray with evidence of ongoing infectious or malignant process
• Patients who ever received biologic immunomodulating agents including those targeting TNFa, IL-6 and IL-12/23 investigational or approved

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Psoriatic
• Psoriatic Arthritis

Intervention

Drug:
• Secukinumab 300 mg
150 mg x 2 s.c. injection
• Secukinumab 150 mg
150 mg s.c. injection

Other:
• Placebo
Placebo

Locations

Country	Name	City	State
Puerto Rico	Novartis Investigative Site	Santurce
United States	Novartis Investigative Site	Albany	New York
United States	Novartis Investigative Site	Arlington	Texas
United States	Novartis Investigative Site	Arlington	Texas
United States	Novartis Investigative Site	Austin	Texas
United States	Novartis Investigative Site	Aventura	Florida
United States	Novartis Investigative Site	Baltimore	Maryland
United States	Novartis Investigative Site	Battle Creek	Michigan
United States	Novartis Investigative Site	Birmingham	Alabama
United States	Novartis Investigative Site	Boston	Massachusetts
United States	Novartis Investigative Site	Brooklyn	New York
United States	Novartis Investigative Site	Charleston	South Carolina
United States	Novartis Investigative Site	Charlotte	North Carolina
United States	Novartis Investigative Site	Clearwater	Florida
United States	Novartis Investigative Site	Dallas	Texas
United States	Novartis Investigative Site	Dallas	Texas
United States	Novartis Investigative Site	DeBary	Florida
United States	Novartis Investigative Site	Duluth	Georgia
United States	Novartis Investigative Site	Duncansville	Pennsylvania
United States	Novartis Investigative Site	Eagan	Minnesota
United States	Novartis Investigative Site	El Cajon	California
United States	Novartis Investigative Site	Fountain Valley	California
United States	Novartis Investigative Site	Greensboro	North Carolina
United States	Novartis Investigative Site	Greenville	South Carolina
United States	Novartis Investigative Site	Houston	Texas
United States	Novartis Investigative Site	Jackson	Tennessee
United States	Novartis Investigative Site	Jacksonville	Florida
United States	Novartis Investigative Site	Kalamazoo	Michigan
United States	Novartis Investigative Site	La Jolla	California
United States	Novartis Investigative Site	La Mesa	California
United States	Novartis Investigative Site	Lake Success	New York
United States	Novartis Investigative Site	Las Vegas	Nevada
United States	Novartis Investigative Site	Lincoln	Nebraska
United States	Novartis Investigative Site	Little Rock	Arkansas
United States	Novartis Investigative Site	Marion	Ohio
United States	Novartis Investigative Site	Mesquite	Texas
United States	Novartis Investigative Site	New Bern	North Carolina
United States	Novartis Investigative Site	North Naples	Florida
United States	Novartis Investigative Site	Orangeburg	South Carolina
United States	Novartis Investigative Site	Orchard Park	New York
United States	Novartis Investigative Site	Palm Harbor	Florida
United States	Novartis Investigative Site	Pensacola	Florida
United States	Novartis Investigative Site	Perrysburg	Ohio
United States	Novartis Investigative Site	Philadelphia	Pennsylvania
United States	Novartis Investigative Site	Plantation	Florida
United States	Novartis Investigative Site	Potsdam	New York
United States	Novartis Investigative Site	Ridgewood	New Jersey
United States	Novartis Investigative Site	Salt Lake City	Utah
United States	Novartis Investigative Site	San Antonio	Texas
United States	Novartis Investigative Site	Saranac Lake	New York
United States	Novartis Investigative Site	Sarasota	Florida
United States	Novartis Investigative Site	Seattle	Washington
United States	Novartis Investigative Site	Spokane	Washington
United States	Novartis Investigative Site	Summit	New Jersey
United States	Novartis Investigative Site	Tampa	Florida
United States	Novartis Investigative Site	Tampa	Florida
United States	Novartis Investigative Site	Upland	California
United States	Novartis Investigative Site	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number and Percentage of Patients With ACR20 Response by Visit - in Entire Treatment Period (up to Week 52) (Non-responder Imputation)	Exploratory; The ACR20 is a composite measure defined as both improvement of 20% in the number of tender and number of swollen joints, and a 20% improvement in three of the following five criteria: patient global assessment, physician global assessment, functional ability measure [most often Health Assessment Questionnaire (HAQ)], visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein (CRP)	up to 52 weeks
Other	Number and Percentage of Patients With ACR50, ACR70 Response by Visit - in Entire Treatment Period (up to Week 52) (Non-responder Imputation)	Exploratory	up to 52 weeks
Other	Number and Percentage of Patients With Presence of Dactylitis by Visit - in Entire Treatment Period (up to Week 52) (Non-responder Imputation)	Exploratory	up to 52 weeks
Other	Number and Percentage of Patients With Presence of Enthesitis by Visit - in Entire Treatment Period (up to Week 52) (Non-responder Imputation)	Exploratory	up to 52 weeks
Other	Number and Percentage of Patients With Minimal Disease Activity Response by Visit in Entire Treatment Period (up to Week 52) (Non-responder Imputation)	Exploratory	up to 52 weeks
Other	Number and Percentage of Patients With PASI75, PASI90 and PASI100 Response by Visit - in Entire Treatment Period (up to Week 52) (Non-responder Imputation)	Exploratory	up to 52 weeks
Primary	Percent of Patients Achieving American College of Rheumatology Score of at Least 20% (ACR20) Response Criteria on Secukinumab 300 mg and 150 mg vs. Placebo at Week 16	A patient was considered as improved according to the ACR20 criteria if she/he had at least 20% improvement in two of the following measures:Tender joint count, Swollen joint count and at least 3 of the following 5 measures: Patient's assessment of pain, Patient's global assessment disease activity, Physician's global assessment of disease activity, Health Assessment Questionnaire (HAQ©) score,Acute phase reactant (hsCRP or ESR).; Odds ratio, 95% confidence interval for odds ratio, and p-value are from a logistic regression model with treatment (3 treatment groups), methotrexate usage at baseline (yes, no) and body weight (kg) as explanatory variables.	16 Weeks
Secondary	Percentage of Patients With Dactylitis in the Subset of Subjects Who Have Dactylitis at Week 16	The percent of patients in the Dactylitis Subset with dactylitis in the secukinumab 300 mg group at Week 16. Dactylitis is severe inflammation of the finger and toe joints.; Odds ratio, 95% confidence interval for odds ratio, and p-value are from a logistic regression model with treatment (3 treatment groups), methotrexate usage at baseline (yes, no) and body weight (kg) as explanatory variables.	Week 16
Secondary	Percentage of Patients With Enthesitis in the Subset of Subjects Who Have Enthesitis at Baseline (SPARCC) at Week 16	Enthesitis, also called enthesopathy, is inflammation of the entheses, the sites where tendons or ligaments insert into the bone.; Odds ratio, 95% confidence interval for odds ratio, and p-value are from a logistic regression model with treatment (3 treatment groups), methotrexate usage at baseline (yes, no) and body weight (kg) as explanatory variables.	16 Weeks
Secondary	Percentage of Patients With Enthesitis in the Subset of Subjects Who Have Enthesitis at Week 16 (LEI)	Enthesitis, also called enthesopathy, is inflammation of the entheses, the sites where tendons or ligaments insert into the bone.; LEI=Leeds Enthesitis Index	16 Weeks
Secondary	Percentage of Patients With Enthesitis in the Subset of Subjects Who Have Enthesitis at Week 16 (Combined SPARCC and LEI)	Statistical analysis (logistic regression) of presence of enthesitis (Combined SPARCC and LEI) by visit - in treatment period 1 (non-responder imputation) (Combined SPARCC and LEI Subset); Enthesitis, also called enthesopathy, is inflammation of the entheses, the sites where tendons or ligaments insert into the bone.; Odds ratio, 95% confidence interval for odds ratio, and p-value are from a logistic regression model with treatment (3 treatment groups), methotrexate usage at baseline (yes, no) and body weight (kg) as explanatory variables.	16 Weeks
Secondary	Percentage of Patients Achieving ACR50 Response Criteria on Secukinumab 300 or 150 mg vs. Placebo at Week 16	A patient was considered as improved according the ACR50 criteria if she/he had at least 50% improvement in the two of the following measures: Tender joint count, Swollen joint count and at least 3 of the following 5 measures: Patient's assessment of pain, Patient's global assessment disease activity,Physician's global assessment of disease activity, Health Assessment Questionnaire (HAQ©) score,Acute phase reactant (hsCRP or ESR); Statistical analysis (logistic regression) of ACR50 response by visit - in treatment period 1 (non-responder imputation) (Full Analysis Set); Odds ratio, 95% confidence interval for odds ratio, and p-value are from a logistic regression model with treatment (3 treatment groups), methotrexate usage at baseline (yes, no) and body weight (kg) as explanatory variables.	16 Weeks
Secondary	Percentage of Patients Achieving ACR70 Response Criteria on Secukinumab 300 or 150 mg vs. Placebo at Week 16	A patient was considered as improved according the ACR70 criteria if she/he had at least 70% improvement in the two of the following measures: Tender joint count, Swollen joint count and at least 3 of the following 5 measures: Patient's assessment of pain, Patient's global assessment disease activity,Physician's global assessment of disease activity, Health Assessment Questionnaire (HAQ©) score,Acute phase reactant (hsCRP or ESR); Statistical analysis (logistic regression) of ACR70 response by visit - in treatment period 1 (non-responder imputation); Odds ratio, 95% confidence interval for odds ratio, and p-value are from a logistic regression model with treatment (3 treatment groups), methotrexate usage at baseline (yes, no) and body weight (kg) as explanatory variables.	16 Weeks
Secondary	Percentage of Patients Achieving a PASI75 Response in the Subgroup of Subjects Who Have =3% Skin Involvement With Psoriasis at Week 16	A 75% reduction in the Psoriasis Area and Severity Index (PASI) score (PASI 75) is above the current benchmark of primary endpoints for most clinical trials with endpoints of psoriasis.	16 Weeks
Secondary	Percentage of Patients Achieving a PASI90 Response in the Subgroup of Subjects Who Have =3% Skin Involvement With Psoriasis at Week 16	A 90% reduction in the Psoriasis Area and Severity Index score (PASI 90) is above the current benchmark of primary endpoints for most clinical trials with endpoints of psoriasis.	16 Weeks
Secondary	Percentage of Patients Achieving a PASI100 Response in the Subgroup of Subjects Who Have =3% Skin Involvement With Psoriasis at Week 16	A 100% reduction in the Psoriasis Area and Severity Index score (PASI 100) is above the current benchmark of primary endpoints for most clinical trials with endpoints of psoriasis.; Odds ratio, 95% confidence interval for odds ratio, and p-value are from a logistic regression model with treatment (3 treatment groups), methotrexate usage at baseline (yes, no) and body weight (kg) as explanatory variables.	16 Weeks
Secondary	Change From Baseline to Week 16 in DAS28-CRP	DAS-CRP uses the C-Reactive Protein (CRP) value. Disease Activity Score (DAS28-CRP) values range from 2.0 to 10.0 while higher values mean a higher disease activity. A DAS28-CRP below the value of 2.6 is interpreted as Remission. DAS28-CRP uses 28 different joints for its calculation: proximal interphalangeal joints (10 joints) metacarpophalangeal joints (10) wrists (2) elbows (2) shoulders (2) knees (2) With the above mentioned parameters.; Least squares mean (LSM), Least squares mean (LSM) treatment difference, 95% confidence interval (CI) for treatment difference, and p-values are from an analysis of covariance (ANCOVA) model with treatment (3 treatment groups), baseline DAS28-CRP score, methotrexate usage at baseline (yes, no), and body weight(kg) as explanatory variables.	baseline, 16 weeks
Secondary	Change From Baseline to Week 16 in HAQ-DI	The Health assessment questionnaire disability index (HAQ-DI) is 20-question instrument that assesses the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). Responses in each functional area are scored from 0 (no difficulty), to 3 (inability to perform a task in that area). The average score across the functional areas yields an overall HAQ score which ranges from 0 (no disability) to 3 (completely disabled).	16 Weeks

External Links

•   A Plain Language Trial Summary is available on novartisclinicaltrials.com