Clinical Trials/NCT03162796

NCT03162796

Completed

Phase 3

A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Study Evaluating the Efficacy and Safety of Guselkumab Administered Subcutaneously in Subjects With Active Psoriatic Arthritis Including Those Previously Treated With Biologic Anti-TNF Alpha Agents

Janssen Research & Development, LLC95 sites in 9 countries383 target enrollmentAugust 24, 2017

ConditionsArthritis, Psoriatic

InterventionsGuselkumab Placebo

DrugsGuselkumab Placebo

Overview

Phase: Phase 3
Intervention: Guselkumab
Conditions: Arthritis, Psoriatic
Sponsor: Janssen Research & Development, LLC
Enrollment: 383
Locations: 95
Primary Endpoint: Percentage of Participants Who Achieved an American College of Rheumatology (ACR) 20 Response at Week 24
Status: Completed
Last Updated: 5 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The primary purpose of this study is to evaluate the efficacy of guselkumab treatment in participants with active Psoriatic Arthritis (PsA) by assessing the reduction in signs and symptoms of PsA.

Detailed Description

This is a study of guselkumab in participants with active Psoriatic Arthritis (PsA) who had inadequate response to standard therapies. It will evaluate the clinical efficacy of guselkumab in the reduction of signs and symptoms and the safety profile of guselkumab in the treatment of PsA. The study will consists of 4 phases: a screening phase of up to 6 weeks, a blinded treatment phase of approximately 1 year (that is, 52 weeks), including a placebo controlled period from Week 0 to Week 24 and double-blind active treatment period from Week 24 to Week 52, and a safety follow-up phase of 8 weeks after Week 52 (Week 52 to 60) and will be 12 weeks from the last administration of study agent (at Week 48) to the final safety follow-up visit. Efficacy, safety, pharmacokinetic, immunogenicity, and biomarker evaluations will be performed in the study at defined schedule.

Registry

clinicaltrials.gov

Start Date

August 24, 2017

End Date

November 18, 2019

Last Updated

5 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Janssen Research & Development, LLC

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Have a diagnosis of Psoriatic Arthritis (PsA) for at least 6 months before the first administration of study agent and meet Classification criteria for Psoriatic Arthritis (CASPAR) at screening
•Have active PsA as defined by: at least 3 swollen joints and at least 3 tender joints at screening and at baseline; and C-reactive protein (CRP) greater than or equal to (\>=) 0.3 milligram per deciLitre (mg/dL) at screening from the central laboratory
•Have at least 1 of the PsA subsets: distal interphalangeal joint involvement, polyarticular arthritis with absence of rheumatoid nodules, arthritis mutilans, asymmetric peripheral arthritis, or spondylitis with peripheral arthritis
•Have active plaque psoriasis, with at least one psoriatic plaque of \>= 2 centimeter (cm) diameter or nail changes consistent with psoriasis or documented history of plaque psoriasis
•Have active PsA despite previous non-biologic disease-modifying antirheumatic drugs (DMARD), apremilast, and/or nonsteroidal anti-inflammatory drug (NSAID) therapy : Non-biologic DMARD therapy is defined as taking a non-biologic DMARD for at least 3 months or evidence of intolerance; Apremilast therapy is defined as taking apremilast at the marketed dose approved in the country where the study is being conducted for at least 4 months or evidence of intolerance; NSAID therapy is defined as taking an NSAID for at least 4 weeks or evidence of intolerance
•Participants may have been previously treated with up to 2 anti-TNF (tumor necrosis factor) alpha agents (approximately 30 percent \[%\] of the overall study population), and must document the reason for discontinuation

Exclusion Criteria

•Has other inflammatory diseases that might confound the evaluations of benefit of guselkumab therapy, including but not limited to rheumatoid arthritis (RA), axial spondyloarthritis (this does not include a primary diagnosis of PsA with spondylitis), systemic lupus erythematosus, or Lyme disease
•Has ever received more than 2 anti-TNFalpha agents
•Has previously received any biologic treatment (other than anti-TNF alpha agents), including, but not limited to ustekinumab, abatacept, secukinumab, tildrakizumab, ixekizumab, brodalumab, risankizumab, or other investigative biologic treatment
•Has previously received any systemic immunosuppressants (for example, azathioprine, cyclosporine, 6 thioguanine, mercaptopurine, mycophenolate mofetil, hydroxyurea, tacrolimus) within 4 weeks of the first administration of study agent
•Has received apremilast within 4 weeks prior to the first administration of study agent
•Has previously received tofacitinib, baricitinib, filgotinib, peficitinib (ASP015K), decernotinib (VX-509), or any other Janus kinase (JAK) inhibitor

Arms & Interventions

Group 1: Guselkumab

Participants will receive subcutaneous (SC) guselkumab 100 milligram (mg) once every 4 weeks (q4w) from Week 0 through Week 48.

Intervention: Guselkumab

Group 2: Guselkumab and Placebo

Participants will receive SC guselkumab 100 mg at Weeks 0 and 4, then once every 8 weeks (q8w) (Weeks 12, 20, 28, 36, and 44) and placebo injections at other visits (Weeks 8, 16, 24, 32, 40, 48) to maintain the blind.

Intervention: Guselkumab

Group 2: Guselkumab and Placebo

Intervention: Placebo

Group 3: Placebo Followed by Guselkumab

Participants will receive SC placebo q4w from Week 0 to Week 20, and will crossover at Week 24 to receive guselkumab 100 mg q4w from Week 24 through Week 48.

Intervention: Guselkumab

Group 3: Placebo Followed by Guselkumab

Participants will receive SC placebo q4w from Week 0 to Week 20, and will crossover at Week 24 to receive guselkumab 100 mg q4w from Week 24 through Week 48.

Intervention: Placebo

Outcomes

Primary Outcomes

Percentage of Participants Who Achieved an American College of Rheumatology (ACR) 20 Response at Week 24

Time Frame: Week 24

ACR 20 response: \>=20% improvement from baseline in both swollen joint count (66 joints) and tender joint count (68 joints), and \>=20% improvement from baseline in 3 of 5 assessments: patient's assessment of pain using visual analog scale (VAS; 0-100 mm, 0=no pain and 100=worst possible pain), patient's global assessment of disease activity (arthritis, VAS; 0-100 mm, 0=excellent and 100= poor), physician's global assessment of disease activity (VAS; 0-100 mm, 0=no arthritis activity and 100=extremely active arthritis), patient's assessment of physical function measured by Disability Index of Health Assessment Questionnaire (HAQ-DI; 20-question instrument assessing 8 functional areas; range: 0-3, 0= no difficulty, 3= inability to perform task in that area), and CRP. Treatment Failure (TF) criteria- discontinued study drug, initiated/increased dose of non-biologic disease-modifying antirheumatic drugs (DMARDs) or oral corticosteroids, initiated prohibited psoriatic arthritis treatment.

Secondary Outcomes

Percentage of Participants Who Achieved an American College of Rheumatology (ACR) 50 Response at Week 24(Week 24)
Percentage of Participants With Psoriasis Response of IGA (Score: 0[Cleared] or 1[Minimal] and >=2 Grade Reduction From Baseline) at Week 24 Among Participants With >=3% Body Surface Area (BSA) Psoriatic Involvement and IGA Score of >=2 (Mild) at Baseline(Week 24)
Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS) Score at Week 24(Baseline and Week 24)
Change From Baseline in Enthesitis Score (Based on LEI) at Week 24 Among the Participants With Enthesitis at Baseline(Baseline and Week 24)
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 24(Baseline and Week 24)
Change From Baseline in Disease Activity Score (DAS28) (C-reactive Protein [CRP]) Score at Week 24(Baseline and Week 24)
Percentage of Participants Who Achieved a DAS28 (CRP) Remission by Visit Over Time Through Week 24(Week 4, 8, 12, 16, 20 and 24)
Percentage of Participants Who Achieved an American College of Rheumatology (ACR) 20 Response at Week 16(Week 16)
Percentage of Participants With Resolution of Enthesitis at Week 24 Among the Participants With Enthesitis at Baseline(Week 24)
Change From Baseline in Dactylitis Scores at Week 24 Among the Participants With Dactylitis at Baseline(Baseline and Week 24)
Percentage of Participants Who Achieved ACR 20 Response by Visit Over Time Through Week 24(Weeks 4, 8, 12, 16, 20 and 24)
Percentage of Participants Who Achieved ACR 50 Response by Visit Over Time Through Week 24(Weeks 4, 8, 12, 16, 20 and 24)
ACR Components- Patient's Assessment of Pain, Patient's Global Assessment of Disease Activity, Physician's Global Assessment of Disease Activity Through Week 24(Weeks 4, 8, 12, 16, 20 and 24)
ACR Component- C-reactive Protein (CRP) Through Week 24(Weeks 4, 8, 12, 16, 20 and 24)
Percentage of Participants Who Achieve an American College of Rheumatology (ACR) 70 Response at Week 24(Week 24)
Percentage of Participants Who Achieved an American College of Rheumatology (ACR) 50 Response at Week 16(Week 16)
Change From Baseline in 36-Item Short Form Health Survey (SF-36) Mental Component Summary (MCS) Score at Week 24(Baseline and Week 24)
Percentage of Participants With Resolution of Dactylitis at Week 24 Among the Participants With Dactylitis at Baseline(Week 24)
Change From Baseline in HAQ-DI Score at Weeks 4, 8, 12, 16, 20 and 24(Baseline, Week 4, 8, 12, 16, 20 and 24)
Percentage of Participants Who Achieved ACR 70 Response by Visit Over Time Through Week 24(Weeks 4, 8, 12, 16, 20 and 24)
ACR Components- Swollen Joint Count and Tender Joint Count Through Week 24(Weeks 4, 8, 12, 16, 20 and 24)
ACR Component- Patient's Assessment of Physical Function as Assessed by HAQ-DI Scale Score at Weeks 4, 8, 12, 16, 20 and 24(Weeks 4, 8, 12, 16, 20 and 24)
Change From Baseline in DAS28 (CRP) Score at Weeks 4, 8, 12, 16, 20 and 24(Baseline, Weeks 4, 8, 12, 16, 20 and 24)
Percentage of Participants Who Achieved Minimal Disease Activity (MDA) at Weeks 16 and 24(Weeks 16 and Week 24)
Percentage of Participants Who Achieved PASI 75 Response at Weeks 16 and 24 Among Participants With >=3% BSA Psoriatic Involvement and an IGA Score of >=2 at Baseline(Weeks 16 and 24)
Percentage of Participants Who Achieved PASI 90 Response at Weeks 16 and 24 Among Participants With >=3% BSA Psoriatic Involvement and an IGA Score of >=2 at Baseline(Weeks 16 and 24)
Percent Change From Baseline in ACR Components at Weeks 4, 8, 12, 16, 20 and 24(Baseline, Weeks 4, 8, 12, 16, 20 and 24)
Percentage of Participants Who Achieved a Clinically Meaningful Improvement (>=0.35 Improvement From Baseline) in HAQ-DI Score by Visit Over Time Through Week 24 Among Participants With HAQ-DI Score >=0.35 at Baseline(Week 4, 8, 12, 16, 20 and 24)
Change From Baseline in BASDAI Score at Week 8, 16, and Week 24 Among Participants With Spondylitis and Peripheral Arthritis at Baseline(Baseline, Weeks 8, 16, and 24)
Percentage of Participants Who Achieved PASI 100 Response by Visit Over Time Through Week 24 Among Participants With >=3% BSA Psoriatic Involvement and an IGA Score of >=2 at Baseline(Weeks 16 and 24)
Change From Baseline in PASI Score at Weeks 16 and 24 Among the Participants With >=3% BSA Psoriatic Involvement and an IGA Score of >=2 (Mild) at Baseline(Baseline, Weeks 16 and 24)
Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS) at Weeks 8, 16 and 24(Baseline, Weeks 8, 16 and 24)
Percentage of Participants Who Achieved a DAS28 (CRP) Response by Visit Over Time Through Week 24(Weeks 4, 8, 12, 16, 20 and 24)
Percentage of Participants With Resolution of Dactylitis by Visit Over Time Through Week 24 Among the Participants With Dactylitis at Baseline(Weeks 4, 8, 16 and 24)
Change From Baseline in the Psoriatic Arthritis Disease Activity (PASDAS) Score at Weeks 8, 16 and 24(Baseline, Weeks 8, 16 and 24)
Percentage of Participants With Low Disease Activity or Remission Based on Disease Activity Index for Psoriatic Arthritis (DAPSA) by Visit Over Time Through Week 24(Baseline, Weeks 4, 8, 12, 16, 20 and 24)
Percentage of Participants With Very Low Disease Activity (VLDA) by Visit Over Time Through Week 24(Weeks 16 and 24)
Percentage of Participants Who Achieved a Response Based on Modified Psoriatic Arthritis Responder Criteria (PsARC) by Visit Over Time Through Week 24(Weeks 4, 8, 12, 16, 20 and 24)
Change From Baseline in Enthesitis Score at Weeks 4, 8, 16 and 24 Among the Participants With Enthesitis at Baseline(Baseline, Weeks 4, 8, 16 and 24)
Change From Baseline in Group of Research and Assessment of Psoriasis and Psoriatic Arthritis Composite (GRACE) Score at Weeks 16 and 24(Baseline, Weeks 16 and 24)
Change From Baseline in the Disease Activity Index for Psoriatic Arthritis (DAPSA) Score at Weeks 4, 8, 12, 16, 20 and 24(Baseline, Weeks 4, 8, 12, 16, 20 and 24)
Percentage of Participants With Low Disease Activity Based on Group of Research and Assessment of Psoriasis and Psoriatic Arthritis Composite (GRACE) Score Index by Visit Over Time Through Week 24(Weeks 16 and 24)
Percentage of Participants Who Achieved Resolution of Enthesitis at Weeks 4, 8, 16, and 24 Among the Participants With Enthesitis at Baseline(Weeks 4, 8, 16, and 24)
Change From Baseline in Dactylitis Score at Weeks 4, 8, 16 and 24 Among the Participants With Dactylitis at Baseline(Baseline, Weeks 4, 8, 16 and 24)
Percentage of Participants Who Achieved >= 20%, >=50%, >=70%, and >=90% Improvement From Baseline in BASDAI Score Through Week 24 Among the Participants With Spondylitis and Peripheral Arthritis and BASDAI Score >0 at Baseline(Weeks 8, 16 and 24)
Percentage of Participants With Low or Very Low Disease Activity Based on Psoriatic Arthritis Disease Activity Score (PASDAS) by Visit Over Time Through Week 24(Weeks 8, 16 and 24)
Percentage of Participants Who Achieved Both PASI 75 and ACR 20 Responses at Weeks 16 and 24 Among the Participants With >=3% BSA Psoriatic Involvement and an IGA Score of >=2 (Mild) at Baseline(Weeks 16 and 24)
Change From Baseline in Patient-Reported Outcomes Measurement Information System (PROMIS)-29 Scores at Weeks 8, 16 and 24(Baseline, Weeks 8, 16 and 24)
Change From Baseline in the Disease Activity Index for Psoriatic Arthritis (DAPSA) Score at Weeks 24, 28, 36, 44 and 52(Baseline, Weeks 24, 28, 36, 44 and 52)
Percentage of Participants Who Achieved Both PASI 75 and Modified PsARC Response at Weeks 24 and 52 Among Participants With >=3% BSA Psoriatic Involvement and an IGA Score of >=2 at Baseline(Weeks 24 and 52)
Percentage of Participants Who Achieved Both PASI 75 and Modified PsARC Response by Visit Over Time Through Week 24 Among Participants With >=3% BSA Psoriatic Involvement and an IGA Score of >=2 (Mild) at Baseline(Weeks 16 and 24)
Change From Baseline in 36-Item Short Form Health Survey (SF-36) Mental Component Summary (MCS) at Weeks 8, 16 and 24(Baseline, Weeks 8, 16 and 24)
Change From Baseline in FACIT-Fatigue Score at Week 24 by ACR 20 Response at Week 24(Baseline and Week 24)
Percentage of Participants Who Achieved ACR 20 Response at Weeks 24, 28, 36, 44 and 52(Weeks 24, 28, 36, 44 and 52)
Percentage of Participants With an IGA Score of 0 (Cleared) at Weeks 16 and 24 Among the Participants With >=3% BSA Psoriatic Involvement and an IGA Score of >=2 (Mild) at Baseline(Weeks 16 and 24)
Change From Baseline in Norm Based Scores of SF-36 Scales at Weeks 8, 16 and 24(Baseline, Week 8, 16 and 24)
Percentage of Participants Who Achieved >=5-point Improvement From Baseline in SF-36 MCS Score by Visit Over Time Through Week 24(Weeks 8, 16 and 24)
Percentage of Participants Who Achieved >=5 Point Improvement From Baseline in SF-36 PCS Score Through Week 24(Weeks 8, 16 and 24)
Percentage of Participants Who Achieved >=4-point Improvement From Baseline in FACIT-Fatigue Score at Weeks 8, 16, and 24(Weeks 8, 16, and 24)
Percentage of Participants Who Achieved an Improvement of >=5 Points From Baseline in PROMIS-29 Domain Scores at Weeks 8, 16, and 24(Weeks 8, 16, and 24)
Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score at Weeks 8, 16, and 24(Baseline, Weeks 8, 16 and 24)
Percentage of Participants Who Achieved >=4-point Improvement From Baseline in FACIT-Fatigue Score at Week 24 by ACR 20 Response at Week 24(Week 24)
Percentage of Participants Who Achieved an Improvement of >=3 Points From Baseline in PROMIS-29 Domain Scores at Weeks 8, 16, and 24(Weeks 8, 16, and 24)
Percentage of Participants Who Achieved ACR 50 Response at Weeks 24, 28, 36, 44 and 52(Weeks 24, 28, 36, 44 and 52)
Percentage of Participants Who Achieved ACR 70 Response at Weeks 24, 28, 36, 44 and 52(Weeks 24, 28, 36, 44 and 52)
Change From Baseline in HAQ-DI Score at Weeks 24, 28, 36, 44 and 52(Baseline, Weeks 24, 28, 36, 44 and 52)
Change From Baseline in DAS28 (CRP) Score at Weeks 24, 28, 36, 44 and 52(Baseline, Weeks 24, 28, 36, 44 and 52)
Percent Change From Baseline in ACR Components at Weeks 24, 28, 36, 44 and 52(Baseline, Weeks 24, 28, 36, 44 and 52)
Percentage of Participants Who Achieved a Clinically Meaningful Improvement (>=0.35 Improvement From Baseline) in HAQ-DI Score at Weeks 24, 28, 36, 44 and 52 Among Participants With HAQ-DI Score >=0.35 at Baseline(Weeks 24, 28, 36, 44 and 52)
Percentage of Participants Who Achieved a Response Based on Modified Psoriatic Arthritis Responder Criteria (PsARC) at Weeks 24, 28, 36, 44 and 52(Weeks 24, 28, 36, 44 and 52)
Percentage of Participants Who Achieved Both PASI 75 and ACR 20 Responses at Weeks 24 and 52 Among Participants With >=3% BSA Psoriatic Involvement and an IGA Score of >=2 at Baseline(Weeks 24 and 52)
Change From Baseline in PASI Score at Weeks 24 and 52 Among Participants With >=3% BSA Psoriatic Involvement and an IGA Score of >=2 at Baseline(Baseline, Weeks 24 and 52)
Percentage of Participants Who Achieved PASI 90 Response at Weeks 24 and 52 Among Participants With >=3% BSA Psoriatic Involvement and an IGA Score of >=2 at Baseline(Weeks 24 and 52)
Percentage of Participants Who Achieved >=5 Point Improvement From Baseline in SF-36 MCS Score at Weeks 24, 36 and 52(Weeks 24, 36 and 52)
Percentage of Participants Who Achieved a DAS28 (CRP) Response at Weeks 24, 28, 36, 44 and 52(Weeks 24, 28, 36, 44 and 52)
Percentage of Participants Who Achieved a DAS28 (CRP) Remission at Weeks 24, 28, 36, 44 and 52(Weeks 24, 28, 36, 44 and 52)
Percentage of Participants Who Maintained a HAQ-DI Response (>=0.35 Improvement From Baseline in HAQ-DI Score) at Week 52 Among Participants Who Achieved a HAQ-DI Response at Week 24(Week 52)
Change From Baseline in Group of Research and Assessment of Psoriasis and Psoriatic Arthritis Composite (GRACE) Score Index at Weeks 24 and 52(Baseline, Weeks 24 and 52)
Percentage of Participants Who Maintained an ACR 50 Response at Week 52 Among Participants Who Achieved an ACR 50 Response at Week 24(Week 52)
Change From Baseline in Dactylitis Score at Weeks 24, 36, 44 and 52 Among the Participants With Dactylitis at Baseline(Baseline, Weeks 24, 36, 44 and 52)
Percentage of Participants Who Achieved PASI 75 Response at Weeks 24 and 52 Among Participants With >=3% BSA Psoriatic Involvement and an IGA Score of >=2 at Baseline(Weeks 24 and 52)
Percentage of Participants With Resolution of Enthesitis at Weeks 24, 36, 44 and 52 Among the Participants With Enthesitis at Baseline(Weeks 24, 36, 44 and 52)
Percentage of Participants With an IGA Score of 0 (Cleared) or 1 (Cleared) at Weeks 24 and 52 Among Participants With >=3% BSA Psoriatic Involvement and an IGA Score of >=2 at Baseline(Weeks 24 and 52)
Change From Baseline in Norm Based Scores of SF-36 Scales at Week 24, 36 and 52(Baseline, Weeks 24, 36 and 52)
Percentage of Participants Who Achieved PASI 100 Response at Weeks 24 and 52 Among Participants With >=3% BSA Psoriatic Involvement and an IGA Score of >=2 at Baseline(Weeks 24 and 52)
Percentage of Participants Who Achieved >=5 Point Improvement From Baseline in SF-36 PCS Score at Weeks 24, 36 and 52(Weeks 24, 36 and 52)
Percentage of Participants Who Achieved Minimal Disease Activity (MDA) at Weeks 24 and 52(Weeks 24 and 52)
Percentage of Participants Who Maintained an ACR 20 Response at Week 52 Among Participants Who Achieved an ACR 20 Response at Week 24(Week 52)
Percentage of Participants With Resolution of Dactylitis at Weeks 24, 36, 44 and 52 Among Participants With Dactylitis at Baseline(Weeks 24, 36, 44 and 52)
Change From Baseline in Enthesitis Score (Based on SPARCC) at Weeks 24, 36, 44 and 52 Among the Participants With Enthesitis at Baseline(Baseline, Weeks 24, 36, 44 and 52)
Change From Baseline in Enthesitis Score (Based on LEI) at Weeks 24, 36, 44 and 52 Among the Participants With Enthesitis at Baseline(Baseline, Weeks 24, 36, 44 and 52)
Change From Baseline in Psoriatic Arthritis Disease Activity (PASDAS) Score at Weeks 24 and 52(Baseline, Weeks 24 and 52)
Percentage of Participants Who Maintained an ACR 70 Response at Week 52 Among Participants Who Achieved an ACR 70 Response at Week 24(Week 52)
Percentage of Participants Who Achieved >= 20%, >=50%, >=70%, and >=90% Improvement From Baseline in BASDAI Score at Weeks 24 and 52 Among Participants With Spondylitis and Peripheral Arthritis as Their Primary Arthritic Presentation of PsA(Weeks 24 and 52)
Change From Baseline in SF-36 Mental Component Summary (MCS) Score at Weeks 24, 36 and 52(Baseline, Weeks 24, 36 and 52)
Percentage of Participants Who Achieved >=4-point Improvement From Baseline in FACIT-Fatigue Score at Weeks 24, 36 and 52(Weeks 24, 36 and 52)
Change From Baseline in SF-36 Physical Component Summary (PCS) Score at Weeks 24, 36 and 52(Baseline, Weeks 24, 36 and 52)
Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score at Weeks 24, 36 and 52(Baseline, Weeks 24, 36 and 52)
Change From Baseline in Patient-Reported Outcomes Measurement Information System (PROMIS)-29 Scores at Weeks 24, 36 and 52(Baseline, Weeks 24, 36 and 52)