Clinical Trials/NCT02161406

NCT02161406CompletedPhase 2

A Phase 2 Study to Evaluate Subcutaneous Abatacept vs. Placebo in Diffuse Cutaneous Systemic Sclerosis- a Double-blind, Placebo-controlled, Randomized Controlled Trial.

Dinesh Khanna, MD, MS27 sites in 3 countries88 target enrollmentStarted: September 2014Last updated: February 17, 2020

Conditions

Interventions

Drugs

Trial Snapshot

Phase: Phase 2
Status: Completed
Sponsor
Enrollment: 88
Locations: 27
Primary Endpoint: Proportion of Participants With at Least One Adverse Events (AEs) or Serious AEs (SAEs) in 1 Year

Study Overview Study Design Eligibility Criteria Arms & Interventions Outcomes Investigators Sites Records & Identifiers Similar Trials

Study Overview

Brief Summary

The study hypothesis is that SC abatacept is safe and shows evidence of efficacy (improvement in modified Rodnan score [mRSS]) in patients with diffuse cutaneous systemic sclerosis (dcScc) compared to matching placebo.

Detailed Description

This study is a randomized placebo-controlled double-blind phase 2 trial of patients with dcSSc. Eligible participants will be randomized in a 1:1 ratio to either 125 mg SC abatacept or matching placebo, stratified by duration of dcSSc disease duration (<18 months vs >18 to </=36 months). Study participants will be treated for 12 months on double-blind study medication, followed by an additional 24 weeks of open-label SC abatacept therapy. 86 patients will be randomized in approximately 35 centers in the US, Canada and Europe, with the goal of analyzing 74 participants. The investigators study will test whether abatacept is statistically superior to placebo in reducing the MRSS at month 12 and explore the ability of abatacept to prevent or reverse progression in patients with early disease duration and lower MRSS scores, and reverse established disease in patients with longer disease duration and higher MRSS scores.

Study Design

Study Type: Interventional
Allocation: Randomized
Intervention Model: Parallel
Primary Purpose: Treatment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Eligibility Criteria

Ages: 18 Years to — (Adult, Older Adult)
Sex: All
Accepts Healthy Volunteers: No

Inclusion Criteria

•Diagnosis of Systematic Sclerosis (SSc), as defined using the 2013 American College of Rheumatology/ European Union League Against Rheumatism classification of SSc
•Diffuse Systemic Sclerosis (dcSSc) as defined by LeRoy and Medsger
•Disease duration of ≤ 36 months (defined as time from the first non-Raynaud phenomenon manifestation)
•For disease duration of ≤ 18 months: ≥ 10 and ≤ 35 mRSS units at the screening visit
•For disease duration of >18-36 months: ≥ 15 and ≤ 45 mRSS units at the screening visit and one of the following:
•Increase ≥ 3 in mRSS units compared with the last visit within previous 1-6 months
•Involvement of one new body area with ≥ 2 mRSS units compared with the last visit within the previous 1-6 months
•Involvement of two new body areas with ≥ 1 mRSS units compared with the last visit within the previous 1-6 months
•Presence of 1 or more Tendon Friction Rub
•Age ≥ 18 years at the screening visit
•If female of childbearing potential, the patient must have a negative pregnancy test at screening and baseline visits
•Oral corticosteroids (≤ 10 mg/day of prednisone or equivalent) and NSAIDs are permitted if the patient is on a stable dose regimen for
•2 weeks prior to and including the baseline visit.
•ACE inhibitors, calcium-channel blockers, proton-pump inhibitors, and/or oral vasodilators are permitted if the patient is on a stable dose for ≥ 2 weeks prior to and including the baseline visit.

Exclusion Criteria

•Rheumatic disease other than dcSSc; it is acceptable to include patients with fibromyalgia and scleroderma-associated myopathy
•Limited cutaneous systemic sclerosis or sine scleroderma at the screening visit
•Major surgery (including joint surgery) within 8 weeks prior to screening visit
•Infected ulcer prior to randomization
•Treatment with any investigational agent within ≤ 4 weeks (or 5 half-lives of the investigational drug, whichever is longer) of the baseline visit
•Previous treatment with cell-depleting therapies, including investigational agents, including but not limited to, CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti-CD19, and ABA
•Anti-CD20, and cyclophosphamide within 12 months prior to baseline visit.
•Use of Intravenous Immunoglobulin (IVIG) within 12 weeks prior to baseline visit
•Previous treatment with chlorambucil, bone marrow transplantation, or total lymphoid irradiation
•Immunization with a live/attenuated vaccine within ≤ 4 weeks prior to the baseline visit
•Treatment with methotrexate, hydroxychloroquine, cyclosporine A, azathioprine, mycophenolate mofetil rapamycin, colchicine, or D-penicillamine, within≤ 4 weeks prior to the baseline visit
•Treatment with etanercept within ≤ 2 weeks, infliximab, certolizumab, golimumab, ABA or adalimumab within ≤ 8 weeks, anakinra within ≤ 1 week prior to the baseline visit
•Pulmonary disease with FVC ≤ 50% of predicted, or DLCO (uncorrected for hemoglobin ) ≤ 40% of predicted at the screening visit
•Pulmonary arterial hypertension (PAH) as determined by right heart catheterization or on PAH approved medications for PAH. It is acceptable to use PDFE-5 inhibitors for Raynaud's and digital ulcers.
•Subjects at risk for tuberculosis (TB). Specifically excluded from this study will be participants with a history of active TB within the last 3 years, even if it was treated; a history of active TB greater than 3 years ago, unless there is documentation that the prior anti-TB treatment was appropriate in duration and type; current clinical, radiographic, or laboratory evidence of active TB; and latent TB that was not successfully treated (≥ 4 weeks).
•Positive for hepatitis B surface antigen prior to the baseline visit
•Positive for hepatitis C antigen, if the presence of hepatitis C virus was also shown with polymerase chain reaction or recombinant immunoblot assay prior to baseline visit
•Subjects at risk for tuberculosis (TB). Specifically excluded from this study will be participants with a history of active TB within the last 3 years, even if it was treated; a history of active TB greater than 3 years ago, unless there is documentation that the prior anti-TB treatment was appropriate in duration and type; current clinical, radiographic, or laboratory evidence of active TB; and latent TB that was not successfully treated (≥ 4 weeks).
•Any of the following at the screening visit: Hemoglobin <8.5 g/dL; WBC < 3,000/mm3 (<3 x 109/L); platelets < 100,000/mm3 (<3 x 109/L); serum creatinine > 2 x ULN; serum ALT or AST > 2 x ULN
•Severe skin thickening (mRSS 3) on the inner aspects of thighs, upper arms, or abdomen
•Patients with a history of anaphylaxis to abatacept

Arms & Interventions

Abatacept

Active Comparator

125 mg SC abatacept vs SC placebo administered weekly for 12 months, with a 24-week open-label extension

Intervention: Abatacept (Drug)

Placebo

Placebo Comparator

125mg Placebo

Intervention: Placebo (Drug)

Outcomes

Primary Outcomes

Proportion of Participants With at Least One Adverse Events (AEs) or Serious AEs (SAEs) in 1 Year

Time Frame: 52 weeks

Safety is measured using AEs, including clinical significant changes in vital signs, laboratory test abnormalities and clinical tolerability of abatacept, and using serious AEs

Change From Baseline in the Modified Rodnan Skin Score (mRSS) to Month 12

Time Frame: Baseline and 52 weeks

The efficacy of treatment on skin fibrosis will be measured by changes from baseline to month 12 in mRSS, a measure of skin thickness. mRSS scores have a range from 0 to 51, with higher score indicating greater severity of SSc (worse outcome).

Secondary Outcomes

Change From Baseline to Month 12 in SHAQ-DI VAS - Burden of Digital Ulcers(Baseline and Week 52)
Change From Baseline to Month 12 in PROMIS 29 - Fatigue(Baseline and Week 52)
Change From Baseline to Month 12 in PROMIS-29 - Sleep Disturbance(Baseline and Week 52)
Change From Baseline to Month 12 in PROMIS-29 - Pain Interference(Baseline and Week 52)
Change From Baseline to Month 12 in PROMIS-29 - Ability to Participate in Social Roles & Activities(Baseline and Week 52)
Change From Baseline to Month 12 in SHAQ-DI VAS - Breathing(Baseline and Week 52)
Change From Baseline to Month 12 in Swollen Joint Count(Baseline and 52 weeks)
Change From Baseline to Month 12 in HAQ-DI - Overall(Baseline and Week 52)
Change From Baseline to Month 12 in SHAQ-DI VAS - Overall Disease(Baseline and Week 52)
Change From Baseline to Month 12 in SHAQ-DI VAS - GI Involvement(Baseline and Week 52)
Change From Baseline to Month 12 in SHAQ-DI VAS - Raynaud's(Baseline and Week 52)
Change From Baseline to Month 12 in Patient Global Assessment for Overall Disease(Baseline and Week 52)
Change From Baseline to Month 12 in Physician Global Assessment for Overall Disease(Baseline and Week 52)
Change in % Predicted FVC(Baseline and 52 weeks)
Change From Baseline to Month 12 in FVC (in ml)(Baseline and Week 52)
Change From Baseline to Month 12 in PROMIS-29 - Anxiety(Baseline and Week 52)
Change From Baseline to Month 12 in PROMIS-29 - Depression(Baseline and Week 52)
Change From Baseline to Month 12 in Tender Joint Counts(Baseline and 52 weeks)
Change From Baseline to Month 12 in PROMIS-29 - Physical Function(Baseline and Week 52)
Change From Baseline to Month 12 in PROMIS-29 - Pain Intensity(Baseline and Week 52)
Change From Baseline to Month 12 in SCTC GIT - Composite Score(Baseline and Week 52)
ACR CRISS at 12 Months(Week 52)
Change From Baseline to Month 12 in PROMIS - Fatigue(Baseline and Week 52)
Change From Baseline to Month 12 in HAQ-DI - Common Daily Activities(Baseline and Week 52)
Change From Baseline to Month 12 in PROMIS - Sleep Disturbance(Baseline and Week 52)
Change From Baseline to Month 12 in PROMIS - Sleep Impairment(Baseline and Week 52)
Change From Baseline to Month 12 in HAQ-DI - Dressing and Grooming(Baseline and Week 52)
Change From Baseline to Month 12 in HAQ-DI - Hygiene(Baseline and Week 52)
Change From Baseline to Month 12 in HAQ-DI - Arising(Baseline and Week 52)
Change From Baseline to Month 12 in HAQ-DI - Reach(Baseline and Week 52)
Change From Baseline to Month 12 in HAQ-DI - Eating(Baseline and Week 52)
Change From Baseline to Month 12 in HAQ-DI - Grip(Baseline and Week 52)
Change From Baseline to Month 12 in HAQ-DI - Walking(Baseline and Week 52)

Investigators

Sponsor

Dinesh Khanna, MD, MS

Sponsor Class

Other

Responsible Party

Sponsor Investigator

Principal Investigator

Dinesh Khanna, MD, MS

Associate Professor of Rheumatology/ Internal Medicine

University of Michigan

Study Sites (27)

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