A Study of Subcutaneous Abatacept to Treat Diffuse Cutaneous Systemic Sclerosis

NCT ID: NCT02161406

Last Updated: 2020-02-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 88 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-09-30
• Study Completion Date: 2018-10-17

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.

Conditions

Diffuse Cutaneous Systemic Sclerosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Abatacept

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

Group Type: ACTIVE_COMPARATOR

Abatacept

Intervention Type: DRUG

Subjects will be treated with injections of 125 mg of abatacept or placebo weekly for 52 weeks

Placebo

125mg Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

125 mg of Placebo

Interventions

Abatacept

Subjects will be treated with injections of 125 mg of abatacept or placebo weekly for 52 weeks

Intervention Type: DRUG

Placebo

125 mg of Placebo

Intervention Type: DRUG

Other Intervention Names

Orencia

Eligibility Criteria

Inclusion Criteria

1. Diagnosis of Systematic Sclerosis (SSc), as defined using the 2013 American College of Rheumatology/ European Union League Against Rheumatism classification of SSc

2. Diffuse Systemic Sclerosis (dcSSc) as defined by LeRoy and Medsger

3. Disease duration of ≤ 36 months (defined as time from the first non-Raynaud phenomenon manifestation)

4. For disease duration of ≤ 18 months: ≥ 10 and ≤ 35 mRSS units at the screening visit

5. 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

6. Age ≥ 18 years at the screening visit

7. If female of childbearing potential, the patient must have a negative pregnancy test at screening and baseline visits

8. 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.

9. 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

1. Rheumatic disease other than dcSSc; it is acceptable to include patients with fibromyalgia and scleroderma-associated myopathy

2. Limited cutaneous systemic sclerosis or sine scleroderma at the screening visit

3. Major surgery (including joint surgery) within 8 weeks prior to screening visit

4. Infected ulcer prior to randomization

5. Treatment with any investigational agent within ≤ 4 weeks (or 5 half-lives of the investigational drug, whichever is longer) of the baseline visit

6. 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

7. Anti-CD20, and cyclophosphamide within 12 months prior to baseline visit.

8. Use of Intravenous Immunoglobulin (IVIG) within 12 weeks prior to baseline visit

9. Previous treatment with chlorambucil, bone marrow transplantation, or total lymphoid irradiation

10. Immunization with a live/attenuated vaccine within ≤ 4 weeks prior to the baseline visit

11. Treatment with methotrexate, hydroxychloroquine, cyclosporine A, azathioprine, mycophenolate mofetil rapamycin, colchicine, or D-penicillamine, within≤ 4 weeks prior to the baseline visit

12. Treatment with etanercept within ≤ 2 weeks, infliximab, certolizumab, golimumab, ABA or adalimumab within ≤ 8 weeks, anakinra within ≤ 1 week prior to the baseline visit

13. Pulmonary disease with FVC ≤ 50% of predicted, or DLCO (uncorrected for hemoglobin ) ≤ 40% of predicted at the screening visit

14. 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.

15. 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).

16. Positive for hepatitis B surface antigen prior to the baseline visit

17. 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

18. 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).

19. 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

20. Severe skin thickening (mRSS 3) on the inner aspects of thighs, upper arms, or abdomen

21. Patients with a history of anaphylaxis to abatacept

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: collaborator

Dinesh Khanna, MD, MS

OTHER

Sponsor Role: lead

Responsible Party

Dinesh Khanna, MD, MS

Associate Professor of Rheumatology/ Internal Medicine

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Dinesh Khanna, MD, MS

Role: PRINCIPAL_INVESTIGATOR

University of Michigan

Locations

Arthritis Associates of Southern California

Los Angeles, California, United States

University of California- Los Angeles

Los Angeles, California, United States

Stanford University

Redwood City, California, United States

Georgetown University

Washington D.C., District of Columbia, United States

Northwestern University

Chicago, Illinois, United States

Harvard Mass General

Boston, Massachusetts, United States

Boston University

Boston, Massachusetts, United States

University of Michigan

Ann Arbor, Michigan, United States

University of Minnesota

Minneapolis, Minnesota, United States

Mayo Clinic

Rochester, Minnesota, United States

Rutgers University Clinical Research Center

New Brunswick, New Jersey, United States

Steffens Scleroderma Center

Albany, New York, United States

NorthWell Health

Great Neck, New York, United States

Hospital for Special Surgery

New York, New York, United States

Columbia University

New York, New York, United States

Cleveland Clinic

Cleveland, Ohio, United States

Ohio State University Medical Center

Columbus, Ohio, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Medical University of South Carolina

Charleston, South Carolina, United States

University of Texas Health Center at Houston

Houston, Texas, United States

University of Utah

Salt Lake City, Utah, United States

Swedish Health Services

Seattle, Washington, United States

St. Joseph Health Care London

London, Ontario, Canada

Mount Sinai Hospital

Toronto, Ontario, Canada

Jewish General Hospital

Montreal, Quebec, Canada

Royal Free Hospital

London, , United Kingdom

Countries

United States; Canada; United Kingdom

References

Mehta BK, Espinoza ME, Franks JM, Yuan Y, Wang Y, Wood T, Gudjonsson JE, Spino C, Fox DA, Khanna D, Whitfield ML. Machine-learning classification identifies patients with early systemic sclerosis as abatacept responders via CD28 pathway modulation. JCI Insight. 2022 Dec 22;7(24):e155282. doi: 10.1172/jci.insight.155282.

Reference Type: DERIVED

PMID: 36355434 (View on PubMed)

Chung L, Spino C, McLain R, Johnson SR, Denton CP, Molitor JA, Steen VD, Lafyatis R, Simms RW, Kafaja S, Frech TM, Hsu V, Domsic RT, Pope JE, Gordon JK, Mayes MD, Sandorfi N, Hant FN, Bernstein EJ, Chatterjee S, Castelino FV, Ajam A, Allanore Y, Matucci-Cerinic M, Whitfield ML, Distler O, Singer O, Young A, Nagaraja V, Fox DA, Furst DE, Khanna D. Safety and efficacy of abatacept in early diffuse cutaneous systemic sclerosis (ASSET): open-label extension of a phase 2, double-blind randomised trial. Lancet Rheumatol. 2020 Dec;2(12):e743-e753. doi: 10.1016/S2665-9913(20)30237-X. Epub 2020 Oct 19.

Reference Type: DERIVED

PMID: 34966900 (View on PubMed)

Khanna D, Spino C, Johnson S, Chung L, Whitfield ML, Denton CP, Berrocal V, Franks J, Mehta B, Molitor J, Steen VD, Lafyatis R, Simms RW, Gill A, Kafaja S, Frech TM, Hsu V, Domsic RT, Pope JE, Gordon JK, Mayes MD, Schiopu E, Young A, Sandorfi N, Park J, Hant FN, Bernstein EJ, Chatterjee S, Castelino FV, Ajam A, Wang Y, Wood T, Allanore Y, Matucci-Cerinic M, Distler O, Singer O, Bush E, Fox DA, Furst DE. Abatacept in Early Diffuse Cutaneous Systemic Sclerosis: Results of a Phase II Investigator-Initiated, Multicenter, Double-Blind, Randomized, Placebo-Controlled Trial. Arthritis Rheumatol. 2020 Jan;72(1):125-136. doi: 10.1002/art.41055. Epub 2019 Dec 10.

Reference Type: DERIVED

PMID: 31342624 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

http://www.med.umich.edu/scleroderma

To learn more about the Scleroderma program at the University of Michigan

Other Identifiers

1UM1AI110557

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IM101-344

Identifier Type: -

Identifier Source: org_study_id