A Study of Subcutaneous Abatacept to Treat Diffuse Cutaneous Systemic Sclerosis

NCT02161406 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: IM101-3441UM1AI110557
• Study Type: interventional
• Target: 88
• Locations: 3 countries
• Sites: 27

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.

Conditions

Diffuse Cutaneous Systemic Sclerosis

Keywords

Scleroderma

Outcome Measures

Primary Outcomes (2)

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

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

  52 weeks

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

  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).

  Baseline and 52 weeks

Secondary Outcomes (33)

• 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 HAQ-DI - Overall

  Baseline and Week 52

Study Arms (2)

Abatacept

ACTIVE COMPARATOR

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

Drug: Abatacept

Placebo

PLACEBO COMPARATOR

125mg Placebo

Drug: Placebo

Interventions

Abatacept DRUG

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

Also known as: Orencia

Abatacept

Placebo DRUG

125 mg of Placebo

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Dinesh Khanna, MD, MS: lead
• Bristol-Myers Squibb: collaborator
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (27)

Arthritis Associates of Southern California

Los Angeles, California, 90045, United States

Location

University of California- Los Angeles

Los Angeles, California, 90095, United States

Location

Stanford University

Redwood City, California, 94063, United States

Location

Georgetown University

Washington D.C., District of Columbia, 20009, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Harvard Mass General

Boston, Massachusetts, 02116, United States

Location

Boston University

Boston, Massachusetts, 02118, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Rutgers University Clinical Research Center

New Brunswick, New Jersey, 08831, United States

Location

Steffens Scleroderma Center

Albany, New York, 12203, United States

Location

NorthWell Health

Great Neck, New York, 11021, United States

Location

Hospital for Special Surgery

New York, New York, 10021, United States

Location

Columbia University

New York, New York, 10032, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Ohio State University Medical Center

Columbus, Ohio, 43221, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15261, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

University of Texas Health Center at Houston

Houston, Texas, 77030, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

Swedish Health Services

Seattle, Washington, 98122, United States

Location

St. Joseph Health Care London

London, Ontario, N6A4V2, Canada

Location

Mount Sinai Hospital

Toronto, Ontario, M5T 3L9, Canada

Location

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

Location

Royal Free Hospital

London, NW3 2QG, United Kingdom

Location

Related Publications (3)

• 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.

  PMID: 36355434 DERIVED

• 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.

  PMID: 34966900 DERIVED

• 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.

  PMID: 31342624 DERIVED

Related Links

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

MeSH Terms

Conditions

Scleroderma, Diffuse

Interventions

Abatacept

Condition Hierarchy (Ancestors)

Scleroderma, Systemic; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases

Intervention Hierarchy (Ancestors)

Immunoconjugates; Antibodies; Immunoglobulins; Serum Globulins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Globulins

Results Point of Contact

• Title: Dr. Cathie Spino
• Organization: University of Michigan DCC (SABER)

spino@umich.edu

734-615-5469

Study Officials

• Dinesh Khanna, MD, MS

  University of Michigan

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Rheumatology/ Internal Medicine

Study Record Dates

• First Submitted: June 3, 2014
• First Posted: June 11, 2014
• Study Start: September 1, 2014
• Primary Completion: September 12, 2018
• Study Completion: October 17, 2018
• Last Updated: February 17, 2020
• Results First Posted: June 18, 2019

Record last verified: 2020-02

Locations

US (23); CA (3); GB (1)