Diffuse Cutaneous Systemic SclerosisPhase 2ASSETNCT02161406
A Study of Subcutaneous Abatacept to Treat Diffuse Cutaneous Systemic Sclerosis
A Phase 2 study testing Abatacept in people with Diffuse Cutaneous Systemic Sclerosis, run by Dinesh Khanna, MD, MS at 27 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diffuse Cutaneous Systemic Sclerosis
- What is being tested?
- Abatacept
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 88 participants
- Where
- 27 sitesin 3 countries
- Study dates
- Sep 2014to 17 Oct 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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
Show all 21Show fewer
- 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
Trial locations and contacts
27 sites in 3 countries.
27 sites in 3 countries
United States23 sites
Steffens Scleroderma Center
Albany, New York, 12203
University of Michigan
Ann Arbor, Michigan, 48109
Harvard Mass General
Boston, Massachusetts, 02116
Boston University
Boston, Massachusetts, 02118
Medical University of South Carolina
Charleston, South Carolina, 29425
Northwestern University
Chicago, Illinois, 60611
Cleveland Clinic
Cleveland, Ohio, 44195
Ohio State University Medical Center
Columbus, Ohio, 43221
NorthWell Health
Great Neck, New York, 11021
University of Texas Health Center at Houston
Houston, Texas, 77030
Arthritis Associates of Southern California
Los Angeles, California, 90045
University of California- Los Angeles
Los Angeles, California, 90095
University of Minnesota
Minneapolis, Minnesota, 55455
Rutgers University Clinical Research Center
New Brunswick, New Jersey, 08831
Hospital for Special Surgery
New York, New York, 10021
Columbia University
New York, New York, 10032
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
University of Pittsburgh
Pittsburgh, Pennsylvania, 15261
Stanford University
Redwood City, California, 94063
Mayo Clinic
Rochester, Minnesota, 55905
University of Utah
Salt Lake City, Utah, 84132
Swedish Health Services
Seattle, Washington, 98122
Georgetown University
Washington D.C., District of Columbia, 20009
Canada3 sites
St. Joseph Health Care London
London, Ontario, N6A4V2
Jewish General Hospital
Montreal, Quebec, H3T 1E2
Mount Sinai Hospital
Toronto, Ontario, M5T 3L9
About this study
Official title: A Phase 2 Study to Evaluate Subcutaneous Abatacept vs. Placebo in Diffuse Cutaneous Systemic Sclerosis- a Double-blind, Placebo-controlled, Randomized Controlled Trial.
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.
Read the 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
- Being tested
- Abatacept, Placebo
- Keywords
- Scleroderma
- Medical subject headings
- Scleroderma, Diffuse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AbataceptDrug
Also called Orencia
Subjects will be treated with injections of 125 mg of abatacept or placebo weekly for 52 weeks
PlaceboDrug
125 mg of Placebo
| Study group | Role | What they receive |
|---|---|---|
| Abatacept | Active comparator | 125 mg SC abatacept vs SC placebo administered weekly for 12 months, with a 24-week open-label extension Receives: Drug: Abatacept |
| Placebo | Placebo comparator | 125mg Placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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).
Measured: Baseline and 52 weeks
Secondary outcomes (33)
Change From Baseline to Month 12 in Patient Global Assessment for Overall Disease
Patient global assessment for overall disease represents the patient's assessment of the patient's global scleroderma on a 0 (excellent) -10 (extremely poor) Likert scale. Higher score means worse outcome.
Measured: Baseline and Week 52
Change From Baseline to Month 12 in Physician Global Assessment for Overall Disease
This assessment represents the physician's assessment of the patient's current disease activity on a 0 (excellent) -10 (extremely poor) Likert scale. Higher score means worse outcome.
Measured: Baseline and Week 52
Change in % Predicted FVC
FVC is Forced vital capacity, a measure of lung function. FVC % Predicted is calculated using equations from Hankinson [Hankinson JL, Odencrantz JR, Fedan KB. Spirometric reference values from a sample of the general U.S. population. Am J Respir Crit Care Med. 1999;159(1):179-87], incorporating age, gender, and race. It is calculated as the (FVC Observed / FVC predicted) * 100, where FVC predicted is calculated relative to a reference population.
Measured: Baseline and 52 weeks
Change From Baseline to Month 12 in FVC (in ml)
FVC = forced vital capacity, a measure of lung function
Measured: Baseline and Week 52
Change From Baseline to Month 12 in HAQ-DI - Overall
The HAQ-DI is the Health Assessment Question Disability Index that assesses the extent of a patient's functional ability. The HAQ-DI overall score ranges from 0 (no disability) to 3 (severe disability). Higher score means worse outcome.
Measured: Baseline and Week 52
Change From Baseline to Month 12 in SHAQ-DI VAS - Overall Disease
Scleroderma-Health Assessment Question Disability Index visual analogue scales (VAS) assess the burden of digital ulcers, Raynaud's, gastrointestinal involvement, breathing, and overall disease. The VAS scale for disease severity ranges from 0 (no disease) to 150 (very severe). A higher score means a worse outcome.
Measured: Baseline and Week 52
Change From Baseline to Month 12 in SHAQ-DI VAS - Breathing
Scleroderma-Health Assessment Question Disability Index visual analogue scales (VAS) assess the burden of digital ulcers, Raynaud's, gastrointestinal involvement, breathing, and overall disease. The VAS scale for how much breathing problems interfered with daily activities ranges from 0 (do not limit activities) to 150 (very severe limitation). A higher score means a worse outcome.
Measured: Baseline and Week 52
Change From Baseline to Month 12 in SHAQ-DI VAS - Raynaud's
Scleroderma-Health Assessment Question Disability Index visual analogue scales (VAS) assess the burden of digital ulcers, Raynaud's, gastrointestinal involvement, breathing, and overall disease. The VAS scale for how much Raynaud's interfered with daily activities ranges from 0 (does not limit activities) to 150 (very severe limitation). A higher score means a worse outcome.
Measured: Baseline and Week 52
Change From Baseline to Month 12 in SHAQ-DI VAS - Burden of Digital Ulcers
Scleroderma-Health Assessment Question Disability Index visual analogue scales (VAS) assess the burden of digital ulcers, Raynaud's, gastrointestinal involvement, breathing, and overall disease. The VAS scale for how much finger ulcers interfered with daily activities ranges from 0 (do not limit activities) to 150 (very severe limitation). A higher score means a worse outcome.
Measured: Baseline and Week 52
Change From Baseline to Month 12 in SHAQ-DI VAS - GI Involvement
Scleroderma-Health Assessment Question Disability Index visual analogue scales (VAS) assess the burden of digital ulcers, Raynaud's, gastrointestinal involvement, breathing, and overall disease. The VAS scale for how much intestinal problems interfered with daily activities ranges from 0 (do not limit activities) to 150 (very severe limitation). A higher score means a worse outcome.
Measured: Baseline and Week 52
Change From Baseline to Month 12 in Swollen Joint Count
28 joints are assessed for swelling (positive or negative). The number of swollen joint count ranges from 0 to 28. A higher number indicates worse outcome.
Measured: Baseline and 52 weeks
Change From Baseline to Month 12 in Tender Joint Counts
28 joints are assessed for tenderness (positive or negative). The number of tender joint counts ranges from 0 to 28. A higher number indicates worse outcome.
Measured: Baseline and 52 weeks
Change From Baseline to Month 12 in PROMIS-29 - Physical Function
The Patient-Reported Outcomes Measurement Information System (PROMIS) 29-item short-form health-reported quality of life measures (PROMIS-29) were administered. The transformed score (T-score) for the physical function domain was used, where 50 (10) is the mean (standard deviation) of a relevant reference population. Higher scores equals more of the concept being measured (i.e., better outcome).
Measured: Baseline and Week 52
Change From Baseline to Month 12 in PROMIS-29 - Anxiety
The Patient-Reported Outcomes Measurement Information System (PROMIS) 29-item short-form health-reported quality of life measures (PROMIS-29) were administered. The transformed score (T-score) for the anxiety domain was used, where 50 (10) is the mean (standard deviation) of a relevant reference population. Higher scores equals more of the concept being measured (i.e., worse outcome).
Measured: Baseline and Week 52
Change From Baseline to Month 12 in PROMIS-29 - Depression
The Patient-Reported Outcomes Measurement Information System (PROMIS) 29-item short-form health-reported quality of life measures (PROMIS-29) were administered. The transformed score (T-score) for the depression domain was used, where 50 (10) is the mean (standard deviation) of a relevant reference population. Higher scores equals more of the concept being measured (i.e., worse outcome).
Measured: Baseline and Week 52
Change From Baseline to Month 12 in PROMIS 29 - Fatigue
The Patient-Reported Outcomes Measurement Information System (PROMIS) 29-item short-form health-reported quality of life measures (PROMIS-29) were administered. The transformed score (T-score) for the fatigue domain was used, where 50 (10) is the mean (standard deviation) of a relevant reference population. Higher scores equals more of the concept being measured (i.e., worse outcome).
Measured: Baseline and Week 52
Change From Baseline to Month 12 in PROMIS-29 - Sleep Disturbance
The Patient-Reported Outcomes Measurement Information System (PROMIS) 29-item short-form health-reported quality of life measures (PROMIS-29) were administered. The transformed score (T-score) for the sleep disturbance domain was used, where 50 (10) is the mean (standard deviation) of a relevant reference population. Higher scores equals more of the concept being measured (i.e.,worse outcome).
Measured: Baseline and Week 52
Change From Baseline to Month 12 in PROMIS-29 - Pain Interference
The Patient-Reported Outcomes Measurement Information System (PROMIS) 29-item short-form health-reported quality of life measures (PROMIS-29) were administered. The transformed score (T-score) for the pain interference domain was used, where 50 (10) is the mean (standard deviation) of a relevant reference population. Higher scores equals more of the concept being measured (i.e., worse outcome).
Measured: Baseline and Week 52
Change From Baseline to Month 12 in PROMIS-29 - Ability to Participate in Social Roles & Activities
The Patient-Reported Outcomes Measurement Information System (PROMIS) 29-item short-form health-reported quality of life measures (PROMIS-29) were administered. The transformed score (T-score) for the ability to participate in social roles and activities domain was used, where 50 (10) is the mean (standard deviation) of a relevant reference population. Higher scores equals more of the concept being measured (i.e., better outcome).
Measured: Baseline and Week 52
Change From Baseline to Month 12 in PROMIS-29 - Pain Intensity
The Patient-Reported Outcomes Measurement Information System (PROMIS) 29-item short-form health-reported quality of life measures (PROMIS-29) were administered. The transformed score (T-score) for the pain intensity domain was used, where 50 (10) is the mean (standard deviation) of a relevant reference population. Higher scores equals more of the concept being measured (i.e., worse outcome).
Measured: Baseline and Week 52
Change From Baseline to Month 12 in SCTC GIT - Composite Score
The SCTC GIT is the UCLA Scleroderma Clinical Trial Consortium Gastrointestinal Instrument. It assesses scleroderma-related gastrointestinal symptoms. The composite score ranges from 0 to 2.83; 0 indicates better health and higher score indicates worse health.
Measured: Baseline and Week 52
ACR CRISS at 12 Months
The American College of Rheumatology Combined Response Index in Systemic Sclerosis is a composite endpoint. It is determined in a 2-step process. The first step assesses whether the patient has had a significant decline in renal or cardiopulmonary involvement. If none of these apply, the second step assesses the probability of improvement by measuring changes in five outcomes and integrating them into a single number using an equation described in Khanna D, Berrocal VJ, et al. [The American College of Rheumatology Provisional Composite Response Index for Clinical Trials in Early Diffuse Cutaneous Systemic Sclerosis. Arthritis and Rheumatology. 2016; 68(2):299-311.]. It incorporates changes in the modified Rodnan skin score, percent predicted forced vital capacity (FVC), patient and physician global assessments, and SHAQ-DI over 1 year. The score ranges from 0 to 1; a higher score indicates better outcome.
Measured: Week 52
Change From Baseline to Month 12 in PROMIS - Fatigue
The Patient-Reported Outcomes Measurement Information System (PROMIS) 8-question short-form health-reported quality of life measure fatigue domain was administered. The transformed score (T-score) was used, where 50 (10) is the mean (standard deviation) of a relevant reference population. Higher scores equals more of the concept being measured (i.e., worse outcome).
Measured: Baseline and Week 52
Change From Baseline to Month 12 in PROMIS - Sleep Disturbance
The Patient-Reported Outcomes Measurement Information System (PROMIS) 4-question short-form health-reported quality of life measure sleep disturbance domain was administered. The transformed score (T-score) was used, where 50 (10) is the mean (standard deviation) of a relevant reference population. Higher scores equals more of the concept being measured (i.e., better outcome).
Measured: Baseline and Week 52
Change From Baseline to Month 12 in PROMIS - Sleep Impairment
The Patient-Reported Outcomes Measurement Information System (PROMIS) 8-question short-form health-reported quality of life measure sleep impairment domain was administered. The transformed score (T-score) was used, where 50 (10) is the mean (standard deviation) of a relevant reference population. Higher scores equals more of the concept being measured (i.e., worse outcome).
Measured: Baseline and Week 52
Change From Baseline to Month 12 in HAQ-DI - Dressing and Grooming
The HAQ-DI is the Health Assessment Question Disability Index that assesses the extent of a patient's functional ability. The HAQ-DI subscore ranges from 0 (no disability) to 3 (severe disability). A higher score means worse outcome.
Measured: Baseline and Week 52
Change From Baseline to Month 12 in HAQ-DI - Hygiene
The HAQ-DI is the Health Assessment Question Disability Index that assesses the extent of a patient's functional ability. The HAQ-DI subscore ranges from 0 (no disability) to 3 (severe disability). A higher score means worse outcome.
Measured: Baseline and Week 52
Change From Baseline to Month 12 in HAQ-DI - Arising
The HAQ-DI is the Health Assessment Question Disability Index that assesses the extent of a patient's functional ability. The HAQ-DI subscore ranges from 0 (no disability) to 3 (severe disability). A higher score means worse outcome.
Measured: Baseline and Week 52
Change From Baseline to Month 12 in HAQ-DI - Reach
The HAQ-DI is the Health Assessment Question Disability Index that assesses the extent of a patient's functional ability. The HAQ-DI subscore ranges from 0 (no disability) to 3 (severe disability). A higher score means worse outcome.
Measured: Baseline and Week 52
Change From Baseline to Month 12 in HAQ-DI - Eating
The HAQ-DI is the Health Assessment Question Disability Index that assesses the extent of a patient's functional ability. The HAQ-DI subscore ranges from 0 (no disability) to 3 (severe disability). A higher score means worse outcome.
Measured: Baseline and Week 52
Change From Baseline to Month 12 in HAQ-DI - Grip
The HAQ-DI is the Health Assessment Question Disability Index that assesses the extent of a patient's functional ability. The HAQ-DI subscore ranges from 0 (no disability) to 3 (severe disability). A higher score means worse outcome.
Measured: Baseline and Week 52
Change From Baseline to Month 12 in HAQ-DI - Walking
The HAQ-DI is the Health Assessment Question Disability Index that assesses the extent of a patient's functional ability. The HAQ-DI subscore ranges from 0 (no disability) to 3 (severe disability). A higher score means worse outcome.
Measured: Baseline and Week 52
Change From Baseline to Month 12 in HAQ-DI - Common Daily Activities
The HAQ-DI is the Health Assessment Question Disability Index that assesses the extent of a patient's functional ability. The HAQ-DI subscore ranges from 0 (no disability) to 3 (severe disability). A higher score means worse outcome.
Measured: Baseline and Week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2014 (estimated)
- Study startSep 2014
- Primary completion12 Sep 2018
- Study completion17 Oct 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Diffuse Cutaneous Systemic SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 88 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dinesh Khanna, MD, MS
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Dinesh Khanna, MD, MS, University of Michigan
- Investigators
- Dinesh Khanna, MD, MS, Principal investigator, University of Michigan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02161406
- Sponsor's protocol ID
- IM101-344
- Other IDs
- 1UM1AI110557
- Acronym
- ASSET
- Status last verified
- Feb 2020
- First submitted
- 3 Jun 2014
- Last updated
- 17 Feb 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 36355434Chung 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.
PubMed 34966900Khanna 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.
PubMed 31342624
Study at a glance
From the registry record, last updated by the sponsor on 17 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Study to Evaluate Subcutaneous Abatacept vs. Placebo in Diffuse Cutaneous Systemic Sclerosis- a Double-blind, Placebo-controlled, Randomized Controlled Trial.
- ClinicalTrials.gov ID
- NCT02161406
- Acronym / sponsor ID
- ASSET / IM101-344
- Conditions
- Diffuse Cutaneous Systemic Sclerosis
- Keywords
- Scleroderma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 88 participants (actual)
- Lead sponsor
- Dinesh Khanna, MD, MSUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb, National Institute of Allergy and Infectious Diseases (NIAID)
- Study start
- Sep 2014 (actual)
- Primary completion
- 12 Sep 2018 (actual)
- Study completion
- 17 Oct 2018 (actual)
- First posted
- 11 Jun 2014 (estimated)
- Results
- Posted 18 Jun 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Abatacept | Active comparator | Drug: Abatacept125 mg SC abatacept vs SC placebo administered weekly for 12 months, with a 24-week open-label extension |
| Placebo | Placebo comparator | Drug: Placebo125mg Placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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:
Key exclusion criteria (21 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AbataceptAlso: OrenciaSubjects will be treated with injections of 125 mg of abatacept or placebo weekly for 52 weeks | Drug | Abatacept |
| Placebo125 mg of Placebo | Drug | Placebo |
Primary outcome
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).
33 secondary outcomes
Change From Baseline to Month 12 in Patient Global Assessment for Overall Disease
Time frame: Baseline and Week 52
Change From Baseline to Month 12 in Physician Global Assessment for Overall Disease
Time frame: Baseline and Week 52
Change in % Predicted FVC
Time frame: Baseline and 52 weeks
Change From Baseline to Month 12 in FVC (in ml)
Time frame: Baseline and Week 52
Change From Baseline to Month 12 in HAQ-DI - Overall
Time frame: Baseline and Week 52
Change From Baseline to Month 12 in SHAQ-DI VAS - Overall Disease
Time frame: Baseline and Week 52
Change From Baseline to Month 12 in SHAQ-DI VAS - Breathing
Time frame: Baseline and Week 52
Change From Baseline to Month 12 in SHAQ-DI VAS - Raynaud's
Time frame: Baseline and Week 52
Change From Baseline to Month 12 in SHAQ-DI VAS - Burden of Digital Ulcers
Time frame: Baseline and Week 52
Change From Baseline to Month 12 in SHAQ-DI VAS - GI Involvement
Time frame: Baseline and Week 52
Change From Baseline to Month 12 in Swollen Joint Count
Time frame: Baseline and 52 weeks
Change From Baseline to Month 12 in Tender Joint Counts
Time frame: Baseline and 52 weeks
Change From Baseline to Month 12 in PROMIS-29 - Physical Function
Time frame: Baseline and Week 52
Change From Baseline to Month 12 in PROMIS-29 - Anxiety
Time frame: Baseline and Week 52
Change From Baseline to Month 12 in PROMIS-29 - Depression
Time frame: Baseline and Week 52
Change From Baseline to Month 12 in PROMIS 29 - Fatigue
Time frame: Baseline and Week 52
Change From Baseline to Month 12 in PROMIS-29 - Sleep Disturbance
Time frame: Baseline and Week 52
Change From Baseline to Month 12 in PROMIS-29 - Pain Interference
Time frame: Baseline and Week 52
Change From Baseline to Month 12 in PROMIS-29 - Ability to Participate in Social Roles & Activities
Time frame: Baseline and Week 52
Change From Baseline to Month 12 in PROMIS-29 - Pain Intensity
Time frame: Baseline and Week 52
Change From Baseline to Month 12 in SCTC GIT - Composite Score
Time frame: Baseline and Week 52
ACR CRISS at 12 Months
Time frame: Week 52
Change From Baseline to Month 12 in PROMIS - Fatigue
Time frame: Baseline and Week 52
Change From Baseline to Month 12 in PROMIS - Sleep Disturbance
Time frame: Baseline and Week 52
Change From Baseline to Month 12 in PROMIS - Sleep Impairment
Time frame: Baseline and Week 52
Change From Baseline to Month 12 in HAQ-DI - Dressing and Grooming
Time frame: Baseline and Week 52
Change From Baseline to Month 12 in HAQ-DI - Hygiene
Time frame: Baseline and Week 52
Change From Baseline to Month 12 in HAQ-DI - Arising
Time frame: Baseline and Week 52
Change From Baseline to Month 12 in HAQ-DI - Reach
Time frame: Baseline and Week 52
Change From Baseline to Month 12 in HAQ-DI - Eating
Time frame: Baseline and Week 52
Change From Baseline to Month 12 in HAQ-DI - Grip
Time frame: Baseline and Week 52
Change From Baseline to Month 12 in HAQ-DI - Walking
Time frame: Baseline and Week 52
Change From Baseline to Month 12 in HAQ-DI - Common Daily Activities
Time frame: Baseline and Week 52
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Feb 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36355434Mehta 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.
- Derived from this study: PubMed 34966900Chung 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.
- Derived from this study: PubMed 31342624Khanna 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.
- To learn more about the Scleroderma program at the University of MichiganLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dinesh Khanna, MD, MS principal investigator
University of Michigan
27 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Abatacept in people with Diffuse Cutaneous Systemic Sclerosis, run by Dinesh Khanna, MD, MS at 27 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 27 sites in United States, Canada, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Jun 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of Participants With at Least One Adverse Events (AEs) or Serious AEs (SAEs) in 1 Year (time frame: 52 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02161406, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Feb 2020.