Scleroderma, DiffusePhase 1/2NCT00442611
A Study to Evaluate the Safety and Efficacy of Abatacept in Patients With Diffuse Systemic Sclerosis (Scleroderma)
A Phase 1/2 study testing Abatacept in people with Scleroderma, Diffuse and Scleroderma, Systemic, run by Stanford University at 1 site in United States.
Trial summary
Systemic sclerosis (scleroderma) is an autoimmune connective tissue disease that involves the skin and other internal organs for which there are few effective treatment options. We hypothesize that treatment with abatacept, a new therapy recently approved for the treatment of rheumatoid arthritis, may reduce the… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Scleroderma, Diffuse, Scleroderma, Systemic
- 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
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2008to Jun 2011
- Phase
- Phase 1/2
- 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 diffuse systemic sclerosis
- age 18 years or older
- Adequate renal, pulmonary, and cardiovascular function
- Willingness to use effective contraception for the duration of the study if subject is of childbearing potential\

Who cannot join
- Other connective tissues diseases or overlap syndromes including MCTD, SLE, RA, eosinophilic fasciitis, and limited systemic sclerosis or morphea
- Use of disease modifying agents including methotrexate, cyclosporine,azathioprine, mycophenolate mofetil, minocycline, doxycycline, minocycline, thalidomide, penicillamine, tamoxifen, colchicine, or investigational agent within 90 days of screening visit
- HIV, Hepatitis B or Hepatitis C infection
- use of prednisone greater than 10mg daily for 28 days prior to screening visit
- women who are breastfeeding or pregnant
Trial locations and contacts
1 site in 1 country.
United States1 site
Stanford University School of Medicine
Stanford, California, 94305
About this study
Official title: A Pilot Study to Evaluate the Safety and Efficacy of Abatacept in Patients With Systemic Sclerosis
Systemic sclerosis (scleroderma) is an autoimmune connective tissue disease that involves the skin and other internal organs for which there are few effective treatment options. We hypothesize that treatment with abatacept, a new therapy recently approved for the treatment of rheumatoid arthritis, may reduce the progression of skin thickening and fibrosis in people with scleroderma.
Read the detailed description
Systemic sclerosis is an autoimmune connective tissue disease of unknown etiology characterized by progressive fibrosis of the skin and internal organs, vascular damage, and autoantibody production. Although the disease is relatively rare, it is associated with considerable morbidity and mortality. There have been improvements in survival over the past few decades; however, this has been related to better management of vascular manifestations of disease including renal crisis, pulmonary hypertension, gastroesophageal reflux disease, and Raynaud's phenomenon. Clinical studies of disease modifying therapies for cutaneous disease to date have been relatively unsuccessful.
Although the etiology of the disease remains unknown, several observations support the role of activated T cells in both the blood and skin of affected patients. Abatacept, a recombinant fusion protein that blocks T cell activation, has recently been approved by the FDA for rheumatoid arthritis. We hypothesize that inhibition of T cell activation with abatacept may be efficacious in the treatment of patients with diffuse systemic sclerosis. This is a randomized, double-blinded, placebo-controlled clinical trial of abatacept versus placebo in patients with diffuse systemic sclerosis. Changes in validated measures of skin thickness and disease activity over 6-months of treatment will be compared between patients receiving abatacept and those receiving placebo. Patients will be randomized 2:1 to receive abatacept.
The protocol was amended during the study and the outcome measures "Change in Serum Autoantibody Profile" and "Change in Serum Cytokine Profile" were changed to exploratory outcomes.
- Conditions
- Scleroderma, Diffuse, Scleroderma, Systemic
- Being tested
- Abatacept, Placebo
- Medical subject headings
- Scleroderma, Diffuse, Scleroderma, Systemic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AbataceptDrug
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| Abatacept | Experimental | Abatacept (dosed based upon weight) administered intravenously (IV) on days 1, 15, 30 and monthly thereafter for a total of 7 doses. Receives: Drug: Abatacept |
| IV fluid | Placebo comparator | Placebo to match abatacept (IV fluid) administered on days 1, 15, 30 and monthly thereafter for a total of 7 doses. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Modified Rodnan Skin Score
Modified Rodnan Skin Score measures skin thickness and is the sum of scores from 17 surface anatomic areas rated on a 0-3 scale (0=normal skin; 1=mild thickness; 2=moderate thickness; 3=severe thickness with inability to pinch the skin into a fold). Total modified Rodnan Skin Score ranges from 0 (best possible outcome) to 51 (worst possible outcome).
Measured: 6 months
Secondary outcomes (5)
Oral Aperture at Baseline and Month 6
Measured: Baseline; Month 6
Hand Extension at Baseline and Month 6
Measured: Baseline; Month 6
Digital Ulcerations at Baseline and Month 6
Measured: Baseline; Month 6
Change in Pulmonary Function Tests
FVC (Forced Vital Capacity) is the amount of air that can be forcibly exhaled from the lungs after taking the deepest possible breath. DLCO (Diffusing capacity of the lung for carbon monoxide) is the extent to which oxygen passes from the lungs to the blood.
Measured: 6 months
Change in Scleroderma Health Assessment Questionnaire
The HAQ Disability Index (HAQ-DI) includes 20 items in 8 functional domains (dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities) assessing the patient's usual abilities in the past seven days. Each item is scored on a 0-3 scale (0=without any difficulty; 1=with some difficulty; 2=with much difficulty; 3=unable to do). The use of assistive devices for any domain increases the domain score by 1 point to a maximum of 3. The overall score is calculated by summing the highest item score in each of the domains and dividing the sum by 8, with an overall score of 0 indicating no disability, and a score of 3 indicating severe disability.
The time points compared were 6 months to baseline (6 months minus baseline).
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Mar 2007 (estimated)
- Study startNov 2008
- Primary completionJun 2011
- Study completionJun 2011
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 (1)Papers the sponsor has linked to this study.
- Other trials for Scleroderma, DiffuseStudies of the same condition, open and under way.
- More trials run by Stanford UniversityThe sponsor's other registered studies.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Principal investigator, Lorinda S Chung, Stanford University
- Investigators
- Eliza Farmer Chakravarty, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00442611
- Sponsor's protocol ID
- 100 186
- Status last verified
- Sep 2017
- First submitted
- 1 Mar 2007
- Last updated
- 31 Oct 2017
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Chakravarty EF, Martyanov V, Fiorentino D, Wood TA, Haddon DJ, Jarrell JA, Utz PJ, Genovese MC, Whitfield ML, Chung L. Gene expression changes reflect clinical response in a placebo-controlled randomized trial of abatacept in patients with diffuse cutaneous systemic sclerosis. Arthritis Res Ther. 2015 Jun 13;17(1):159. doi: 10.1186/s13075-015-0669-3.
PubMed 26071192
Study at a glance
From the registry record, last updated by the sponsor on 31 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study to Evaluate the Safety and Efficacy of Abatacept in Patients With Systemic Sclerosis
- ClinicalTrials.gov ID
- NCT00442611
- Acronym / sponsor ID
- 100 186
- Conditions
- Scleroderma, Diffuse, Scleroderma, Systemic
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Study start
- Nov 2008
- Primary completion
- Jun 2011 (actual)
- Study completion
- Jun 2011 (actual)
- First posted
- 2 Mar 2007 (estimated)
- Results
- Posted 24 Apr 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Systemic sclerosis (scleroderma) is an autoimmune connective tissue disease that involves the skin and other internal organs for which there are few effective treatment options. We hypothesize that treatment with abatacept, a new therapy recently approved for the treatment of rheumatoid arthritis, may reduce the progression of skin thickening and fibrosis in people with scleroderma.
Detailed description
Systemic sclerosis is an autoimmune connective tissue disease of unknown etiology characterized by progressive fibrosis of the skin and internal organs, vascular damage, and autoantibody production. Although the disease is relatively rare, it is associated with considerable morbidity and mortality. There have been improvements in survival over the past few decades; however, this has been related to better management of vascular manifestations of disease including renal crisis, pulmonary hypertension, gastroesophageal reflux disease, and Raynaud's phenomenon. Clinical studies of disease modifying therapies for cutaneous disease to date have been relatively unsuccessful.
Although the etiology of the disease remains unknown, several observations support the role of activated T cells in both the blood and skin of affected patients. Abatacept, a recombinant fusion protein that blocks T cell activation, has recently been approved by the FDA for rheumatoid arthritis. We hypothesize that inhibition of T cell activation with abatacept may be efficacious in the treatment of patients with diffuse systemic sclerosis. This is a randomized, double-blinded, placebo-controlled clinical trial of abatacept versus placebo in patients with diffuse systemic sclerosis. Changes in validated measures of skin thickness and disease activity over 6-months of treatment will be compared between patients receiving abatacept and those receiving placebo. Patients will be randomized 2:1 to receive abatacept.
The protocol was amended during the study and the outcome measures "Change in Serum Autoantibody Profile" and "Change in Serum Cytokine Profile" were changed to exploratory outcomes.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Abatacept | Experimental | Drug: AbataceptAbatacept (dosed based upon weight) administered intravenously (IV) on days 1, 15, 30 and monthly thereafter for a total of 7 doses. |
| IV fluid | Placebo comparator | Drug: PlaceboPlacebo to match abatacept (IV fluid) administered on days 1, 15, 30 and monthly thereafter for a total of 7 doses. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Diagnosis of diffuse systemic sclerosis
- age 18 years or older
- Adequate renal, pulmonary, and cardiovascular function
- Willingness to use effective contraception for the duration of the study if subject is of childbearing potential\

Key exclusion criteria (5 listed)
- Other connective tissues diseases or overlap syndromes including MCTD, SLE, RA, eosinophilic fasciitis, and limited systemic sclerosis or morphea
- Use of disease modifying agents including methotrexate, cyclosporine,azathioprine, mycophenolate mofetil, minocycline, doxycycline, minocycline, thalidomide, penicillamine, tamoxifen, colchicine, or investigational agent within 90 days of screening visit
- HIV, Hepatitis B or Hepatitis C infection
- use of prednisone greater than 10mg daily for 28 days prior to screening visit
- women who are breastfeeding or pregnant
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 |
|---|---|---|
| Abatacept | Drug | Abatacept |
| Placebo | Drug | IV fluid |
Primary outcome
Change in Modified Rodnan Skin Score
Time frame: 6 months
Modified Rodnan Skin Score measures skin thickness and is the sum of scores from 17 surface anatomic areas rated on a 0-3 scale (0=normal skin; 1=mild thickness; 2=moderate thickness; 3=severe thickness with inability to pinch the skin into a fold). Total modified Rodnan Skin Score ranges from 0 (best possible outcome) to 51 (worst possible outcome).
5 secondary outcomes
Oral Aperture at Baseline and Month 6
Time frame: Baseline; Month 6
Hand Extension at Baseline and Month 6
Time frame: Baseline; Month 6
Digital Ulcerations at Baseline and Month 6
Time frame: Baseline; Month 6
Change in Pulmonary Function Tests
Time frame: 6 months
Change in Scleroderma Health Assessment Questionnaire
Time frame: 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Oct 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 26071192Chakravarty EF, Martyanov V, Fiorentino D, Wood TA, Haddon DJ, Jarrell JA, Utz PJ, Genovese MC, Whitfield ML, Chung L. Gene expression changes reflect clinical response in a placebo-controlled randomized trial of abatacept in patients with diffuse cutaneous systemic sclerosis. Arthritis Res Ther. 2015 Jun 13;17(1):159. doi: 10.1186/s13075-015-0669-3.
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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.
Eliza Farmer Chakravarty principal investigator
Stanford University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Abatacept in people with Scleroderma, Diffuse and Scleroderma, Systemic, run by Stanford University at 1 site in United States.
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 4 inclusion and 5 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 31 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 24 Apr 2015). 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?
Change in Modified Rodnan Skin Score (time frame: 6 months). 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 NCT00442611, which also lists 1 linked publication.
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 31 Oct 2017.