Evaluation of Tofacitinib in Early Diffuse Cutaneous Systemic Sclerosis (dcSSc)
NCT03274076
ABOUT THIS STUDY
FOR MORE INFORMATION
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1. Diagnosis of systemic sclerosis (SSc), as classified using the 2013 American College of Rheumatology/ European Union League Against Rheumatism classification of SSc.
2. Diffuse Cutaneous Systemic Sclerosis (dcSSc) as defined by 2001 LeRoy and Medsger
3. Disease duration ≤ 60 months (defined as time from the first non-Raynaud phenomenon manifestation)
4. Modified Rodnan Skin Score (mRSS) units ≥ 10 and ≤ 45 at screening.
5. Agreement to receive varicella-zoster vaccination (Zostavax®) or have received vaccination prior to screening.
6. Oral corticosteroids (≤ 10 mg/day of prednisone or equivalent) are permitted if the patient is on a stable dose regimen for ≥ 2 weeks prior to and including the baseline visit.
7. Ability to provide informed consent.
1. Rheumatic disease other than dcSSc; it is acceptable to include patients with
fibromyalgia, Sjogren syndrome, and scleroderma-associated myopathy
2. Limited cutaneous SSc or sine scleroderma
3. Major surgery (including joint surgery) within 8 weeks prior to baseline.
4. Any infected ulcer at screening
5. Subjects with any serious bacterial infection within the last 3 months, unless treated
and resolved with antibiotics, or any chronic bacterial infection (e.g., chronic
pyelonephritis, osteomyelitis, or bronchiectasis)
6. Oral corticosteroids >10 mg/day of prednisone or equivalent.
7. Hydroxychloroquine >400 mg/day, methotrexate >25 mg/week, D-Penicillamine >1000mg/day
or mycophenolate mofetil > 2 grams/day prior to baseline. **Subjects can be on
combination therapy of hydroxychloroquine and methotrexate or hydroxychloroquine and
mycophenolate mofetil and must have been on a stable dose for at least 1 month prior
to baseline visit.
8. Prior history of treatment in the 3 months prior to baseline with biological disease
modifying anti-rheumatic drugs (DMARDs)potent immunosuppressants such as cyclosporine
and azathioprine
9. Treatment with etanercept within ≤ 2 weeks of baseline: infliximab, certolizumab,
golimumab, abatacept, tocilizumab, or adalimumab within ≤ 8 weeks of baseline; and
anakinra within ≤ 1 week prior to the baseline visit.
10. Intravenous corticosteroids within 2 weeks prior to baseline visit.
11. Treatment with any investigational agent ≤ 4 weeks prior to baseline (or 5 half-lives
of the investigational drug, whichever is longer)
12. Other investigational or marketed biologics with immunomodulatory properties within 3
months prior to baseline.
13. Treatment with anti-CD20 6 months prior to baseline and B cell counts 14. Any prior treatment with cell-depleting therapies other than anti-CD20 such as 15. Any prior treatment with chlorambucil, bone marrow transplantation, or total lymphoid 16. Vaccinated or exposed to a live/attenuated vaccine (other than Zostavax®) ≤ 6 weeks 17. Pulmonary disease with Forced Vital Capacity (FVC) ≤ 50% of predicted, or Diffusing 18. History of pulmonary arterial hypertension (PAH) with mean PAP> 30 mmHg on right heart 19. Subjects at risk for tuberculosis (TB): A. Specifically excluded from this study will be participants with a history of active - An indeterminate QuantiFERON® unless followed by a subsequent negative PPD or 20. Positive for hepatitis B surface antigen at or within 30 days of screening 21. Positive for hepatitis C antigen at or within 30 days of screening 22. Current or recent history of uncontrolled clinically significant renal, hepatic, 23. History of human immunodeficiency virus (HIV), (as determined by medical records or 24. History of diverticulitis or chronic, ulcerative lower gastrointestinal (GI) disease 25. Pregnant or breastfeeding female subjects; and female subjects of childbearing 26. Severe acute or chronic medical or psychiatric condition or laboratory abnormality 27. History of systemic sclerosis (SSc) Renal Crisis within the 6 months prior to 28. Any of the following lab results at screening: - Hemoglobin <9 g/dL or Hematocrit <30% - White Blood Cell count <3.0 x 109/L; - Absolute Neutrophil count <1.2 x 109/L; - White Blood Cell count <3.0 x 109/L; - Absolute Neutrophil count <1.2 x 109/L; - Platelet count <100 x 109/L; - Absolute Lymphocyte count <0.75 x 109/L. - ALT or AST > 1.5 × the upper limit of normal (ULN) of normal at screening or any - Total bilirubin > upper limit of normal (ULN) at Screening. - Estimated glomerular filtration rate [GFR] <40mL/min/1.73 m2 29. Prior rituximab use without documentation of normalized b cell counts. 30. History of recurrent (more than one episode) herpes zoster or disseminated (at least 31. History of any lymphoproliferative disorder, such as Epstein Barr Virus (EBV) related 32. History of any malignancy in the last 5 years with the exception of adequately treated 33. Significant trauma or surgery procedure within 1 month prior to first dose of study 34. History of alcohol or substance abuse, unless in full remission for greater than 6
CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti-CD19
irradiation
prior to baseline; or is expected to be vaccinated or to have household exposure to
these vaccines during treatment or during the 6 weeks following discontinuation of
study medication. (**See additional inclusion for obtaining Zostavax® prior to
entering the study)
capacity of the lungs for carbon monoxide (DLCO),(uncorrected for hemoglobin) ≤ 40% of
predicted
catheterization requiring subcutaneous or intravenous prostacyclin or dual use of oral
PAH therapies
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; (TB results within 30 days of screening will be accepted and
will not to be repeated. B. Latent TB at or within 30 days of screening, history of or
current positive purified protein derivative tuberculin skin test (PPD) ( >5mm
induration, regardless of Bacille Calmette Guerin [BCG] vaccine and/or QuantiFERON
Gold, a negative chest x-ray, and no symptoms or risk factors), unless one month of
prophylaxis has been completed prior to inclusion
negative QuantiFERON® or a consultation with and clearance by local infectious
disease (ID) department is required.
hematologic, gastrointestinal, metabolic, endocrine, pulmonary, cardiac or neurologic
disease.
patient reported).
such as Crohns disease, ulcerative colitis, or other symptomatic, lower GI conditions
that might predispose a patient to perforations.
potential who are unwilling or unable to use a highly effective method of
contraception as outlined in the protocol for the duration of the study and for at
least 28 days after discontinuation of study drug.
that may increase risk associated with study participation and in the judgment of the
investigator would make the subject inappropriate for entry into this study.
baseline.
uncontrolled clinically significant laboratory abnormality that would affect
interpretation of study data or the patient's participation in the study
one episode) herpes zoster, or disseminated (at least one episode) herpes simplex
lymphoproliferative disorder, history of lymphoma, leukemia, or signs and symptoms
suggestive of current lymphatic disease.
or excised basal cell or squamous cell or cervical cancer in situ.
drug.
months prior to first dose of study drug.
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Descriptive Information | |||||||
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Brief Title ICMJE | Evaluation of Tofacitinib in Early Diffuse Cutaneous Systemic Sclerosis (dcSSc) | ||||||
Official Title ICMJE | Evaluation of Tofacitinib in Early Diffuse Cutaneous Systemic Sclerosis (dcSSc): A Phase I/II Two Center Safety and Tolerability Study | ||||||
Brief Summary | This Phase I/II placebo controlled trial will evaluate tofacitinib in subjects with diffuse cutaneous systemic scleroderma (dcSSc). This trial is intended to provide safety, and tolerability data in participants with dcSSc when dosed to target exposures similar to that used in adult participants with rheumatoid arthritis. | ||||||
Detailed Description | The purpose of this clinical research study is to evaluate the safety, tolerability and efficacy of treatment with tofacitinib (study drug) versus placebo (a substance with no active ingredients and therefore may have no treatment benefit) in people with diffuse cutaneous systemic scleroderma. Subjects will be randomized to tofacitinib vs. placebo in a 2:1 ratio at 5 mg twice a day for 24 weeks. Subjects will then be offered to participate in an open label phase during which they will receive tofacitinib 5 mg twice a day for 24 weeks. | ||||||
Study Type ICMJE | Interventional | ||||||
Study Phase ICMJE | Phase 1 Phase 2 | ||||||
Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment Intervention Model Description: Eligible subjects will be randomized to tofacitinib or placebo in a 2:1 manner. Masking: Double (Participant, Investigator)Masking Description: The study staff (with the exception of the study pharmacist) and the patient are blinded to the treatment assignment. Primary Purpose: Treatment
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Condition ICMJE |
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Intervention ICMJE |
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Study Arms ICMJE |
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Publications * | Not Provided | ||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. | |||||||
Recruitment Information | |||||||
Recruitment Status ICMJE | Completed | ||||||
Actual Enrollment ICMJE | 15 | ||||||
Original Estimated Enrollment ICMJE | Same as current | ||||||
Actual Study Completion Date ICMJE | November 15, 2019 | ||||||
Actual Primary Completion Date | April 8, 2019 (Final data collection date for primary outcome measure) | ||||||
Eligibility Criteria ICMJE | Inclusion Criteria:
Exclusion Criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years to 70 Years (Adult, Older Adult) | ||||||
Accepts Healthy Volunteers ICMJE | No | ||||||
Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | ||||||
Listed Location Countries ICMJE | United States | ||||||
Removed Location Countries | |||||||
Administrative Information | |||||||
NCT Number ICMJE | NCT03274076 | ||||||
Other Study ID Numbers ICMJE | HUM00131837 | ||||||
Has Data Monitoring Committee | Yes | ||||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE | Not Provided | ||||||
Responsible Party | Dinesh Khanna, MD, MS, University of Michigan | ||||||
Study Sponsor ICMJE | University of Michigan | ||||||
Collaborators ICMJE | Pfizer | ||||||
Investigators ICMJE |
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PRS Account | University of Michigan | ||||||
Verification Date | April 2020 | ||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |