Evaluation of Tofacitinib in Early Diffuse Cutaneous Systemic Sclerosis (dcSSc) (TOFA-SSc)
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|ClinicalTrials.gov Identifier: NCT03274076|
Recruitment Status : Completed
First Posted : September 6, 2017
Results First Posted : May 8, 2020
Last Update Posted : May 8, 2020
|Condition or disease||Intervention/treatment||Phase|
|Systemic Sclerosis Scleroderma||Drug: Tofacitinib Drug: Placebo Oral Tablet||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||15 participants|
|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.|
|Official Title:||Evaluation of Tofacitinib in Early Diffuse Cutaneous Systemic Sclerosis (dcSSc): A Phase I/II Two Center Safety and Tolerability Study|
|Actual Study Start Date :||September 25, 2017|
|Actual Primary Completion Date :||April 8, 2019|
|Actual Study Completion Date :||November 15, 2019|
Active Comparator: Tofacitinib
5mg Tofacitinib twice a day
Oral medication tofacitinib 5 mg twice a day for 24 weeks.
Other Name: Xeljanz
Placebo Comparator: Placebo
5mg Placebo twice a day
Drug: Placebo Oral Tablet
Oral Placebo 5 mg twice a day for 24 weeks
- Number of Participants Who Experience Grade 3 or Higher Adverse Events That Occur at or Before Week 24 [ Time Frame: 24 weeks ]
Primary outcome is met if any participants experience a grade 3 or higher event prior to Week 24. A grade 3 AE would constitute as "severe". Grading was following using CTCAE v 4.03.
Note that the planned statistical analysis (Fisher's exact test) could not be performed because there were no events.
- Number of Grade 3 (Severe) or Higher Adverse Events That Occur Throughout the Study [ Time Frame: Week 12, 24, 36, and 48 ]
Grade 3 or higher adverse events (AEs) assessed throughout the study ( 48 weeks). A grade 3 AE would constitute as "severe". Grading was following using CTCAE v 4.03.
Note that the planned statistical analysis (calculation of rate ratio and 90% CI) could not be performed at Weeks 12 and 24 due to no events, and could not be performed at Week 36 because there were no events in the placebo group (denominator).
- Number of Grade 2 (Moderate) or Higher Adverse Events That Occur Throughout the Study [ Time Frame: Week: 12, 24, 36, and 48 ]Grade 2 or higher assessed 12 weeks apart. Grade 2 AEs are determined as " moderate". Grading was performed following CTCAE v 4.03 guidance.
- Number of Adverse Events of Special Interest (AESI) Throughout the Study [ Time Frame: Weeks 12, 24, 36 and 48 ]
AESI are pre-defined adverse events as indicated in the protocol. They include: infections, stomach perforations, malignancy, herpes zoster and lab abnormalities.
Note that the planned statistical analysis (calculation of rate ratio and 90% CI) could not be performed at Weeks 12 and 24 because there were no events in placebo group (denominator).
- Change in Modified Rodnan Skin Score (mRSS) [ Time Frame: Change from Baseline at weeks: 12, 24, 36, and 48 ]The Modified Rodnan Skin Score (mRSS) is a measure of skin thickness. Skin thickness in 17 anatomic areas was rated on a 0-3 scale and scores are summed to obtain the mRSS (range from 0 - 51), with higher mRSS scores indicating worse disease activity
- Provisional American College of Rheumatology Combined Response Index (CRISS) Systemic Sclerosis [ Time Frame: Week:12, 24, and 48 ]CRISS components included the following domains: modified Rodnan skin score, forced vital capacity percent predicted, Physician Global Assessment, Patient Global Assessment, and Health Assessment Questionnaire Disability-Index. An algorithm determines the predicted probability of improvement from baseline by incorporating change in the mRSS, FVC percent predicted, Physician and Patient Global Assessments, and HAQ-DI. The outcome is a continuous variable between 0.0 and 1.0 (0 - 100%). A cut-off at 0.6 in the predicted probability of being improved has yielded the smallest misclassification error. Subjects are not considered improved if, between Visit 1 and 6, they develop new: 1) renal crisis; 2) decline in FVC% predicted by 15% (relative) from baseline and confirmed after 1 month; or 3) left ventricular failure (systolic ejection fraction < 45%) or pulmonary artery hypertension. Higher CRISS scores indicates improvement.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03274076
|United States, Michigan|
|University of Michigan|
|Ann Arbor, Michigan, United States, 48104|
|United States, Pennsylvania|
|University of Pittsburgh|
|Pittsburgh, Pennsylvania, United States, 15261|
|Principal Investigator:||Dinesh Khanna, MD||University of Michigan|