Evaluation of Tofacitinib in Early Diffuse Cutaneous Systemic Sclerosis (dcSSc)

NCT03274076 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: HUM00131837
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 2

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.

Conditions

Systemic Sclerosis; Scleroderma

Keywords

diffuse; scleroderma; systemic sclerosis

Outcome Measures

Primary Outcomes (1)

• Number of Participants Who Experience Grade 3 or Higher Adverse Events That Occur at or Before Week 24

  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.

  24 weeks

Secondary Outcomes (5)

• Number of Grade 3 (Severe) or Higher Adverse Events That Occur Throughout the Study

  Week 12, 24, 36, and 48

• Number of Grade 2 (Moderate) or Higher Adverse Events That Occur Throughout the Study

  Week: 12, 24, 36, and 48

• Number of Adverse Events of Special Interest (AESI) Throughout the Study

  Weeks 12, 24, 36 and 48

• Change in Modified Rodnan Skin Score (mRSS)

  Change from Baseline at weeks: 12, 24, 36, and 48

• Provisional American College of Rheumatology Combined Response Index (CRISS) Systemic Sclerosis

  Week:12, 24, and 48

Study Arms (2)

Tofacitinib

ACTIVE COMPARATOR

5mg Tofacitinib twice a day

Drug: Tofacitinib

Placebo

PLACEBO COMPARATOR

5mg Placebo twice a day

Drug: Placebo Oral Tablet

Interventions

Tofacitinib DRUG

Oral medication tofacitinib 5 mg twice a day for 24 weeks.

Also known as: Xeljanz

Tofacitinib

Placebo Oral Tablet DRUG

Oral Placebo 5 mg twice a day for 24 weeks

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of systemic sclerosis (SSc), as classified using the 2013 American College of Rheumatology/ European Union League Against Rheumatism classification of SSc.
• Diffuse Cutaneous Systemic Sclerosis (dcSSc) as defined by 2001 LeRoy and Medsger
• Disease duration ≤ 60 months (defined as time from the first non-Raynaud phenomenon manifestation)
• Modified Rodnan Skin Score (mRSS) units ≥ 10 and ≤ 45 at screening.
• Agreement to receive varicella-zoster vaccination (Zostavax®) or have received vaccination prior to screening.
• 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.
• Ability to provide informed consent.

You may not qualify if:

• Rheumatic disease other than dcSSc; it is acceptable to include patients with fibromyalgia, Sjogren syndrome, and scleroderma-associated myopathy
• Limited cutaneous SSc or sine scleroderma
• Major surgery (including joint surgery) within 8 weeks prior to baseline.
• Any infected ulcer at screening
• 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)
• Oral corticosteroids \>10 mg/day of prednisone or equivalent.
• 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.
• 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
• 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.
• Intravenous corticosteroids within 2 weeks prior to baseline visit.
• Treatment with any investigational agent ≤ 4 weeks prior to baseline (or 5 half-lives of the investigational drug, whichever is longer)
• Other investigational or marketed biologics with immunomodulatory properties within 3 months prior to baseline.
• Treatment with anti-CD20 6 months prior to baseline and B cell counts \<LLN
• Any prior treatment with cell-depleting therapies other than anti-CD20 such as CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti-CD19
• Any prior treatment with chlorambucil, bone marrow transplantation, or total lymphoid irradiation

Sponsors & Collaborators

• University of Michigan: lead
• Pfizer: collaborator

Study Sites (2)

University of Michigan

Ann Arbor, Michigan, 48104, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15261, United States

Location

Related Publications (1)

• Khanna D, Padilla C, Tsoi LC, Nagaraja V, Khanna PP, Tabib T, Kahlenberg JM, Young A, Huang S, Gudjonsson JE, Fox DA, Lafyatis R. Tofacitinib blocks IFN-regulated biomarker genes in skin fibroblasts and keratinocytes in a systemic sclerosis trial. JCI Insight. 2022 Sep 8;7(17):e159566. doi: 10.1172/jci.insight.159566.

  PMID: 35943798 DERIVED

MeSH Terms

Conditions

Scleroderma, Systemic; Scleroderma, Diffuse

Interventions

tofacitinib

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases

Results Point of Contact

• Title: Dinesh Khanna
• Organization: University of Michigan

khannad@med.umich.edu

734-763-7182

Study Officials

• Dinesh Khanna, MD

  University of Michigan

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: The study staff (with the exception of the study pharmacist) and the patient are blinded to the treatment assignment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Frederick G L Huetwell Professor of Rheumatology and Professor of Internal Medicine, Medical School

Model Details: Eligible subjects will be randomized to tofacitinib or placebo in a 2:1 manner.

Study Record Dates

• First Submitted: August 28, 2017
• First Posted: September 6, 2017
• Study Start: September 25, 2017
• Primary Completion: April 8, 2019
• Study Completion: November 15, 2019
• Last Updated: May 8, 2020
• Results First Posted: May 8, 2020

Record last verified: 2020-04

Locations

US (2)