Open-label Study of Tofacitinib for Moderate to Severe Skin Involvement in Young Adults With Lupus

NCT03288324 | Completed Phase 1 Results FDA Drug

• 1 other identifier: WI211648
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 2

Brief Summary

This 76-week, 3-part Phase 1b/2 study is intended to evaluate the pharmacological properties (pharmacokinetics and pharmacodynamics), safety, tolerability and preliminary effectiveness of TOFA administrated to young adults (18-45 years) with moderately to severely active SLE-CL. Subjects will be studied at the Cincinnati Children's Hospital Medical Center (CCHMC) and in Cleveland at MetroHealth Medical Center.

Conditions

Cutaneous Lupus; Systemic Lupus Erythematosus

Outcome Measures

Primary Outcomes (1)

• Oral Clearance (CL/F) (Cohort 1 Only)

  Apparent total clearance of the drug from plasma after oral administration

  Day 5

Secondary Outcomes (7)

• Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) Activity Score

  weeks 4, 8 and 24 compared to baseline.

• AUCt (Cohort 1 Only)

  Day 5

• Cmax (Cohort 1 Only)

  Day 5

• Tmax (Cohort 1 Only)

  Day 5

• Vz/F (Cohort 1 Only)

  Day 5

Other Outcomes (4)

• Steroid Dose Comparison at 72 Weeks

  72 weeks

• Change in SLE Disease Activity Index (SLEDAI) Score

  72 weeks

• Change in SKINDEX Score

  Baseline, week 24 and week 72

Study Arms (1)

Tofacitinib Arm

EXPERIMENTAL

open-label study

Drug: Tofacitinib

Interventions

Tofacitinib DRUG

Tofacitinib 5 mg twice daily

Also known as: Xeljanz

Tofacitinib Arm

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Male or female \> 18 years of age and \< 45 years of age and \> 40 kg body weight.
• Fulfilled at least 4 out of the 11 Classification Criteria for SLE by the time of screening.
• Willing to give written informed consent, must fully understand the requirements of the trial, and must be willing to comply with all trial visits and assessments.
• CLASI activity score of 8 or higher at screening and baseline despite standard of care therapy.
• Stable dose of prednisone of ≤ 20 mg/day within 2 weeks of enrollment.
• Female subjects of childbearing potential must use a highly effective method of contraception to prevent pregnancy (abstinence is considered highly effective) and must agree to continue to practice adequate contraception for the duration of their participation in the trial and for 28 days after their last dose of TOFA.
• Female subjects of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test at Trial Day 1 before dosing.
• For subjects receiving leflunomide treatment, total daily dose does not exceed 20 mg.
• A negative QuantiFERON-TB Gold In-Tube test performed within the 3 months prior to screening, or within the screening period prior to baseline. A negative PPD test can be substituted for the QuantiFERON-TB.
• Subjects either have protective varicella titers or evidence of having been vaccinated against varicella.

You may not qualify if:

• Mild SLE-CL defined as a CLASI activity score of 7 or lower at screening and baseline.
• Increase in CS dosing within 2 weeks prior to Trial Day 1, or expected to require an increase in CS dosing during the first 4 weeks of the study.
• Use of i.v. corticosteroids within 4 weeks prior to Trial Day 1.
• Increase in dosing of methotrexate, leflunomide, within 4 weeks before Trial Day 1 or expected to require an increase during the first 8-weeks of the study.
• Increase in dosing of hydroxychloroquine, or chloroquine within 4 weeks before Trial Day 1 or expected to require an increase during the first 8-weeks of the study.
• Rituximab within 1 year of Trial Day 1.
• Increase in dosing of any medication or herbal treatment considered to have immunosuppressive properties with 4 weeks before Trial Day 1.
• Prior treatment with or known intolerability of TOFA.
• Use of cyclophosphamide (i.v. or oral), cyclosporine, or tacrolimus within 12 weeks prior to Trial Day 1.
• Treatment with other investigational agents within the last 6 months or 5 half-lives, or as per washout requirement from the previous protocol, whichever is longer.
• Estimated glomerular filtration rate less than or equal to 60 mL/min /1.73 m2.
• Known positive Human Immunodeficiency Virus (HIV), Hepatitis C Virus (HCV), or Hepatitis B surface antigen (HBsAg) serology.
• Any condition, including findings in the laboratory tests, medical history, or other screening assessments, that, in the opinion of the Investigator, constitutes an inappropriate risk or a contraindication for participation in the trial or that could interfere with the trial's objectives, conduct, or evaluation.
• Active central nervous system SLE deemed to be severe or progressive and/or associated with significant cognitive impairment leading to inability to provide informed consent and/or comply with the protocol.
• Significant renal disease due to a reason(s) other than Lupus Nephritis (e.g. diabetes mellitus, renovascular disease, or antiphospholipid syndrome).

Sponsors & Collaborators

• Children's Hospital Medical Center, Cincinnati: lead
• Pfizer: collaborator

Study Sites (2)

Cincinnati Childrens Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

MetroHealth Medical Center

Cleveland, Ohio, 44109, United States

Location

MeSH Terms

Conditions

Lupus Erythematosus, Systemic

Interventions

tofacitinib

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Hermine Brunner
• Organization: Cincinnati Childrens Hospital Medical Center

hermine.brunner@cchmc.org

(513) 636-6320

Study Officials

• Hermine Brunner, MD

  Cincinnati Childrens Hospital Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 29, 2017
• First Posted: September 20, 2017
• Study Start: August 23, 2017
• Primary Completion: November 1, 2022
• Study Completion: December 1, 2023
• Last Updated: March 3, 2026
• Results First Posted: July 30, 2024

Record last verified: 2026-02

Locations

US (2)