Tofacitinib for Inflammatory Eye Disease

• Sponsor: Washington University School of Medicine (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT03580343
• Collaborator: (none)
• Enrollment: 5
• Location: 1
• Arm: 1
• Anticipated Duration (Months): 24
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

Non-infectious inflammatory eye disease, such as uveitis and scleritis, is a chronic, auto-immune process that leads to vision loss. While steroids are effective in the short term, the side-effect profile of chronic steroid use necessitates the identification of effective steroid-sparing therapies. Tofacitinib is a small molecule that inhibits the signaling pathways of multiple inflammatory cytokines. The investigators plan to evaluate whether tofacitinib may have efficacy for patients with uveitis and / or scleritis.

Condition or Disease	Intervention/Treatment	Phase
Uveitis; Scleritis	Drug: tofacitinib	Phase 2

Detailed Description

This study is a prospective, single-site, open-label investigation of tofacitinib for refractory uveitis. The study will be for 24 weeks, with potential 1-year extension for treatment responders. The patients will self-administer the medication.

Eligible patients would be those patients with a diagnosis of uveitis who meet the following criteria:

1. Disease sufficiently severe to require treatment with systemic corticosteroids, and

2. Referred from Ophthalmology to Rheumatology or Uveitis specialist for a steroid-sparing agent

For patients naive to oral steroid-sparing therapy (e.g., methotrexate, azathioprine, or mycophenolate), tofacitinib will be initiated as monotherapy. For patients who have failed or had only a partial response to oral steroid-sparing therapy, tofacitinib will be initiated as an add-on therapy. For patients intolerant to a conventional agent, tofacitinib will be initiated as replacement monotherapy. For patients who have failed biologic therapy (e.g. adalimumab), biologic therapy will be discontinued and tofacitinib will be initiated as replacement therapy without change to concurrent conventional steroid-sparing agents. Study visits will occur at baseline/enrollment, and weeks 4, 8, 12, 16, & 24 (+/- 2 weeks). Clinic visits may occur more frequently as determined by the treating physician. Laboratory monitoring (Table 1) will be obtained according to standard of care for drug toxicity monitoring. Clinical responses will be evaluated at 24 weeks, with the primary outcome defined as treatment failure.

All patients will undergo a predetermined oral steroid taper starting at 60mg of prednisone (or equivalent) and tapering over 14 weeks (Table 2). All patients will undergo a predetermined topical steroid drop taper starting at their current dose (Table 3).

Patients will have an ophthalmological evaluation by their treating ophthalmologist at Washington University. Steroid sparing therapy will be managed by rheumatologists or uveitis specialists at Washington University. All patients will be evaluated for an associated systemic rheumatologic condition.

Study Design

• Study Type: Interventional
• Actual Enrollment: 5 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Tofacitinib for the Treatment of Inflammatory Eye Disease
• Actual Study Start Date: Apr 4, 2019
• Actual Primary Completion Date: Dec 1, 2019
• Anticipated Study Completion Date: Apr 4, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Tofacitinib Treatment 11mg extended-release tofacitinib, once daily, oral	Drug: tofacitinib; tofacitinib extended release, 11mg, daily, oral; Other Names: TOFA

Outcome Measures

Primary Outcome Measures

1. Treatment Failure (Composite Outcome) [180 days]

   new inflammatory lesions relative to baseline OR 2-step increase in anterior chamber cell or vitreous haze OR worsening of visual acuity by two or more rows on ETDRS chart

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• diagnosis of uveitis

• a clinical response to steroids

• active disease requiring at least 10mg of prednisone daily (or steroid equivalent)

Exclusion Criteria:

• suspected or confirmed ocular infection

• chronic or recurring infections, such as HIV

• renal insufficiency that would preclude safe administration of tofacitinib

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Washington University in Saint Louis	Saint Louis	Missouri	United States	63110

Sponsors and Collaborators

• Washington University School of Medicine

Investigators

• Principal Investigator: Lynn M Hassman, MD PhD, Washington University School of Medicine

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Dec 1, 2020

More Information

Publications

None provided.

• Responsible Party: Washington University School of Medicine
• ClinicalTrials.gov Identifier: NCT03580343
• Other Study ID Numbers: tofacitinib_eye_disease
• First Posted: Jul 9, 2018
• Last Update Posted: Feb 1, 2021
• Last Verified: Jan 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Eye Diseases; Uveitis; Scleritis; Tofacitinib

Study Results

Participant Flow

Pre-assignment Detail	Active uveitis despite at least 10mg prednisone for 2 weeks.

Arm/Group Title	Tofacitinib Treatment
Arm/Group Description	tofacitinib: tofacitinib extended release, 11mg, daily, oral
Period Title: Overall Study
STARTED	5
COMPLETED	4
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Tofacitinib
Arm/Group Description	single arm- tofacitinib 11mg daily
Overall Participants	5
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	4 80%
>=65 years	1 20%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	58.8
Sex: Female, Male (Count of Participants)
Female	3 60%
Male	2 40%
Race and Ethnicity Not Collected (Count of Participants)
Region of Enrollment (participants) [Number]
United States	5 100%

Outcome Measures

1. Primary Outcome

Title	Treatment Failure (Composite Outcome)
Description	new inflammatory lesions relative to baseline OR 2-step increase in anterior chamber cell or vitreous haze OR worsening of visual acuity by two or more rows on ETDRS chart
Time Frame	180 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tofacitinib Treatment
Arm/Group Description	tofacitinib: tofacitinib extended release, 11mg, daily, oral
Measure Participants	5
Count of Participants [Participants]	0 0%

Adverse Events

Time Frame	18 months
Arm/Group Title	Tofacitinib Treatment
Arm/Group Description	tofacitinib: tofacitinib extended release, 11mg, daily, oral
All Cause Mortality
	Tofacitinib Treatment
	Affected / at Risk (%)	# Events
Total	0/5 (0%)
Serious Adverse Events
	Tofacitinib Treatment
	Affected / at Risk (%)	# Events
Total	2/5 (40%)
Skin and subcutaneous tissue disorders
cutaneous melanoma	1/5 (20%)	1
squamous cell carcinoma	1/5 (20%)	1
Other (Not Including Serious) Adverse Events
	Tofacitinib Treatment
	Affected / at Risk (%)	# Events
Total	0/5 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.