Baricitinib for the Treatment of Ocular Mucous Membrane Pemphigoid

NCT05263505 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: 202107009
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

Ocular mucous membrane pemphigoid (MMP) is an autoimmune, scarring conjunctivitis that can lead to vision loss and permanent disability. It is a rare disorder with an estimated incidence of 1 in 60,000. There are currently no FDA-approved medications for the treatment of mucous membrane pemphigoid, highlighting a clear unmet need. At present, moderate to severe disease requires off-label use of potent immunosuppressive agents, such as oral anti-proliferatives (methotrexate, azathioprine, and mycophenolate), rituximab (RTX) or cyclophosphamide (CyC). Recently, Janus kinase (JAK) inhibition with baricitinib or tofacitinib been reported to be successful in one case of ocular MMP. This is a randomized, single-masked, two-arm study of baricitinib vs anti-proliferatives for ocular MMP.

Conditions

Mucous Membrane Pemphigoid; Cicatrizing Conjunctivitis

Outcome Measures

Primary Outcomes (1)

• Treatment Response

  Treatment response of ocular inflammation based on conjunctival injection measured by ophthalmologic exam of the palpebral conjunctiva. Each eye is divided into quadrants and each quadrant is scored from 0 (white and quite) to 3 (severe). The score will be the sum of all 4 quadrants for a total score of 0-12 for each eye. A clinically meaningful response will be defined as a ≥30% reduction in the total score for both eyes.

  8 weeks

Study Arms (2)

Baricitinib

EXPERIMENTAL

4mg daily

Drug: Baricitinib 2 MG [Olumiant]

Antiproliferative

ACTIVE COMPARATOR

methotrexate, azathioprine, or mycophenolate

Drug: Methotrexate; Drug: Azathioprine; Drug: Mycophenolate

Interventions

Baricitinib 2 MG [Olumiant] DRUG

Two tabs daily

Baricitinib

Methotrexate DRUG

Target dose: 20mg weekly

Antiproliferative

Azathioprine DRUG

Target dose: 2mg/kg daily

Antiproliferative

Mycophenolate DRUG

Target Dose: 1g twice daily

Antiproliferative

Eligibility Criteria

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

You may qualify if:

• Patients are eligible to be included in the study only if they meet all the following criteria:
• Type of Patient and Disease Characteristics
• Are at least 18 years of age
• Have a clinical diagnosis of Ocular Mucous Membrane Pemphigoid
• a. The treating ophthalmologist will have excluded alternative etiologies that can cause cicatrizing conjunctivitis such as:
• Rosacea
• Atopic dermatitis
• Lichen Planus
• Iatrogenic interventions, e.g. glaucoma eye drops
• Stevens-Johnsons Syndrome
• Graft vs Host Disease
• Have active disease based on ophthalmologic exam
• Patient Characteristics
• Nonpregnant, nonbreastfeeding female or male patient
• Female patients of child-bearing potential who are abstinent (if this is complete abstinence, as their preferred and usual lifestyle) or in a same-sex relationship (as part of their preferred and usual lifestyle) must agree to either remain abstinent or stay in a same-sex relationship without sexual relationships with the opposite sex.

You may not qualify if:

• Patients will be excluded from study enrollment if they meet any of the following criteria:
• Disease Characteristics
• Have rapidly progressive disease, as determined by the treating ophthalmologist, that places the patient at an unacceptable risk for participating in the study
• Medical Conditions
• Have had any major surgery within 8 weeks prior to screening or will require major surgery during the study that, in the opinion of the investigator would pose an unacceptable risk to the patient.
• Have experienced any of the following within 12 weeks of screening: VTE (DVT/pulmonary embolism \[PE\]), myocardial infarction (MI), unstable ischemic heart disease, stroke, or New York Heart Association Stage III/IV heart failure.
• Have a history of recurrent (≥ 2) VTE (DVT/PE).
• Have a history or presence of cardiovascular, respiratory, hepatic, gastrointestinal, endocrine, hematological, neurological, or neuropsychiatric disorders or any other serious and/or unstable illness that in the opinion of the investigator, could constitute an unacceptable risk when taking investigational product or interfere with the interpretation of data.
• Have a history of lymphoproliferative disease; have signs or symptoms suggestive of possible lymphoproliferative disease, including lymphadenopathy or splenomegaly; have active primary or recurrent malignant disease; or have been in remission from clinically significant malignancy for \<5 years prior to randomization.
• The following may be exempted:
• Patients with cervical carcinoma in situ that has been resected with no evidence of recurrence or metastatic disease for at least 3 years may participate in the study.
• Patients with basal cell or squamous epithelial skin cancers that have been completely resected with no evidence of recurrence for at least 3 years may participate in the study.
• Have a current or recent (\<4 weeks prior to randomization) clinically serious viral, bacterial, fungal, or parasitic infection or any other active or recent infection that in the opinion of the investigator, would pose an unacceptable risk to the patient if participating in the study.
• Note: For example, a recent viral upper respiratory tract infection or uncomplicated urinary tract infection need not be considered clinically serious.
• Have symptomatic herpes simplex at the time of randomization

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Eli Lilly and Company: collaborator

Study Sites (1)

Barnes Jewish Hospital / Washington University in St. Louis

St Louis, Missouri, 63110, United States

Location

MeSH Terms

Conditions

Pemphigoid, Benign Mucous Membrane

Interventions

baricitinib; Methotrexate; Azathioprine; Mycophenolic Acid

Condition Hierarchy (Ancestors)

Conjunctival Diseases; Eye Diseases; Skin Diseases, Vesiculobullous; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Thionucleosides; Sulfur Compounds; Organic Chemicals; Mercaptopurine; Purines; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids

Results Point of Contact

• Title: Dr. Michael Paley, Director of the Ocular Rheumatology Clinic
• Organization: Washington University School of Medicine

paleym@wustl.edu

314-273-7556

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Instructor

Study Record Dates

• First Submitted: February 16, 2022
• First Posted: March 2, 2022
• Study Start: February 21, 2022
• Primary Completion: September 11, 2023
• Study Completion: September 11, 2023
• Last Updated: November 7, 2023
• Results First Posted: November 7, 2023

Record last verified: 2023-10

Locations

US (1)