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Janus Kinase Inhibition in Granuloma Annulare

Primary Purpose

Granuloma Annulare

Status
Not yet recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Abrocitinib 200 mg
Sponsored by
William Damsky
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Granuloma Annulare focused on measuring Granuloma Annulare, Inhibition

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Written informed consent Male and female patients 18 years old or older Diagnosis of GA with supportive skin biopsy BSA involvement of at least 5% If patients are on systemic therapies or phototherapy for their GA, they must discontinue these therapies with a washout period of 4 weeks and must remain off them during the study If patients are on topical therapies for their GA, they must discontinue these therapies with a washout period of 2 weeks and must remain off them during the study Females of childbearing potential must agree to use birth control during the study and there must be a negative pregnancy test documented prior to starting the medication. Patients must be willing to have skin biopsies, blood collection, and total body photography and to comply with clinic visits Exclusion Criteria: Age <18 years old Patients with a history of malignancy (except history of successfully treated basal cell or squamous cell carcinoma of the skin) Patients known to be HIV or hepatitis B or C positive, or have an active, serious infection herpes simplex, herpes zoster, and pneumonia. This would also include localized infections. Patients with positive tuberculin skin test or positive QuantiFERON® Tuberculosis test Patients with significant hepatic impairment Patients with moderate renal impairment Patients with uncontrolled peptic ulcer disease Patients with a history of deep vein thrombosis and/or pulmonary embolism and/or clotting disorder Patients with any history of myocardial infarction or stroke. Patients taking concomitant immunosuppressive medications, with the exception of methotrexate and/or low-dose prednisone, including but not limited to mycophenolate mofetil, azathioprine, tacrolimus, cyclosporine, or TNF-α inhibitors Women of childbearing potential who are unable or unwilling to use birth control while taking the medication Women who are pregnant or nursing Current smoker or history of any tobacco use Screening labs outside the normal range for parameters associated with potential risk for treatment under investigation. Including but not limited to: i. Platelets <150,000/mm3 ii. Absolute neutrophil count <1,000/mm3 iii. Hemoglobin levels <8 g/dL iv. Absolute lymphocyte count <500/mm3 Patients who are taking moderate to strong inhibitors of both CYP2C19 and CYP2C9, or strong CYP2C19 or CYP2C9 inducers, as well as P-gp substrate where small concentration changes may lead to serious or life-threatening toxicities. Patients who have received a live vaccine. Patients should wait a minimum of 2 weeks, if recently vaccinated, prior to initiating treatment and should not receive a live vaccine during treatment or 2 weeks post-treatment. Patients with any medical, psychiatric, or social condition that is likely to unfavorably affect the risk-benefit of continued study participation, interfere with study compliance or confound safety or efficacy assessments

Sites / Locations

  • Yale University

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Abrocitinib 200 mg daily

Arm Description

6 months of treatment with abrocitinib 200 mg daily

Outcomes

Primary Outcome Measures

Percentage Change in BSA involvement by active GA
The percentage change in the body surface area (BSA) involvement by GA after 6 months of treatment with abrocitinib 200 mg daily in 10 patients with moderate to severe GA affecting at least 5% body surface area (BSA).

Secondary Outcome Measures

Changes in Granuloma Annulare Severity and Morphology Instrument (GASMI) score
Changes in GASMI score baseline vs. after 6 months of treatment. The Granuloma Annulare Severity and Morphology Instrument is a clinical severity scoring tool for GA. The score is determined by the study team who will examine the participants skin to determine the severity of the GA in different anatomic areas. Scores range from 0-165 with higher score indicating a worse outcome.
Changes in Skindex-16 (Skin related quality of life index)
Changes in Skindex-16 (Skin related quality of life index) baseline vs. after 6 months of treatment. This is a 16 item validated skin related Quality of Life questionnaire which will be administered by the study team to assess how GA affects the participants quality of life. Scores range from 0-96, higher scores indicating more significant impact on quality of life.
Changes in molecular signatures in skin and blood before and after treatment
Changes in molecular signatures in skin and blood at baseline vs. after 6 months of treatment. Molecular signatures will be assessed in the skin and in the blood. RNA-sequencing will be used to examine transcriptional profiles in this skin. A high throughput proteomic assay will be used to examine molecular profiles in the blood.

Full Information

First Posted
December 6, 2022
Last Updated
July 11, 2023
Sponsor
William Damsky
Collaborators
Yale University, Pfizer
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1. Study Identification

Unique Protocol Identification Number
NCT05650736
Brief Title
Janus Kinase Inhibition in Granuloma Annulare
Official Title
JAK1 Inhibition in Granuloma Annulare: an Opportunity for Pathogenesis Directed Therapy
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
August 1, 2023 (Anticipated)
Primary Completion Date
February 1, 2024 (Anticipated)
Study Completion Date
February 1, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
William Damsky
Collaborators
Yale University, Pfizer

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The primary objective is to determine if JAK1 specific inhibition is effective in treating granuloma annulare (GA), a problematic inflammatory skin disease without an FDA approved treatment. The primary outcome will be the percentage change in the body surface area (BSA) involvement by GA after 6 months of treatment with abrocitinib 200 mg daily in 10 patients with moderate to severe GA affecting at least 5% body surface area (BSA).
Detailed Description
There are no effective treatments for GA. Systemic corticosteroids can be effective in temporarily controlling GA; however, GA patients are almost never treated with systemic steroids due to the myriad potential adverse effects of this drug class and its transient effect on disease control. Intralesional (intradermal) steroid injections can be effective in patients with localized GA but are not really an option for patients with BSA > 1-2%, require frequent clinic visits for injection, are painful, and also only transiently control disease. A variety of other treatment approaches have been described and include: antibiotics (minocycline, doxycycline, others), hydroxychloroquine, phototherapy, tumor necrosis factor inhibitors, among others. However, these therapies are rarely effective. GA is notoriously recalcitrant to treatment. With no FDA approved therapies for GA and current approaches being broadly ineffective; there is a large unmet need for an effective treatment. Likely in part because of under recognition, GA is designated as a rare disease by the National Organization for Rare Disorders. Progress in the treatment of GA has been impaired by a poor understanding of disease pathogenesis. Not only will this study allow for greater clarity regarding the pathogenesis of GA, but an oral treatment option for patients that is easier to administer compared to other therapies (such as injections) and with less potential systemic side effects.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Granuloma Annulare
Keywords
Granuloma Annulare, Inhibition

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
moderate to severe GA affecting at least 5% body surface area
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Abrocitinib 200 mg daily
Arm Type
Experimental
Arm Description
6 months of treatment with abrocitinib 200 mg daily
Intervention Type
Drug
Intervention Name(s)
Abrocitinib 200 mg
Intervention Description
Abrocitinib (Cibinqo) is FDA approved at 200 mg dose once daily for the treatment of atopic dermatitis. It is not currently FDA approved for the treatment of GA.
Primary Outcome Measure Information:
Title
Percentage Change in BSA involvement by active GA
Description
The percentage change in the body surface area (BSA) involvement by GA after 6 months of treatment with abrocitinib 200 mg daily in 10 patients with moderate to severe GA affecting at least 5% body surface area (BSA).
Time Frame
Baseline and 6 months
Secondary Outcome Measure Information:
Title
Changes in Granuloma Annulare Severity and Morphology Instrument (GASMI) score
Description
Changes in GASMI score baseline vs. after 6 months of treatment. The Granuloma Annulare Severity and Morphology Instrument is a clinical severity scoring tool for GA. The score is determined by the study team who will examine the participants skin to determine the severity of the GA in different anatomic areas. Scores range from 0-165 with higher score indicating a worse outcome.
Time Frame
Baseline and 6 months
Title
Changes in Skindex-16 (Skin related quality of life index)
Description
Changes in Skindex-16 (Skin related quality of life index) baseline vs. after 6 months of treatment. This is a 16 item validated skin related Quality of Life questionnaire which will be administered by the study team to assess how GA affects the participants quality of life. Scores range from 0-96, higher scores indicating more significant impact on quality of life.
Time Frame
Baseline and 6 months
Title
Changes in molecular signatures in skin and blood before and after treatment
Description
Changes in molecular signatures in skin and blood at baseline vs. after 6 months of treatment. Molecular signatures will be assessed in the skin and in the blood. RNA-sequencing will be used to examine transcriptional profiles in this skin. A high throughput proteomic assay will be used to examine molecular profiles in the blood.
Time Frame
Baseline and 6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Written informed consent Male and female patients 18 years old or older Diagnosis of GA with supportive skin biopsy BSA involvement of at least 5% If patients are on systemic therapies or phototherapy for their GA, they must discontinue these therapies with a washout period of 4 weeks and must remain off them during the study If patients are on topical therapies for their GA, they must discontinue these therapies with a washout period of 2 weeks and must remain off them during the study Females of childbearing potential must agree to use birth control during the study and there must be a negative pregnancy test documented prior to starting the medication. Patients must be willing to have skin biopsies, blood collection, and total body photography and to comply with clinic visits Exclusion Criteria: Age <18 years old Patients with a history of malignancy (except history of successfully treated basal cell or squamous cell carcinoma of the skin) Patients known to be HIV or hepatitis B or C positive, or have an active, serious infection herpes simplex, herpes zoster, and pneumonia. This would also include localized infections. Patients with positive tuberculin skin test or positive QuantiFERON® Tuberculosis test Patients with significant hepatic impairment Patients with moderate renal impairment Patients with uncontrolled peptic ulcer disease Patients with a history of deep vein thrombosis and/or pulmonary embolism and/or clotting disorder Patients with any history of myocardial infarction or stroke. Patients taking concomitant immunosuppressive medications, with the exception of methotrexate and/or low-dose prednisone, including but not limited to mycophenolate mofetil, azathioprine, tacrolimus, cyclosporine, or TNF-α inhibitors Women of childbearing potential who are unable or unwilling to use birth control while taking the medication Women who are pregnant or nursing Current smoker or history of any tobacco use Screening labs outside the normal range for parameters associated with potential risk for treatment under investigation. Including but not limited to: i. Platelets <150,000/mm3 ii. Absolute neutrophil count <1,000/mm3 iii. Hemoglobin levels <8 g/dL iv. Absolute lymphocyte count <500/mm3 Patients who are taking moderate to strong inhibitors of both CYP2C19 and CYP2C9, or strong CYP2C19 or CYP2C9 inducers, as well as P-gp substrate where small concentration changes may lead to serious or life-threatening toxicities. Patients who have received a live vaccine. Patients should wait a minimum of 2 weeks, if recently vaccinated, prior to initiating treatment and should not receive a live vaccine during treatment or 2 weeks post-treatment. Patients with any medical, psychiatric, or social condition that is likely to unfavorably affect the risk-benefit of continued study participation, interfere with study compliance or confound safety or efficacy assessments
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
William Damsky, M.D.
Phone
203-785-4092
Email
william.damsky@yale.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
William Damsky, M.D.
Organizational Affiliation
Yale University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Yale University
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06510
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
William Damsky, M.D.
Phone
203-785-4092
Email
william.damsky@yale.edu
First Name & Middle Initial & Last Name & Degree
Yvette Strong
Phone
203-737-2506
Email
yvette.strong@yale.edu

12. IPD Sharing Statement

Plan to Share IPD
No

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Janus Kinase Inhibition in Granuloma Annulare

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