Pilot Study to Evaluate the Efficacy of Ruxolitinib in Alopecia Areata

• ClinicalTrials.gov Identifier: NCT01950780
• Recruitment Status: Completed
• First Posted: September 25, 2013
• Results First Posted: May 7, 2019
• Last Update Posted: May 7, 2019
• Sponsor: Columbia University
• Collaborators: Alopecia Areata Initiative - Gates Foundation; Locks of Love
• Information provided by (Responsible Party): Columbia University

Tracking Information

• First Submitted Date: September 23, 2013
• First Posted Date: September 25, 2013
• Results First Submitted Date: July 28, 2017
• Results First Posted Date: May 7, 2019
• Last Update Posted Date: May 7, 2019
• Study Start Date: August 2013
• Actual Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 15, 2019)

Change in SALT Score [ Time Frame: Baseline, 3 months and 6 months ]

Severity of Alopecia Tool Score (SALT) calculation is based on a scoring system. The scalp is divided into the following 4 areas: 1) Vertex: 40% (0.4) of scalp surface area, 2) Right profile of scalp: 18% (0.18) of scalp surface area, 3) Left profile of scalp: 18% (0.18) of scalp surface area, and 4) Posterior aspect of scalp: 24% (0.24) of scalp surface area. The percentage of hair loss in any of these areas is the percentage hair loss multiplied by percent surface area of the scalp in that area. The SALT score is the sum of percentage of hair loss in all the above-mentioned areas, so a lower number indicates a better outcome. The reported SALT score range is from a minimum of 0 (no hair loss) to a maximum of 100 (100% hair loss).

Original Primary Outcome Measures (submitted: September 23, 2013)

Change in SALT Score [ Time Frame: Baseline to week 12. ]

The study's primary efficacy endpoint will be the proportion of responders after 3 months of treatment, with response defined as 50% or greater hair re-growth from baseline as assessed by SALT score at week 12.

Current Secondary Outcome Measures (submitted: April 15, 2019)

Percentage of Regrowth [ Time Frame: Up to 6 months ]

Mean percentage of regrowth was calculated at the end of treatment for all subjects.

Original Secondary Outcome Measures (submitted: September 23, 2013)

• Change in Percentage of Hair Loss [ Time Frame: Baseline to week 12 or week 24 ]
  Efficacy will be measured by changes in hair re-growth as a continuous variable as determined by percentage change in total hair loss measured by physical exam and Canfield photography, at end of treatment week 12 and 3 months after end of treatment week 24 (end of study)
• Change in Patient Global Assessment [ Time Frame: Baseline, weeks 8, 12, 18 and 24 ]
  Change in patient global assessment between baseline, Weeks 8, 12, 18 and 24
• Change in Physician Global Assessment (PGA) Score [ Time Frame: Baseline, weeks 4, 8, 12, 18 and 24 ]
  Change in PGA (Physician Global Assessment) based on live evaluations and evaluation of standardized photographs between baseline, weeks 4, 8, 12, 18 and 24.
• Patient Quality of Life Assessment Score [ Time Frame: Baseline to weeks 8, 12, 18 and 24 ]
  Change in patient quality of life assessment from baseline to weeks 8, 12, 18 and 24.
• Incidence of Adverse Effects [ Time Frame: Baseline through end of study (week 24) ]
  Safety will be assessed by summarizing the incidence and type of Adverse Events. The proportion of patients who discontinued treatment will be summarized

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Pilot Study to Evaluate the Efficacy of Ruxolitinib in Alopecia Areata
• Official Title: An Open-Label Pilot Study to Evaluate the Efficacy of Ruxolitinib in Moderate to Severe Alopecia Areata

Brief Summary

Alopecia areata (AA) is a common disease of the immune system, known as an "autoimmune" disease. In the disease, the immune system mistakenly destroys the hair follicle, causing hair to fall out. Despite many people having this disease, research into its cause and into new, better ways to treat AA has lagged far behind other similar diseases of the immune system. Currently, there are no Federal Drug Administration approved drugs for AA.

Ruxolitinib (made by Incyte) is an intervention known to effectively treat a disease of the bone marrow, known as myelofibrosis. It is also being studied in the treatment of rheumatoid arthritis, another "autoimmune" disease, by fighting inflammation. There are some genetic and chemical similarities between those with myelofibrosis, active rheumatoid arthritis and AA, suggesting that treatment with ruxolitinib may be effective in AA. In mice specially designed for testing drugs for the treatment of human alopecia areata, this medication worked to prevent the disease AA from starting in mice that would have otherwise developed the disease. To test Ruxolitinib, we are going to treat 12 patients with moderate to severe AA for a minimum of 3 months up to 6 months. This is an "open-label" study, meaning that there will not be a placebo group; all patients enrolled in the study will receive the active medication. The effectiveness of the medication will be measured by changes in hair re-growth as determined by physical exam and photography, as well as by patient and physician scoring. Patients will be followed for another 3 months off of the drug to see if the effects of treatment last and if there is delayed response. The safety of the medication, ruxolitinib, in patients with alopecia areata will also be evaluated.

Blood work will be collected before medication is started, during the treatment period, and after ruxolitinib is stopped, in order to monitor for adverse effects of the medication. Small scalp biopsies and peripheral blood will be taken at the beginning of the study before treatment and also after 12 and possibly 24 weeks. Optional biopsies may also be taken at additional time points based on clinical considerations. The chemical analysis of these skin samples and blood will help us to understand how the disease happens, how the treatment works, and may even guide us to better treatments in the future.

• Detailed Description: Alopecia areata (AA) is a common autoimmune disease resulting from immune destruction of the hair follicle and subsequent hair loss. Despite its high prevalence, research into the pathogenesis and the development of innovative therapies in AA has lagged far behind other autoimmune diseases. Currently, there are no FDA approved drugs for AA. Ruxolitinib (Incyte) is an intervention known to effectively treat myelofibrosis and also rheumatoid arthritis by modulating the inflammatory response of the interferon response pathway by inhibition of Jak1/Jak2. Rheumatoid arthritis shares several susceptibility genes in common with AA. All three diseases share the central role of the interferon-gamma response pathway, which is the rationale for selecting Ruxolitinib for evaluation in this clinical trial. Both systemic and topical Ruxolitinib have been shown to prevent the onset of AA in the C3H-HeJ animal model of AA, demonstrating preclinical proof-of-concept data in AA. To test the safety and efficacy of Ruxolitinib in patients with moderate to severe AA, we propose this open-label, single arm pilot study with a total of 12 patients, treated for a minimum of 3 months up to 6 months. Efficacy will be measured by changes in hair re-growth as determined by physical exam and photography, as well as by patient and physician global evaluation scores. Patients will be followed for another 3 months to evaluate durability of response following the treatment phase. Punch biopsies and peripheral blood will be obtained at baseline prior to treatment and then after 12 and possibly 24 weeks for immune monitoring and for molecular studies.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Alopecia Areata

Intervention

Drug: Ruxolitinib

A fixed dose of ruxolitinib (20mg) will be self-administered orally twice daily for 12 to 24 weeks. Dosing may be decreased or held if needed due to adverse effects.

Other Name: Jakavi

Study Arms

Experimental: Ruxolitinib

A fixed dose of ruxolitinib (20mg) will be self-administered orally twice daily for 12 to 24 weeks. Dosing may be decreased or held if needed due to adverse effects.

Intervention: Drug: Ruxolitinib

• Publications *: Mackay-Wiggan J, Jabbari A, Nguyen N, Cerise JE, Clark C, Ulerio G, Furniss M, Vaughan R, Christiano AM, Clynes R. Oral ruxolitinib induces hair regrowth in patients with moderate-to-severe alopecia areata. JCI Insight. 2016 Sep 22;1(15):e89790. doi: 10.1172/jci.insight.89790.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 3, 2014): 12
• Original Estimated Enrollment (submitted: September 23, 2013): 10
• Actual Study Completion Date: April 2016
• Actual Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Patients between 18 to 75 years of age.
• Patients with a diagnosis of patch type alopecia areata.
• Patients will have >30% and <95% total scalp hair loss at baseline as measured using the SALT score. Two patients with current episodes of alopecia totalis/universalis may be included in this study.
• Duration of hair loss greater than 3 months.
• No evidence of regrowth present at baseline.
• Patients may be naïve to treatment or unresponsive to intralesional (IL) steroids or other treatments for alopecia areata.

Exclusion Criteria:

• Patients with a history of or active skin disease on the scalp such as psoriasis or seborrheic dermatitis.
• Patients in whom the diagnosis of alopecia areata is in question.
• Patients with active medical conditions or malignancies (except adequately treated basal or squamous cell carcinoma) that in the opinion of the investigator would increase the risks associated with study participation, including patients with a history of recurrent infections.
• Women of childbearing potential who are unable or unwilling to use two forms of birth control for the study duration.
• Women who are pregnant or nursing.
• Patients known to be HIV or hepatitis B or C positive.
• Patients with history or evidence of hematopoietic abnormality.
• Patients with <200K platelet count at baseline.
• Patients with history or evidence of renal or hepatic impairment.
• Patients with history of immunosuppression or history of recurrent serious infections.
• Patients unwilling or unable to discontinue treatments known to affect hair regrowth in AA.
• Patients taking any medication considered a strong CYP3A4 inhibitor who is unable or unwilling to stop this medication for the duration of the study.
• Patients receiving treatment deemed to affect alopecia areata within 2 weeks to one month of baseline visit depending on the specific treatment.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01950780
• Other Study ID Numbers: AAAL7102
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Columbia University
• Original Responsible Party: Julian M. Mackay-Wiggan, Columbia University, Principal Investigator
• Current Study Sponsor: Columbia University
• Original Study Sponsor: Same as current

Collaborators

• Alopecia Areata Initiative - Gates Foundation
• Locks of Love

Investigators

• Principal Investigator: Julian Mackay-Wiggan, MD, MS; Columbia University

• PRS Account: Columbia University
• Verification Date: April 2019