An Open-Label Pilot Study to Evaluate the Efficacy of Ruxolitinib in Moderate to Severe Alopecia Areata

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Alopecia Areata Initiative
Information provided by (Responsible Party):
Julian M. Mackay-Wiggan, Columbia University
ClinicalTrials.gov Identifier:
NCT01950780
First received: September 23, 2013
Last updated: July 3, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Alopecia Areata
Drug: Ruxolitinib
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-Label Pilot Study to Evaluate the Efficacy of Ruxolitinib in Moderate to Severe Alopecia Areata

Resource links provided by NLM:


Further study details as provided by Columbia University:

Primary Outcome Measures:
  • Change in SALT Score [ Time Frame: Baseline to week 12. ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Change in Percentage of Hair Loss [ Time Frame: Baseline to week 12 or week 24 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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, 24 up to week 36 ] [ Designated as safety issue: No ]
    Change in PGA (Physician Global Assessment) based on live evaluations and evaluation of standardized photographs between baseline, weeks 4, 8, 12, 18, 24, up to week 36

  • Patient Quality of Life Assessment Score [ Time Frame: Every 4 weeks during treatment and every 6 weeks during follow-up off treatment ] [ Designated as safety issue: No ]
    Change in patient quality of life assessment every 4 weeks during treatment and every 6 weeks during follow-up off treatment.

  • Incidence of Adverse Effects [ Time Frame: Baseline through end of study (week 36) ] [ Designated as safety issue: Yes ]
    Safety will be assessed by summarizing the incidence and type of Adverse Events. The proportion of patients who discontinued treatment will be summarized


Estimated Enrollment: 12
Study Start Date: August 2013
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01950780

Locations
United States, New York
Columbia University Medical Center, Department of Dermatology
New York, New York, United States, 10032
Sponsors and Collaborators
Columbia University
Alopecia Areata Initiative
Investigators
Principal Investigator: Julian Mackay-Wiggan, MD, MS Columbia University
  More Information

No publications provided

Responsible Party: Julian M. Mackay-Wiggan, Principal Investigator, Columbia University
ClinicalTrials.gov Identifier: NCT01950780     History of Changes
Other Study ID Numbers: AAAL7102
Study First Received: September 23, 2013
Last Updated: July 3, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Columbia University:
Alopecia Areata

Additional relevant MeSH terms:
Alopecia
Alopecia Areata
Hypotrichosis
Hair Diseases
Skin Diseases
Pathological Conditions, Anatomical

ClinicalTrials.gov processed this record on September 18, 2014