An Open-Label Single-Arm Clinical Trial to Evaluate The Efficacy of Abatacept in Moderate to Severe Patch Type Alopecia Areata
Alopecia areata (AA) is a common disease of the immune system, known as an "autoimmune" disease. In this 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 Alopecia Areata has lagged far behind other similar diseases of the immune system. Currently, there are no Federal Drug Administration approved drugs for Alopecia Areata.
Abatacept (made by Bristol-Myers Squibb) is a safe intervention known to effectively treat rheumatoid arthritis, another "autoimmune" disease, by fighting inflammation. There are some genetic and chemical similarities between those with active rheumatoid arthritis and Alopecia Areata, suggesting that treatment with the same drug is likely to be effective. In mice specially designed for testing drugs for the treatment of human alopecia, this medication worked to prevent the disease Alopecia Areata from starting.
To test Abatacept, we are going to treat 15 patients with moderate to severe Alopecia Areata for 6 months. Each person enrolling into this study will receive the active study drug. 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 6 months off of the drug to see if the effects of treatment last and if there is delayed response. We have recently changed the study to allow testing of abatacept in a few patients with alopecia totalis and universalis.
Small scalp biopsies and peripheral blood will be taken at the beginning of the study before treatment and then after 4,12 and 24 weeks. The chemical analysis of these skin samples and blood will help us to understand how the disease happens, how the treatment works, and perhaps even guide us to better treatments in the future.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||An Open-Label Single-Arm Clinical Trial to Evaluate The Efficacy of Abatacept in Moderate to Severe Patch Type Alopecia Areata|
- SALT Score (Severity of Alopecia Tool) [ Time Frame: 24 Weeks ] [ Designated as safety issue: No ]The study's primary efficacy endpoint will be the proportion of responders after 6 months of treatment, with response defined as 50% or greater hair re-growth from baseline as assessed by SALT score (Olsen et al, 1999) at week 24. This is a relatively strict definition for defining responders and non-responders and was chosen to minimize the potential for spontaneous remission, in which fewer than 10% are expected to achieve this magnitude of hair regrowth spontaneously. To assess the durability of responses, patients who achieve 50% regrowth from baseline during the first 6 months, will continue to be followed for an additional 6 months off treatment or until it is determined that relapse has occurred.
- Efficacy [ Time Frame: 24 Weeks of Treatment and an additional 6 months off treatment or until determined that relapse has ocurred ] [ Designated as safety issue: Yes ]Efficacy will be measured by changes in hair re-growth as a continuous variable as determined by physical exam and Canfield photography, as well as patient and physician global evaluation scores. To assess the durability of responses, patients will continue to be followed for an additional 6 months off treatment. The occurrence of adverse events will also be captured as a secondary endpoint.
- Safety [ Time Frame: 24 Weeks of Treatment and an additional 6 months off treatment or until determined that the relapse ocurred ] [ Designated as safety issue: Yes ]
Patient reported outcomes, safety measures, incidence and timing of relapse will be important secondary outcomes.
To assess safety, frequent and close monitoring of clinical and laboratory findings have been implemented. Adverse events will be captured and analyzed as a secondary endpoint.
Safety will be evaluated as a secondary endpoint using descriptive statistics to summarize the cumulative incidence and types of Adverse Events.
|Study Start Date:||September 2013|
|Estimated Study Completion Date:||July 2016|
|Estimated Primary Completion Date:||July 2016 (Final data collection date for primary outcome measure)|
Patients will be treated with abatacept 125mg subcutaneous (SC) self-administered each week. Treatment will be continued for 6 months to provide adequate time to assess the short-term efficacy and safety of abatacept in patients with alopecia areata. Patients will then be followed for an additional 6 months to assess the timing and incidence of relapse.
After the screening period, subjects will begin weekly self-administered subcutaneous abatacept and will continue treatment for 6 months. Patients will be instructed in self-administration of study medication at baseline (week zero) and will be observed self-administering medication at each visit. Instructions regarding study drug administration will be reinforced as needed.
The 6-month treatment period is expected to provide adequate time to assess the short-term efficacy and safety of abatacept in patients with moderate to severe AAP. Responders will then be followed for 6 months off drug.
Other Name: Orencia
Among patients with alopecia areata, patients with higher disease burdens are unlikely to have satisfactory outcomes with current therapies. Our hypothesis is that CTLA4-Ig will be effective therapy in moderate-severe alopecia areata by blocking re-activation of CD8+ memory T cells, thereby aborting the cytotoxic T cell inflammatory response underlying alopecia areata.
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 Alopecia Areata has lagged far behind other autoimmune diseases. Currently, there are no FDA approved drugs for Alopecia Areata. Abatacept is a safe intervention known to block costimulation and inflammatory responses in rheumatoid arthritis, which shares several susceptibility genes in common with Alopecia Areata. Both diseases share the involvement of CTLA4, which is the rationale for selecting Abatacept for evaluation in this clinical trial. CTLA4-Ig has been shown to prevent the onset of Alopecia Areata in the C3H-HeJ animal model of Alopecia Areata, demonstrating preclinical proof of concept data in Alopecia Areata.
We will conduct an open label pilot study of 15 patients with moderate to severe Alopecia Areata treated with SC abatacept 125mg once per week for 6 months. A few subjects with alopecia totalis or universalis will also be included. Subjects will be followed for another 6 months to evaluate durability of response following the treatment phase. The primary efficacy outcome will be the proportion of responders after 6 months of treatment compared to the historically known rate of response in untreated/placebo-treated subjects of 8 to 10%. Punch biopsies and peripheral blood will be obtained at baseline prior to treatment and then after 4, 12 and 24 weeks for immunomonitoring and molecular studies.
The safety of and incidence of adverse events related to abatacept in this population of patients will also be analyzed as a secondary endpoint.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02018042
|United States, New York|
|Columbia University Medical Center - Department of Dermatology|
|New York, New York, United States, 10032|
|Principal Investigator:||Julian Mackay-Wiggan, MD, MS||Columbia University|