None listed
Conditions
Brief summary
This study will investigate cyclosporin in AA. This randomised, double-blind, parallel group, study will enrol a maximum of 38 subjects. The study will be conducted at Sinclair Dermatology. Subjects who have moderate to severe AA (at least 50% hair loss of the scalp without evidence of hair regrowth within the previous 6 months; current episode of fixed hair loss up to 7 years) present at the screening and baseline visits will be included in the study. Subjects will be randomised to cyclosporin or matching placebo in a 1:1 ratio. Investigators and subjects will be blinded as to treatment group. Subjects will be screened within the 35 days prior to the first dose of study drug to confirm that they meet the subject selection criteria for the study. The 12-week treatment period is followed by a 4-week follow up period after the last dose of investigational product. Non-responders will be eligible to participate in the extension phase of this clinical trial, investigating open-label tofacitinib.
Interventions
Intervention: Cyclosporin 2mg/kg twice daily orally for 12 weeks.
Cyclosporin is an immunosuppressant agent of the class of calcineurin inhibitors and inhibits T-cell activation. It has been used to alone or with low-dose corticosteroids in the prophylaxis of organ rejection following solid organ transplants. Beneficial effects of cyclosporin therapy have also been shown in some cases of nephrotic syndrome, rheumatoid arthritis, psoriasis and atopic dermatitis.
Cyclosporin is a treatment opti
Intervention: Cyclosporin 2mg/kg twice daily orally for 12 weeks. Cyclosporin is an immunosuppressant agent of the class of calcineurin inhibitors and inhibits T-cell activation. It has been used to alone or with low-dose corticosteroids in the prophylaxis of organ rejection following solid organ transplants. Beneficial effects of cyclosporin therapy have also been shown in some cases of nephrotic syndrome, rheumatoid arthritis, psoriasis and atopic dermatitis. Cyclosporin is a treatment option for patients with alopecia areata, however has only been studied in retrospective reviews, uncontrolled single-arm trials and case series. These studies show a promising effect of cyclosporin in alopecia areata. It is currently used for atopic dermatitis and psoriasis at doses up to 2.5mg/kg/day. Extension Phase Intervention: Tofacitinib 5mg twice daily orally for 12 weeks. Tofacitinib is a JAK inhibitor. It is currently a medication used for rheumatoid arthritis at the same dose. Beneficial effects of tofacitinib on alopecia areata have been demonstrated in case series. These studies show a promising effect on hair regrowth. This medication will be investigated in the extension phase of this clinical trial in all non-responders. The extension phase is an open-label, uncontrolled, single-arm pilot study. All participants of the extension phase receive tofacitinib; there is no placebo. Only non-responders (defined as less than 50% improvement in hair loss) at the end of the parent study will be eligible for the extension phase. Adherence will be monitored by counting drug tablet return.
Sponsors
Sinclair Dermatology
Study design
Allocation
Randomised controlled trial
Primary purpose
Treatment
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Subjects must meet all of the following inclusion criteria to be eligible for enrolment into the study: 1. Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study. 2. Willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures. 3. Male or female subjects between 18 to 65 years of age, inclusive, at time of informed consent. 4. Female subjects (except those at least 2 years post-menopausal or surgically sterile) with a negative serum pregnancy test during screening and a negative urine pregnancy test at baseline. 5. Male subjects able to father children and female subjects of childbearing potential must agree to the use of highly effective contraception (methods which result in low failure rate, i.e. less than 1% per year, when used consistently and correctly) throughout the study and until 30 days after the last dose of assigned treatment. 6. Must meet the following alopecia areata criteria: a. Have a clinical diagnosis of moderate to severe alopecia areata (at least 50% hair loss of the scalp without evidence of hair regrowth within 6 months) at the screening and baseline visits; b. Current episode of hair loss at most 7 years.
Exclusion criteria
Subjects with any of the following characteristics/conditions will not be included in the study: 1. Other acute or chronic medical or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study. 2. Subjects have other types of alopecia (including but not limited to traction, scarring, androgenetic alopecia). 3. Currently have active forms of other inflammatory skin diseases or evidence of skin conditions (e.g. psoriasis, seborrheic dermatitis, lupus) at the time of Screening or Day 1 that in the opinion of the investigator would interfere with evaluation of AA or response to treatment. 4. Have received any of the following treatment regimens specified in the timeframes outlined below: a. Within 6 months of first dose of study drug: i. Any cell-depleting agents including but not limited to rituximab: within 6 months of first dose of study drug, or 5 half-lives (if known), or until lymphocyte count returns to normal, whichever is longer. b. Within 12 weeks of first dose of study drug: i. Cyclosporin ii. Biologics: within 8 weeks of first dose of study drug or within 5 half-lives (if known), whichever is longer. c. Within 8 weeks of first dose of study drug: i. Systemic treatments that could affect AA within 8 weeks of first dose of study drug or within 5 half-lives (if known), whichever is longer. ii. Use of oral immune suppressants (e.g. azathioprine, methotrexate, systemic corticosteroids, mycophenolate-mofetil) within 8 weeks of first dose of study drug or within 5 half-lives (if known), whichever is longer. iii. Intralesional steroid injection within 8 weeks of first dose of study drug or within 5 half-lives (if known), whichever is longer. iv. Participation in other studies involving investigational drug(s) within 8 weeks of first dose of study drug or within 5 half-lives (if known), whichever is longer. d. Within 6 weeks of first dose of study drug: i. Have been vaccinated with live or attenuated live vaccine. e. Within 4 weeks of first dose of study drug: i. Ultra-Violet B (UVB) phototherapy and/or Psoralen Ultra-Violet A therapy. f. Within 2 weeks of first dose of study drug: i. Topical treatments that could affect AA (e.g. steroid cream, medicated shampoo, herbal hair care that could affect AA). 5. Female subjects of childbearing potential and fertile male subjects who are unwilling or unable to use highly effective contraception as outlined in this protocol for the duration of the study and for at least 30 days after the last dose of investigational product. 6. Pregnant or breastfeeding female subjects 7. Have current or recent history of clinically significant severe, progressive, or uncontrolled renal, hepatic, haematological, gastrointestinal, metabolic, endocrine, pulmonary, cardiovascular, psychiatric, immunologic/rheumatologic or neurologic disease; or have any other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration, or interfere with the interpretation of study results; or in the opinion of the investigator, the subject is inappropriate for entry into this study, or unwilling/unable to comply with study procedures. 8. Have a history of any lymphoproliferative disorder such as Epstein Barr Virus (EBV) related lymphoproliferative disorder, history of lymphoma, leukemia, or signs and symptoms suggestive of current lymphatic or lymphoid disease. 9. Have current active herpes simplex infection 10. Have a history of systemic infection requiring hospitalization, parenteral antimicrobial therapy, or as otherwise judged clinically significant by the investigator within 6 months prior to Day 1. 11. A Screening 12-lead electrocardiogram (ECG) that demonstrates clinically significant abnormalities requiring treatment (e.g. acute myocardial infarction, serious tachy- or brady-arrhythmias) or that are indicative of serious underlying heart disease (e.g. cardiomyopathy, major congenital heart disease, low voltage in all leads, Wolff-Parkinson–White syndrome). 12. Have a known immunodeficiency disorder or a first-degree relative with a hereditary immunodeficiency. 13. Have any malignancies or have a history of malignancies with the exception of adequately treated or excised non-metastatic basal cell or squamous cell cancer of the skin or cervical carcinoma in situ. 14. Require treatment with prohibited concomitant medication(s) (Appendix 8: Prohibited Concomitant Medications) or have received a prohibited concomitant medication within 7 days or 5 half-lives (whichever is longer) prior to Day 1. 15. History of human immunodeficiency virus (HIV) or positive HIV serology at screening. 16. Infected with hepatitis B or hepatitis C viruses. 17. Subjects with a history of hypersensitivity or allergies to any ingredient of the study medication. 18. ANY of the following abnormalities in clinical laboratory tests at screening, as assessed by the study-specific laboratory and confirmed by a single repeat, if deemed necessary: a. Absolute neutrophil count of <2.5 x 109/L (<2500/mm3); b. Haemoglobin <10.0 g/dL or haematocrit <30%; c. Platelet count below the lower limit of normal (LLN) at Screening; d. Absolute lymphocyte count of <0.5 x 109 /L (<500/mm3); e. Serum creatinine > upper limit of normal (ULN) or eGFR <90 ml/min/1.73m2 based on the age appropriate calculation; f. Enzymes aspartate transaminase (AST) or alanine transaminase (ALT) values >2 times the ULN; g. Total bilirubin 1.5 times or more the ULN; subjects with a history of Gilbert's syndrome may have a direct bilirubin measured and would be eligible for this study provided the direct bilirubin is not more than the ULN; h. In the opinion of the investigator, have any uncontrolled clinically significant laboratory abnormality that would affect interpretation of study data or the subject’s participation in the study.
Outcome results
None listed