A Pilot Study of Tralokinumab in Subjects With Moderate to Severe Alopecia Areata
Condition: Alopecia Areata
MeSH terms: Alopecia; Alopecia Areata
Intervention: Tralokinumab; Placebo
Intervention description: All groups will receive study drug every two weeks for 24 weeks.; Matching placebo given every two weeks for 24 weeks
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 22.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Alopecia, Alopecia Totalis, Alopecia Universalis

Summary:

      The purpose of this study is to assess whether tralokinumab can be a helpful treatment for
      alopecia areata. This is a randomized, double-blind, placebo-controlled pilot study of a
      total of 30 subjects with moderate to severe alopecia areata involving 30-100% of the scalp.
      Expected is 50% of these subjects to have concomitant alopecia areata (AA) and atopic
      dermatitis (AD). Subjects with AA alone (15 subjects) will be randomized (2:1) to either
      receive tralokinumab or placebo via subcutaneous injection every 2 weeks for 24 weeks.
      Subjects with concomitant alopecia areata and atopic dermatitis (15 subjects) will be
      randomized separately in a 2:1 ratio to receive tralokinumab or placebo via subcutaneous
      injection every 2 weeks for 24 weeks.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female, aged from 18 to 75 years, inclusively at the time of signing the
             informed consent document.

          -  Subject has provided written informed consent prior to any study specific procedures.

          -  Body weight of ≥40 and <150 kg at enrollment.

          -  Subject has a history of alopecia areata for at least 3 months.

          -  Subject has extensive patchy alopecia areata (at least 30% scalp hair loss).

          -  No evidence of hair regrowth at Baseline.

          -  For WOCBP only: have a negative urine pregnancy test prior to administration of the
             IP.

          -  For inclusion in the voluntary pharmacogenetic research, subjects should fulfill the
             following criterion: Provision of a signed and dated written informed consent for the
             pharmacogenetic sample and analysis. If a subject declines to participate in the
             pharmacogenetic research, there will be no consequence or loss of benefit to the
             subject. The subject will not be excluded from the other aspects of the study
             described in the protocol, as long as they consent to participate in the study.

          -  Subject is judged to be in good general health as determined by the principal
             investigator based upon the results of medical history, laboratory profile, and
             physical examination performed at Screening.

          -  Subjects may be naïve to treatment or unresponsive to intralesional steroids or other
             treatments for alopecia areata.

        Exclusion Criteria:

          -  History of male or female pattern hair loss Ludwig stage III or Hamilton > stage V.

          -  Subjects in whom the diagnosis of alopecia areata is in question.

          -  Any disorder, including but not limited to, cardiovascular, gastrointestinal, hepatic,
             renal, neurological, musculoskeletal, infectious, endocrine, metabolic,
             haematological, psychiatric, or major physical impairment that is not stable in the
             opinion of the Investigator and could:

               1. Affect the safety of the subject throughout the study

               2. Influence the findings of the studies or their interpretations

               3. Impede the subject's ability to complete the entire duration of study

          -  Known history of allergy or reaction to any component of the IP formulation.

          -  History of anaphylaxis following any biologic therapy.

          -  The following treatments within 4 weeks before the Baseline visit, or any condition
             that, in the opinion of the investigator, will likely require such treatment(s) at any
             time during the study:

               1. Systemic corticosteroids

               2. Immunosuppressive/immunomodulating drugs (eg, cyclosporine,
                  mycophenolate-mofetil, IFN-γ, Janus kinase (JAK) inhibitors, azathioprine or
                  methotrexate), Ultra-Violet (UV) B phototherapy; and/or Psoralen Ultra-Violet A
                  (PUVA) therapy.

          -  Treatment with topical corticosteroids, tacrolimus and/or pimecrolimus within 1 week
             before the Baseline visit.

          -  Subject has taken enzyme-modifying drugs that are moderate inhibitors/potent inducers
             of cytochrome P450 3A4 or potent inhibitors of cytochrome P450 2C19 enzymes (such as
             cimetidine, quinidine, erythromycin, ciprofloxacin, fluconazole, ketoconazole etc…)
             and strong inducers of CYP enzymes (such as rifampin etc…), in the previous 28 days
             before day 0.

          -  A helminth parasitic infection diagnosed within 6 months prior to the date informed
             consent or assent obtained that has not been treated with, or has failed to respond
             to, standard of care therapy.

          -  History of clinically significant infection, including acute upper or lower
             respiratory infections, requiring antibiotics or antiviral medication within 30 days
             prior to the date informed consent or assent is obtained or during the run-in period.

          -  Tuberculosis requiring treatment within the 12 months prior to enrolment (Visit 1).

          -  Any clinically significant abnormal findings in physical examination, vital signs,
             ECG, hematology, clinical chemistry, or urinalysis during the run-in period, which in
             the opinion of the Investigator, may put the subject at risk because of his/her
             participation in the study, or may influence the results of the study, or the
             subject's ability to complete entire duration of the study.

          -  History of chronic alcohol or drug abuse within 12 months of the enrolment visit, or a
             condition associated with poor compliance as judged by the Investigator.

          -  Positive hepatitis B surface antigen or hepatitis C virus antibody serology. Subjects
             with a history of hepatitis B vaccination without a history of hepatitis B are allowed
             to be enrolled.

          -  History of any known primary immunodeficiency disorder including a positive human
             immunodeficiency virus (HIV) test at enrolment, or the subject taking antiretroviral
             medications as determined by medical history and/or subject's verbal report.

          -  Current tobacco smoking (smoking must have stopped for ≥ 3 months prior to enrollment)
             or a history of tobacco smoking for ≥ 10 pack-years (one pack year = 20 cigarettes
             smoked per day for 1 year).

          -  History of cancer: - Subjects who have had basal cell carcinoma, localized squamous
             cell carcinoma of the skin or in situ carcinoma of the cervix are eligible provided
             that the subject is in remission and curative therapy was completed at least 12 months
             prior to the date informed consent was obtained Subjects who have had other
             malignancies are eligible provided that the subject is in remission and curative
             therapy was completed at least 5 years prior to the date informed consent was obtained

          -  Use of immunosuppressive medication (including but not limited to: methotrexate,
             troleandomycin, cyclosporine, azathioprine, systemic corticosteroids including regular
             treatment with OCS or intramuscular long-acting depot corticosteroids, or any
             experimental anti-inflammatory therapy) within 3 months prior to the date informed
             consent or assent is obtained.

          -  Clinically significant asthma exacerbation, in the opinion of the Investigator,
             including those requiring use of oral corticosteroids 30 days prior to the date of
             informed consent or during the screening/run-in period.

          -  Receipt of immunoglobulin or blood products within 30 days prior to the date informed
             consent or assent is obtained.

          -  Receipt of any marketed or investigational biologic agent within 4 months or 5
             half-lives prior to the enrolment visit, whichever is longer.

          -  Receipt of live attenuated vaccines 30 days prior to the date of randomization and
             during the study including the follow-up period Receipt of inactive/killed
             vaccinations (eg, inactive influenza) are allowed, provided they are not administered
             within 5 days before/after any study visit.

          -  Receipt of any investigational non-biologic agent within 30 days or 5 half lives prior
             to informed consent or assent being obtained, whichever is longer.

          -  Previous receipt of tralokinumab (CAT-354).

          -  Initiation of new allergen immunotherapy or change in existing immunotherapy is not
             allowed within 30 days prior to the date of informed consent. However allergen
             immunotherapy initiated prior to this period may be continued provided there is a span
             of at least 5 days between the immunotherapy and IP administration.

          -  Current use of oral or ophthalmic non-selective β-adrenergic antagonist (eg,
             propranolol).

          -  Current use of five- lipoxygenase inhibitors (eg, Zileuton) or roflumilast.

          -  Major surgery within 8 weeks prior to the enrolment visit, or planned in-subject
             surgery or hospitalization during the study period.

          -  Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level ≥2.5 times
             the upper limit of normal (ULN) at enrolment

          -  Pregnant, currently breast-feeding, or lactating women.

          -  Previous randomization in the present study.

          -  Concurrent enrollment in another clinical study where the subject is receiving an IP.

          -  Involvement in the planning and/or conduct of the study (applies to both AstraZeneca
             staff and/or staff at the study site).

          -  Employees of the clinical study site or any other individuals directly involved with
             the planning or conduct of the study, or immediate family members of such individuals.

          -  Individuals who are legally institutionalized.

        For exclusion from the voluntary pharmacogenetic research:

          -  Previous allogeneic bone marrow transplant.

          -  Non-leukocyte depleted whole blood transfusion within 120 days of genetic sample
             collection.