KPL-301 for Subjects With Giant Cell Arteritis

This Phase 2 randomized, double-blind, placebo-controlled proof of concept study will evaluate the efficacy and safety of mavrilimumab co-administered with a 26-week corticosteroid taper in subjects with GCA. The study will consist of a screening period (up to 6 weeks), a 26-week double-blind placebo-controlled period during which subjects will receive blinded mavrilimumab or placebo co-administered with a 26-week corticosteroid taper, and a 12-week washout safety follow-up period during which subjects will discontinue and wash off blinded mavrilimumab or placebo.

Selected Inclusion Criteria:

• Subjects with new-onset or relapsing/refractory GCA.
• Westergren erythrocyte sedimentation rate > 30 mm/hour or c-reactive protein ≥ 1 mg/ dL.
• Remission of GCA at or before Day 0.
• Female subjects must be postmenopausal or permanently sterile following documented hysterectomy, bilateral salpingectomy, bilateral oophorectomy, or tubal ligation or having a male partner with vasectomy as affirmed by the subject, or nonpregnant, nonlactating, and if sexually active having agreed to use a highly effective method of contraception.
• Male subjects must have documented vasectomy or if sexually active must agree to use a highly effective method of contraception with their partners of childbearing potential.

Selected Exclusion Criteria:

• Transplanted organs (except corneal transplant performed more than 3 months prior to randomization).
• Concurrent enrollment in another interventional clinical study.
• Treatment with non-biologic investigational drug therapy within 4 weeks or 5 half-lives of the study agent, whichever was longer, prior to screening.
• Cell-depleting biological therapies within 12 months prior to Day 0, or noncell-depleting biological therapies within 8 weeks (or 5 half-lives, whichever is longer) prior to screening.
• Treatment with alkylating agents within 12 weeks prior to screening.
• Intramuscular, Intra-articular or IV corticosteroids within 4 weeks prior to screening.
• Receipt of live (attenuated) vaccine within the 4 weeks before Day 0.
• Treatment with hydroxychloroquine, cyclosporine A, azathioprine, cyclophosphamide, or mycophenolate mofetil (MMF) within 4 weeks of screening.
• Female subjects who are pregnant, intending to become pregnant, or are breastfeeding.
• Known history of allergy or reaction to any component of the mavrilimumab or placebo formulation or to any other biologic therapy or prednisone or any of its excipients.
• Positive (or 2 indeterminate) QuantiFERON test results.
• Clinically significant active infection or infection requiring hospitalization or IV antibiotics within 12 weeks before screening or opportunistic infection within 6 months before screening.
• Chronic active hepatitis B infection.
• Subjects at a high risk of infection, a history of an infected joint prosthesis still in situ, leg ulcers, indwelling urinary catheter, or persistent or recurrent chest infections.
• History of cancer within the last 10 years, except for basal and squamous cell carcinoma of the skin or in situ carcinoma of the cervix treated and considered cured.
• Evidence of clinically-uncontrolled respiratory disease.
• History of chronic respiratory tract infections.