A Study to Assess Subcutaneous Lirentelimab (AK002) in Chronic Spontaneous Urticaria

A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Lirentelimab in Adult Subjects With H-1 Antihistamine Refractory Chronic Spontaneous Urticaria

This is a Phase 2, multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of subcutaneous lirentelimab (AK002) in adult subjects with H-1 antihistamine refractory chronic spontaneous urticaria. Subjects who complete the randomized, double-blind, placebo-controlled treatment period may have the option to enroll in an open-label extension period and receive up to 6 doses of subcutaneous lirentelimab.

Key Inclusion Criteria:

1. Subject is able to understand the information on the study, has the capacity to consent, and has provided written informed consent.
2. Male and female subjects ≥18 years of age at the time of screening.
3. CSU diagnosis for ≥6 months.
4. Diagnosis of moderate-severe CSU refractory to H1-antihistamine (H1-AH) at a minimum of the licensed dose at the licensed frequency at the time of randomization as defined by the following: presence of hives and itch for ≥6 consecutive weeks prior to Screening Visit 1; UAS7 score (range 0-42) ≥16 and HSS7 score (range 0-21) ≥8 during the 7 days prior to randomization.
5. Subjects that are omalizumab-naïve or omalizumab-exposed.
6. Subjects must be on stable dose of H1-AH, between 1x and 4x of the licensed dose and at the licensed frequency, for treatment of CSU for at least 1 week prior to screening and willing to remain on a stable dose throughout the study.
7. Able and compliant with completing a daily symptom eDiary for the duration of the study and adherent to the study visit schedules.

Key Exclusion Criteria:

1. History of hypersensitivity to the study drugs or their excipients or to drugs of similar chemical classes (i.e., murine, chimeric or human antibodies).
2. Current use of biologics for any indication.
3. Demonstrated lack of primary response to treatment with a biologic therapy (e.g., omalizumab) for the treatment of CSU.
4. Use of any of the following treatments within 4 weeks prior to the baseline visit or any condition that in the opinion of the Investigator is likely to require such treatment(s) during the first 4 weeks of study treatment: (i) immunosuppressive or immunomodulatory drugs, including but not limited to systemic calcineurin inhibitors (e.g., cyclosporin, tacrolimus), mTOR inhibitors (e.g., sirolimus, everolimus), anti-metabolites (e.g., azathioprine, methotrexate, 6-mercaptopurine, leflunomide, mycophenolate mofetil), alkylating agents (e.g., cyclophosphamide), TNF inhibitors (e.g., infliximab, adalimumab), and eosinophil-depleting drugs (e.g., benralizumab, pramipexole); (ii) routine (daily or every other day during 5 or more consecutive days) doses of systemic hydroxychloroquine; (iii) intravenous immunoglobulin (IVIG); (iv) plasmapheresis.
5. Use of oral Janus kinase (JAK) inhibitors within 8 weeks of the baseline visit.
6. Use of any of the following treatments within 3 weeks prior to the baseline visit: (i) H2 antihistamines (H2-AH); (ii) routine (daily or every other day during 5 or more consecutive days) doses of systemic corticosteroids; (iii) regular (daily or every other day) doxepin (oral); (iv) leukotriene receptor antagonists (LTRA) (e.g., montelukast, zafirlukast).
7. H1-AH use at greater than approved doses or greater than local CSU guideline recommended doses after Screening Visit 1.
8. Previous treatment with biologics: (i) any cell-depleting agents including but not limited to rituximab within 6 months prior to the baseline visit or until lymphocyte count returns to normal, whichever is longer; (ii) other biologics, including investigational biologics (e.g., dupilumab, omalizumab, benralizumab, etc) within 5 half-lives if known or 8 weeks prior to the baseline visit, whichever is longer.
9. Planned or anticipated use of any prohibited medication.
10. Subjects having causes other than CSU for their urticaria including symptomatic dermographism, cholinergic urticaria, or any inducible urticaria.
11. Subjects with known or suspected urticarial vasculitis.
12. Subjects with known or suspected hereditary angioedema.
13. Any other skin disease associated with chronic itch, including atopic dermatitis, that in the Investigator's opinion might influence study outcome and subject's interpretation of symptoms caused by CSU.
14. A helminth parasitic infection diagnosed within 6 months prior to the date that informed consent is obtained and has not been treated with or has failed to respond to standard-of-care therapy.
15. Participation in a concurrent interventional study with the last intervention occurring within 30 days prior to study drug administration (or 90 days or 5 half-lives, whichever is longer, for biologic products).
16. Vaccination with live attenuated vaccines within 30 days prior to initiation of treatment in the study, during the treatment period, or vaccination expected within 5 half-lives (4 months) of study drug administration. This exclusion criterion does not apply to all types and formulations of vaccines (including live attenuated vaccines) currently authorized/approved by FDA or other regulatory authority for the prevention of COVID-19, which may be administered before, during, or after the study. The vaccine should not be administered within 3 days before and within 3 days after the administration of lirentelimab so that any side effects caused by either of the 2 medications can more easily be determined.