A Study to Assess the Efficacy and Safety of AK002 in Subjects With Antihistamine-Resistant Chronic Urticaria
Condition: Chronic Urticaria
MeSH terms: Urticaria; Chronic Urticaria
Intervention: AK002
Intervention description: AK002 is a humanized non-fucosylated immunoglobulin G1 (IgG1) monoclonal antibody directed against Siglec-8, a member of the CD33-related family of sialic acid-binding, immunoglobulin-like lectins (Siglecs).
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 47.0
Sex: All
Minimum age: 18 Years
Maximum age: 85 Years
Healthy volunteers: No

Summary:

      This is a Phase 2a, open-label study to assess the effects of AK002
    

Eligibility criteria:

        Inclusion Criteria:

          1. Adults (≥ 18 and ≤ 85 years old)

          2. Body weight <125 Kg

          3. Informed consent signed and dated

          4. Able to read, understand, and willing to sign the informed consent form and comply
             with study procedures

          5. Diagnosis of CU for at least three months, refractory to antihistamine treatment in
             single or 4-fold dosage

          6. Willing, committed, and able to return for all clinic visits and complete all
             study-related procedures, including willingness to have IV infusion of study drug
             administered by a qualified person

          7. Females of childbearing potential must have a negative pregnancy test at Baseline.
             Female subjects must be willing to use highly effective contraception (Pearl- 4 Index
             < 1). A woman will be considered not of childbearing potential if she is
             post-menopausal for greater than two years (FSH >40mL) or surgically sterile
             (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy)

          8. No participation in other clinical trials 4 weeks before participation in this study

          9. Uncontrolled CU (UCT <12) at the time of enrollment

        Exclusion Criteria:

          1. Acute urticaria

          2. Concurrent/ongoing treatment with immunosuppressives (e.g., cyclosporine,
             methotrexate, dapsone, or others) within 4 weeks or 5 half-lives prior to Baseline,
             whichever is longer

          3. Significant medical condition rendering the patient immunocompromised or not suitable
             for a clinical trial

          4. Significant concomitant illness that would adversely affect the subject's
             participation or evaluation in this study

          5. History of malignancies within five years prior to screening other than a successfully
             treated non-metastatic cutaneous, basal, or squamous cell carcinoma and/or in situ
             cancer

          6. Presence of clinically significant laboratory abnormalities

          7. Lactating women or pregnant women

          8. Substance abuse (drug or alcohol) or any other factor (e.g., serious psychiatric
             condition) within the last 5 years that could limit the subject's ability to comply
             with study procedures

          9. Subjects who are detained officially or legally to an official institute or those that
             have been committed to an institution by virtue of an order issued either by the
             judicial or the administrative authorities will be excluded from the study

         10. Use of omalizumab within the last 3 months

         11. Receipt of intravenous IgG therapy 30 days prior to Baseline

         12. Plasmapheresis 30 days prior to Baseline

         13. Use (daily or every other day) of Doxepin 14 days prior to Baseline

         14. Receipt of inactive vaccination or live attenuated vaccine 30 days prior to Baseline

         15. Use of H2 antihistamines 7 days before Baseline

         16. Intake of leukotriene antagonists within 7 days prior to enrollment

         17. Intake of systemic corticosteroids (e.g., oral or depot) within 14 days prior to
             enrollment

         18. Positive screening for ova and parasite test at Baseline

         19. Treatment of helminthic parasite within 6 months of screening

         20. Positive HIV serology at screening

         21. Positive Hepatitis serology at baseline, except for vaccinated patients or patients
             with past but resolved hepatitis at screening

         22. Donation or loss of >500ml of blood within 56 days prior to administration of study
             drug or donation of plasma within 7 days prior to administration of drug

         23. Known hypersensitivity to any ingredients of AK002 or drugs related to AK002 (e.g.,
             monoclonal antibodies, polyclonal gamma globulin)