A Study to Assess the Efficacy and Safety of AK002 in Subjects With Antihistamine-Resistant Chronic Urticaria

Study Overview
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Brief Summary
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This is a Phase 2a, open-label, study to assess the effects of AK002, given as monthly intravenous infusions at up to 3 mg/kg. A total of 47 patients will be enrolled across 2-4 sites. All patients enrolled in the study will receive 6 monthly infusions of AK002 and will then be followed for another 8 weeks. Some patients will have the option to receive an additional 12 months of extended dosing.

Official Title
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An Open-Label, Pilot Study to Assess the Efficacy and Safety of AK002 (Siglec-8) in Subjects With Antihistamine-Resistant Chronic Urticaria

Conditions
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Chronic Urticaria

Intervention / Treatment
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* Drug: AK002


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults (≥ 18 and ≤ 85 years old) Body weight <125 Kg Informed consent signed and dated Able to read, understand, and willing to sign the informed consent form and comply with study procedures Diagnosis of CU for at least three months, refractory to antihistamine treatment in single or 4-fold dosage 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 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) No participation in other clinical trials 4 weeks before participation in this study Uncontrolled CU (UCT <12) at the time of enrollment Exclusion Criteria: Acute urticaria 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 Significant medical condition rendering the patient immunocompromised or not suitable for a clinical trial Significant concomitant illness that would adversely affect the subject's participation or evaluation in this study 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 Presence of clinically significant laboratory abnormalities Lactating women or pregnant women 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 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 Use of omalizumab within the last 3 months Receipt of intravenous IgG therapy 30 days prior to Baseline Plasmapheresis 30 days prior to Baseline Use (daily or every other day) of Doxepin 14 days prior to Baseline Receipt of inactive vaccination or live attenuated vaccine 30 days prior to Baseline Use of H2 antihistamines 7 days before Baseline Intake of leukotriene antagonists within 7 days prior to enrollment Intake of systemic corticosteroids (e.g., oral or depot) within 14 days prior to enrollment Positive screening for ova and parasite test at Baseline Treatment of helminthic parasite within 6 months of screening Positive HIV serology at screening Positive Hepatitis serology at baseline, except for vaccinated patients or patients with past but resolved hepatitis at screening 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 Known hypersensitivity to any ingredients of AK002 or drugs related to AK002 (e.g., monoclonal antibodies, polyclonal gamma globulin)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: AK002|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).|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in Urticaria Control Test (UCT), a score for symptom control in chronic urticaria, in CU subjects after treatment with AK002. |  | Day 1 (baseline) to Week 22 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in disease activity as assessed by UAS7 |  | From Day 1 to day 29, 85, 155, and 197 | 
| Change in disease activity as assessed by CholUAS7 |  | From Day 1 to day 29, 85, 155, and 197 | 
| Change in number of symptom-free days per week (patient diary based CSU score) |  | From Day 1 to day 29, 85, 155, and 197 | 
| Change in quality-of-life scores assessed by AE-QoL |  | From Day 1 to day 29, 85, 155, and 197 |