Patients with different types of chronic urticaria resistant to standard dose antihistamines MedDRA version: 20.0 Level: PT Classification code 10052568 Term: Urticaria chronic System Organ Class: 10040785 - Skin and subcutaneous tissue disorders
Conditions
Interventions
Product Code: AK002
Pharmaceutical Form: Infusion
INN or Proposed INN: AK002
Current Sponsor code: AK002
Other descriptive name: AK002
Concentration unit: mg/kg milligram(s)/kilogram
Concentration typ
Sponsors
Allakos Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Adults (= 18 and = 85 years old) 2) Body weight 40 mL) or surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy) Male patients with female partners of childbearing potential must agree to use a highly effective method of contraception from Screening until the end of the study or for 120 days following the last dose of study drug, whichever is longer. All fertile men with female partners of childbearing potential should be instructed to contact the Investigator immediately if they suspect their partner might be pregnant (e.g., missed or late menstrual period) at any time during study participation. 8) No participation in other clinical trials 4 weeks before participation in this study 9) Uncontrolled CU (UCT =65 years) yes F.1.3.1 Number of subjects for this age range 8
Exclusion criteria
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 2 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)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy of AK002 on symptoms in subjects with CU (change in urticaria control test [UCT] score).;Secondary Objective: The efficacy, safety and pharmacodynamics of AK002 on urticaria symptoms, QoL, provocation testing, and histological criteria. Extended dosing: To evaluate the long-term safety and tolerability of up to 12 additional doses of AK002 in subjects with CU.;Primary end point(s): The primary endpoint is the change in Urticaria Control Test (UCT), a score for symptom control in chronic urticaria, from Day 1 (baseline) to Week 22 in CU subjects after treatment with AK002. At Baseline, a 4-week recall will be recorded, prior to first study drug administration. A change of the UCT score of 3 or more points is regarded as clinically relevant (minimal clinically important difference [MCID]).;Timepoint(s) of evaluation of this end point: The total study duration for each patient will be approximately 32 weeks. This includes: • A screening period of 4 weeks prior to study drug administration • Administration of study drug at Day 1, Day 29, Day 57, Day 85, Day 113, Day 141. • Follow-up through Day 197 (8 weeks post last dose). | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: included in secondary endpoints;Secondary end point(s): 1) Safety of subjects treated with AK002: This includes physical examination, routine safety laboratory assessments, vital signs, electrocardiogram (ECG), urine safety, and adverse event reporting (Visits 2–10) 2) Change in disease activity as assessed by UAS7 and/or CholUAS7 (from Baseline to Visits 3, 5, 8, and 10) 3) Change in number of symptom-free days per week (patient diary based CSU score; wheals, flares, itch, avoidance behavior) from Baseline to Visits 3, 5, 8, and 10 4) Change in quality-of-life scores assessed by DLQI, CU-Q2oL, AE-QoL, SD-QoL and CholU-QoL from Baseline to Visits 3, 5, 8, and 10 5) Change in number of intake of rescue medication from Baseline to Visits 3, 5, 8, and 10 6) In case of angioedema, change in occurrence of angioedema from Visit 2 to Visit 3, 5, 8, and 10, as assessed by AAS 7) Change in number of hives and itch severity (from UAS7/CholuAS7) from Baseline to Visits 3, 5, 8, and 10 8) Change in physician and patient global assessment from Baseline (Day 1) to Visits 3, 5, 8, and 10 9) Changes in trigger threshold from Baseline (Day 1) to Visits 2, 3, 5, 8, and 10, as assessed by Pulse Controlled Ergometry Test (PCE) and FricTest®, as applicable 10) Rates of complete response, partial response, and non-response based on UCT, UAS7/CholUAS7, trigger thresholds (where applicable), and QoL from Baseline to Visits 3, 5, 8, and 10 11) Serum levels at baseline (Day 1) and change from Baseline to Visits 3, 5, 8, and 10 of serum levels of potential biomarkers in AK002-treated subjects (e.g., tryptase, eosinophils, total IgE, basophils, eosinophil cationic protein) 12) Rates of AK002-treated subjects with relapse, rebound, sustained treatment effects at Visit 7 | — |
Countries
Germany, United States
Contacts
Public ContactMarcus Maurer
Charité - Universitätsmedizin Berlin, Dpt. of Dermatology and Allergy
Outcome results
None listed