Chronic spontaneous Urticaria MedDRA version: 20.0 Level: PT Classification code 10072757 Term: Chronic spontaneous urticaria System Organ Class: 10040785 - Skin and subcutaneous tissue disorders
Conditions
Interventions
Product Name: avdoralimab
Product Code: IPH5401
Pharmaceutical Form: Lyophilisate and solvent for solution for injection
INN or Proposed INN: Avdoralimab
CAS Number: 2226393-85-5
Current Sponsor code:
Sponsors
Charité Universitätsmedizin Berlin
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patient is capable of giving informed consent 2. Patient has given written informed consent before any study related procedures. 3. Patient is able to communicate with the investigator, understands and is willing to comply with the requirements of the study. 4. Male or Female 5. Patient is 18-75 years of age 6. Patient is diagnosed with moderate to severe CSU and refractory to standard of care treatment at the time of randomization, as defined by the following: a. The presence of itch and hives for = 6 consecutive weeks at any time prior to enrollment despite current use of H1-AH, and b. Urticaria activity score UAS7 score (range 0-42) = 16, within 7 days prior to randomization (Day 1), and c. CSU diagnosis for at least 6 months 7. Patient has not been treated with omalizumab or was last treated three months ago and did not respond to omalizumab. 8. Willing and able to complete a daily symptom diary for the duration of the study and adhere to the study visit schedules. 9. Patients must not have more than one missing diary entry in the 7 days prior to randomization. Re-screening may be considered. 10. Male patients who are sexually active with a female partner of childbearing potential must agree to a highly effective form of contraception and have to continue its use for the duration of the study and until at least 6 months (180 days) after the last dose of avdoralimab 11. Women of childbearing potential have to agree to use a highly effective form of contraception and have to continue its use for the duration of the study and until at least 6 months (180 days) after the last dose of avdoralimab: Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 30 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 6
Exclusion criteria
Exclusion criteria: 1. Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer; 2. Patients whose urticaria is solely due to inducible urticaria 3. Other diseases with symptoms of urticaria or angioedema, including urticarial vasculitis, erythema multiforme, cutaneous mastocytosis (urticaria pigmentosa), and hereditary or acquired angioedema (e.g., due to C1 inhibitor deficiency) 4. Any other active skin disease that might confound the study evaluations and results (e.g. atopic dermatitis, bullous pemphigoid, dermatitis herpetiformis, etc.) 5. Patients who have received concomitant prohibited medication within the last 3 months prior to screening: • Anti-IgE therapy (e.g. omalizumab) • Routine (daily or every other day during 5 or more consecutive days) doses of systemic corticosteroids or other immunosupressants • Intravenous immunoglobulins • Biological therapy • Systemic immunosuppressants • Live/attenuated vaccines • Other investigational drug 6. Use of prohibited treatment detailed in protocol (see under 6.5.8 Table 3) 7. Patients with low IgE (= 40 kU/l) and without elevated IgG-anti-TPO (= 34 kU/l) as well as patients without low IgE and with elevated IgG-anti-TPO 8. History of anaphylaxis. 9. Presence of clinically significant cardiovascular, renal, bronchial, neurological, psychiatric, metabolic or other pathological conditions that could interfere with the interpretation of the study results and or compromise the safety of the patients. 10. Medical examination or laboratory findings that suggest the possibility of decompensation of co-existing conditions for the duration of the study. Any items that are cause for uncertainty must be reviewed with the Medical Monitor. 11. Inability to comply with study and follow-up procedures. 12. History of malignancy of any organ system (other than localized basal cell carcinoma or actinic keratosis or Bowen disease: carcinoma in situ of skin; carcinoma in situ of the cervix or non-invasive malignant colon polyps that have been removed), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases. 13. History or evidence of ongoing drug or alcohol abuse, within the last 6 months prior to randomization. 14. Study personnel or first-degree relatives of investigator(s) . 15. Subjects who live in detention on court order or on regulatory action as per local and national law (see §40 subsection 1 sentence 3 no. 4 Arzneimittelgesetz) 16. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to assess the explorative efficacy pf avdoralimab (450 mg weekly) as compared to placebo regarding the change in urticaria activity score 7 (UAS7) from baseline to week 12 in adult patients diagnosed with CSU who remain symptomatic despite H1-AH at approved doses. ;Secondary Objective: Efficacy QoL Proportion of clinical (MID) responders Time to first clinical (MID) response Proportion of complete responders Time to first complete response Proportion of non-response (symptom reocurrence after study-drug dis-continuation) Safety of subjects treated with avdoralimab ;Primary end point(s): UAS7;Timepoint(s) of evaluation of this end point: Change from baseline (week 1, V1) to the end of week 12 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy: UAS7, AAS, Angioedema burdened days, HSS7, ISS7; UCT, Rescue medication use per week QoL: DLQI, Cu-Q2oL, AE-QoL Proportion of clinical (MID) responders: Clinical responder regarding UAS7, Clinical responder regarding HSS7, Clinical responder regarding ISS7, Clinical responder regarding UCT, Clinical responder regarding CU-Q2oL Time to first clinical (MID) response: Time to first clinical response regarding UAS7, Time to first clinical response regarding HSS7, Time to first clinical response regarding ISS7, Time to first clinical response regarding UCT, Time to first clinical response regarding CU-Q2oL Proportion of complete responders: Complete responder regarding UAS7, Complete responder regarding HSS7, Complete responder regarding ISS7 Complete responder regarding UCT, Complete responder regarding AAS, Complete responder regarding CU-Q2oL Time to first complete response: Time to first complete response regarding UAS7, Time to first complete response regarding HSS7, Time to first complete response regarding ISS7, Time to first complete response regarding UCT, Time to first complete response regarding AAS, Time to first complete response regarding CU-Q2oL Proportion of non-response (symptom reocurrence after study-drug dis-continuation): Non-response regarding UAS7, Non-response regarding HSS7, Non-response regarding ISS7, Non-response regarding UCT, Non-response regarding AAS Safety of subjects treated with avdoralimab: This includes physical examination and clinical observation, routine safety laboratory assessments, vital signs, and safety monitoring: frequency of adverse events (AE/SAE/TEAE). ;Timepoint(s) of evaluation of this end point: Efficacy: Change from baseline to all assessment time points* QoL: Change from baseline to all assessment time points* Proportion of clinical (MID) responders: Change from baseline to all assessment time points* Time to first clinical (MID) response: Change from baseline to all assessmen | — |
Countries
Germany
Contacts
Public ContactClinical Trial Manager
Charité Universitätsmedizin Berlin
Outcome results
None listed