Warm Autoimmune Hemolytic Anemia MedDRA version: 20.0 Level: LLT Classification code 10003825 Term: Autoimmune hemolytic anemia System Organ Class: 100000004851
Conditions
Interventions
Product Code: ANX005
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: ANX005
Other descriptive name: ANX005
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
C
Sponsors
Annexon, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects must meet ALL the following criteria to be eligible to participate in the study: 1. Male or female = 18 years of age on the day of signing informed consent 2. Diagnosis of wAIHA at least 3 months prior to screening with a DAT =1 positive for IgG ±C3, or a diagnosis of mixed AIHA that is DAT positive for both IgG and C3, with a presence of a cold antibody with a thermal amplitude =30ºC 3. Hemoglobin level =10.0 g/dL (pre-transfusion) in wAIHA-01 within 6 weeks of the Day 1 dosing day or during the Week -6 or rescreening visits 4. Evidence of classical complement pathway activation in wAIHA-01 within 6 weeks of the Day 1 dosing date or during the wAIHA-02 screening: a. Serum complement component 4 (C4) level no greater than 1.5 times the lower limit of normal and/or b. CH50 below the lower limit of normal (LLN) 5. Evidence of active hemolysis based on at least one of the following: a. LDH above the upper limit of normal (ULN) b. Indirect bilirubin above the ULN c. Haptoglobin below the LLN 6. Patients must have been previously vaccinated for encapsulated bacteria within 5 years prior to screening or be willing to receive prophylaxis against infections with encapsulated bacteria via vaccination and/or the use of prophylactic antibiotics in accordance with local standards of practice and/or guidelines. 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 10 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 2
Exclusion criteria
Exclusion criteria: Subjects must not meet any of the following criteria: 1. Active lymphoma, lymphoproliferative disorder, or other malignancy requiring therapy and/or not clinically stable or in remission for at least 3 months prior to screening 2. Elevated aspartate aminotransferase or alanine aminotransferase levels > 2.5 times the upper limit of normal at screening unless associated with wAIHA 3. Platelet count < 30 x 109/L 4. History of isolated cold agglutinin disease 5. History of solid organ, bone marrow, or stem cell transplantation 6. History of splenectomy within the 3 months prior to screening 7. Received rituximab or other B cell depleting monoclonal antibody (eg. daratumumab) <90 days prior to screening 8. Signs and symptoms of, or a diagnosis consistent with, a chronic autoimmune disorder and/or an ANA titer =1:160 9. Known genetic deficiencies of the complement cascade system
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this repeat dose Phase 2 study are as follows: • To evaluate the safety and tolerability of two once-weekly intravenous infusions of 100 mg/kg ANX005 in patients with wAIHA • To evaluate the clinical effect of two once-weekly intravenous infusions of 100 mg/kg ANX005 in patients with wAIHA;Secondary Objective: The secondary objectives of the study are as follows: • To evaluate the pharmacokinetic (PK) profile of ANX005 in subjects with wAIHA • To evaluate the effect of ANX005 on classical complement pathway inhibition as measured by complement system related biomarkers in subjects with wAIHA;Primary end point(s): • Number and percent of patients experiencing treatment-emergent adverse events (TEAEs) • Change from baseline in hemoglobin over time up to Day 71 • Change from baseline in biomarkers of hemolysis (reticulocyte count, haptoglobin, LDH, total and indirect bilirubin) over time up to Day 71;Timepoint(s) of evaluation of this end point: 10 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • ANX005 plasma concentration profiles and PK parameters such as AUC, Cmax, Tmax, accumulation ratio, t1/2, ?z, CL and Vss • Inhibition of classical complement activity as measured by serum CH50 from baseline over time up to Day 71 • Change and percent change from baseline in serum C4 concentrations over time up to Day 71 • Change and percent change from baseline in serum free C1q concentrations over time up to Day 71;Timepoint(s) of evaluation of this end point: 10 weeks | — |
Countries
Australia, Austria, Bulgaria, Czechia, France, Germany, Italy, Spain, United States
Contacts
Public ContactClinical Trials Information
Annexon, Inc.
Outcome results
None listed