Primary Cold Agglutinin Disease (CAD)
Conditions
Interventions
Product Code: ANX005
Pharmaceutical Form: Solution for injection
INN or Proposed INN: ANX005
Current Sponsor code: ANX005
Other descriptive name: Recombinant humanized IgG4 monoclonal antibody
Concent
Sponsors
Annexon, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female = 18 years of age on the day of signing informed consent 2. Body weight upper limit of normal (ULN) ii. Indirect bilirubin > ULN iii. Haptoglobin =65 years) yes F.1.3.1 Number of subjects for this age range 3
Exclusion criteria
Exclusion criteria: Exclusion Criteria: 1. History of cold agglutinin disease secondary to infection, rheumatologic disease, or active malignancy 2. History of hemolytic anemia due to another condition besides CAD including, but not limited to, paroxysmal nocturnal hemoglobinuria (PNH), Evan’s syndrome, sickle cell disease, thalassemia, thrombotic thrombocytopenia purpura, hemolytic-uremic syndrome (HUS), red cell membrane disorders (e.g. hereditary spherocytosis, hereditary elliptocytosis, hereditary pyropoikliocytosis, hereditary stomatocytosis, hereditary exocytosis), pyruvate kinase deficiency, glucose-6-phosphate deficiency, or hemolytic anemia secondary to autoimmunity (e.g. systemic lupus erythematosus, rheumatoid arthritis), infectious cause (e.g. Epstein-Barr Virus, cytomegalovirus, mycoplasma, hepatitis virus, human immunodeficiency virus), malignancy (e.g. lymphoproliferative disorder requiring treatment, lymphoma, leukemia, multiple myeloma), or medications (e.g. anti-neoplastics, non-steroidal anti-inflammatory drugs, antibiotics). Note: Mixed autoimmune hemolytic anemia may potentially be enrolled, but should first be discussed with the medical monitor 3. History of solid organ, bone marrow, or stem cell transplantation 4. History of splenectomy within the 3 months prior to screening 5. Clinically significant ongoing illness or medical condition affecting any major organ system, including chronic infections, or a medical history that would jeopardize the safety of the participant, limit participation in the study, or compromise the interpretation of the data derived from the participant 6. History of active lymphoma, lymphoproliferative disorder requiring therapy, or any other active malignant disease that has not been adequately treated 7. Signs and symptoms of, or a diagnosis consistent with, a chronic autoimmune disorder not resulting from primary CAD 8. History of meningitis or septicemia within the past 2 years 9. Clinically significant infection that required systemic medical intervention (not including antibiotic prophylaxis; i.e., viral, bacterial, fungal, or mycobacterial) within 1 month prior to screening 10. Positive serology for human immunodeficiency virus (HIV) 1 or 2 at screening 11. Evidence of hepatitis C virus (HCV) antibody at screening require reflex testing for HCV RNA. Participant with positive HCV RNA viral load at screening will be excluded. Participants with positive HCV Ab, but negative HCV RNA viral load are eligible but should be monitored throughout the study 12. Evidence of active or prior hepatitis B virus (HBV) infection. Participants with positive hepatitis B surface antigen (HBsAg) at screening are excluded from the study. Participants with positive HBV core Ab and HBV DNA viral load at screening are excluded from the study 13. Known genetic deficiencies of the complement cascade system 14. Active alcohol or substance abuse or any other reason that makes it unlikely that the participant will comply with study procedures 15. Females who are pregnant (positive serum pregnancy test at screening or positive urine pregnancy test on Day 1) or lactating 16. Hypersensitivity to any of the excipients in the ANX005 drug product 17. Hypersensitivity to or previous allergic reaction to the active substance or to any of the excipients in any of the immunizations required for this study 18. History of previous sensitivities or allergic or anaphylactic reactions to previous IV medication 19. Platelet count <30 × 109/L 20
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the safety and tolerability of multiple intravenous doses of 100 mg/kg ANX005 in participants with CAD;Primary end point(s): Incidence and severity of treatment-emergent adverse events (AEs);Secondary Objective: - To evaluate the pharmacokinetics (PK) of ANX005 in participants with CAD - To evaluate the effect of ANX005 on classical complement pathway inhibition as measured by complement system related biomarkers in participants with CAD - To assess the effect of multiple intravenous doses of ANX005 on the markers of disease activity in participants with CAD - To assess the effect of multiple intravenous doses of ANX005 on fatigue;Timepoint(s) of evaluation of this end point: Continuous evaluation for the duration of the subject's participation in the study | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Continuous evaluation for the duration of the subject's participation in the study;Secondary end point(s): - Serum ANX005 concentrations over time - Change from baseline in levels of classical complement pathway biomarkers (e.g. C1q, C4, CH50, cellular complement deposition) - Change from baseline in levels of the following disease activity markers: Hemoglobin (Hgb) Lactate dehydrogenase (LDH) Total and indirect bilirubin Haptoglobin Absolute reticulocyte count - Change from baseline in FACIT-Fatigue scores over time - Proportion of participants achieving FACIT-Fatigue score =40 over time | — |
Countries
Austria
Contacts
Public ContactClinical Project Manager at CRO
Celerion Austria GmbH
Outcome results
None listed