autoimmune hemolytic anemia cold antibody hemolytic anemia
Conditions
Interventions
Part A
Double-blind treatment period (24 weeks):
Patients randomized into the study will receive s.c. IMP (pegcetacoplan or
placebo) twice weekly for 24 weeks.
Part B
Open-label treatment period (24
Sponsors
Swedish Orphan Biovitrum AB
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: 1. Age18 years or older. 2. Diagnosis of primary CAD on the basis of the presence of all the following criteria at screening: a. Signs of hemolysis with abnormal values by at least 2 of the following hemolytic markers: i. Reduced haptoglobin level ( ULN). iii. Elevated indirect bilirubin level (> ULN; > 3 x ULN for patients with Gilbert-Meulengracht Syndrome). iv. Increased ARC (above the ULN). b. Monospecific direct antiglobulin test strongly positive for C3d. c. Cold agglutinin titer >= 64 at 4 °C. 3. Hb level = 1500 cells/mm3 at screening. 5. Documented results from bone marrow biopsy within 1 year of screening with lymphoproliferative infiltration
Exclusion criteria
Exclusion criteria: 1. Have received other anticomplement therapies (approved or investigational) within 5 half-lives of the agent prior to randomization (e.g., eculizumab within 10 weeks, ravulizumab within 36 weeks or sutimlimab within 15 weeks) and are not able or willing to refrain from using them during the study. Patients previously treated with > 1 dose of sutimlimab will be excluded if they have not experienced a documented increase in Hb >= 1.0 g/dL during sutimlimab treatment. 2. Treatment with belimumab, rituximab or other anti-CD20 antibody (such as obinutuzumab or ocrelizumab), or with bendamustine, fludarabine, other cytotoxic drugs, or Bruton tyrosine kinase inhibitors such as ibrutinib, acalabrutinib and zanubrutinib, alone or in combination with rituximab within 16 weeks prior to randomization. 3. Use of prohibited medications as described in the protocol. The list of acceptable medications and required stable regimen periods are outlined in the study protocol. 4. Diagnosis of systemic lupus erythematosus or other autoimmune diseases with antinuclear antibodies (antinuclear antibodies of long-standing duration without associated clinical symptoms will be adjudicated on a case-by-case basis by the investigator after discussion with the medical monitor). 5. History of an aggressive lymphoma or presence of a lymphoma requiring therapy. 6. Have received an organ transplant. 7. Cold agglutinin syndrome secondary to Mycoplasma pneumoniae, Epstein-Barr virus or other specific causative infection. In patients with long history of CAD, positive IgM titer and IgG titer without associated clinical symptoms will be adjudicated on a case-by-case basis by the investigator after discussion with the medical monitor. 8. HIV or hepatitis C virus detectable by polymerase chain reaction at screening or documented in the patient*s medical record. 9. Chronic hepatitis B virus carriers with viral loads > 1000 IU/mL (> 5000 copies/mL) at screening or documented in the patient*s medical record. Eligible patients who are chronic inactive carriers ( 1+. 12. Presence or suspicion of liver dysfunction as indicated by elevated alanine aminotransferase (ALT) > 2.5 x ULN, or direct bilirubin levels > 2 x ULN. For any patient with increased direct bilirubin, the investigator should exercise medical judgement to ensure that the increased direct bilirubin value is due to hemolysis and discuss inclusion with the medical monitor. If the direct bilirubin is higher than the indirect bilirubin, in addition a thorough search for exclusion of underlying liver or cholestatic disease, including but not necessarily limited to abdominal ultrasound, is warranted to exclude liver and/or cholestatic disorders. 13. Hypersensitivity to pegcetacoplan or to any of the excipients or placebo compounds. 14. Known or suspected hereditar
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Response to treatment at Week 24. Response is defined as: • An increase in hemoglobin (Hb) of >= 1.5 g/dL from Baseline or Hb normalization at Week 16; AND • Maintenance of this effect from Week 16 to Week 24; AND • The absence of PRBC transfusions (between Week 5 and Week 24). Note: Hb normalization is defined as within normal range (between the defined upper and lower limits of normal [ULN and LLN]), as set by the testing laboratory. | — |
Secondary
| Measure | Time frame |
|---|---|
| Key secondary endpoints: • Change from Baseline to Week 24 in Hb level. • Transfusion avoidance (Yes/No) from Week 5 to Week 24. • Change from Baseline to Week 24 in the Functional Assessment of Cancer Therapy-Anemia/Fatigue (FACT-An) score. | — |
Countries
Netherlands
Outcome results
None listed