Patients with Cold Agglutinin Disease (CAD) MedDRA version: 20.0 Level: PT Classification code 10073785 Term: Autoimmune haemolytic anaemia System Organ Class: 10005329 - Blood and lymphatic system disorders
Conditions
Interventions
Trade Name: APL-2
Product Name: PEGCETACOPLAN (APL-2)
Product Code: [2019171-69-6]
Pharmaceutical Form: Solution for injection/infusion
INN or Proposed INN: Pegcetacoplan
CAS Number: 2019171-69-6
Curr
Sponsors
SWEDISH ORPHAN BIOVITRUM AB (PUBL)
Eligibility
Sex/Gender
All
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: 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 >= to 64 at 4 °C. 3. Hb level =65 years) no F.1.3.1 Number of subjects for this age range
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 4 weeks) and are not able or willing to refrain from using them during the study. 2. Treatment with rituximab monotherapy within 12 weeks prior to randomization, or rituximab combination therapies (e.g., with bendamustine, fludarabine, other cytotoxic drugs or ibrutinib) 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. 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. 8. HIV or hepatitis C virus detectable by polymerase chain reaction at screening or documented in the patient's medical record. 9. Chronic inactive hepatitis B virus with viral loads > 1000 IU/mL (>5000 copies/mL) at screening or documented in the patient's medical record. Eligible patients who are chronic active carriers ( 1+. 12. Presence or suspicion of liver dysfunction as indicated by elevated alanine aminotransferase (ALT) >¿2.5 x ULN, or direct bilirubin levels > 2x ULN . 13. Presence or suspicion of severe recurrent or chronic infections that, in the opinion of the investigator, increase the patient's risk by participating in the study. 14. Participation in any other investigational drug trial or exposure to other investigational agent, device or procedure within 30 days prior to screening period. 15. If breastfeeding, is unwilling to discontinue for the duration of study and for at least 8 weeks after the final IMP dose. 16. Inability to cooperate with study procedures. 17. Any disease(s), psychiatric condition, metabolic dysfunction, or findings from a physical examination or clinical laboratory test result that would cause reasonable suspicion of a disease or condition that may jeopardize the patient's wellbeing, that may increase the risk associated with study participation, that may affect the interpretation of the results, or that would make the patient unsuitable for this study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate the efficacy of twice-weekly subcutaneous (s.c.) 1080-mg infusions of pegcetacoplan compared with that of placebo in patients with CAD;Secondary Objective: • To demonstrate the effect of pegcetacoplan on the number of packed red blood cell (PRBC) transfusions in patients with CAD. • To demonstrate the effect of pegcetacoplan on health-related quality of life in patients with CAD. • To assess the effect of pegcetacoplan on clinical laboratory markers of hemolysis and transfusion dependence in patients with CAD. • To determine the durability of response in patients with CAD receiving pegcetacoplan. • To assess tolerability, safety and immunogenicity of pegcetacoplan in patients with CAD. • To describe long-term effect of pegcetacoplan in patients with CAD.;Primary end point(s): 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.;Timepoint(s) of evaluation of this end point: week 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Part A: • Number of PRBC transfusions from Week 5 to Week 24. • Change from Baseline to Week 24 in the following: • Lactate dehydrogenase (LDH) level. • Haptoglobin level. • Indirect bilirubin level. • Absolute reticulocyte counts (ARC). • D-dimer level. • Normalization of markers of hemolysis at Week 24, specifically: • LDH level. • Indirect bilirubin level. • ARC. • Time to normalization from Baseline to Week 24 for the following: • Hb level. • LDH level. • Indirect bilirubin level. • ARC. • Number of PRBC units transfused from Week 5 to Week 24. • Change from Baseline to Week 24 in the following: • 12-Item Short Form Survey (SF-12) score. • 5-Level EuroQol 5-Dimension (EQ-5D-5L) score. Part B: • Change from Baseline to Week 48 in the following: • Hb level. • LDH level. • Haptoglobin level. • Indirect bilirubin level. • ARC. • D-dimer level. • Normalization of markers of hemolysis at Week 48, specifically: • LDH level. • Indirect bilirubin level. • ARC. • Time to normalization from Baseline to Week 48 for the following: • Hb level. • LDH level. • Indirect bilirubin level. • ARC. • Durability of response for patients randomized to pegcetacoplan who achieve the primary endpoint at Week 24 (patients are considered to maintain response until they receive a blood transfusion or they experience Hb decrease by at least 1.5 g/dL from the highest level achieved or to below 10.0 g/dL). • Change from Baseline to Week 48 in the following: • FACT-An score. • SF-12 score. • EQ-5D-5L score.;Timepoint(s) of evaluation of this end point: From Week 5 to Week 24. From Baseline to Week 48 | — |
Countries
Austria, Bulgaria, Canada, Finland, France, Georgia, Germany, Hungary, Italy, Japan, Norway, Russian Federation, Spain, Ukraine, United Kingdom, United States
Contacts
Public ContactAnke Arnold
Swedish Orphan Biovitrum AB
Outcome results
None listed