Primary Cold Agglutinin Disease MedDRA version: 20.0 Level: PT Classification code 10073785 Term: Autoimmune haemolytic anaemia System Organ Class: 10005329 - Blood and lymphatic system disorders
Conditions
Interventions
Product Name: BIVV009
Product Code: BIVV009
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: BIVV009
Current Sponsor code: BIVV009
Other descriptive name: COMPLEMENT C1 ESTERASE INHIBIT
Sponsors
Bioverativ USA Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: All patients must meet all the following inclusion criteria to be enrolled: 1.Adult male and female patients = 18 years of age at Screening 2.Body weight of = 39 kg at Screening 3.Confirmed diagnosis of primary CAgD based on the following criteria: a.Chronic hemolysis b.Polyspecific direct antiglobulin test (DAT) positive c.Monospecific DAT strongly positive for C3d d.Cold agglutinin titer = 64 at 4 degrees Celsius e.IgG DAT = 1+, and f.No overt malignant disease 4.Hemoglobin level = 10.0 g/dL 5.Bilirubin level above the normal reference range 6.Ferritin levels within the normal reference ranges unless outside normal range and deemed not clinically significant by the Investigator (or designee) 7.Presence of one or more of the following CAgD-related signs or symptoms within 3 months of Screening: a.Symptomatic anemia defined as: i.Fatigue ii.Weakness iii.Shortness of breath iv.Palpitations, fast heart beat v.Light headedness and/or vi.Chest pain b.Acrocyanosis c.Raynaud’s syndrome d.Hemoglobinuria e.Disabling circulatory symptoms, and/or f.Major adverse vascular event (including thrombosis) 8.Bone marrow biopsy within 6 months of Screening with no overt evidence of lymphoproliferative disease or other hematological malignancy. An additional bone marrow biopsy will be required if the prior bone marrow is deemed unsuitable for analysis by the Sponsor. 9.Vaccinations against encapsulated bacterial pathogens (Neisseria meningitis, Meningitis B, Haemophilus influenzae, and Streptococcus pneumoniae) within 5 years of enrollment or as specified in Appendix B 10.Adequate IV access 11.If female, must be post-menopausal, surgically sterile, or be established on (= 3 months prior to Screening) and agree to continue to use the same highly effective methods of birth control throughout the study and for 6 weeks following administration of the last dose of study drug 12.Males must be surgically sterile for at least 90 days or when sexually-active with female partners of child-bearing potential will agree to use highly effective contraception from Day 0 until 6 weeks following administration of the last dose of study drug 13.Able to comprehend and give informed consent 14.Able to comply with the requirements of the study and to complete the full sequence of protocol-related procedures. 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 4 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 36
Exclusion criteria
Exclusion criteria: Patients who meet any of the following criteria will be excluded from the study: 1.Cold agglutinin syndrome secondary to infection, rheumatologic disease, or active hematologic malignancy 2.History of 1 or more blood transfusions within 6 months of enrollment 3.Clinically relevant infection of any kind within the month preceding enrollment (eg, active hepatitis C, pneumonia) 4.Clinical diagnosis of SLE; or other autoimmune disorders with anti-nuclear antibodies at Screening 5.Positive hepatitis panel (including hepatitis B surface antigen and/or hepatitis C virus antibody) prior to or at Screening 6.Positive human immunodeficiency virus (HIV) antibody at Screening 7.Treatment with rituximab monotherapy within 3 months or rituximab combination therapies (eg, with bendamustine, fludarabine, ibrutinib, or cytotoxic drugs) within 6 months prior to enrollment 8.Concurrent treatment with corticosteroids other than a stable daily dose equivalent to = 10 mg/day prednisone for previous 3 months 9.Erythropoietin deficiency. Concurrent treatment with erythropoietin is permitted if the patient has been on a stable dose for the previous 3 months 10.Concurrent usage of iron supplementation unless the patient has been on a stable dose for at least 4 weeks 11.Clinically significant medical history or ongoing chronic illness that would jeopardize the safety of the patient or compromise the quality of the data derived from his/her participation in this study (as determined by the Investigator [or designee]) at Screening 12.Concurrent treatment with other experimental drugs or participation in another clinical trial with any investigational drug within 30 days or 5 half lives, whichever is greater, prior to treatment start 13.Females who are pregnant, lactating, or, if having reproductive potential, are considered potentially unreliable with respect to contraceptive practice.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of Part A is to determine whether BIVV009 administration results in a = 1.5 g/dL increase in hemoglobin (Hgb) level and avoidance of transfusion in patients with primary CAgD without a recent history of blood transfusion. The primary objective of Part B is to evaluate the long-term safety and tolerability of BIVV009 in patients with primary CAgD.;Secondary Objective: The secondary efficacy objectives of Part A are: To assess the effect of BIVV009 on clinical events and laboratory parameters related to hemolysis and anemia in patients with primary CAgD To assess the effect of BIVV009 on specific complications of CAgD To assess the effect of BIVV009 on quality of life (QOL) in patients with primary CAgD. The secondary objective of Part B is to investigate the durability of response during long-term treatment with BIVV009 in patients with primary CAgD.;Primary end point(s): The primary efficacy endpoint is the responder rate: A patient will be considered a responder if he or she did not receive a blood transfusion from Week 5 through Week 26 (EOT) and did not receive treatment for CAgD beyond what is permitted per protocol. Additionally, the patient’s Hgb level must meet the following criterion: •Hgb increase = 1.5 g/dL from baseline (defined as the last Hgb value before administration of the first dose of study drug) at treatment assessment endpoint (defined as mean value from Weeks 23, 25, and 26);Timepoint(s) of evaluation of this end point: Week 26 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Efficacy Endpoints (Part A) Mean change from baseline in Hgb at treatment assessment endpoint (mean of values at Week 23, 25, and 26) Mean change from baseline in bilirubin (excluding patients with Gilbert’s Syndrome) at treatment assessment endpoint Mean change from baseline in QOL, as assessed by the change in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale (Appendix E) scores at the treatment assessment endpoint Mean change from baseline in lactate dehydrogenase (LDH) at the treatment assessment endpoint Incidence of solicited symptomatic anemia at EOT Efficacy Endpoints (Part B) The following parameters of disease activity will be assessed: ?Hemoglobin ?Bilirubin (total) ?QOL assessments (FACIT-fatigue, EQ-5D-5L, SF-12, and PGIC Scale) ?LDH ?Transfusion requirements?Haptoglobin;Timepoint(s) of evaluation of this end point: Week 23, 25, and 26 | — |
Countries
Australia, Austria, Belgium, Canada, Denmark, France, Germany, Hungary, Israel, Italy, Japan, Norway, Poland, Spain, Switzerland, United Kingdom, United States
Contacts
Public ContactClinical Trial Dept
Bioverativ USA Inc.
Outcome results
None listed