Clinical Drug Experience Knowledgebase

Criteria

Inclusion Criteria:

Part A/B:

healthy male or female volunteers, age >= 18 years old
if female, must be post-menopausal, surgically sterilized, or willing/able to use dual, redundant methods of contraception (e.g., barrier plus oral contraceptives) throughout the study
previously vaccinated against encapsulated bacterial pathogens (Neisseria meningitidis, Haemophilus influenzae, and Streptococcus pneumoniae) or willing to undergo vaccination
able to comprehend and to give informed consent
able to co-operate with the investigator, to comply with the requirements of the study, and to complete the full sequence of protocol-related procedures

Part C:

male or female, age >=18 years old
if female, must be post-menopausal, surgically sterilized, or willing/able to use dual, redundant methods of contraception (e.g., barrier plus oral contraceptives) throughout the study
previously vaccinated against encapsulated bacterial pathogens (Neisseria meningitidis, Haemophilus influenzae, and Streptococcus pneumoniae) or willing to undergo vaccination
able to comprehend and to give informed consent
able to co-operate with the investigator, to comply with the requirements of the study, and to complete the full sequence of protocol-related procedures

History of one of the following complement-mediated disorders:

bullous pemphigoid (BP)
cold agglutinin disease (CAD)
warm autoimmune hemolytic anemia (WAIHA)
active Antibody-Mediated Rejection (AMR) (acute or chronic) after kidney transplantation

If CAD, by medical history within the 3 months preceding enrollment, and again at the screening visit:

- Has hemoglobin < 11.0 g/dL

If AMR:

is >= 180 days post-kidney transplantation with biopsy-proven late AMR
has a functioning kidney graft with epidermal growth factor receptor (eGFR) >= 20ml/min/1.73m^2
has evidence of late, active AMR (acute or chronic) present on renal allograft biopsy:
molecular signature indicating AMR (molecular AMR score > 0.2)
morphological and immunohistochemical findings consistent with AMR according to the criteria of the Banff 2013 classification
morphological findings consistent with an active rejection process: presence of glomerulitis (g score > 0) and / or peritubular capillaritis (ptc score > 0)
has immunoglobulin G (IgG) type donor-specific antibody (DSA) present in serum (at time of renal allograft biopsy) with MFI > 1000 in single antigen bead assays
is willing and able to take routine antibiotic prophylaxis with ciprofloxacin

Part E:

male or female, age >= 18 years old
Body weight of >=39 kg at Screening
history of cold agglutinin disease (CAD) and previously treated with BIVV009 in a BIVV009 clinical trial or named patient program use

For subjects currently being treated in a BIVV009 named patient program:

- Evidence of treatment response

For subjects previously treated in a BIVV009 clinical trial or named patient program not currently receiving BIVV009:

Prior evidence of treatment efficacy and hemoglobin <=10.5 g/dL at Screening or Visit 1 (Day 1) or
Successful treatment of underlying malignancy or warm autoimmune hemolytic anemia as defined as either:
Bone marrow biopsy without evidence of overt hematologic malignancy within the prior 3 months
IgG Direct Antiglobulin Test with <=1+ at Screening Visit
active hemolysis, with total bilirubin > upper limit of normal (ULN) at the Screening Visit or Visit 1 (Day 1)
adequate IV access
negative hepatitis panel (including hepatitis B surface antigen and hepatitis C virus antibody), negative human immunodeficiency virus (HIV) antibody screen and no further clinically significant infection (e.g., pneumonia) at Screening
if female, must be post-menopausal, surgically sterilised or willing and able to use highly effective methods of birth control throughout the study and for 9 weeks after the last administration of study drug
able to comprehend and to give informed consent

Exclusion Criteria:

Part A/B:

clinically significant medical history or ongoing chronic illness that would jeopardize the safety of the subject or compromise the quality of the data derived from his/her participation in this study
clinically relevant infection of any kind within the preceding month
clinically relevant abnormal findings on physical examination or clinically relevant laboratory abnormalities
history of infusion hypersensitivity, allergic or anaphylactic reactions to other therapeutic proteins
substance abuse, mental illness, or any reason that makes it unlikely in the judgment of the Investigator for the subject to be able to comply fully with study procedures
use of medication during 2 weeks before the start of the study, which in the judgment of the investigator may adversely affect the subject's welfare or the integrity of the study's results (excluding hormonal contraception in female subjects)
females who are pregnant (positive pregnancy test at screening or during study phase), lactating, or, if having reproductive potential, are considered potentially unreliable with respect to contraceptive practice
concurrent treatment with other experimental drugs or participation in another clinical trial with any investigational drug within 30 days prior to treatment start
body weight > 98 kg for all subjects in all dose cohorts other than the 100 mg/kg dose cohort of Part A, for which the body weight upper limit is 58 kg

Part C:

active acute or chronic viral, bacterial, fungal, or mycobacterial infection, or history of same within preceding month
autoimmune disorder other than the complement-mediated disorders listed in the Inclusion Criteria
known malignancy (other than locally limited, previously surgically removed basal cell carcinoma of the skin, lymphoproliferative disorders causally related to the complement-mediated diseases under study, etc.)
clinically significant hepatobiliary disorder
history of infusion hypersensitivity, allergic or anaphylactic reactions to other therapeutic proteins
substance abuse, mental illness, or any reason that makes it unlikely in the judgment of the Investigator for the subject to be able to comply fully with study procedures
females who are pregnant (positive pregnancy test at screening or during study phase), lactating, or, if having reproductive potential, are considered potentially unreliable with respect to contraceptive practice
concurrent treatment with other experimental drugs or participation in another clinical trial with any investigational drug within 30 days prior to treatment start
body weight >98 kg

Solely for kidney transplantation patients with AMR:

acute graft dysfunction within preceding 1 month
rejection treatment within preceding 1 month
morphological or molecular features of T cell-mediated rejection on renal allograft biopsy
contraindication to ciprofloxacin

Part E:

concurrent or prior treatment within the 3 months immediately preceding the Screening Visit (although more remote prior treatment is permitted) with rituximab, azathioprine, or other immune-suppressive therapy (concurrent treatment with corticosteroids is allowed if on stable dose <= 10mg/day prednisone for previous 3 months)
concurrent or prior treatment within the 6 months immediately preceding the Screening Visit with rituximab combination therapy or other cytotoxic therapy (e.g., fludarabine, bendamustine, cyclophosphamide, ibrutinib or any other cytotoxic drugs)

For subjects previously treated in a BIVV009 clinical trial not currently receiving BIVV009:

Ferritin below the lower limit of normal. Concurrent treatment with iron supplementation is permitted if the patient has been on a stable dose for the previous 4 weeks
Erythropoietin deficiency. Concurrent treatment with erythropoietin is permitted if the patient has been on a stable dose for the previous 6 weeks
Clinical diagnosis of systemic lupus erythematosus (SLE); or other autoimmune disorders with anti-nuclear antibodies at Screening
Clinically significant medical history or ongoing illness that is new or progressed since last BIVV009 therapy 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.
concurrent plasma exchange therapy
females who are pregnant (positive pregnancy test at screening or during study phase), lactating, or, if having reproductive potential, are considered potentially unreliable with respect to contraceptive practice
concurrent treatment with other experimental drugs or participation in another clinical trial with any investigational drug within 30 days prior to treatment start or during the entire study
history of infusion hypersensitivity, or allergic or anaphylactic reactions to BIVV009.