Safety, Tolerability and Activity of BIVV009 in Healthy Volunteers and Patients With Complement Mediated Disorders

• Register: ClinicalTrials.gov
• Last refreshed on: 2 May 2022
• Main ID: NCT02502903
• Date of registration: 07/07/2015
• Prospective Registration: Yes
• Primary sponsor: Bioverativ, a Sanofi company
• Public title: Safety, Tolerability and Activity of BIVV009 in Healthy Volunteers and Patients With Complement Mediated Disorders BIVV009-01
• Scientific title: Safety, Tolerability and Activity of BIVV009 in Healthy Volunteers and Patients With Complement-mediated Disorders. A Single/Multiple Ascending Dose Phase 1 Study.
• Date of first enrolment: July 13, 2015
• Target sample size: 122
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02502903
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 1

Countries of recruitment

Austria

Contacts

• Name: Clinical Sciences & Operations
• Affiliation: Sanofi

Key inclusion & exclusion 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


Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

End-stage Renal Disease (ESRD)

Bullous Pemphigoid (BP)

Warm Autoimmune Hemolytic Anemia (WAIHA)

Cold Agglutinin Disease (CAD)

Intervention(s)

Drug: BIV009

Other: Placebo

Primary Outcome(s)

Drug-related Adverse Event profile of BIVV009 [Time Frame: 6 weeks]

Secondary Outcome(s)

Classical pathway complement system activity [Time Frame: 6 weeks]

Disease-Related Biomarkers [Time Frame: 6 weeks]

Coagulation System-Related biomarkers [Time Frame: 6 weeks]

Pharmacokinetic profile of BIVV009 [Time Frame: 6 weeks]

Complement System-Related biomarkers [Time Frame: 6 weeks]

Secondary ID(s)

LTS16214

2014-003881-26

BIVV009-01

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

ABF Pharmaceutical Services GmbH

PPD Laboratories - Virginia

Celerion Clinical Research GmbH

Assign Data Management and Biostatistics GmbH

Softworld Inc. - Cambridge, MA

Covance Laboratories - Chantilly

Quest Diagnostics-Nichols Insitute