Primary: The safety and tolerability of BIVV020Secondary: - The effect of BIVV020 on complement mediated hemolysis.- The pharmacodynamics (PD) of BIVV020 relating to complement inhibition.- The pharmacokinetics (PK) of BIVV020.- The immunogenicity…
ID
Source
Brief title
Condition
- Autoimmune disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Safety
* Assessment of adverse events (AE)/treatment-emergent adverse events (TEAE).
* Clinical laboratory evaluations including hematology, biochemistry, systemic
lupus erythematosus (SLE) panel testing, and urinalysis.
* Electrocardiographic (ECG) intervals (heart rate, PR, QRS, QT, and QTcF).
* Vital signs (blood pressure and heart rate).
Secondary outcome
Hematologic BA
* Total bilirubin.
* Hemoglobin.
Pharmacodynamics
* CP.
* Complement alternative pathway (AP).
* CH50.
* Total C4.
Pharmacokinetics
* Parameters (not limited to): Cmax, tmax, tlast, AUClast, AUC0-*, t1/2z, CL,
Vd.
Immunogenicity
* Anti-BIVV020 antibodies (ADA).
Background summary
BIVV020 is a humanized monoclonal antibody that binds to and selectively
inhibits the activated form of human serine protease complement component 1, s
subcomponent (C1s). By binding to activated C1s, BIVV020 prevents enzymatic
action of the C1 complex on its substrates, complement factors C4 and C2, and
thereby blocks formation of the C3 convertase. The result of this mechanism is
inhibition of complement classical pathway (CP) activity proximal in the
complement activation pathway to C3 which allows the alternative and lectin
pathways to remain functionally intact for the purpose of host defense. The CP
has been implicated in many diseases that are driven by the presence of a
pathogenic antibody;
primary Cold Agglutin Disease is one such example.
Cold agglutinin disease is an autoimmune hemolytic anemia caused by IgM-induced
CP activation.
This study will provide clinical data on the safety, tolerability,
pharmacokinetics (PK) and pharmacodynamics (PD) of BIVV020 in adults with CAD
to facilitate the dose/dosing regimen selection for future clinical studies
with BIVV020.
Study objective
Primary:
The safety and tolerability of BIVV020
Secondary:
- The effect of BIVV020 on complement mediated hemolysis.
- The pharmacodynamics (PD) of BIVV020 relating to complement inhibition.
- The pharmacokinetics (PK) of BIVV020.
- The immunogenicity of BIVV020.
Study design
The study initiates with an IV cohort and on-study decisions about selection of
the next cohort and/or expansion within a cohort are made based on clinical
response (total bilirubin and hemoglobin) and variability of response across
patients.
The study design includes up to three IV cohorts. The study will begin dosing
in Cohort 1a at a dose of 30 mg/kg. Following Cohort 1a, additional IV dose
levels, specifically Cohort 1b (higher dose) and/or 1c (lower dose), may be
used up to a maximum of 50 mg/kg IV or the highest tolerated dose tested in
normal healthy volunteers.
Intervention
Dosing will begin with a single dose of 30 mg/kg IV. Dosing will not exceed 50
mg/kg or the highest tolerated dose tested in normal healthy volunteers in any
cohort.
Study burden and risks
Risks and burdens related to blood collection, study procedures and possible
adverse events of study medication.
Paasheuvelweg 25
Amsterdam 1105 BP
NL
Paasheuvelweg 25
Amsterdam 1105 BP
NL
Listed location countries
Age
Inclusion criteria
- Male and/or female patients, * 18 years of age with cold agglutinin disease
as defined by:
a) Chronic hemolysis per Investigator*s judgement,
b) Polyspecific direct antiglobulin test (DAT) positive,
c) Monospecific DAT strongly positive for C3d,
d) Cold agglutinin (CAg) titer * 64 at 4°C; and,
e) IgG DAT *1+.
- A hemoglobin level *11 mg/dL.
- A total bilirubin level above the normal reference range that is thought to
be due to hemolysis.
- Documented vaccinations against encapsulated bacterial pathogens (Neisseria
meningitidis,
including serogroup B meningococcus and Streptococcus pneumoniae) within five
years of
screening or willing to complete protocol specified vaccinations.
- Having given written informed consent prior to undertaking any study-related
procedure.
Exclusion criteria
- Cold agglutinin syndrome secondary to infection, rheumatologic disease, or
known high grade
hematologic malignancy, or known solid organ tumor.
- Clinically relevant infection of any kind within one month preceding
screening.
- Treatment with anti-CD20 monotherapy within three months or anti CD20
combination therapies
within six months prior to screening.
- Concurrent treatment with systemic immunosuppressive agents targeting B- or
T-cell function
and/or cytotoxic agents within 3 months prior to screening. Concurrent
treatment with other
systemic immunosuppressants within 5.5 half-lives of the drug prior to
screening.
- Any specific complement system inhibitor within three months prior to
screening.
- Concurrent treatment with systemic corticosteroids other than a stable daily
dose equivalent to
*10 mg/day prednisone within three months prior to screening.
- If female, pregnant or lactating.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| Other | 2019-001844-22 |
| EudraCT | EUCTR2019-001844-22-NL |
| CCMO | NL74337.018.20 |