Primary:• Part A: To evaluate the safety and tolerability of subcutaneous injections of isatuximab in adults with wAIHA.• Part B: To evaluate the efficacy of the selected dose in adults with wAIHA.Secondary:• Part A (Cohorts 2 and 3 only)-To…
ID
Source
Brief title
Condition
- Autoimmune disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Part A:
- To assess safety and tolerability
Part B:
- To evaluate overall response rate (R) or complete response (CR) at Day 85
Secondary outcome
Part A (Cohorts 2 and 3 Only):
- To evaluate overall response rate (R) or complete response (CR) at Day 85
- Proportion of participants with durable hemoglobin response by Day 169
- Overall response rate at Day 169, median time to R or CR, median time to loss
of R or CR, proportion of participants requiring rescue therapy (any
wAIHA-directed therapy other than prednisone or transfusion) or splenectomy
- FACIT-fatigue scale score
Part B
- To assess safety and tolerability
- Proportion of participants with durable hemoglobin response by Day 169
- Overall response rate at Day 169, median time to PR or CR, median time to
loss of PR or CR, proportion of participants requiring rescue therapy (any
wAIHA-directed therapy other than prednisone or transfusion) or splenectomy
- FACIT-fatigue scale score
Part A (All cohorts) and B
- Change from baseline in LDH, haptoglobin, reticulocytes, and total bilirubin
- PK parameters after subcutaneous administrations
- Incidence and titer (if relevant) of anti-isatuximab antibodies
Background summary
The purpose of the study is to evaluate the safety of isatuximab injected
subcutaneously, how well tolerated it is, and to see if it can increase
hemoglobin levels and reduce the need for blood transfusions and other
medications for anemia in adults who have warm autoimmune hemolytic anemia.
Additional purposes of the study are to see how treatment with isatuximab may
help fatigue, to measure how isatuximab is distributed and
removed from the body, and to determine if the body develops antibodies against
isatuximab.
Study objective
Primary:
• Part A: To evaluate the safety and tolerability of subcutaneous injections of
isatuximab in adults with wAIHA.
• Part B: To evaluate the efficacy of the selected dose in adults with wAIHA.
Secondary:
• Part A (Cohorts 2 and 3 only)
-To evaluate the efficacy of isatuximab in adults with wAIHA
-To evaluate the durability of response to isatuximab and time to response
-To evaluate the impact of isatuximab treatment on fatigue
• Part B
-To evaluate the safety and tolerability of isatuximab in adults with wAIHA
-To evaluate the durability of response to isatuximab and time to response
-To evaluate the impact of isatuximab treatment on fatigue
• Parts A (all Cohorts) and B
-To evaluate the effect of isatuximab on markers of hemolysis
-To characterize the pharmacokinetic profile of isatuximab in adults with wAIHA
-To evaluate the immunogenicity of isatuximab
Study design
Multicenter, open-label, non-randomized, Phase 1b/2 study.
Intervention
Part A, Cohort 1: 140 mg every 2 weeks x 2
Part A, Cohort 2: 70 mg, or 140 mg, or 280 mg every 2 weeks x 6
Part A, Cohort 3, and Part B: every 2 weeks x 6; dose level to be determined
based on results from prior Cohorts; the dose will not exceed 560 mg
Study burden and risks
Risks and burdens related to blood collection, study procedures and possible
adverse events.
Paasheuvelweg 25
Amsterdam 1105 BP
NL
Paasheuvelweg 25
Amsterdam 1105 BP
NL
Listed location countries
Age
Inclusion criteria
Participant must be >=18 to years of age, inclusive, at the time of signing the
informed consent.
- Males and females with a confirmed diagnosis of primary w AIHA or systemic
lupus erythematosus (SLE)-associated wAIHA (without other SLE-related
manifestations apart from cutaneous and musculoskeletal manifestations) who
meet the following criteria:
a) Hemoglobin level <10 g/dL at screening.
b) Hemolysis (haptoglobin <=40 mg/dL and total or indirect/unconjugated
bilirubin above the upper limit of normal).
c) Positive direct antiglobulin test (DAT) (IgG or IgG + complement C3d pattern
or IgM warm autoantibodies (positive dual DAT)).
- Participants who have previously failed to maintain a sustained response
after treatment with corticosteroids (corticosteroid-refractory or
corticosteroid-dependent primary wAIHA).
- Part A only: Participants who have previously failed to maintain a sustained
response after treatment with rituximab (or other anti-CD20 monoclonal
antibodies). The last dose of the anti-CD20 antibody must have been
administered at least 12 weeks before enrollment.
- Part B: Participants who have had an insufficient response to at least 1
prior therapy in addition to corticosteroids (splenectomy is regarded as a
prior therapy).
- Contraceptive use by men and women.
Exclusion criteria
Participants are excluded from the study if any of the following criteria apply:
- Clinically significant medical history or ongoing chronic illness that would
jeopardize the safety of the participant or compromise the quality of the data
derived from his or her participation in the study as determined by the
Investigator.
- Serious infection that required hospitalization within 3 months prior to
enrollment.
- Secondary wAIHA from any cause including drugs, lymphoproliferative
disorders, infectious or autoimmune disease (SLE without other SLE-related
manifestations apart from cutaneous and musculoskeletal manifestations is
allowed), or active hematologic malignancies. Participants with positive
antinuclear antibodies but without a definitive diagnosis of an autoimmune
disease are allowed.
- History of coagulation or bleeding disorders (Evans Syndrome is allowed).
- Uncontrolled or active HBV or HCV infection.
- HIV infection.
- Serum gammaglobulin levels <3 g/L.
- Females who are pregnant, lactating, or considered unreliable with respect to
contraceptive practice.
- Concurrent treatment with corticosteroids, unless the participant has been on
a stable daily dose for >= 15 days prior to enrollment.
- Treatment with cyclophosphamide within 4 weeks prior to enrollment.
- Treatment with cytotoxic drugs (other than cyclophosphamide) within 12 weeks
prior to enrollment.
- Treatment with non-cytotoxic, immunomodulatory drugs (including but not
limited to Cyclosporine, Sirolimus, Tacrolimus, Idelalisib, Ibrutinib),
excluding biologic agents, within 4 weeks prior to enrollment.
- Treatment with any biologic agent within 12 weeks prior to enrollment.
Design
Recruitment
Medical products/devices used
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
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 | 202000388024 |
EudraCT | EUCTR202000388024-NL |
CCMO | NL75800.058.21 |