To evaluate the effect of crizanlizumab + standard of care compared to standard of care alone on albuminuria (ACR) decrease at 12 months
ID
Source
Brief title
Condition
- Haemoglobinopathies
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Proportion of patients with * 30% decrease in ACR at 12 months compared to
baseline
Secondary outcome
Mean change in ACR from baseline to 3, 6, 9, and 12 months of treatment
Proportion of patients with * 30% decrease in ACR at 6 months compared to
baseline
Proportion of patients with * 20% improvement of PCR at 12 months compared to
baseline
Proportion of patients with a stable (within ± 20% change) PCR at 12 months
compared to baseline
Percentage change in eGFR from baseline to 3, 6, 9, and 12 months of treatment
Background summary
Sickle cell disease is a genetic blood disorder, which early on progresses into
a systemic disease. Vaso-occlusion is
the hallmark of SCD and can lead to serious acute and chronic complications.
Vascular dysfunction, inflammation, and
P-selectin mediated cell-to-cell and cell-to-endothelium adhesion play an
important role in the pathophysiology of SCD.
Vaso-occlusive crisis (VOC) is the most common clinical manifestation of SCD.
Every VOC increases morbidity and
can result in organ damage/failure and/or death .
Preventive treatments to reduce the number of VOCs are limited. HU/HC is
approved to reduce the frequency of
painful crises and the need for transfusions
Kidney injury is a common problem in sickle cell patients and causes
complications. Of crizanlizumab there are indications that it can help to
prevent injury of the kidneys.
Study objective
To evaluate the effect of crizanlizumab + standard of care compared to standard
of care alone on albuminuria (ACR) decrease at 12 months
Study design
multicenter, randomized, open label, 2-arm phase 2 study
randomized 1:1
Intervention
crizanlizumab infusion over 30 minutes, every 4 weeks.
Study burden and risks
RISK : adverse events due to treatment with crizanlizumab of placebo
burden: cycles of 4 weeks during 5 years of study participation
during monthly visits : physical examinations, blooddraws, administration of
study medication
Haaksbergweg 16
Amsterdam 1101 BX
NL
Haaksbergweg 16
Amsterdam 1101 BX
NL
Listed location countries
Age
Inclusion criteria
1. Male and female patients * 16 years on the day that signed informed consent
is obtained
2. Confirmed diagnosis of SCD. Homozygous HbS and HbS*0-thal SCD genotypes are
eligible
3. eGFR * 45 to * 140 mL/min/1.73 m2 based on CKD-EPI formula (patients * 18)
or the Creatinine-based *Bedside Schwartz* equation (patients < 18)
4. ACR of * 100 to < 2000 mg/g (taken as an average of the three screening ACR
values to determine eligibility)
5. Receiving standard of care drug(s) for SCD and/or CKD.
6. Hb * 4.0 g/dL, ANC * 1.0 x 109/L, and platelet count * 75 x 109/L
7. ECOG performance status * 2.0
Exclusion criteria
1. History of stem cell transplant
2. Patients with evidence of AKI within 3 months of study entry (can decrease
interval to within 6 weeks of study entry only if renal function has returned
to pre-AKI values prior to study entry)
3. Blood pressure > 140/90 mmHg despite treatment
4.Patients undergoing renal replacement therapy (i.e. hemodialysis, peritoneal
dialysis, hemofiltration and kidney transplantation)
5. Participating in a chronic transfusion program
6. History of kidney transplant
7. Patients with hypoalbuminemia
8.Patient has received crizanlizumab and/or other selectin inhibitor or plans
to receive it during the duration of the study
9. History of or current diagnosis of ECG abnormalities indicating significant
risk of safety
10. Current drug or alcohol abuse:
11. Pregnant or nursing (lactating) women
Design
Recruitment
Medical products/devices used
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 |
|---|---|
| EudraCT | EUCTR2018-003608-38-NL |
| ClinicalTrials.gov | NCT04053764 |
| CCMO | NL71644.018.19 |