Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202006732730001 Date of Approval: 30/06/2020
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Study exploring the effect of crizanlizumab on kidney function in patients with chronic kidney disease caused by sickle cell disease
Official scientific title A Phase II, multicenter, randomized, open label two arm study comparing the effect of crizanlizumab + standard of care to standard of care alone on renal function in sickle cell disease patients ≥ 16 years with chronic kidney disease due to sickle cell nephropathy (STEADFAST)
Brief summary describing the background and objectives of the trial The purpose of this study is to explore the effect of P-selectin inhibition with crizanlizumab on renal function in sickle cell disease (SCD) patients with chronic kidney disease (CKD) who are receiving standard of care medications for SCD and/or CKD, have albuminuria and Stage 1-3a CKD, and have evidence of a rapid decline in their estimated glomerular filtration rate (eGFR). The presence of P selectin expression in the kidneys has been established based on in vitro and in vivo data, and there is evidence that P selectin is upregulated in the kidney in response to renal ischemia-reperfusion injury in SCD. Expression of P-selectin in a glomerulonephritis induced mouse model was associated with rapid accumulation of neutrophils in glomeruli and significant proteinuria. P-selectin inhibition in this model was shown to abrogate glomerular neutrophil accumulation and prevented development of proteinuria. The hypothesis is that administration of crizanlizumab, a P selectin inhibitor, might have a beneficial effect in SCD patients with CKD by blocking P-selectin mediated multicellular adhesion (including leukocytes), and proteinuria, and also reducing vaso occlusion and potentially its downstream effects in the renal vasculature, which can be clinically demonstrated by a decrease in proteinuria and slowing the decline in glomerular filtration rate (GFR). If the study is able to demonstrate a positive effect of crizanlizumab on albumin to creatinine ratio (ACR) reduction and the progression of CKD, this could provide positive evidence of a reno protective effect of crizanlizumab.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) STEADFAST
Disease(s) or condition(s) being studied Haematological Disorders
Sub-Disease(s) or condition(s) being studied
Purpose of the trial Treatment: Drugs
Anticipated trial start date 22/10/2020
Actual trial start date
Anticipated date of last follow up 29/07/2022
Actual Last follow-up date
Anticipated target sample size (number of participants) 41
Actual target sample size (number of participants)
Recruitment status Recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Randomised Stratified allocation where factors such as age, gender, center, or previous treatment are used in the stratification Central randomisation by phone/fax Masking/blinding used Care giver/Provider,Outcome Assessors,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group SEG101 Crizanlizumab Crizanlizumab will be supplied in single use vials containing 10 mL at a concentration of 10 mg/mL. One vial contains 100 mg of crizanlizumab. Other Name: SEG101 12 months Patients will be randomly assigned to one of the following treatment arms in a ratio of 1:1: • Crizanlizumab + standard of care • Standard of care alone Any of the following drugs that the patient is receiving at study entry will be considered the patients standard of care: HU/HC, ACE inhibitors, and ARBs. The patient will continue to take their usual standard of care drugs during the study; thus, there may be some variation in the standard of care regimens used by patients in the study. 41
Control Group Placebo Comparotor The doses chosen for the SUSTAIN study (see Section 1.1.4.2 for further details) were based on P selectin inhibition by SelG1 evaluated in healthy patients, as well as the acceptable safety experience observed in the Phase I study [CSEG101A2101]. 12 months A placebo controlled study would allow a robust double blind assessment of the efficacy of crizanlizumab added to standard of care. While acknowledging the limitations of an open label study, the benefits of a blinded study design incorporating a placebo infusion were deemed not to outweigh the burden to the study patients for the current study. The open label nature of this study is considered acceptable as the assessment of the primary endpoint is based on an objective laboratory assessment, rather than a subjective measure. 41 Placebo
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
• Male and female patients ≥ 16 years on the day that signed informed consent is obtained • Confirmed diagnosis of SCD by hemoglobin (Hb) electrophoresis or high performance liquid chromatography [performed locally]. HbSS and HbSβ0 thal SCD genotypes are eligible • Patients with eGFR ≥ 45 to ≤ 120 mL/min/1.73 m2 based on Chronic Kidney Disease Epidemiology Collaboration formula • Patients with ACR of ≥ 100 to < 2000 mg/g • Receiving standard of care drug(s) for SCD and/or CKD. If receiving hydroxyurea (HU)/hydroxycarbamide (HC), angiotensin converting enzyme (ACE) inhibitor, and/or angiotensin receptor blocker (ARB) (and still with abnormal ACR despite treatment), must have been receiving the drug(s) for at least 6 months prior to study entry and plan to continue taking the drug(s) at the same dose and schedule until the patient has reached the end of the study • Hb ≥ 4.0 g/dL, absolute neutrophil count ≥ 1.0 x 109/L, and platelet count ≥ 75 x 109/L • Patients who are clinically stable and are in a non crisis state • History of stem cell transplant • Patients with evidence of AKI within 3 months of study entry • Blood pressure > 140/90 mmHg despite treatment • Patients undergoing hemodialysis • Received blood products within 30 days of Week 1 Day 1 • Participating in a chronic transfusion program (pre-planned series of transfusions for prophylactic purposes). Transfusions for acute complications are permitted (acute chest syndrome, acute splenic sequestration, acute hepatic sequestration, worsened anemia) • History of kidney transplant • Patients with hypoalbuminemia • Use of therapeutic anticoagulation or antiplatelet therapy (other than aspirin or non steroid anti inflammatory drugs) within the 10 days prior to Week 1 Day 1. Note: Prophylactic anticoagulant dose is permitted, as per local guidelines • Patients with active human immunodeficiency virus, Hepatitis B and Hepatitis C infection • Evidence of CKD attributed to causes other than SCN 80 and over: 80+ Year,Adolescent: 13 Year-18 Year,Adult: 19 Year-44 Year,Aged: 65+ Year(s),Child: 6 Year-12 Year,Middle Aged: 45 Year(s)-64 Year(s),Preschool Child: 2 Year-5 Year 1 Year(s) 80 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
No 03/07/2020 Korle Bu Teaching Hospital Independent Review Board
Ethics Committee Address
Street address City Postal code Country
Guggisberg Avenue, Accra, Accra 0000 Ghana
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 17/01/2020 University of the Witwatersrand Human Research Ethics Committe
Ethics Committee Address
Street address City Postal code Country
31 Princess of Wales Terrace, Parktown Johannesburg 2041 South Africa
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
No 03/07/2020 Gertrudes Institute of Child Health and Research Ethics Review Committee
Ethics Committee Address
Street address City Postal code Country
Muthaiga Road, Nairobi Nairobi 0000 Kenya
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
No 03/07/2020 KEMRI Scientific Ethics Review Unit SERU
Ethics Committee Address
Street address City Postal code Country
Muthaiga Road Nairobi 0000 Kenya
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome The primary endpoint of this study is the proportion of patients with ≥ 30% decrease in ACR at 12 months compared to baseline 12 moths
Secondary Outcome This will be supported by a secondary endpoint evaluating the proportion of patients with a ≥ 20% decrease in PCR. 12 months
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Ghana Institute Of Clinical Genetics Korle Bu Teaching Hospital Airport Road, Accra Ghana
Sickle Cell Office Directorate of Child Health Komfo Anokye Teaching Hospital Kumasi Ghana
Hemophilia Comprehensive Care Centre Charlotte Maxeke Johannesburg Academic Hospital York Road Johannesburg 2193 South Africa
WCR Wits Clinical Research Chris Hani Baragwanath Hospital Chris Hani Road Soweto 2013 South Africa
CREATES Strathmore University Ole Sangale Road Nairobi 0000 Kenya
International Cancer Institute Nandi Road Block 8/102 Eldoret 0000 Kenya
FUNDING SOURCES
Name of source Street address City Postal code Country
Novartis Pharma AG Lichtstrasse 35 Basel 4056 Switzerland
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Novartis Pharma AG Lichtstrasse 35 Basel 4056 Switzerland Commercial Sector/Industry
COLLABORATORS
Name Street address City Postal code Country
Professor Berhards Ogutu CREATES Strathmore University Ole Sangale Road, Madaraka Estate, PO Box 59857-00200 Nairobi, Kenya Nairobi 0000 Kenya
Dr Asirwa Fredrick Chite International Cancer Institute, Nandi Road Block 8/102. P O Box 8088-30100, Eldoret, Kenya Eldoret 0000 Kenya
Prof Johnny Mahlangu Hemophilia Comprehensive Care Centre Area 454 Room 31 Green Block Charlotte Maxeke Johannesburg Academic Hospital York Road Parktown Johannesburg South Africa 2193 Johannesburg 2193 South Africa
Professor Moosa Patel WCR Wits Clinical Research, Chris Hani Baragwanath Hospital, Chris Hani Road, Soweto, 2013 Soweto 2013 South Africa
Dr Yvonne Dei Adomakoh Ghana Institute Of Clinical Genetics, Korle Bu Teaching Hospital Airport Road, Korle Bu, Accra Accra Ghana
Dr Eunice Agyeman Ahmed Sickle Cell Office Directorate of Child Health Komfo Anokye Teaching Hospital Kumasi Ghana Kumasi Ghana
Dr Doreen Karimi Mutua Gertrude s Children s Hospital 34 Muthaiga Road Nairobi, Kenya Nairobi 0000 Kenya
CONTACT PEOPLE
Role Name Email Phone Street address
Public Enquiries Clinical Disclosure Officer Clinical Disclosure Officer Trialandresults.registries@novartis.com +41613241111 Novartis Pharma AG CH-4002
City Postal code Country Position/Affiliation
Basel 4002 Switzerland Clinical Disclosure Officer
Role Name Email Phone Street address
Principal Investigator Yvonne Dei Adomakoh deiadom@yahoo.com +233243550980 Ghana Institute Of Clinical Genetics, Korle Bu Teaching Hospital
City Postal code Country Position/Affiliation
Accra 0000 Ghana Head of Department
Role Name Email Phone Street address
Scientific Enquiries Clinical Disclosure Officer Clinical Disclosure Officer Trialandresults.registries@novartis.com +41613241111 Novartis Pharma AG CH 4002
City Postal code Country Position/Affiliation
Basel 4002 Switzerland Clinical Disclosure Officer
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com Clinical Study Report This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
URL Results Available Results Summary Result Posting Date First Journal Publication Date
No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information