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.: PACTR202308685033448 Date of Approval: 17/08/2023
Trial Status: Retrospective registration - This trial was registered after enrolment of the first participant
TRIAL DESCRIPTION
Public title A Study Evaluating the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Crovalimab as Adjunct Treatment in Prevention of Vaso-Occlusive Episodes (VOE) in Sickle Cell Disease (SCD) (CROSSWALK-c)
Official scientific title A randomized double-blind phase 2A study evaluating the efficacy, safety, pharmacokinetics, and pharmacodynamics of crovalimab as adjunct treatment in prevention of vaso-occlusive episodes (voe) in sickle cell disease (scd)
Brief summary describing the background and objectives of the trial Sickle cell disease (SCD) is an autosomal recessive genetic disorder caused by the inheritance of a point mutation at position 6 in the beta-globin gene, replacing a glutamic acid with a valine (beta S). SCD affects millions of patients worldwide, with an estimated incidence of 300,000-400,000 affected neonates annually (Kato et al. 2018). This study will evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of crovalimab compared with placebo as adjunct treatment for the prevention of vaso-occlusive episodes (VOEs) in patients with sickle cell disease (SCD).
Type of trial RCT
Acronym (If the trial has an acronym then please provide) CROSSWALK c
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 09/03/2022
Actual trial start date 09/03/2022
Anticipated date of last follow up 26/07/2024
Actual Last follow-up date
Anticipated target sample size (number of participants) 90
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 Allocation was determined by the holder of the sequence who is situated off site Masking/blinding used Care giver/Provider,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Crovalimab Participants will receive a loading series of Crovalimab comprised of an intravenous (IV) loading dose on Day 1, followed by weekly Crovalimab subcutaneous (SC) doses for 4 weeks on Week 1 Day 2, then on Weeks 2, 3 and 4. Maintenance SC dosing will begin at Week 5 and will continue every 4 weeks (Q4W) thereafter for a total of 48 weeks of treatment. Participants will receive a loading series of Crovalimab comprised of an intravenous (IV) loading dose on Day 1, followed by weekly Crovalimab subcutaneous (SC) doses for 4 weeks on Week 1 Day 2, then on Weeks 2, 3 and 4. Maintenance SC dosing will begin at Week 5 and will continue every 4 weeks (Q4W) thereafter for a total of 48 weeks of treatment. Crovalimab will be administered at a dose of 1000 mg IV (for participants with body weight between 40 kg and 100 kg) or 1500 mg IV (for participants with body weight >= 100 kg) on Week 1 Day 1. On Week 1 Day 2 and on Weeks 2, 3 and 4, crovalimab will be administered at a dose of 340 mg SC. For Week 5 and Q4W thereafter, crovalimab will be administered at a dose of 680 mg SC (for participants with body weight between 40 kg and 100 kg) or 1020 mg SC (for participants with body weight >= 100 kg). Dosing schedule will be as per Arm Description. 45
Control Group Placebo Participants will receive matching Placebo administered by IV infusion and SC injection over the same duration as Crovalimab, for a total of 48 weeks of treatment. Participants will receive matching Placebo administered by IV infusion and SC injection over the same duration as Crovalimab, for a total of 48 weeks of treatment. Matching Placebo will be administered with the same dosing schedule and equivalent IV and SC volume as weight-based Crovalimab. 45 Dose Comparison
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
- Body weight >=40 kg. - Male or female with confirmed diagnosis of HbSS (SCD genotype of sickle cell anemia) or HbSβ0 (SCD genotype of sickle cell beta zero thalassemia). - Two or more (>=2) to <=10 documented VOEs in the 12 months prior to randomisation. - If receiving concurrent SCD-directed therapy, the participant must have been on a stable dose for a minimum of 3 months prior to study enrollment. There should be no plans to modify the participants' dosing throughout the study duration, other than for safety reasons. - If receiving erythropoietin, the participant must have been prescribed this medication for the preceding 3 months and be dose-stabilised for at least 3 months prior to study enrollment. - Vaccination against N. meningitides serotypes A, C, W, and Y and Vaccinations against H. influenza type B and S. pneumonia. - Participants who have been vaccinated (partially or in full) against SARS-CoV-2 with a locally approved vaccine are eligible to be enrolled in the study, 3 days or longer after inoculation. - Adequate hepatic and renal function. - For women of childbearing potential: agreement to remain abstinent or use contraception during the treatment period and for 10.5 months after the final dose of study treatment. - History of hematopoietic stem cell transplant. - Participating in a chronic transfusion program and/or planning on undergoing an exchange transfusion during the duration of the study. - History of hypersensitivity, allergic, or anaphylactic reactions to any ingredient contained in the study treatment. - Received active treatment on another investigational trial within 28 days (or within five half-lives of that agent, whichever is greater) prior to screening visit, or plans to participate in another investigational drug trial. - Hemoglobin <6 g/dL. - Known or suspected hereditary complement deficiency. - Active systemic bacterial, viral, or fungal infection within 14 days before first drug administration. - Presence of fever (>=38 degrees Celsius) within 7 days before the first drug administration. - Immunised with a live attenuated vaccine within 1 month before first drug administration. - Pregnant or breastfeeding, or intending to become pregnant during the study or within 10.5 months after the final dose of study treatment. - Known HIV infection with documented CD4 count <200 cells/microliter within 24 weeks prior to screening. - History of N. meningitis infection within the prior 6 months. Adolescent: 13 Year-18 Year,Adult: 19 Year-44 Year,Middle Aged: 45 Year(s)-64 Year(s) 12 Year(s) 55 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
Yes 13/06/2023 Gertrudes Childrens Hospital Ethics and Research Committee
Ethics Committee Address
Street address City Postal code Country
42325 Nairobi Nairobi 00100 Kenya
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome - Annualized rate of medical facility VOEs (AVR) [ Time Frame: Baseline up to Week 49 ] Timeline indicated in outcome section
Secondary Outcome - Annualized rate of home VOE [ Time Frame: Baseline up to Week 49 ] - Annualized rate of uncomplicated medical facility VOE [ Time Frame: Baseline up to Week 49 ] - Annualized rate of Acute Chest Syndrome (ACS) [ Time Frame: Baseline to up Week 49 ] - Annualized rate of days hospitalized for medical facility VOE [ Time Frame: Baseline up to Week 49 ] - Annualized rate of days hospitalized for treatment of non-VOE complications of SCD [ Time Frame: Baseline up to Week 49 ] - Time to first medical facility VOE from randomization [ Time Frame: Baseline up to Week 49 ] - Change in urinary albumin-creatinine ratio [ Time Frame: Baseline up to Week 49 ] - Change in Tricuspid Regurgitant Jet Velocity (TRV) [ Time Frame: Baseline up to Week 49 ] - Percentage of Participants with TRV >2.5 m/s [ Time Frame: Week 49 ] - Change in Patient-Reported Outcomes Measurement Information System (PROMIS)-Fatigue Score in Adults [ Time Frame: Baseline up to Week 49 ] - Percentage of Participants with Adverse Events (AEs) [ Time Frame: Up to 91 weeks ] - Serum Concentrations of Crovalimab over time [ Time Frame: Baseline up to Week 49 ] - Percentage of Participants with Anti-Drug Antibodies to Crovalimab [ Time Frame: Baseline up to Week 49 ] Timeline indicated in outcome section
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Gertrudes Childrens Hospital 42325 Nairobi 00100 Kenya
FUNDING SOURCES
Name of source Street address City Postal code Country
Roche The Atrium, 6th Floor Chaka Road, off Lenana Road P.O. Box 44212-00100 Nairobi, Kenya Nairobi 00100 Kenya
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Roche The Atrium, 6th Floor Chaka Road, off Lenana Road P.O. Box 44212-00100 Nairobi, Kenya Nairobi 00100 Kenya Commercial Sector/Industry
COLLABORATORS
Name Street address City Postal code Country
CONTACT PEOPLE
Role Name Email Phone Street address
Public Enquiries Eileen Koske eileen.koske@roche.com +254721375237 P.O. Box 44212-00100 Nairobi, Kenya
City Postal code Country Position/Affiliation
Nairobi Kenya Clinical Operations Lead
Role Name Email Phone Street address
Principal Investigator Doreen Terry Karimi tessmutua@gmail.com +254722384218 Gertrudes Children Hospital Nairobi
City Postal code Country Position/Affiliation
Nairobi Kenya Hospital Resident Pediatrician
Role Name Email Phone Street address
Scientific Enquiries Diana Gradinaru diana.gradinaru@roche.com +410762893066 CH 4070 Basel
City Postal code Country Position/Affiliation
Basel Kenya Medical monitor
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes There is a plan to share IPD. Plan description: - Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). - Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). - For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm) ClinicalTrials.gov Identifier: NCT04543617 Where available, the following anonymized patient level data and information is provided for each clinical study: - Raw dataset. This is the dataset collected for each patient in the clinical study. - Analysis-ready dataset. This is the dataset used for Roche’s analysis. Please note: only clinical data that underlies the CSR is made available. Therefore some data types may not be routinely provided (eg. Exploratory Biomarker data, Images, Genomic data, PK data). If individual patient data from the same study is made available outside of Vivli this can not and should not be linked to data on the Vivli platform by researchers external to Roche due to a potential increase in risk of patient re-identification. The following information will be provided: 1. Protocol. 2. Annotated case report form. 3. Reporting and analysis plan. 4. Dataset specifications. This is the meta-data which describes the datasets e.g., variable labels, variable descriptions, code lists, formats. 5. Clinical study report. Analytic Code,Clinical Study Report,Statistical Analysis Plan,Study Protocol After the medicine studied has been approved by regulators for the indication in both the US and EU or terminated from development (all indications) 18 months after completion of the study report( to enable a publication to be submitted) Available studies are listed and available on the Vivli platform. Data requestors should use the Vivli data request form to request companies data Package(s). If approved requestors will need to sign a Data Use Agreement and the anonymized data will be shared in the Vivli secure research environment.
URL Results Available Results Summary Result Posting Date First Journal Publication Date
https://vivli.org/ourmember/roche/ 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