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.: PACTR202308825367505 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 Safety, Pharmacokinetics, Pharmacodynamics and Efficacy of Crovalimab for the Management of Acute Uncomplicated Vaso-Occlusive Episodes (VOE) in Participants With Sickle Cell Disease (SCD). (CROSSWALK-a)
Official scientific title A phase 1B randomized, placebo-controlled study evaluating the safety, pharmacokinetics, pharmacodynamics, and efficacy of crovalimab for the management of acute uncomplicated vaso-occlusive episodes (voe) in patients with 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 safety, pharmacokinetics, pharmacodynamics, and efficacy of crovalimab compared with placebo for the management of acute uncomplicated vaso-occlusive episodes (VOE) in patients with sickle cell disease (SCD).
Type of trial RCT
Acronym (If the trial has an acronym then please provide) CROSSWALK Chronic
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 26/03/2022
Actual trial start date 26/03/2022
Anticipated date of last follow up 14/01/2025
Actual Last follow-up date
Anticipated target sample size (number of participants) 30
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 Permuted block randomization 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 single intravenous (IV) infusion of Crovalimab based on body weight. Crovalimab will be administered as a single dose of 1000 milligrams (mg) IV (for participants with a body weight between 40 kilograms (kg) and 100 kg) or 1500 mg IV (for participants with a body weight >=100 kg). single dose Participants will receive a single intravenous (IV) infusion of Crovalimab based on body weight. Crovalimab will be administered as a single dose of 1000 milligrams (mg) IV (for participants with a body weight between 40 kilograms (kg) and 100 kg) or 1500 mg IV (for participants with a body weight >=100 kg). 20
Control Group Placebo Participants will receive a single IV infusion of matching Placebo. Placebo will be administered as a single IV infusion, with an equal volume and over the same duration as weight- based crovalimab Single IV infusion Participants will receive a single IV infusion of matching Placebo. Placebo will be administered as a single IV infusion, with an equal volume and over the same duration as weight- based crovalimab 10 Dose Comparison
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
-Body weight >=40 kg. -Confirmed diagnosis of HbSS (SCD genotype of sickle cell anemia) or HbSβ0 (SCD genotype of sickle cell beta zero thalassemia). --Vaccination against Neisseria Meningitidis serotypes A, C, W, and Y. Vaccinations against H. influenzae type B and S. pneumoniae. -Participants vaccinated against SARS-CoV-2 are eligible, as long as it has been 3 days or more after inoculation with the vaccine. -Diagnosis of an acute uncomplicated VOE, that requires admission to a hospital/acute medical facility and treatment with parenteral opioid analgesics. -Adequate hepatic and renal function. -Hemoglobin >=5 grams/deciliter (g/dL) -Platelet count >=100,000/microliter (µL) -Participants receiving sickle cell therapies must be on a stable dose for >=28 days. -For female participants of childbearing potential, an agreement to remain abstinent or use contraception for 322 days (approximately 10.5 months) after the dose of study treatment. -More than 10 VOEs within the last 12 months prior to presentation, that have required a medical facility visit. -Pain related to the current VOE ongoing for >48 hours. -Acute pain related to avascular necrosis, hepatic or splenic sequestration, or priapism. -Pain atypical of an acute uncomplicated VOE. -Evidence of or suspicion of ACS. -Evidence or high suspicion of a severe systemic infection. -Major surgery and/or hospitalization for any reason within 30 days. -History of Neisseria meningitidis infection within 6 months prior. -Known HIV infection with a documented CD4 count <200 cells/µL. -Transfusion or receipt of blood products within 3 months or current participation in a chronic transfusion protocol. -Immunized with a live attenuated vaccine within 30 days. -History of hematopoietic stem cell transplant. -Known or suspected hereditary complement deficiency. -Pregnant or breastfeeding, or intending to become pregnant during the study or within 322 days (approximately 10.5 months) after the study drug administration. -Participation in another interventional treatment study with an investigational agent or use of any experimental therapy within the prior 28 days or within five half-lives of that investigational product, whichever was greater. 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 26/06/2023 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 -Percentage of Participants With Adverse Events (AEs) [ Time Frame: Baseline up to Day 322 ] -Percentage of Participants with Infusion-Related Reactions and Hypersensitivity [ Time Frame: Baseline up to Day 84 ] Indicated on outcome section
Secondary Outcome -Time to improvement of the primary acute uncomplicated VOE from Baseline [ Time Frame: Baseline up to Day 84 ] -Total cumulative opioid dose from Baseline [ Time Frame: Baseline up to Day 84 ] -Time to discontinuation of all parenteral opioids from baseline [ Time Frame: Baseline up to Day 84 ] -Time to readiness for hospital discharge from baseline [ Time Frame: Baseline up to Day 84 ] -Time to hospital discharge from baseline [ Time Frame: Baseline up to Day 84 ] -Time to a confirmed decrease in pain score of at least 2 points from the maximal pre-dose pain score [ Time Frame: Baseline up to Day 84 ] -Change in pain score from the maximal pre-dose pain score to the score at hospital discharge [ Time Frame: Baseline up to Day 84 ] -Percentage of Participants who develop Acute Chest Syndrome (ACS) [ Time Frame: Baseline up to Day 28 ] -Percentage of Participants requiring intensive care unit (ICU)/critical care admission for SCD-related complications [ Time Frame: Baseline up to Day 84 ] -Percentage of Participants requiring blood transfusion for SCD-related complications [ Time Frame: Baseline up to Day 84 ] -Readmission rate for a VOE or VOE-related event within 28 days of discharge of the primary VOE [ Time Frame: Baseline up to Day 84 ] -Serum Concentrations of Crovalimab over time [ Time Frame: Baseline up to Day 84 ] -Change in PD biomarkers including complement activity (CH50) over time [ Time Frame: Baseline up to Day 84 ] Assessed by a Liposome Immunoassay (LIA) -Change over time in free C5 concentration [ Time Frame: Baseline up to Day 84 ] -Change over time in soluble complement 5b 9 (sC5b-9) concentration [ Time Frame: Baseline up to Day 84 ] -Percentage of Participants with Anti-Drug Antibodies to Crovalimab [ Time Frame: Baseline up to Day 84 ] Indicated on 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 Karimi tessmutua@gmail.com +254722384218 Gertrudes Children Hospital
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 Switzerland Medical monitor
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Plan description: There is no plan to share IPD. Clinical studies with a sample size of less than 50 patients or in rare diseases. This is because anonymization of these data is more difficult to achieve. For these studies, Roche will assess the feasibility of anonymization as part of the review of enquiries. 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). Clinical Study Report There is no plan to share IPD. Clinical studies with a sample size of less than 50 patients or in rare diseases. This is because anonymization of these data is more difficult to achieve. For these studies, Roche will assess the feasibility of anonymization as part of the review of enquiries. 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. 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).
URL Results Available Results Summary Result Posting Date First Journal Publication Date
https://vivli.org/ourmember/roche/ No
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Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information