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 0835 or +27 21 938 0967
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202007890194806 Date of Registration: 02/07/2020
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Phase I Safety and Dose finding Trial of Sevuparin in children with severe malaria
Official scientific title A Phase I Trial of Sevuparin in severe malaria as a potential adjunctive treatment
Brief summary describing the background and objectives of the trial A novel new drug candidate for adjunctive treatment of severe malaria, sevuparin, has been identified that can blocks merozoite invasion, prevent cytoadherence and transiently de-sequesters infected erythrocytes in humans with uncomplicated P. falciparum malaria. If given, in addition to antimalarial treatment, early in the course of admission (<24 hours) this could result in improvements in outcomes from severe malaria for the subgroups at greatest risk and during the period of greatest risk (first day of hospitalisation). Sevuparin has been shown to be safe and well tolerated in adults with only some mild effects on activated partial thromboplastin time (APTT) at higher doses given over longer periods of time (3 days), which are not clinically relevant to the time of greatest risk. In this Phase I trial dose-finding paediatric study, we aim to use only 3 doses given at admission (0 hours), and 8 and 16 hours later, and measure APTT 1 hour after each dose (to assess maximum toxicity based on adult data). The Phase I trial is designed to obtain data on safety, dosing, feasibility and potentially lactate clearance of sevuparin given as an adjuvant therapy in severe malaria in children. We aim to study 20 children admitted to hospital with severe malaria which will allow sufficient data on safety to be generated across a range of doses to identify the maximum tolerated dose (MTD) using the Continual Reassessment Method (CRM), which adapts or informs subsequent doses for each child entering the trial based on the data from previously enrolled children. The maximum tolerated dose (MTD) will be identified based on the dose-toxicity model being updated by each previous patient’s APTT results using standard methods. The trial will be conducted as two hospitals (Kilifi County Hospital, Kenya and St Pauls Mission Hospital, Nchelenge, Zambia).
Type of trial CCT
Acronym (If the trial has an acronym then please provide) SEVUSMART
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied Malaria
Purpose of the trial Treatment: Drugs
Anticipated trial start date 15/07/2020
Actual trial start date 02/09/2022
Anticipated date of last follow up 30/06/2024
Actual Last follow-up date
Anticipated target sample size (number of participants) 20
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 Non-randomised Numbered containers Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Sevuparin Between 1.5/kg/dose Three infusions at 0, 8 and 16 hours after enrolment Adjunctive therapy 2
Experimental Group Sevuparin 3 mg/kg Three infusions at 0, 8 and 16 hours after enrolment Adjunctive 8
Experimental Group Sevuparin 6mg/kg Three infusions at 0, 8 and 16 hours after enrolment Adjunctive 10
Control Group control none none no control arm 0 Uncontrolled
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
1. Aged between 3 months and 12 years admitted to the paediatric wards within the last 24h 2. Current or recent evidence of P. falciparum malaria (slide positive) 3. Clinical evidence of severe malaria (impaired consciousness or deep breathing) 4. Lactate > 2 mmol/L 5. Guardian or parent willing and able to provide consent 1. Clinical evidence or a history of a bleeding/coagulation disorder 2. A comorbidity which clinician believes has a significant risk of poor outcome e.g. malignancy, end-stage renal failure, major cardiac condition 3. Thrombocytopenia (platelet count <25 x109/L). Child: 6 Year-12 Year,Infant: 13 Month(s)-24 Month(s),Preschool Child: 2 Year-5 Year 3 Month(s) 12 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 25/02/2019 KEMRI SERU
Ethics Committee Address
Street address City Postal code Country
PO Box 5440 00200 Nairobi 54400020 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
Yes 27/03/2023 Imperial College Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
Room 221 Medical School Building St Marys Campus London W21PG United Kingdom
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 24/07/2023 National Health Research Ethics Board
Ethics Committee Address
Street address City Postal code Country
Chalala Office Lot No 18961/M, Off Kasama Road Lusaka POB30075 Zambia
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome  APTT>2.5 x upper limit of normal 1h post any sevuparin dose 1 hour post infusion
Secondary Outcome  Change in lactate from 0 to 8 hours 8 hours
Secondary Outcome Presence of mature infected erythrocytes on the blood films at 8 and 24 hours 8 and 24 hours post enrolment
Secondary Outcome APTT 24h post enrolment 24 hours post enrolment
Secondary Outcome Neurological sequelae through day 28 Day 28 post enrolment
Secondary Outcome Mortality to Day 28 Day 28 post enrolment
Secondary Outcome Serious adverse events through day 28 Grade 3/4 adverse events through day 28 To Day 28 post enrolment
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Kilifi County Hospital KEMRI Wellcome Trust Research Programme PO BOX 23 Kilifi Kenya
St Pauls Mission Hospital Hospital Road Nchelenge 00000 Zambia
FUNDING SOURCES
Name of source Street address City Postal code Country
Wellcome 215 Euston Road London United Kingdom
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Imperial College London Medical School Building St Marys Campus London United Kingdom University
COLLABORATORS
Name Street address City Postal code Country
Nicholas Day 420/6 Rajvithi Road, Rajthevee Bangkok Thailand
Arjen Dondorp 420/6 Rajvithi Road, Rajthevee, Bangkok Thailand
Sarah Walker 90, High Holborn London United Kingdom
Diana Gibb 90, High Holborn London United Kingdom
Elizabeth George 90, High Holborn London United Kingdom
Mainga Hamaluba PO Box 230 Kilifi Kenya
Nchafatso Obonyo PO Box 230 Kilifi Kenya
Mike Chaponda Tropical Diseases Research Centre, 6th and 7th Floor of Ndola Teaching Hospital building Ndola PB71769 Zambia
CONTACT PEOPLE
Role Name Email Phone Street address
Public Enquiries Emmanuel Oguda EOguda@kemri-wellcome.org +254748588041 Po Box 230
City Postal code Country Position/Affiliation
Kilifi Kenya Clinical Trial Manager
Role Name Email Phone Street address
Principal Investigator Kathryn Maitland k.maitland@imperial.ac.uk +2540722203417 Po Box 230
City Postal code Country Position/Affiliation
Kilifi Kenya Professor of Paediatric Infectious Diseases
Role Name Email Phone Street address
Scientific Enquiries Kathryn Maitland k.maitland@imperial.ac.uk +254722205901 Po Box 230
City Postal code Country Position/Affiliation
Kilifi Kenya Chief Investigator
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes We have a data sharing plan for investigator and external requests. Data from the SEVUSMAART trial will be shared according to a controlled access approach (outlined above) in accordance to Wellcome (the funders) policy based on the following principles:  No data should be released that would compromise an ongoing trial or study.  There must be a strong scientific or other legitimate rationale for the data to be used for the requested purpose.  Investigators who have invested time and effort into developing a trial or study should have a period of exclusivity in which to pursue their aims with the data, before key trial data are made available to other researchers.  The resources required to process requests should not be under-estimated, particularly successful requests which lead to preparing data for release. Therefore adequate resources must be available in order to comply in a timely manner or at all, and the scientific aims of the study must justify the use of such resources.  Data exchange complies with Information Governance and Data Security Policies in all of the relevant countries Analytic Code,Clinical Study Report,Informed Consent Form,Statistical Analysis Plan,Study Protocol IPD will be shared following a period of exclusivity as outlined above. The minimum period of exclusivity will be 2 years following the publication of the trial results. The study protocol, statistical analysis plan and ICF will be published after all ethics and regulatory approvals in an open access journal. Standard data request form should be completed and access granted by Trial Steering Committee (custodians of the trial data) where the resources required to process requests should not be under-estimated, particularly successful requests which lead to preparing data for release. Requests for access to appropriately anonymized data from this trial can be made by application to the data access committee at the KEMRI-Wellcome Trust research Programme by e-mail to MMunene@kemri-wellcome.org
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