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.: PACTR202402599048090 Date of Approval: 02/02/2024
Trial Status: Retrospective registration - This trial was registered after enrolment of the first participant
TRIAL DESCRIPTION
Public title Efficacy and safety of pyronaridine/artesunate and pyronaridine/artesunate/praziquantel for treatment of uncomplicated Schistosoma haematobium infection in Gabonese adolescents and children
Official scientific title Efficacy and safety of pyronaridine/artesunate and pyronaridine/artesunate/praziquantel for treatment of uncomplicated Schistosoma haematobium infection in Gabonese adolescents and children
Brief summary describing the background and objectives of the trial Currently, treatment of urogenital schistosomiasis is based on praziquantel [PZQ], which is the only available drug for this indication. Occasionally, specific antimicrobial agents demonstrate simultaneous activity against multiple microorganisms. In this regard, pyronaridine [PY] and artesunate [ART], two important antimalarial drugs, have been shown to exert clinically important activity against Schistosoma spp. It is of mention that a currently ongoing study of our research group (i.e. CORMA-MAL study) recently yielded favourable interim results with some evidence of antimalarial activity of PZQ. This introduces the promising possibility of creating a drug regimen to be potentially used for schistosomiasis and malaria. The value of such a multi-disease drug regimen is even further highlighted, as epidemiologic data indicate that malaria and urogenital schistosomiasis affect largely overlapping target populations. This aspect makes such a potential regimen appealing to be operationally implemented as part of schistosomiasis and malaria control campaigns for which mass drug administration is often applied within intermittent preventive treatment programmes. These potential platform synergisms make such a multi-disease drug regimen interesting not only, but particularly in low resource settings. A treatment study evaluating a combination of PZQ with ART in school children with urogenital schistosomiasis demonstrated a favourable safety profile. This favourable safety profile was confirmed by another treatment study evaluating a combination of praziquantel (PZQ) with ART and mefloquine [MFQ] in school children with urogenital schistosomiasis. Given the established safety profile of PY/ART, its availability as fixed-dose paediatric drug formulation, PY/ART may become an attractive option as partner drug combination for antischistosomal therapy with PZQ. In the CORMA-BIL study, existing preliminary evidence of PY/ART antischistosomal activity will be further investigated. CORMA-BIL is a randomised controlled trial to evaluate the in vivo efficacy, safety and tolerability of PY/ART and PY/ART/PZQ. Adolescent and children participants with uncomplicated Schistosoma haematobium infection will be randomly allocated to one of four study arms: A) Placebo, B) pyronaridine/artesunate, C) praziquantel and D) pyronaridine/artesunate/praziquantel. Objectives will be answered each by two study arm pairs, the first pair being ‘PY/ART and PLACEBO’ and the second pair being ‘PY/ART/PZQ and PZQ.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) CORMA BIL
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied Urogenital schistosomiasis
Purpose of the trial Treatment: Drugs
Anticipated trial start date 01/09/2023
Actual trial start date 18/09/2023
Anticipated date of last follow up 31/12/2024
Actual Last follow-up date 31/12/2024
Anticipated target sample size (number of participants) 108
Actual target sample size (number of participants) 108
Recruitment status Closed to recruitment,follow-up continuing
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
Factorial: participants randomly allocated to either no, one, some or all interventions simultaneously Randomised Simple randomization using a randomization table created by a computer software program Sealed opaque envelopes Masking/blinding used Care giver/Provider
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Control Group STUDY ARM PAIR I in the study ARM PAIR I, pyronaridine/artusunate or PLACEBO will be given once daily, orally for three days independent of food 3 days 60 participants will be randomized in the study ARM PAIR I, 30 in the pyronaridine/artusunate group and 30 in the PLACEBO. 60 Active-Treatment of Control Group
Experimental Group STUDY ARM PAIR II In the STUDY ARM PAIR II, there will be 3 treatment groups, 24 participants will recieve a single dose of Praziquantel on D1 then consecutive placebo doses on D2 and D3. 24 participants will recieve PYRONARIDINE/ARTESUNATE once daily for 3 days. 3 days 48 participantswill be randomized in this treatment group, either recieve Praziqantel or PYRONARIDINE/ARTESUNATE 48
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
Participants aged between 5 years and below 18 years • Microscopically-determined Schistosoma haematobium infection • Uncomplicated Schistosoma haematobium infection defined by: presence of microscopically-determined Schistosoma haematobium eggs in urine with absence of Katayama fever and absence of clinically significant urinary tract pathology (see exclusion criteria). • Written informed consent must be obtained before any study assessment is performed. • Willingness not to take drugs or substances which could have an impact on study drug blood levels (see inclusion/exclusion criteria in study protocol). • Women only of reproductive age: Must agree to practice continuous contraception for the duration of the study. • Presence of Katayama fever • Presence of axillary temperature of >37.5°C • Presence of clinically significant urinary tract pathology. The diagnoses of clinically significant urinary tract pathologies are made by the clinical investigator • Pregnancy or breast-feeding • Use of drugs with known antischistosomal activity within 2 months of enrolment into study (including praziquantel and antimalarial treatment with artemisinin-combination therapies) • Contraindications or known allergy to pyronaridine/artesunate or praziquantel • Any other significant disease, disorder or finding which, in the opinion of the investigator, may significantly increase the risk to the participant because of participation in the study (e.g. renal transplantation etc.), affect the ability of the participant to participate in the study or impair interpretation of the study data • Participants unable to be closely followed for social, geographic or psychological reasons • Haemoglobin level below 8 g/dL • Previous participation in the CORMA-BIL study (multiple participation not possible) Adolescent: 13 Year-18 Year,Child: 6 Year-12 Year,Preschool Child: 2 Year-5 Year 5 Year(s) 17 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 19/06/2023 CEI
Ethics Committee Address
Street address City Postal code Country
Hopital Albert Schweitzer Lambarene BP:242 Gabon
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome To assess the efficacy of pyronaridine/artesunate and pyronaridine/artesunate/praziquantel in participants with uncomplicated Schistosoma haematobium parasites D42
Primary Outcome To assess the time to re-infection with Schistosoma haematobium after treatment with PYR/ART/PZQ compared with PZQ standard treatment assessed by light microscopy D42
Secondary Outcome - To assess the safety and tolerability of study regimens in each study arm during the observation period - To assess the proportion of participants with haematuria in each study arm at D42 after administration of study drugs - To assess the proportion of participants with an incidental Plasmodium parasitaemia during the observation period D42
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Centre de Recherches Medicales de Lambarene CERMEL Hpital Albert Schweitzer Lambarene BP:242 Gabon
FUNDING SOURCES
Name of source Street address City Postal code Country
German Center for Infection Research DZIF Inhoffen Strasse 7 Braunschweig 38124 Germany
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Bernhard Nocht Institute for Tropical Medicine BNITM Bernhard-Nocht-Strasse 74 Hamburg 20359 Germany Hospital
COLLABORATORS
Name Street address City Postal code Country
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Ghyslain Mombo Ngoma ghyslain.mombongoma@cermel.org +24106072578 Hopital Alert Schweitzer
City Postal code Country Position/Affiliation
Lambarene 242 Gabon CERMEL BNITM
Role Name Email Phone Street address
Scientific Enquiries Johannes Mischlinger mischlinger@bnitm.de +494042818480 Bernhard-Nocht-str 74
City Postal code Country Position/Affiliation
Hamburg 20359 Germany BNITM
Role Name Email Phone Street address
Public Enquiries Lidwine Badjina lidwine.badjina@bnitm.de +4940285380705 Bernhard-Nocht-str 74
City Postal code Country Position/Affiliation
Hamburg 20359 Germany BNITM
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Data obtained through this study may be provided to qualified researchers with academic interest in malaria drug development. Data or samples shared will be coded, with no PHI included. Approval of the request and execution of all applicable agreements (i.e. a material transfer agreement) are prerequisites to the sharing of data with the requesting party. Clinical Study Report,Study Protocol Data requests can be submitted starting 60 days after article publication and the data will be made accessible for up to 24 months. Extensions will be considered on a case-by-case basis. Access to trial IPD can be requested by qualified researchers engaging in independent scientific research, and will be provided following review and approval of a research proposal and execution of a Data Sharing Agreement (DSA). For more information or to submit a request to the sponsor.
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