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.: PACTR202004535453508 Date of Approval: 24/04/2020
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Pharmacokinetics, safety, tolerability and efficacy of a new artemether-lumefantrine dispersible tablet in infants and neonates <5 kg body weight with acute uncomplicated Plasmodium falciparum malaria.
Official scientific title A multicenter, open-label, single-arm study to evaluate the PK, safety, tolerability and efficacy of a new artemether-lumefantrine (2.5 mg:30 mg) dispersible tablet in the treatment of infants and neonates <5 kg body weight with acute uncomplicated Plasmodium falciparum malaria.
Brief summary describing the background and objectives of the trial This study aims to evaluate PK, safety, tolerability and efficacy of a new formulation of artemether-lumefantrine dispersible tablet in neonates and infants <5 kg body weight with acute uncomplicated Plasmodium falciparum malaria. Malaria is a disease that has a much higher prevalence and severity in infants and children. Although relatively infrequent as compared to the number of cases in infants and children ≥5 kg, confirmed malaria in neonates and infants <5 kg does exist in certain endemic countries and calls for evaluation of appropriate treatment. It is still a significant unmet medical need as there are no approved treatments for this vulnerable group of patients. A previous clinical study with a similar design found that artemether exposure in patients <5 kg body weight following administration of dispersible tablets (artemether:lumefantrine 20 mg:120 mg; i.e. 1:6) was around 2-3 fold higher than anticipated safe exposures, whereas exposure to lumefantrine was as expected. Given the potential neurotoxicity of artemether at high exposures, this is undesirable and therefore, following detailed Physiology-Based Pharmacokinetic modeling (PBPK), new doses, using a dispersible tablet with a lower amount of artemether relative to lumefantrine (2.5 mg:30 mg, i.e.1:12) have been selected for investigation in this study.
Type of trial CCT
Acronym (If the trial has an acronym then please provide) CALINA
Disease(s) or condition(s) being studied Infections and Infestations,Paediatrics
Sub-Disease(s) or condition(s) being studied Malaria
Purpose of the trial Treatment: Drugs
Anticipated trial start date 26/10/2020
Actual trial start date 21/12/2020
Anticipated date of last follow up 31/12/2023
Actual Last follow-up date 10/05/2024
Anticipated target sample size (number of participants) 44
Actual target sample size (number of participants) 28
Recruitment status Completed
Publication URL
Secondary Ids Issuing authority/Trial register
NCT04300309 clinicaltrials.gov
CCOA566B2307 Novartis Study Number
2023 000804 21 EU CTR
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 Non-randomised Allocation was determined by the holder of the sequence who is situated off site Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group artemether lumefantrine Starting dose in infants >28 days is 5mg:60mg arthemether:lumefantrine, twice daily for 3 consecutive days Twice daily for 3 consecutive days Arthemether:lumefantrine 2.5mg:30mg dispersible tablet 44
Control Group No Control group in this study No Control group in this study No Control group in this study 0 Historical
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
1. Male or female neonates / infants 2. Body weight <5 kg but ≥ 2kg 3. In Cohort 1, infants aged >28 days; in Cohort 2, neonates aged 1 to ≤28 days (3 subgroups: 15-28 days; 8-14 days; 1-7 days) 4. Microscopically confirmed diagnosis of P. falciparum malaria (or mixed infections) • in Cohort 1: of ≥500 and <100,000 parasites/µL asexual P. falciparum parasitemia • in Cohort 2: of ≥100 and <100,000 parasites/µL asexual P. falciparum parasitemia • either congenital or neonatal • either symptomatic or asymptomatic 1. Head circumference < - 2 SD z-score in cm following WHO age and sex-specific reference curves (suspicion of microcephaly) 2. Severe malnutrition 3. Presence of severe malaria (according to WHO 2015 definition) 4. HIV status: • in Cohort 1 : patient’s or patient's mother's current treatment with ARV • in Cohort 2 : Mother’s known HIV positive status at patient's birth or mother's current treatment with ARV 5. Presence of the following signs of a critical condition: apnea-bradycardia, sustained bradycardia, tachycardia, desaturation, hypotension, hypothermia; or other severely deteriorated general condition (based on IMCI criteria in sick infants, WHO 2005) 6. Presence of any clinically significant neurological condition: • any episode of convulsion during the present illness (in keeping with the IMCI list of general danger signs) • known neurological disorders (e.g. chronic seizure disorders, cerebral palsy) 7. Presence of clinically significant abnormality of the hepatic and renal systems 8. History of malabsorption or previous gastrointestinal surgery, or history of radiation therapy that could affect drug absorption or metabolism, or any other disorder or history of a condition that could interfere with drug absorption, distribution, metabolism, or excretion 9. Known hypersensitivity of the patient or either patient's parent to artemether, lumefantrine, any of the excipients of Coartem®/Riamet® Dispersible tablet, or to drugs of similar chemical classes 10. Known family history of congenital prolongation of the QTc interval or sudden death or with any other clinical condition known to be associated with prolongation of the QTc interval such as history of symptomatic cardiac arrhythmias, with clinically relevant bradycardia or with severe cardiac disease 11. Disturbances of electrolyte balance (e.g. hypokalaemia or hypomagnesaemia) 12. Presence of any age-adjusted clinically or hematologically relevant laboratory and blood chemistry abnormalities Infant: 13 Month(s)-24 Month(s),New born: 0 Day-1 Month 1 Day(s) 1 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 25/03/2020 Comite d ethique pour la recherche en sante
Ethics Committee Address
Street address City Postal code Country
09 BP 7009 9 Ouagadougou 00000 Burkina Faso
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 10/06/2020 Comite d ethique pour la recherche en sante
Ethics Committee Address
Street address City Postal code Country
09 BP 7009 9 Ouagadougou 00000 Burkina Faso
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Artemether Cmax (represents the higher concentration between the concentrations at 1 hour and 2 hours after first dose) 1h and 2h after first dose
Secondary Outcome Lumefantrine Day 8 concentration (C168h) Artemether AUC, DHA and Lumefantrine Cmax and AUC as appropriate 1h, 2h, 62h, 66h, 68h, 84h, 168h post first dose
Secondary Outcome Serious adverse events (SAEs), adverse events (AEs), and routine safety laboratory assessments All study time points
Secondary Outcome PCR-corrected Adequate Clinical and parasitological Response (ACPR) at Days 15, 29, and 43 Uncorrected ACPR at Days 8, 15, 29, and 43 Incidence rate of recrudescence and new infections at Days 15, 29 and 43 Parasite and Fever clearance Times (PCT and FCT) Days 8, 15, 29, and 43
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Groupe de Recherche Action en Sante GRAS N3 Somgande Ouagadougou Burkina Faso
Unite de Recherche Clinique CMA Saint Camille - 01 BP 1047 Nanoro Burkina Faso
Hopital General de Reference St Luc N16 Kisantu Democratic Republic of the Congo
FUNDING SOURCES
Name of source Street address City Postal code Country
PAMAfrica research consortium 20 Route de Pre Bois Geneva Switzerland
European and Developing Countries Clinical Trials Partnership PO Box 93015 The Hague 2509 AA Netherlands
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Novartis Pharma AG Fabrikstrasse 2 Basel 4056 Switzerland Commercial Sector/Industry
COLLABORATORS
Name Street address City Postal code Country
Medicines for Malaria Venture 20 Route de Pre Bois Geneva Switzerland
Groupe de Recherche Action en Sante GRAS N3 Somgande Ouagadougou Burkina Faso
Institut de Recherche en sciences de la Sante CMA Saint Camille Nanoro Burkina Faso
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Berenger Kabore kaboreberenger@gmail.com +22671947481 Unite de Recherche Clinique de Nanoro
City Postal code Country Position/Affiliation
Nanoro Burkina Faso Institut de Recherche en Science de la Sante
Role Name Email Phone Street address
Public Enquiries Novartis Pharma AG Novartis Pharma AG novartis.email@novartis.com +41613241111 Fabrikstrasse 2
City Postal code Country Position/Affiliation
Basel 4056 Switzerland Trial Director
Role Name Email Phone Street address
Scientific Enquiries Novartis Pharma AG Novartis Pharma AG novartis.email@novartis.com +41613241111 Fabrikstrasse 2
City Postal code Country Position/Affiliation
Basel 4056 Switzerland Trial Director
Role Name Email Phone Street address
Principal Investigator Berenger Kabore kaboreberenger@gmail.com +22671947481 Unite de Recherche Clinique de Nanoro
City Postal code Country Position/Affiliation
Nanoro Burkina Faso Institut de Recherche en Science de la Sante
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. Study Protocol This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com 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
Yes 03/12/2024
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result - 03/12/2024
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Actual trial start date 27/10/2021 entered actual start date 21 Dec 2020
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Anticipated date of last follow up 27/10/2021 delays in study startup 30 Apr 2023 31 Dec 2023
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Completion date 03/12/2024 updated to actual completion date 10 May 2024
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Final no of participants 03/12/2024 updated with actual number of participants 28
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Recruitment status 27/10/2021 study recruiting now Not yet recruiting Recruiting
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Recruitment status 03/12/2024 updated status Recruiting Completed
Section Name Field Name Date Reason Old Value Updated Value
SecondaryID SecondaryID List 03/12/2024 added Secondary ID NCT04300309, clinicaltrials.gov
Section Name Field Name Date Reason Old Value Updated Value
SecondaryID SecondaryID List 03/12/2024 added Secondary ID 202300080421, EU Clinical Trials Register
Section Name Field Name Date Reason Old Value Updated Value
SecondaryID SecondaryID List 03/12/2024 added Secondary ID 202300080421, EU Clinical Trials Register CCOA566B2307, Novartis Study Number
Section Name Field Name Date Reason Old Value Updated Value
SecondaryID SecondaryID List 03/12/2024 added Secondary ID 202300080421, EU Clinical Trials Register CCOA566B2307, Novartis Study Number
Section Name Field Name Date Reason Old Value Updated Value
SecondaryID SecondaryID List 09/12/2024 EU CTR number added 2023 000804 21, EU CTR
Section Name Field Name Date Reason Old Value Updated Value
Recruitment Centre RecruitmentCentre List 09/12/2024 did not randomize participants into trial KEMRI Kombewa Clinical Research Centre, at J.O. Odinga Hospital, Kisumu , 40100, Kenya
Section Name Field Name Date Reason Old Value Updated Value
Recruitment Centre RecruitmentCentre List 09/12/2024 did not randomize participants into trial MRTC University of Science Techniques and Technology, PO Box 1805 Point G, Bamako, , Mali
Section Name Field Name Date Reason Old Value Updated Value
Recruitment Centre RecruitmentCentre List 09/12/2024 did not randomize participants into trial Department of Paediatrics University of Calabar, Etagbor, PMB 1115 , Calabar, , Nigeria
Section Name Field Name Date Reason Old Value Updated Value
Recruitment Centre RecruitmentCentre List 27/10/2021 addition of a new site St Pauls Mission Hospital, Nchelenge, Nchelenge, , Zambia
Section Name Field Name Date Reason Old Value Updated Value
Recruitment Centre RecruitmentCentre List 09/12/2024 did not randomize participants into trial St Pauls Mission Hospital, Nchelenge, Nchelenge, , Zambia
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 24/04/2020 Ethics document added TRUE, Comite d ethique pour la recherche en sante, 09 BP 7009 9 , Ouagadougou, 00000, Burkina Faso, 20 Feb 2020, 25 Mar 2020, 00000000000, xxxx@xxx.xxx, TRUE, Comite d ethique pour la recherche en sante, 09 BP 7009 9 , Ouagadougou, 00000, Burkina Faso, 20 Feb 2020, 25 Mar 2020, 00000000000, xxxx@xxx.xxx, 9668_11275_4737.pdf
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 24/04/2020 phone number and email address added TRUE, Comite d ethique pour la recherche en sante, 09 BP 7009 9 , Ouagadougou, 00000, Burkina Faso, , 25 Mar 2020, 00000000000, xxxx@xxx.xxx, 9668_11275_4737.pdf TRUE, Comite d ethique pour la recherche en sante, 09 BP 7009 9 , Ouagadougou, 00000, Burkina Faso, , 25 Mar 2020, 0022650366674, contact@sante.gov.bf, 9668_11275_4737.pdf
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 27/10/2021 addition of approval TRUE, Comite d ethique pour la recherche en sante, 09 BP 7009 9, Ouagadougou, 00000, Burkina Faso, , 10 Jun 2020, 0022650366674, contact@sante.gov.bf,
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 09/12/2024 letter added TRUE, Comite d ethique pour la recherche en sante, 09 BP 7009 9, Ouagadougou, 00000, Burkina Faso, , 10 Jun 2020, 0022650366674, contact@sante.gov.bf, TRUE, Comite d ethique pour la recherche en sante, 09 BP 7009 9, Ouagadougou, 00000, Burkina Faso, , 10 Jun 2020, 0022650366674, contact@sante.gov.bf, 9668_15628_4737.pdf
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 09/12/2024 duplicate
Section Name Field Name Date Reason Old Value Updated Value
Funding Source FundingSources List 27/10/2021 addition of funding source European and Developing Countries Clinical Trials Partnership, PO Box 93015, The Hague, 2509 AA, Netherlands, Funding Agency,
Section Name Field Name Date Reason Old Value Updated Value
Contact People Contacs List 03/12/2024 Updated Principal Investigator Information Principal Investigator, Bernhards, Ogutu, Prof., bernhards.ogutu@usamru-k.org, , +254733966065, Jaramogi Oginga Odinga Hospita, Kisumu, , Kenya, KEMRI Kombewa Clinical Research Centre Principal Investigator, Berenger, Kabore, Dr., kaboreberenger@gmail.com, , +254733966065, Unite de Recherche Clinique de Nanoro, Nanoro, , Burkina Faso, Institut de Recherche en Science de la Sante
Section Name Field Name Date Reason Old Value Updated Value
Contact People Contacs List 09/12/2024 Updated Principal Investigator Information Principal Investigator, Berenger, Kabore, Dr., kaboreberenger@gmail.com, , +254733966065, Unite de Recherche Clinique de Nanoro, Nanoro, , Burkina Faso, Institut de Recherche en Science de la Sante Principal Investigator, Berenger, Kabore, Dr., kaboreberenger@gmail.com, , +22671947481, Unite de Recherche Clinique de Nanoro, Nanoro, , Burkina Faso, Institut de Recherche en Science de la Sante
Section Name Field Name Date Reason Old Value Updated Value
Reporting Results & Publication URL 03/12/2024 Link to results on clinicaltrials.gov added https://www.clinicaltrials.gov/study/NCT04300309?term=CCOA566B2307&rank=1&tab=results
Section Name Field Name Date Reason Old Value Updated Value
Reporting Results Available 03/12/2024 Results added No Yes
Section Name Field Name Date Reason Old Value Updated Value
Reporting Result Summary Pdf file1 03/12/2024 Results added 9668_9265_1045.pdf