Malaria,FalciparumPhase 2NCT03814616
Pyramax in Asymptomatic Carriers of P. Falciparum Monoinfections
A Phase 2 study testing Pyronaridine tetraphosphate 180mg:artesunate 60mg in people with Malaria,Falciparum, run by Shin Poong Pharmaceutical Co. Ltd. at 2 sites in 2 countries.
Trial summary
This study will assess the efficacy of Pyramax administered for three-day, two-day or one day, in clearing a P. falciparum infection in asymptomatic carriers. . Read more about this study
- Who is it for?
- Ages 5 years and older
- Conditions the study is for
- Malaria,Falciparum
- What is being tested?
- Pyronaridine tetraphosphate 180mg:artesunate 60mg
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 300 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 3 Oct 2018to Oct 2019
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Evidence of asymptomatic infection with Plasmodium falciparum monoinfection on thin and thick blood smears with parasite density between 20/µL and 50,000/µL
- Absence of any clinical symptoms of malaria at the time of enrolment and within 72 hours before enrolment
- Age >5 years old and >20 kg body weight
- Ability to swallow oral medication
- Evidence of a personally signed and dated Informed Consent document indicating that the participant (or a legally acceptable representative if a participant is <18 years of age) has been informed of all pertinent aspects of the study and that all questions by the participant have been sufficiently answered. Assent will be obtained from participants <18 years of age as required by national regulations.
- Participants who are willing to and are able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
Who cannot join
- Haemoglobin <7 g/dL (measured at screening)
- History of having received any antimalarial treatment (alone or in combination) during the following periods before screening:
- Piperaquine, mefloquine, naphthoquine or sulfadoxine-pyrimethamine within 6 weeks prior to screening
- Amodiaquine, chloroquine within 4 weeks prior to screening
- Any artemisinin derivative (artesunate, artemether or dihydroartemisinin), quinine, lumefantrine or any other anti-malarial treatment or antibiotic with antimalarial activity (including cotrimoxazole, tetracyclines, quinolones and fluoroquinolones and azithromycin) within 14 days prior to screening
- Any herbal products or traditional medicines during the 7 days prior to screening (if spontaneously reported by the patient)
Show all 18Show fewer
- Known allergy to the study drugs (pyronaridine and/or any artemisinin derivatives)
- Positive urinary pregnancy test for women of reproductive age
- Lactating women
- Evidence of severe malnutrition
- Participation in other studies within 30 days before the current study begins and/or during study participation
- Inability to comprehend and/or unwillingness to follow the study protocol
- Previously randomized in this study
- Severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this study. Examples would include but not limited to:
- Immunological disorders (including known seropositive HIV antibody),
- Severe psychiatric disorders (active depression, recent history of depression, generalised anxiety, psychosis, schizophrenia or other major psychiatric disorders) and major medical disorders related to cardiovascular, respiratory (including active tuberculosis), renal, gastrointestinal, endocrine, infectious, malignancy, neurological (including auditory) and history of convulsions or other abnormality (including recent head trauma),
- Clinical signs or symptoms of hepatic injury (such as nausea, abdominal pain associated with jaundice) or known severe liver disease (i.e. decompensated cirrhosis, Child-Pugh stage 3 or 4)
- Participant the Investigator considers at particular risk of receiving an anti-malarial or of participating in the study
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
The Gambia1 site
MRC Unit The Gambia at the London School of Hygiene and Tropical Medicine,
Fajara, City of Banjul
About this study
Official title: A Randomized, Open-Label Exploratory Study To Determine The Efficacy Of Different Treatment Regimens Of Pyramax® (Pyronaridine-Artesunate) In Asymptomatic Carriers Of Plasmodium Falciparum Monoinfections
This study will assess the efficacy of Pyramax administered for three-day, two-day or one day, in clearing a P. falciparum infection in asymptomatic carriers.
.
Read the detailed description
This is a randomized, open-label, three-arm, out-patient study in asymptomatic individuals with P. falciparum monoinfection confirmed at baseline, who are >5 years of age and >20kg body weight. A total of 300 participants will be randomised into the study; 100 participants in each of three treatment arms.
Patients who fulfil the entry criteria (all inclusion and none of the exclusion criteria) will be recruited and randomized to receive Pyramax orally for three days, two days or one day in a randomization ratio of 1:1:1.
All participants will be followed until Day 63 (counted from day 0) and blood samples will be taken on Days 0, 1, 2, 3, 7, 14, 21, 28, 35, 42 and 63 for malaria diagnostics, parasite density and qPCR. In addition, blood samples reverse-transcriptase (RT)-PCR will be taken on Days 0, 1, 2, 3, 7 and 14.
Participants will be administered local SOC treatment if they meet any of the protocol-specific criteria of treatment failure: Early treatment failure, Late clinical failure, or Late parasitological failure up to and including Day 63, or if the participant withdraws at any time before Day 63, and is parasite positive.
- Conditions
- Malaria,Falciparum
- Being tested
- Pyronaridine tetraphosphate 180mg:artesunate 60mg
- Keywords
- Asymptomatic malaria
- Medical subject headings
- Malaria, Falciparum
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pyronaridine tetraphosphate 180mg:artesunate 60mgDrug
Also called Pyramax
ACT
| Study group | Role | What they receive |
|---|---|---|
| Arm Pyramax 3 days | Experimental | Pyramax (pyronaridine tetraphosphate 180mg:artesunate 60mg) will be administered, once per day according to body weight for three days (Arm A) Receives: Drug: Pyronaridine tetraphosphate 180mg:artesunate 60mg |
| Arm Pyramax 2 days | Experimental | Pyramax (pyronaridine tetraphosphate 180mg:artesunate 60mg) will be administered, once per day according to body weight for two days (Arm B) Receives: Drug: Pyronaridine tetraphosphate 180mg:artesunate 60mg |
| Arm Pyramax 1 day | Experimental | Pyramax (pyronaridine tetraphosphate 180mg:artesunate 60mg) will be administered, once per day according to body weight for one day (Arm C) Receives: Drug: Pyronaridine tetraphosphate 180mg:artesunate 60mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
PCR-adjusted APR at Day 28 (based on slide assessment by microscopy)
To assess the efficacy of each dosing regimen PCR-adjusted Adequate parasitological response (APR) at Day 28
Measured: Day 28
Secondary outcomes (13)
PCR-adjusted APR
To assess the efficacy of each dosing regimen PCR-adjusted APR at Day 63
Measured: 63 days
PCR-unadjusted APR
To assess the efficacy of each dosing regimen PCR-unadjusted APR at Day 63
Measured: 63 days
Rate of recurrent infections, recrudescence and new infections
To assess the efficacy of each dosing regimen on rate of recurrent infections, recrudescence and new infections
Measured: 63 days
Proportion of parasite free participants
Proportion of participants who are parasite free by 4-8 hours, Day 1, Day 2 and Day 3 post first dosing
Measured: 4 days
Gametocyte incidence
The area under the curve (AUC) up to Day 14 (post first dose) of gametocytes in participants with gametocytes at baseline, and separately in participants without gametocytes at baseline
Measured: 14 days
Adverse Events
- Number (%) of patients and number of events with:
- TEAEs,
- serious TEAEs,
- study drug related TEAEs,
- study drug related serious TEAEs,
- malaria-related TEAEs,
- malaria-related serious TEAEs
- Number (%) of patients with TEAEs and drug-related TEAEs by maximum severity, based on Grade 1 to Grade 5 (CTCAE V4.03) severity grading Adverse events will be coded by MedDRA primary system organ class and preferred term.
- Hepatotoxicity related TEAEs o The number and percentage of patients with hepatotoxicity related TEAEs, based on the Standard MedDRA Query (SMQ) narrow search "Drug-related hepatic disorders" will be summarised and clinical biochemistry parameters
Measured: 63 days
Clinical laboratory data - Haematology
Haemoglobin, haematocrit, erythrocytes, platelets, white blood cells, neutrophils, lymphocytes, monocytes, eosinophils, basophils will be summarised over time, as absolute values and changes from baseline with the number of observations, mean, standard deviation, median, quartiles, minimum and maximum. SI units will be used to summarise the data.
Measured: 63 days
Clinical laboratory data - Biochemistry
Total and conjugated bilirubin will be summarised over time, as absolute values and changes from baseline with the number of observations, mean, standard deviation, median, quartiles, minimum and maximum. SI units will be used to summarise the data.
Measured: 63 days
Clinical laboratory data - Liver Enzymes
Alanine aminotransaminase (ALT), Aspartate aminotransaminase (AST), Alkaline Phosphatase will be summarised over time, as absolute values and changes from baseline with the number of observations, mean, standard deviation, median, quartiles, minimum and maximum. IU/L units will be used to summarise the data
Measured: 63 days
Clinical laboratory data - Liver Enzyme Elevations
The number (%) of participants with liver enzyme elevations after first drug administration as defined below will be summarised.
- ALT or AST > 3 x Upper Limit of Normal (ULN)
- ALT or AST > 5 x ULN
- ALT or AST > 8 x ULN
- ALT or AST > 3 x ULN and bilirubin > 2 x ULN at the same time point (when conjugated bilirubin fraction is missing)
- ALT or AST > 3 x ULN and bilirubin > 2 x ULN, together with a conjugated bilirubin fraction >35% (Potential Hy's law cases), at the same time point
Measured: 63 days
Vital signs - Blood pressure
Supine systolic and diastolic blood pressure (mm Hg) absolute values and changes from baseline will be summarised by time point with the number of observations, mean, standard deviation, median, minimum and maximum, and quartiles
Measured: 63 days
Vital signs - Pulse rate
Pulse rate (bpm) absolute values and changes from baseline will be summarised by time point with the number of observations, mean, standard deviation, median, minimum and maximum, and quartiles
Measured: 63 days
Vital signs - Temperature
Temperature (degrees Celsius) absolute values and changes from baseline will be summarised by time point with the number of observations, mean, standard deviation, median, minimum and maximum, and quartiles
Measured: 63 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jan 2019
- Study start3 Oct 2018
- Primary completionOct 2019 (estimated)
- Study completionOct 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Malaria,FalciparumStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 300 participants (actual)
Sponsor and investigators
- Lead sponsor
- Shin Poong Pharmaceutical Co. Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Medicines for Malaria Venture
- Responsible party
- Sponsor
- Investigators
- Jang Sik Shin, Study director, Shin Poong
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03814616
- Sponsor's protocol ID
- SP-C-026-18
- Status last verified
- Sep 2019
- First submitted
- 13 Sep 2018
- Last updated
- 30 Sep 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Dabira ED, Hachizovu S, Conteh B, Mendy A, Nyang H, Lawal B, Ndiath MO, Mulenga JM, Mwanza S, Borghini-Fuhrer I, Arbe-Barnes S, Miller R, Shin J, Duparc S, D'Alessandro U, Manyando C, Achan J. Efficacy, Safety and Tolerability of Pyronaridine-artesunate in Asymptomatic Malaria-infected Individuals: a Randomized Controlled Trial. Clin Infect Dis. 2022 Jan 29;74(2):180-188. doi: 10.1093/cid/ciab425.
PubMed 33983371
Study at a glance
From the registry record, last updated by the sponsor on 30 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Open-Label Exploratory Study To Determine The Efficacy Of Different Treatment Regimens Of Pyramax® (Pyronaridine-Artesunate) In Asymptomatic Carriers Of Plasmodium Falciparum Monoinfections
- ClinicalTrials.gov ID
- NCT03814616
- Acronym / sponsor ID
- SP-C-026-18
- Conditions
- Malaria,Falciparum
- Keywords
- Asymptomatic malaria
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 300 participants (actual)
- Lead sponsor
- Shin Poong Pharmaceutical Co. Ltd.Industry (pharma, biotech, devices)
- Collaborators
- Medicines for Malaria Venture
- Study start
- 3 Oct 2018 (actual)
- Primary completion
- Oct 2019 (estimated)
- Study completion
- Oct 2019 (estimated)
- First posted
- 24 Jan 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will assess the efficacy of Pyramax administered for three-day, two-day or one day, in clearing a P. falciparum infection in asymptomatic carriers.
.
Detailed description
This is a randomized, open-label, three-arm, out-patient study in asymptomatic individuals with P. falciparum monoinfection confirmed at baseline, who are >5 years of age and >20kg body weight. A total of 300 participants will be randomised into the study; 100 participants in each of three treatment arms.
Patients who fulfil the entry criteria (all inclusion and none of the exclusion criteria) will be recruited and randomized to receive Pyramax orally for three days, two days or one day in a randomization ratio of 1:1:1.
All participants will be followed until Day 63 (counted from day 0) and blood samples will be taken on Days 0, 1, 2, 3, 7, 14, 21, 28, 35, 42 and 63 for malaria diagnostics, parasite density and qPCR. In addition, blood samples reverse-transcriptase (RT)-PCR will be taken on Days 0, 1, 2, 3, 7 and 14.
Participants will be administered local SOC treatment if they meet any of the protocol-specific criteria of treatment failure: Early treatment failure, Late clinical failure, or Late parasitological failure up to and including Day 63, or if the participant withdraws at any time before Day 63, and is parasite positive.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Arm Pyramax 3 days | Experimental | Drug: Pyronaridine tetraphosphate 180mg:artesunate 60mgPyramax (pyronaridine tetraphosphate 180mg:artesunate 60mg) will be administered, once per day according to body weight for three days (Arm A) |
| Arm Pyramax 2 days | Experimental | Drug: Pyronaridine tetraphosphate 180mg:artesunate 60mgPyramax (pyronaridine tetraphosphate 180mg:artesunate 60mg) will be administered, once per day according to body weight for two days (Arm B) |
| Arm Pyramax 1 day | Experimental | Drug: Pyronaridine tetraphosphate 180mg:artesunate 60mgPyramax (pyronaridine tetraphosphate 180mg:artesunate 60mg) will be administered, once per day according to body weight for one day (Arm C) |
Who may qualify
- Ages
- 5 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- Evidence of asymptomatic infection with Plasmodium falciparum monoinfection on thin and thick blood smears with parasite density between 20/µL and 50,000/µL
- Absence of any clinical symptoms of malaria at the time of enrolment and within 72 hours before enrolment
- Age >5 years old and >20 kg body weight
- Ability to swallow oral medication
- Evidence of a personally signed and dated Informed Consent document indicating that the participant (or a legally acceptable representative if a participant is <18 years of age) has been informed of all pertinent aspects of the study and that all questions by the participant have been sufficiently answered. Assent will be obtained from participants <18 years of age as required by national regulations.
Key exclusion criteria (18 listed)
- Haemoglobin <7 g/dL (measured at screening)
- History of having received any antimalarial treatment (alone or in combination) during the following periods before screening:
- Any herbal products or traditional medicines during the 7 days prior to screening (if spontaneously reported by the patient)
- Known allergy to the study drugs (pyronaridine and/or any artemisinin derivatives)
- Positive urinary pregnancy test for women of reproductive age
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pyronaridine tetraphosphate 180mg:artesunate 60mgAlso: PyramaxACT | Drug | Arm Pyramax 1 day, Arm Pyramax 2 days, Arm Pyramax 3 days |
Primary outcome
PCR-adjusted APR at Day 28 (based on slide assessment by microscopy)
Time frame: Day 28
To assess the efficacy of each dosing regimen PCR-adjusted Adequate parasitological response (APR) at Day 28
13 secondary outcomes
PCR-adjusted APR
Time frame: 63 days
PCR-unadjusted APR
Time frame: 63 days
Rate of recurrent infections, recrudescence and new infections
Time frame: 63 days
Proportion of parasite free participants
Time frame: 4 days
Gametocyte incidence
Time frame: 14 days
Adverse Events
Time frame: 63 days
Clinical laboratory data - Haematology
Time frame: 63 days
Clinical laboratory data - Biochemistry
Time frame: 63 days
Clinical laboratory data - Liver Enzymes
Time frame: 63 days
Clinical laboratory data - Liver Enzyme Elevations
Time frame: 63 days
Vital signs - Blood pressure
Time frame: 63 days
Vital signs - Pulse rate
Time frame: 63 days
Vital signs - Temperature
Time frame: 63 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Sep 2019.
- Derived from this study: PubMed 33983371Dabira ED, Hachizovu S, Conteh B, Mendy A, Nyang H, Lawal B, Ndiath MO, Mulenga JM, Mwanza S, Borghini-Fuhrer I, Arbe-Barnes S, Miller R, Shin J, Duparc S, D'Alessandro U, Manyando C, Achan J. Efficacy, Safety and Tolerability of Pyronaridine-artesunate in Asymptomatic Malaria-infected Individuals: a Randomized Controlled Trial. Clin Infect Dis. 2022 Jan 29;74(2):180-188. doi: 10.1093/cid/ciab425.
- Individual participant dataSharing planned: Undecided
Related trials for Malaria,Falciparum
RecruitingPhase 1
Safety, Tolerability and Efficacy of PfSPZ-LARC2 Vaccine Against CHMI in Malaria-Naïve Adults
Malaria Falciparum
Not yet recruiting
Three-arm Cluster Randomised Control Trial Evaluation of Guardian Spatial Emanator as a Complimentary Vector Control Tool in Papua New Guinea
Malaria
Active, not recruitingPhase 4
Improving Neonatal Health Through Rapid Malaria Testing in Early Pregnancy With High-Sensitivity Diagnostics
Malaria,Falciparum, Malaria in Pregnancy
Not yet recruiting
Permethrin-Treated Baby Wraps for Malaria Prevention in Refugee Settings
Malaria (Plasmodium Falciparum), Malaria Incidence
RecruitingPhase 1/2
DON in Pediatric Cerebral Malaria
Malaria, Cerebral
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jang Sik Shin study director
Shin Poong
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pyronaridine tetraphosphate 180mg:artesunate 60mg in people with Malaria,Falciparum, run by Shin Poong Pharmaceutical Co. Ltd. at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 30 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in The Gambia, Zambia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
PCR-adjusted APR at Day 28 (based on slide assessment by microscopy) (time frame: Day 28). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03814616, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Sep 2019.