Malaria,FalciparumPhase 4NCT03201770
Cohort Event Monitoring Study of Pyramax®
A Phase 4 study testing pyronaridine artesunate in people with Malaria,Falciparum, run by Shin Poong Pharmaceutical Co. Ltd. at 5 sites in 5 countries.
Trial summary
The study is to be performed in public health facilities in Central and West Africa where Pyramax will be used as treatment of uncomplicated malaria episodes, including repeat episodes. Read more about this study
- Who is it for?
- Ages 3 months and older
- Conditions the study is for
- Malaria,Falciparum
- What is being tested?
- pyronaridine artesunate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8,572 participants
- Where
- 5 sitesin 5 countries
- Study dates
- 22 Jun 2017to 10 Apr 2019
- Phase
- Phase 4
- 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 3 months and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Uncomplicated malaria (Plasmodia of any species) diagnosed as per national policies and in line with WHO recommendations:
- Fever or history of fever in the previous 24 h and/or the presence of anaemia, for which pallor of the palms appears to be the most reliable sign in young children.
- Confirmation of malaria by a parasitological diagnosis (RDT or Microscopy (thick blood smear). analysis).
- Weight ≥5 kg - < 20 kg (granules); ≥20 kg (tablets).
- Ability to take an oral medication.
- Ability and willingness to participate based on signed informed consent (a parent or a guardian has to sign for children below 18 years old) and on signed assent form for minors that could be required per national regulations in each participating country.
- The patient has to comply with all scheduled follow-up visits.
Who cannot join
- Patients with 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).
- Known allergy to artemisinin and/or to pyronaridine.
- Known pregnancy.
- Lactating women should be excluded if other anti-malarial treatments are available.
- Complicated malaria as per WHO definition (Annex 2)
- Patients that the investigator considers would be at particular risk if receiving an anti-malarial or if participating in the study.
- Patients having been treated with Pyramax in the previous 28 days.
Trial locations and contacts
5 sites in 5 countries.
5 sites in 5 countries
Cameroon1 site
The Biotechnology Center Nkolbisson, Univ of Yaounde I, Messa
Yaoundé
Côte d’Ivoire1 site
Institut Pierre Richet / Institut National de SanPublique (IPR/INSP)
Bouaké, BP 1500
Democratic Republic of the Congo1 site
Centre de Recherche du Centre Hospitalier du Mont Amba
Kinshasa, XI
Republic of the Congo1 site
Centre de Santé FCRM, Hospital of Talangai
Brazzaville
About this study
Official title: Phase IIIb/IV Cohort Event Monitoring Study To Evaluate, In Real Life Setting, The Safety And Tolerability In Malaria Patients Of The Fixed-Dose Artemisinin-Based Combination Therapy Pyramax®
The study is to be performed in public health facilities in Central and West Africa where Pyramax will be used as treatment of uncomplicated malaria episodes, including repeat episodes. The study is to assess the safety of Pyramax, particularly in patients with underlying liver function abnormalities, in patients who have co-morbid conditions, such as HIV, and also in very small children (<1 year of age).
Read the detailed description
This is a non-comparative Cohort Event Monitoring study. The study will assess the safety of Pyramax in terms of the evaluation and identification of the hepatic safety events in a sub group of patients enrolled with liver function tests (LFT)s >2x upper limit of normal (ULN) from blood taken immediately prior to treatment without any clinical signs or symptoms of hepatotoxicity and with signs and symptoms of uncomplicated malaria confirmed by a Rapid Diagnostic Test (RDT) or microscopy (thick blood smear). The study will compare the clinical hepatic safety of Pyramax between a cohort of patients enrolled with LFTs >2xULN and a cohort of patients enrolled with normal LFTs matched for demographic characteristics.
An estimated 8,572 malaria episodes are to be recruited to provide 120 malaria episodes in patients with baseline raised LFTs >2xULN for follow up of liver function. A cohort of at least 2% of children who are <1 year of age will be included for monitoring of liver function.
- Conditions
- Malaria,Falciparum
- Being tested
- pyronaridine artesunate
- Keywords
- Uncomplicated Malaria, Pyramax, Pyronaridine artesunate
- 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 artesunateDrug
Also called Pyramax
Antimalarial treatment
| Study group | Role | What they receive |
|---|---|---|
| Pyramax | Experimental | Pyronaridine artesunate tablets (180/60mg) and granules (60/20mg) Receives: Drug: pyronaridine artesunate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluation and identification of hepatic safety events, including raised liver function tests
Evaluation and identification of hepatic safety events (including raised liver function tests - LFTs) of Pyramax in a sub group of malaria patients enrolled with LFTs >2xUL.
Measured: Assessment up to Day 28.
Secondary outcomes (2)
Overall safety
Evaluation of the adverse event reporting of Pyramax in the treatment of uncomplicated malaria under real life conditions.
Measured: Assessment up to Day 28.
Evaluation of Efficacy
Evaluation of the efficacy based on crude Day 28 cure rate by species and PCR adjusted cure rate for Day 28 cure rate for P. falciparum of Pyramax in the treatment of uncomplicated malaria under real life conditions
Measured: Assessment up to Day 28.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jun 2017
- Study start22 Jun 2017
- Primary completion10 Apr 2019
- Study completion10 Apr 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)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 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 8,572 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
- Michael Ramharter, MD, DTM&H, Principal investigator, CERMEL, University of Tübingen, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03201770
- Sponsor's protocol ID
- SP-C-021-15
- Status last verified
- Jan 2018
- First submitted
- 21 Jun 2017
- Last updated
- 26 Jun 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Ramharter M, Djimde AA, Borghini-Fuhrer I, Miller R, Shin J, Aspinall A, Richardson N, Wibberg M, Fleckenstein L, Arbe-Barnes S, Duparc S. Safety and efficacy of pyronaridine-artesunate paediatric granules in the treatment of uncomplicated malaria in children: insights from randomized clinical trials and a real-world study. Malar J. 2024 Feb 28;23(1):61. doi: 10.1186/s12936-024-04885-3.
PubMed 38418982Koehne E, Zander N, Rodi M, Held J, Hoffmann W, Zoleko-Manego R, Ramharter M, Mombo-Ngoma G, Kremsner PG, Kreidenweiss A. Evidence for in vitro and in vivo activity of the antimalarial pyronaridine against Schistosoma. PLoS Negl Trop Dis. 2021 Jun 24;15(6):e0009511. doi: 10.1371/journal.pntd.0009511. eCollection 2021 Jun.
PubMed 34166393Tona Lutete G, Mombo-Ngoma G, Assi SB, Bigoga JD, Koukouikila-Koussounda F, Ntamabyaliro NY, Ntoumi F, Agnandji ST, Groger M, Shin J, Borghini-Fuhrer I, Arbe-Barnes S, Allen SJ, Kremsner PG, Miller R, Duparc S, Ramharter M; CANTAM study group. Pyronaridine-artesunate real-world safety, tolerability, and effectiveness in malaria patients in 5 African countries: A single-arm, open-label, cohort event monitoring study. PLoS Med. 2021 Jun 15;18(6):e1003669. doi: 10.1371/journal.pmed.1003669. eCollection 2021 Jun.
PubMed 34129601
Study at a glance
From the registry record, last updated by the sponsor on 26 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase IIIb/IV Cohort Event Monitoring Study To Evaluate, In Real Life Setting, The Safety And Tolerability In Malaria Patients Of The Fixed-Dose Artemisinin-Based Combination Therapy Pyramax®
- ClinicalTrials.gov ID
- NCT03201770
- Acronym / sponsor ID
- SP-C-021-15
- Conditions
- Malaria,Falciparum
- Keywords
- Uncomplicated Malaria, Pyramax, Pyronaridine artesunate
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8,572 participants (actual)
- Lead sponsor
- Shin Poong Pharmaceutical Co. Ltd.Industry (pharma, biotech, devices)
- Collaborators
- Medicines for Malaria Venture
- Study start
- 22 Jun 2017 (actual)
- Primary completion
- 10 Apr 2019 (actual)
- Study completion
- 10 Apr 2019 (actual)
- First posted
- 28 Jun 2017 (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.
The study is to be performed in public health facilities in Central and West Africa where Pyramax will be used as treatment of uncomplicated malaria episodes, including repeat episodes. The study is to assess the safety of Pyramax, particularly in patients with underlying liver function abnormalities, in patients who have co-morbid conditions, such as HIV, and also in very small children (<1 year of age).
Detailed description
This is a non-comparative Cohort Event Monitoring study. The study will assess the safety of Pyramax in terms of the evaluation and identification of the hepatic safety events in a sub group of patients enrolled with liver function tests (LFT)s >2x upper limit of normal (ULN) from blood taken immediately prior to treatment without any clinical signs or symptoms of hepatotoxicity and with signs and symptoms of uncomplicated malaria confirmed by a Rapid Diagnostic Test (RDT) or microscopy (thick blood smear). The study will compare the clinical hepatic safety of Pyramax between a cohort of patients enrolled with LFTs >2xULN and a cohort of patients enrolled with normal LFTs matched for demographic characteristics.
An estimated 8,572 malaria episodes are to be recruited to provide 120 malaria episodes in patients with baseline raised LFTs >2xULN for follow up of liver function. A cohort of at least 2% of children who are <1 year of age will be included for monitoring of liver function.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pyramax | Experimental | Drug: pyronaridine artesunatePyronaridine artesunate tablets (180/60mg) and granules (60/20mg) |
Who may qualify
- Ages
- 3 months and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- Uncomplicated malaria (Plasmodia of any species) diagnosed as per national policies and in line with WHO recommendations:
- Weight ≥5 kg - < 20 kg (granules); ≥20 kg (tablets).
- Ability to take an oral medication.
- Ability and willingness to participate based on signed informed consent (a parent or a guardian has to sign for children below 18 years old) and on signed assent form for minors that could be required per national regulations in each participating country.
- The patient has to comply with all scheduled follow-up visits.
Key exclusion criteria (7 listed)
- Patients with 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).
- Known allergy to artemisinin and/or to pyronaridine.
- Known pregnancy.
- Lactating women should be excluded if other anti-malarial treatments are available.
- Complicated malaria as per WHO definition (Annex 2)
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 artesunateAlso: PyramaxAntimalarial treatment | Drug | Pyramax |
Primary outcome
Evaluation and identification of hepatic safety events, including raised liver function tests
Time frame: Assessment up to Day 28.
Evaluation and identification of hepatic safety events (including raised liver function tests - LFTs) of Pyramax in a sub group of malaria patients enrolled with LFTs >2xUL.
2 secondary outcomes
Overall safety
Time frame: Assessment up to Day 28.
Evaluation of Efficacy
Time frame: Assessment up to Day 28.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jun 2019.
- Derived from this study: PubMed 38418982Ramharter M, Djimde AA, Borghini-Fuhrer I, Miller R, Shin J, Aspinall A, Richardson N, Wibberg M, Fleckenstein L, Arbe-Barnes S, Duparc S. Safety and efficacy of pyronaridine-artesunate paediatric granules in the treatment of uncomplicated malaria in children: insights from randomized clinical trials and a real-world study. Malar J. 2024 Feb 28;23(1):61. doi: 10.1186/s12936-024-04885-3.
- Derived from this study: PubMed 34166393Koehne E, Zander N, Rodi M, Held J, Hoffmann W, Zoleko-Manego R, Ramharter M, Mombo-Ngoma G, Kremsner PG, Kreidenweiss A. Evidence for in vitro and in vivo activity of the antimalarial pyronaridine against Schistosoma. PLoS Negl Trop Dis. 2021 Jun 24;15(6):e0009511. doi: 10.1371/journal.pntd.0009511. eCollection 2021 Jun.
- Derived from this study: PubMed 34129601Tona Lutete G, Mombo-Ngoma G, Assi SB, Bigoga JD, Koukouikila-Koussounda F, Ntamabyaliro NY, Ntoumi F, Agnandji ST, Groger M, Shin J, Borghini-Fuhrer I, Arbe-Barnes S, Allen SJ, Kremsner PG, Miller R, Duparc S, Ramharter M; CANTAM study group. Pyronaridine-artesunate real-world safety, tolerability, and effectiveness in malaria patients in 5 African countries: A single-arm, open-label, cohort event monitoring study. PLoS Med. 2021 Jun 15;18(6):e1003669. doi: 10.1371/journal.pmed.1003669. eCollection 2021 Jun.
- Individual participant dataSharing planned: No
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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.
Michael Ramharter, MD, DTM&H principal investigator
CERMEL, University of Tübingen, Germany
5 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing pyronaridine artesunate in people with Malaria,Falciparum, run by Shin Poong Pharmaceutical Co. Ltd. at 5 sites in 5 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 7 inclusion and 7 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: finished, as of the sponsor's last update on 26 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Cameroon, Côte d’Ivoire, Democratic Republic of the Congo, Gabon, Republic of the Congo. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Evaluation and identification of hepatic safety events, including raised liver function tests (time frame: Assessment up to 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 NCT03201770, which also lists 3 linked publications.
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 26 Jun 2019.