MalariaPhase 3NCT04368910
Safety and Efficacy of Pyronaridine Artesunate Vs Chloroquine in Children and Adult Patients With Acute Vivax Malaria
A Phase 3 study testing Pyronaridine - artesunate and Chloroquine in people with Malaria, run by Medicines for Malaria Venture at 2 sites in South Korea.
Trial summary
The primary objective of this clinical study is to compare the efficacy and safety of the fixed combination of pyronaridine artesunate (180:60 mg) with that of standard chloroquine therapy in children and adults with acute, uncomplicated Plasmodium vivax (P. vivax) malaria Read more about this study
- Who is it for?
- Ages 3 to 60 years
- Conditions the study is for
- Malaria
- What is being tested?
- Pyronaridine - artesunate and Chloroquine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 2 sitesSouth Korea
- Study dates
- 6 Sep 2007to 15 Nov 2010
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 to 60 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Male or female patients between the age of 3 and 60 years, inclusive.
- Body weight between 20 kg and 90 kg with no clinical evidence of severe malnutrition.
- Presence of acute uncomplicated P. vivax mono-infection confirmed by:
- Fever, as defined by axillary/tympanic temperature ≥37.5°C or oral/rectal temperature ≥38°C, or history of fever in the previous 24 hours (history of fever must be documented) and,
- Positive microscopy of P. vivax with parasite density ≥250/ μL of blood (including at least 50% of asexual parasites).
- Written informed consent, in accordance with local practice, provided by patient and/or parent/guardian/spouse. If the patient is unable to write, witnessed consent is permitted according to local ethical considerations.
- Ability to swallow oral medication.
- Ability and willingness to participate based on information given to patient or parent or guardian and access to health facility.
Who cannot join
- Presence of a mixed Plasmodium infection.
- Presence of other clinical condition requiring hospitalization.
- Presence of significant anaemia, as defined by Hb <8 g/dL.
- Known history or evidence of clinically significant disorders such as cardiovascular (including arrhythmia, QTc interval greater than or equal to 450 msec), respiratory (including active tuberculosis), hepatic, renal, gastrointestinal, immunological (including active HIV-AIDS), neurological (including auditory), endocrine, infectious, malignancy, psychiatric or other abnormality (including recent head trauma).
- Known history of hypersensitivity, allergic or adverse reactions to pyronaridine, chloroquine or artesunate or other artemisinins.
- Known history of hypersensitivity, allergic or adverse reactions to chloroquine, primaquine and related agents.
Show all 15Show fewer
- Known active Hepatitis A IgM (HAV-IgM), Hepatitis B surface antigen (HBsAg) or Hepatitis C antibody (HCV Ab).
- Known seropositive HIV antibody.
- Have received any antimalarial treatment in the preceding 2 weeks, as determined by history and, whenever feasible, by screening test.
- Have received antibacterial with known antimalarial activity in the preceding 2 weeks.
- Have received any investigational drug within the past 4 weeks.
- Liver function tests (AST/ALT levels) >2.5 times the upper limit of normal range.
- Known significant renal impairment as indicated by serum creatinine levels of >1.4 mg/dL.
- Female patients of child-bearing potential must be neither pregnant (as demonstrated by a negative pregnancy test) nor lactating, and must be willing to take measures to not become pregnant during the study period.
- Previous participation in the present clinical trial with pyronaridine artesunate.
Trial locations and contacts
2 sites in 1 country.
South Korea2 sites
Inje University Ilsan Paik Hospital
Goyang-si, 411-706
Eulji General Hospital
Seoul, 139-711
About this study
Official title: A Phase III Randomised, Double-blind, Double-dummy, Comparative Study to Assess the Safety and Efficacy of Pyronaridine Artesunate (180:60 mg) Versus Chloroquine (155 mg) in Children and Adult Patients in Korea With Acute P. Vivax Malaria
The primary objective of this clinical study is to compare the efficacy and safety of the fixed combination of pyronaridine artesunate (180:60 mg) with that of standard chloroquine therapy in children and adults with acute, uncomplicated Plasmodium vivax (P. vivax) malaria
Read the detailed description
This is a multi-centre, randomised, double-blind, double-dummy, parallel group, comparative trial. It is a Phase III study designed to meet the regulatory requirements for registration of pyronaridine artesunate (PA) in Korea. Chloroquine will be used as a comparator, which is recognized as an effective and well-tolerated anti-malarial therapy, and is standard blood-stage therapy for patients with P. vivax malaria in Korea. This study will be conducted in a total of 40 male and female children (≥20 kg body weight) and adult patients suffering from acute symptomatic uncomplicated P. vivax malaria recruited from study sites in Korea.
Patients will be randomised in a 1:1 ratio to receive either oral PA (180:60-mg tablets) plus chloroquine-placebo or oral chloroquine (155 mg tablets) plus PA-placebo, once a day for 3 consecutive days (Days 0, 1, and 2). For PA, posology will be based on body weight ranges, with patients receiving 1 to 4 tablets per day depending on their body weight. The actual dose range covered by this regimen is 7.2:2.4 mg/kg to 13.8:4.6 mg/kg per day, which has been shown to be effective and safe in Phase I and II studies. The chloroquine daily dose is 10 mg/kg on Days 0 and 1 and 5 mg/kg on Day 2 for children and 620 mg on Days 0 and 1 and 310 mg on Day 2 for adults.
Patients will be confined to the study facility for ≥4 days (Days 0, 1, 2, and 3) and remain near the study site for ≥7 days, or once fever and parasite clearance has been confirmed for ≥24 hours - whichever occurs later.
The primary efficacy end point for the study is the crude cure rate on Day 14. Scheduled follow-up visits will continue until completion of the study at Day 42. In the case of adverse events reported and unresolved at Day 42, patients will be followed up for a further 30 days, or until resolution of the event.
It is anticipated that the study results will be pooled with the results of study SP-C-006-06 entitled "A Phase III Comparative (Double-blind, Double-dummy) Randomized Multicentre Study to Assess the Safety \& Efficacy of Oral Pyronaridine Artesunate (180:60 mg) Versus Chloroquine (155 mg) in Children \& Adult Patients with Acute Vivax Malaria " for a formal non-inferiority analysis.
- Conditions
- Malaria
- Being tested
- Pyronaridine - artesunate, Chloroquine
- Keywords
- Artemisinin-based combination therapy (ACT), Pyramax, Pyronaridine artesunate, Chloroquine, Children, Adults, Plasmodium vivax, Republic of Korea
- Medical subject headings
- Malaria, Malaria, Vivax
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pyronaridine - artesunateDrug
Also called Pyramax
Oral pyronaridine artesunate (180:60 mg tablets), plus chloroquine-placebo once a day for 3 consecutive days.
ChloroquineDrug
Oral chloroquine (155 mg tablets), plus pyronaridine artesunate-placebo, once a day for 3 consecutive days.
| Study group | Role | What they receive |
|---|---|---|
| Pyronaridine - artesunate | Experimental | Oral pyronaridine artesunate (180:60 mg tablets), plus chloroquine-placebo once a day for 3 consecutive days.
For patients who complete the study up to Day 28 and who have normal G-6-PD activity, a 14-day course of primaquine (15 mg/day) shall be administered starting on Day 28, after all required assessments have been performed, to complete their radical cure. Patients who are deficient in G-6-PD and who complete the study up to Day 28 will be treated as per country policy. Receives: Drug: Pyronaridine - artesunate |
| Chloroquine | Active comparator | Oral chloroquine (155 mg tablets), plus pyronaridine artesunate-placebo, once a day for 3 consecutive days.
For patients who complete the study up to Day 28 and who have normal G-6-PD activity, a 14-day course of primaquine (15 mg/day) shall be administered starting on Day 28, after all required assessments have been performed, to complete their radical cure. Patients who are deficient in G-6-PD and who complete the study up to Day 28 will be treated as per country policy. Receives: Drug: Chloroquine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Crude Cure Rate on Day 14
Percentage of subjects with crude cure rate at Day 14, defined as absence of parasitaemia on Day 14, irrespective of body temperature without previously meeting any of the criteria of treatment failure
Measured: Day 14
Secondary outcomes (6)
Crude Cure Rate on Day 28
Percentage of subjects with crude cure rate at Day 28, defined as absence of parasitaemia on Day 28, irrespective of body temperature without previously meeting any of the criteria of treatment failure
Measured: Day 28
Parasite Clearance Time (PCT)
Parasite clearance time is defined as the time from first dosing to the time of first blood draw with parasite clearance. Parasite clearance was defined as zero presence of asexual parasites for 2 consecutive negative readings taken between 7 and 25 hours apart
Measured: Days 0, 3, 7, 14, 21, 28, 35, and 42 (or on any other day if the subject spontaneously returned within the 42-day period)
Fever Clearance Time (FCT)
Fever clearance time is defined as the time from first dosing to the first normal reading of temperature for 2 consecutive normal temperature readings taken between 7 and 25 hours apart
Measured: Day 0 and every 8 hours over ≥72 hours following first study drug administration or temperature normalization for ≥2 readings between 7 and 25 hours apart, then at each visit (Days 7, 14, 28 and 42)
Percentage of Patients Who Had Cleared Parasite on Days 1, 2, and 3
Parasite clearance is defined as at least 2 consecutive negative smears for asexual parasites obtained within an interval of 7 to 25 hours post-dosing
Measured: Days 1, 2, and 3
Percentage of Patients Who Had Cleared Fever on Days 1, 2, and 3
Fever clearance is defined as at least 2 consecutive normal body temperature measurements (<37.5 C axillary/tympanic or <38.0 C oral/rectal) obtained within an interval of 7 to 25 hours postdosing
Measured: Days 1, 2, and 3
Number of Participants With Adverse Events (AEs)
Number of Participants with AEs, including clinically significant laboratory results, electrocardiogram (ECG), vital signs or physical examination abnormalities
Measured: Day 0 to 42. Subjects experiencing AEs at Day 42 were followed for up to 30 days after the end of study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Apr 2020
- Study start6 Sep 2007
- Primary completion16 Oct 2010
- Study completion15 Nov 2010
Why it stopped: Due to slow recruitment the study was terminated prematurely by the Sponsor after 30 subjects had been included
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for MalariaStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medicines for Malaria Venture
- Sponsor type
- University, hospital or other
- Collaborators
- Shin Poong Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Stephan Duparc, MD, Study director, Medicine for Malaria Venture
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04368910
- Sponsor's protocol ID
- SP-C-008-07
- Status last verified
- Nov 2021
- First submitted
- 23 Apr 2020
- Last updated
- 26 Jan 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III Randomised, Double-blind, Double-dummy, Comparative Study to Assess the Safety and Efficacy of Pyronaridine Artesunate (180:60 mg) Versus Chloroquine (155 mg) in Children and Adult Patients in Korea With Acute P. Vivax Malaria
- ClinicalTrials.gov ID
- NCT04368910
- Acronym / sponsor ID
- SP-C-008-07
- Conditions
- Malaria
- Keywords
- Artemisinin-based combination therapy (ACT), Pyramax, Pyronaridine artesunate, Chloroquine, Children, Adults, Plasmodium vivax, Republic of Korea
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Due to slow recruitment the study was terminated prematurely by the Sponsor after 30 subjects had been included
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Medicines for Malaria VentureUniversity, hospital or other
- Collaborators
- Shin Poong Pharmaceuticals
- Study start
- 6 Sep 2007 (actual)
- Primary completion
- 16 Oct 2010 (actual)
- Study completion
- 15 Nov 2010 (actual)
- First posted
- 30 Apr 2020 (actual)
- Results
- Posted 26 Jan 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of this clinical study is to compare the efficacy and safety of the fixed combination of pyronaridine artesunate (180:60 mg) with that of standard chloroquine therapy in children and adults with acute, uncomplicated Plasmodium vivax (P. vivax) malaria
Detailed description
This is a multi-centre, randomised, double-blind, double-dummy, parallel group, comparative trial. It is a Phase III study designed to meet the regulatory requirements for registration of pyronaridine artesunate (PA) in Korea. Chloroquine will be used as a comparator, which is recognized as an effective and well-tolerated anti-malarial therapy, and is standard blood-stage therapy for patients with P. vivax malaria in Korea. This study will be conducted in a total of 40 male and female children (≥20 kg body weight) and adult patients suffering from acute symptomatic uncomplicated P. vivax malaria recruited from study sites in Korea.
Patients will be randomised in a 1:1 ratio to receive either oral PA (180:60-mg tablets) plus chloroquine-placebo or oral chloroquine (155 mg tablets) plus PA-placebo, once a day for 3 consecutive days (Days 0, 1, and 2). For PA, posology will be based on body weight ranges, with patients receiving 1 to 4 tablets per day depending on their body weight. The actual dose range covered by this regimen is 7.2:2.4 mg/kg to 13.8:4.6 mg/kg per day, which has been shown to be effective and safe in Phase I and II studies. The chloroquine daily dose is 10 mg/kg on Days 0 and 1 and 5 mg/kg on Day 2 for children and 620 mg on Days 0 and 1 and 310 mg on Day 2 for adults.
Patients will be confined to the study facility for ≥4 days (Days 0, 1, 2, and 3) and remain near the study site for ≥7 days, or once fever and parasite clearance has been confirmed for ≥24 hours - whichever occurs later.
The primary efficacy end point for the study is the crude cure rate on Day 14. Scheduled follow-up visits will continue until completion of the study at Day 42. In the case of adverse events reported and unresolved at Day 42, patients will be followed up for a further 30 days, or until resolution of the event.
It is anticipated that the study results will be pooled with the results of study SP-C-006-06 entitled "A Phase III Comparative (Double-blind, Double-dummy) Randomized Multicentre Study to Assess the Safety \& Efficacy of Oral Pyronaridine Artesunate (180:60 mg) Versus Chloroquine (155 mg) in Children \& Adult Patients with Acute Vivax Malaria " for a formal non-inferiority analysis.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pyronaridine - artesunate | Experimental | Drug: Pyronaridine - artesunateOral pyronaridine artesunate (180:60 mg tablets), plus chloroquine-placebo once a day for 3 consecutive days. For patients who complete the study up to Day 28 and who have normal G-6-PD activity, a 14-day course of primaquine (15 mg/day) shall be administered starting on Day 28, after all required assessments have been performed, to complete their radical cure. Patients who are deficient in G-6-PD and who complete the study up to Day 28 will be treated as per country policy. |
| Chloroquine | Active comparator | Drug: ChloroquineOral chloroquine (155 mg tablets), plus pyronaridine artesunate-placebo, once a day for 3 consecutive days. For patients who complete the study up to Day 28 and who have normal G-6-PD activity, a 14-day course of primaquine (15 mg/day) shall be administered starting on Day 28, after all required assessments have been performed, to complete their radical cure. Patients who are deficient in G-6-PD and who complete the study up to Day 28 will be treated as per country policy. |
Who may qualify
- Ages
- 3 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (8 listed)
- Male or female patients between the age of 3 and 60 years, inclusive.
- Body weight between 20 kg and 90 kg with no clinical evidence of severe malnutrition.
- Presence of acute uncomplicated P. vivax mono-infection confirmed by:
- Written informed consent, in accordance with local practice, provided by patient and/or parent/guardian/spouse. If the patient is unable to write, witnessed consent is permitted according to local ethical considerations.
- Ability to swallow oral medication.
Key exclusion criteria (15 listed)
- Presence of a mixed Plasmodium infection.
- Presence of other clinical condition requiring hospitalization.
- Presence of significant anaemia, as defined by Hb <8 g/dL.
- Known history or evidence of clinically significant disorders such as cardiovascular (including arrhythmia, QTc interval greater than or equal to 450 msec), respiratory (including active tuberculosis), hepatic, renal, gastrointestinal, immunological (including active HIV-AIDS), neurological (including auditory), endocrine, infectious, malignancy, psychiatric or other abnormality (including recent head trauma).
- Known history of hypersensitivity, allergic or adverse reactions to pyronaridine, chloroquine or artesunate or other artemisinins.
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: PyramaxOral pyronaridine artesunate (180:60 mg tablets), plus chloroquine-placebo once a day for 3 consecutive days. | Drug | Pyronaridine - artesunate |
| ChloroquineOral chloroquine (155 mg tablets), plus pyronaridine artesunate-placebo, once a day for 3 consecutive days. | Drug | Chloroquine |
Primary outcome
Crude Cure Rate on Day 14
Time frame: Day 14
Percentage of subjects with crude cure rate at Day 14, defined as absence of parasitaemia on Day 14, irrespective of body temperature without previously meeting any of the criteria of treatment failure
6 secondary outcomes
Crude Cure Rate on Day 28
Time frame: Day 28
Parasite Clearance Time (PCT)
Time frame: Days 0, 3, 7, 14, 21, 28, 35, and 42 (or on any other day if the subject spontaneously returned within the 42-day period)
Fever Clearance Time (FCT)
Time frame: Day 0 and every 8 hours over ≥72 hours following first study drug administration or temperature normalization for ≥2 readings between 7 and 25 hours apart, then at each visit (Days 7, 14, 28 and 42)
Percentage of Patients Who Had Cleared Parasite on Days 1, 2, and 3
Time frame: Days 1, 2, and 3
Percentage of Patients Who Had Cleared Fever on Days 1, 2, and 3
Time frame: Days 1, 2, and 3
Number of Participants With Adverse Events (AEs)
Time frame: Day 0 to 42. Subjects experiencing AEs at Day 42 were followed for up to 30 days after the end of study
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jan 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Malaria
Active, not recruitingObservational study
Trajectories and Mechanisms of Recovery From Malaria: An Observational Study
Malaria
Not yet recruiting
Positron Emission Tomography and Organ-Specific Changes in Participants Co-Enrolled in NIH Studies of Plasmodium Vivax Controlled Human Malaria Infection
Healthy Volunteer, Malaria
Recruiting
The Effects of Iron Treatment on Vaccine Immunogenicity in Kenyan Infants With Iron Deficiency
Iron Deficiencies
RecruitingObservational study
Host and Parasite Factors That Influence Susceptibility to Malaria Infection and Disease During Pregnancy and Early Childhood in Ouelessebougou and Bamako, Mali
Malaria
RecruitingPhase 1
Safety, Tolerability and Efficacy of PfSPZ-LARC2 Vaccine Against CHMI in Malaria-Naïve Adults
Malaria Falciparum
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.
Stephan Duparc, MD study director
Medicine for Malaria Venture
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Pyronaridine - artesunate and Chloroquine in people with Malaria, run by Medicines for Malaria Venture at 2 sites in South Korea.
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 8 inclusion and 15 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: stopped early, as of the sponsor's last update on 26 Jan 2022. 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 South Korea. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Jan 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Crude Cure Rate on Day 14 (time frame: Day 14). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 Jan 2022.