Malaria, FalciparumPhase 2NCT01213966
Efficacy, Tolerability, PK of OZ439 in Adults With Acute, Uncomplicated P.Falciparum or Vivax Malaria Mono-infection
A Phase 2 study testing OZ439 in people with Malaria, Falciparum and Malaria, Vivax, run by Medicines for Malaria Venture.
Trial summary
A Phase IIa Exploratory, Open label, Single Dose Regimen, Multiple Dose Testing Clinical Study to Assess the Preliminary Efficacy, Tolerability and Pharmacokinetics of OZ439 in adult patients with acute, uncomplicated Plasmodium falciparum or vivax malaria mono-infection. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Malaria, Falciparum, Malaria, Vivax
- What is being tested?
- OZ439
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 82 participants
- Where
- No sites listed yet
- Study dates
- Oct 2010to May 2012
- Phase
- Phase 2
- 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 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Male or female patients between the age of 18 and 60 years, inclusive
- Body weight between 40 kg and 90 kg inclusive
- Presence of mono-infection of P. falciparum or P. vivax confirmed by:
- Fever, as defined by axillary temperature ≥ 37.5°C or oral/rectal/tympanic temperature ≥ 38°C, or history of fever in the previous 24 hours (history of fever must be documented) and,
- Microscopically confirmed parasite infection, 5,000 to 50,000 asexual parasite count/µl of blood
- Written informed consent, in accordance with local practice, provided by patient. If the patient is unable to write, witnessed consent is permitted according to local ethical considerations
Show all 9Show fewer
- Ability to swallow oral medication
- Ability and willingness to participate and access the health facility
- Agree to minimum of 4 days hospitalisation for drug administration and pharmacokinetic sampling
Who cannot join
- Patients with signs and symptoms of severe/complicated malaria requiring parenteral treatment according to the World Health Organisation Criteria 2010 (Attachment 2)
- Mixed Plasmodium infection
- Severe vomiting, defined as more than three times in the 24 hours prior to inclusion in the study or inability to tolerate oral treatment, or severe diarrhoea defined as 3 or more watery stools per day
- Presence of other serious or chronic clinical condition requiring hospitalisation.
- Severe malnutrition (defined as the weight-for-height being below -3 standard deviation or less than 70% of median of the NCHS/WHO normalised reference values).
- 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), history of jaundice, hepatic, renal, gastrointestinal, immunological (including active HIV-AIDS), neurological (including auditory), endocrine, infectious, malignancy, psychiatric, history of convulsions or other abnormality (including head trauma).
Show all 16Show fewer
- Known history of hypersensitivity, allergic or adverse reactions to artemisinin containing compounds or mefloquine or drug in the national guidelines for P. vivax.
- Known active Hepatitis A IgM (HAV-IgM), Hepatitis B surface antigen (HBsAg) or Hepatitis C antibody (HCV Ab).
- Have received any antimalarial treatment in the preceding 14 days, as determined by history and screening test.
- Have received antibacterial with known antimalarial activity in the preceding 14 days.
- Have received an investigational drug within the past 4 weeks.
- Liver function tests (ASAT/ALAT levels) more than 2 x ULN
- Hb level below 10 g/dL.
- Bilirubin levels greater than 40 µmol/L.
- Serum creatinine levels more than 2 times the upper limit of normal range in absence of dehydration. In case of important dehydration the creatinine should be lower than 2X ULN after oral/parenteral rehydration.
- Female patients must be neither pregnant (as demonstrated by a negative serum pregnancy test) nor lactating, and must be willing to take measures not to become pregnant during the study period and safety follow-up period
About this study
Official title: Phase IIa Exploratory, Open Label, Single/Multiple Dose Testing Clinical Study to Assess the Preliminary Efficacy, Tolerability and PK of OZ439 in Adult Patients With Acute, Uncomplicated P. Falciparum or Vivax Malaria Mono-infection
A Phase IIa Exploratory, Open label, Single Dose Regimen, Multiple Dose Testing Clinical Study to Assess the Preliminary Efficacy, Tolerability and Pharmacokinetics of OZ439 in adult patients with acute, uncomplicated Plasmodium falciparum or vivax malaria mono-infection.
Read the detailed description
This exploratory Phase IIa study aims to investigate the preliminary efficacy in terms of parasite reduction and clearance in malaria patients, and the tolerability of OZ439 administered as single dose regimen at 3 different doses in parallel cohorts of patients with either acute uncomplicated Plasmodium falciparum or Plasmodium vivax malaria mono-infection (10 patients per plasmodium species per dose level).
Treatment with OZ439 will be given as a single dose on Day 0, starting in the first cohort at a dose of 800 mg. Established antimalarial therapy will be given at the latest at 36 hours post dosing.
The primary endpoint will be the derived parasite reduction rate (PRR) at 24 hours after study drug administration.
A review of each individual study cohort (dose/species) will be conducted with the Principal Investigator and the Sponsor and a decision will be reached on whether the dose for the next cohort should increase or decrease (within 200mg-1600mg range). This decision will be based on parasite reduction rate over the first 24 hours following administration of OZ439, tolerability and exposure.
- Conditions
- Malaria, Falciparum, Malaria, Vivax
- Being tested
- OZ439
- Keywords
- Acute uncomplicated Plasmodium Falciparum malaria, Blood stage Plasmodium Vivax malaria
- Medical subject headings
- Malaria, Falciparum, Malaria, Vivax
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OZ439Drug
Also called Artefenomel
po, single dose
| Study group | Role | What they receive |
|---|---|---|
| 800 mg OZ439 po single dose | Experimental | 800 mg OZ439 po single dose Receives: Drug: OZ439 |
| 400 mg OZ439 p.o. single dose | Experimental | 400 mg OZ439 p.o. single dose Receives: Drug: OZ439 |
| 200mg OZ439 p.o. single dose | Experimental | 200mg OZ439 p.o. single dose Receives: Drug: OZ439 |
| 1200 mg OZ439 po single dose | Experimental | 1200 mg OZ439 po single dose Receives: Drug: OZ439 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Derived Parasite Reduction Rate at 24 Hours (PPR24)
PRR24 is the log10 change in parasitemia over 24 hours estimated from a regression model fit separately for each patient. The relationship between parasite counts and time was analyzed by fitting a variable lag phase, then a linear decline to the natural log of parasite count versus time relationship. The slope of this log linear relationship is the primary end-point.
The time points chosen for the regression are those that yield the highest degree of significance when assessing the regression when the number of time points are greater than or equal to 3. No extrapolation was performed.
Measured: 24 hours after study drug administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Oct 2010 (estimated)
- Study startOct 2010
- Primary completionMay 2012
- Study completionMay 2012
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.
- 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 82 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medicines for Malaria Venture
- Sponsor type
- University, hospital or other
- Collaborators
- Mahidol University
- Responsible party
- Sponsor
- Investigators
- Sasithon Pukrittayakamee, MD, Principal investigator, Mahidol University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01213966
- Sponsor's protocol ID
- MMV_OZ439_10_002
- Status last verified
- Nov 2014
- First submitted
- 1 Oct 2010
- Last updated
- 3 Dec 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Phyo AP, Jittamala P, Nosten FH, Pukrittayakamee S, Imwong M, White NJ, Duparc S, Macintyre F, Baker M, Mohrle JJ. Antimalarial activity of artefenomel (OZ439), a novel synthetic antimalarial endoperoxide, in patients with Plasmodium falciparum and Plasmodium vivax malaria: an open-label phase 2 trial. Lancet Infect Dis. 2016 Jan;16(1):61-69. doi: 10.1016/S1473-3099(15)00320-5. Epub 2015 Oct 5.
PubMed 26448141
Study at a glance
From the registry record, last updated by the sponsor on 3 Dec 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase IIa Exploratory, Open Label, Single/Multiple Dose Testing Clinical Study to Assess the Preliminary Efficacy, Tolerability and PK of OZ439 in Adult Patients With Acute, Uncomplicated P. Falciparum or Vivax Malaria Mono-infection
- ClinicalTrials.gov ID
- NCT01213966
- Acronym / sponsor ID
- MMV_OZ439_10_002
- Conditions
- Malaria, Falciparum, Malaria, Vivax
- Keywords
- Acute uncomplicated Plasmodium Falciparum malaria, Blood stage Plasmodium Vivax malaria
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 82 participants (actual)
- Lead sponsor
- Medicines for Malaria VentureUniversity, hospital or other
- Collaborators
- Mahidol University
- Study start
- Oct 2010
- Primary completion
- May 2012 (actual)
- Study completion
- May 2012 (actual)
- First posted
- 4 Oct 2010 (estimated)
- Results
- Posted 18 Nov 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A Phase IIa Exploratory, Open label, Single Dose Regimen, Multiple Dose Testing Clinical Study to Assess the Preliminary Efficacy, Tolerability and Pharmacokinetics of OZ439 in adult patients with acute, uncomplicated Plasmodium falciparum or vivax malaria mono-infection.
Detailed description
This exploratory Phase IIa study aims to investigate the preliminary efficacy in terms of parasite reduction and clearance in malaria patients, and the tolerability of OZ439 administered as single dose regimen at 3 different doses in parallel cohorts of patients with either acute uncomplicated Plasmodium falciparum or Plasmodium vivax malaria mono-infection (10 patients per plasmodium species per dose level).
Treatment with OZ439 will be given as a single dose on Day 0, starting in the first cohort at a dose of 800 mg. Established antimalarial therapy will be given at the latest at 36 hours post dosing.
The primary endpoint will be the derived parasite reduction rate (PRR) at 24 hours after study drug administration.
A review of each individual study cohort (dose/species) will be conducted with the Principal Investigator and the Sponsor and a decision will be reached on whether the dose for the next cohort should increase or decrease (within 200mg-1600mg range). This decision will be based on parasite reduction rate over the first 24 hours following administration of OZ439, tolerability and exposure.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 800 mg OZ439 po single dose | Experimental | Drug: OZ439800 mg OZ439 po single dose |
| 400 mg OZ439 p.o. single dose | Experimental | Drug: OZ439400 mg OZ439 p.o. single dose |
| 200mg OZ439 p.o. single dose | Experimental | Drug: OZ439200mg OZ439 p.o. single dose |
| 1200 mg OZ439 po single dose | Experimental | Drug: OZ4391200 mg OZ439 po single dose |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- Male or female patients between the age of 18 and 60 years, inclusive
- Body weight between 40 kg and 90 kg inclusive
- Presence of mono-infection of P. falciparum or P. vivax confirmed by:
- Written informed consent, in accordance with local practice, provided by patient. If the patient is unable to write, witnessed consent is permitted according to local ethical considerations
- Ability to swallow oral medication
Key exclusion criteria (16 listed)
- Patients with signs and symptoms of severe/complicated malaria requiring parenteral treatment according to the World Health Organisation Criteria 2010 (Attachment 2)
- Mixed Plasmodium infection
- Severe vomiting, defined as more than three times in the 24 hours prior to inclusion in the study or inability to tolerate oral treatment, or severe diarrhoea defined as 3 or more watery stools per day
- Presence of other serious or chronic clinical condition requiring hospitalisation.
- Severe malnutrition (defined as the weight-for-height being below -3 standard deviation or less than 70% of median of the NCHS/WHO normalised reference values).
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 |
|---|---|---|
| OZ439Also: Artefenomelpo, single dose | Drug | 1200 mg OZ439 po single dose, 200mg OZ439 p.o. single dose, 400 mg OZ439 p.o. single dose, 800 mg OZ439 po single dose |
Primary outcome
Derived Parasite Reduction Rate at 24 Hours (PPR24)
Time frame: 24 hours after study drug administration
PRR24 is the log10 change in parasitemia over 24 hours estimated from a regression model fit separately for each patient. The relationship between parasite counts and time was analyzed by fitting a variable lag phase, then a linear decline to the natural log of parasite count versus time relationship. The slope of this log linear relationship is the primary end-point. The time points chosen for the regression are those that yield the highest degree of significance when assessing the regression when the number of time points are greater than or equal to 3. No extrapolation was performed.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Dec 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 26448141Phyo AP, Jittamala P, Nosten FH, Pukrittayakamee S, Imwong M, White NJ, Duparc S, Macintyre F, Baker M, Mohrle JJ. Antimalarial activity of artefenomel (OZ439), a novel synthetic antimalarial endoperoxide, in patients with Plasmodium falciparum and Plasmodium vivax malaria: an open-label phase 2 trial. Lancet Infect Dis. 2016 Jan;16(1):61-69. doi: 10.1016/S1473-3099(15)00320-5. Epub 2015 Oct 5.
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.
Sasithon Pukrittayakamee, MD principal investigator
Mahidol University
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing OZ439 in people with Malaria, Falciparum and Malaria, Vivax, run by Medicines for Malaria Venture.
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 9 inclusion and 16 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 3 Dec 2014. Status can change between updates, so confirm with the study contact before making plans.
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?
Yes. Results are posted in the registry (first posted 18 Nov 2014). 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?
Derived Parasite Reduction Rate at 24 Hours (PPR24) (time frame: 24 hours after study drug administration). 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 NCT01213966, 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 3 Dec 2014.