MalariaPhase 1NCT02453581

Effectiveness of OZ439 Against Early Plasmodium Falciparum Blood Stage Infection in Healthy Volunteers

A Phase 1 study testing OZ439 in people with Malaria, run by Medicines for Malaria Venture at 1 site in Australia.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

A single centre, open, controlled study using Blood Stage Plasmodium falciparum challenge inoculum (BSPC) as a model to assess the effectiveness of three dose levels of the experimental anti-malarial product, OZ439. Read more about this study

Who is it for?: Ages 18 to 45 yearsHealthy volunteers can take part
Conditions the study is for: Malaria
What is being tested?: OZ439
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 24 participants
Where: 1 siteAustralia
Study dates: Sep 2012to Mar 2013
Phase: Phase 1
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 45 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

Volunteers will be adults (males or non pregnant females), aged between 18 and 45 years who do not live alone (from Day 1 until at least the end of the antimalarial drug treatment).
Volunteers must have a BMI within the range 18-30.
Volunteers must understand the procedures involved and agree to participate in the study by giving fully informed, written consent.
Be contactable and available for the duration of the trial (maximum of 4 weeks).
Volunteers must be non-smokers and in good health, as assessed during pre-study medical examination and by review of screening results.
Female participants of childbearing potential, should be surgically sterile or using an insertable, injectable, transdermal, or combination oral contraceptive approved by the US FDA or Therapeutic Goods Administration (TGA) combined with a barrier contraceptive through completion of the study and have negative results on a serum or urine pregnancy test done before administration of study medication.
Good peripheral venous access.

Who cannot join

History of malaria.
Travelled to or lived (2 weeks or more) in a malaria-endemic country during the past 12 months or planned travel to a malaria-endemic country during the course of the study.
Has evidence of increased cardiovascular disease risk (defined as greater than 10%, 5 year risk)
History of splenectomy.
History of a severe allergic reaction, anaphylaxis or convulsions following any vaccination or infusion.
Presence of current or suspected serious chronic diseases such as cardiac or autoimmune disease (HIV or other immunodeficiencies), insulin dependent diabetes, progressive neurological disease, severe malnutrition, acute or progressive hepatic disease, acute or progressive renal disease, psoriasis, rheumatoid arthritis, asthma, epilepsy or obsessive compulsive disorder, skin carcinoma excluding non-spreadable skin cancers such as basal cell and squamous cell carcinoma.

Show all 13Show fewer

Known inherited genetic anomaly (known as cytogenetic disorders) e.g., Down's syndrome
Volunteers unwilling to defer blood donations to the Australian Red Cross Blood Service (ARCBS) for 6 months.
The volunteer has a diagnosis of schizophrenia, severe depression, bi-polar disease, or other severe (disabling) chronic psychiatric diagnosis. Participants who are receiving a single antidepressant drug and are stable for at least 3 months prior to enrollment without decompensating may be allowed to enroll in the study at the investigator's discretion. 10) Presence of acute infectious disease or fever (e.g., sub-lingual temperature 38.5 degrees C) within the five days prior to study product administration.
Evidence of acute illness within the four weeks before trial prior to screening.
Significant intercurrent disease of any type, in particular liver, renal, cardiac, pulmonary, neurologic, rheumatologic, or autoimmune disease by history, physical examination, and/or laboratory studies including urinalysis.
Have ever received a blood transfusion.
Evidence of any condition that, in the opinion of the clinical investigator, might interfere with the evaluation of the study objectives or pose excessive risks to participants.

Trial locations and contacts

1 site in 1 country.

Australia1 site

Q-Pharm
Herston, Queensland, QLD 4006

Other trials in Australia

About this study

Official title: An Experimental Study To Characterize the Effectiveness of OZ439 Against Early Plasmodium Falciparum Blood Stage Infection In Healthy Volunteers

Read the detailed description

This was a single center study using blood stage Plasmodium falciparum challenge inoculum to characterize the effectiveness of OZ439 against early blood stage Plasmodium Falciparum infection.

The study was conducted in three cohorts (n=8) using different doses of OZ439. Dose escalation took place after review of the observed OZ439 safety and pharmacodynamic outcome for the previous cohort by the Safety Review Team.

Single doses of 100 mg, 200 mg and 500 mg were administered orally to participants in Cohort 1, Cohort 2 and Cohort 3 respectively.

Conditions: Malaria
Being tested: OZ439
Medical subject headings: Malaria

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

OZ439Drug
OZ439 Powder for Oral Suspension

Study groups in NCT02453581
Study group	Role	What they receive
OZ439 100mg	Experimental	OZ439 100mg Powder for Oral Suspension Receives: Drug: OZ439
OZ439 200mg	Experimental	OZ439 200mg Powder for Oral Suspension Receives: Drug: OZ439
OZ439 500mg	Experimental	OZ439 500mg Powder for Oral Suspension Receives: Drug: OZ439

What is being measured

The primary outcome is the main question the study is designed to answer.

Individual Parasite Reduction Ratio (PRR)
PRR estimates the efficacy of an anti-malarial treatment and is the ratio of the parasite density between admission and 48 hours post-treatment.
Individual subject PRR and corresponding 95% CI were calculated using the slope and corresponding standard error of mean (SE) of the optimal regression model.
Measured: 48 hours
500mg Cohort Mean Parasite Reduction Ratio (PRR)
OZ439 500mg individual subject PRR and corresponding 95% CI were used to calculate the OZ439 500mg cohort specific PRR and the corresponding 95% CI: the weighted average slope estimate and corresponding SE were calculated by the inverse-variance method.
Measured: 48 hours

Secondary outcomes (2)

OZ439 Cmax
OZ439 Maximum concentration (Cmax)
Measured: Pre-dose, and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose
OZ439 AUC(0-144)
OZ439 Area under the curve to 144 hours
Measured: Pre-dose, and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Sep 2012Mar 2013

First posted25 May 2015 (estimated)
Study startSep 2012
Primary completionMar 2013
Study completionMar 2013

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 1
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 24 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02453581
Sponsor's protocol ID: QP12C10
Status last verified: Aug 2015
First submitted: 21 May 2015
Last updated: 17 Aug 2015
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 17 Aug 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An Experimental Study To Characterize the Effectiveness of OZ439 Against Early Plasmodium Falciparum Blood Stage Infection In Healthy Volunteers
ClinicalTrials.gov ID: NCT02453581
Acronym / sponsor ID: QP12C10
Conditions: Malaria
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 24 participants (actual)
Lead sponsor: Medicines for Malaria VentureUniversity, hospital or other
Collaborators: Queensland Institute of Medical Research
Study start: Sep 2012
Primary completion: Mar 2013 (actual)
Study completion: Mar 2013 (actual)
First posted: 25 May 2015 (estimated)
Results: Posted 13 Jul 2015

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

This was a single center study using blood stage Plasmodium falciparum challenge inoculum to characterize the effectiveness of OZ439 against early blood stage Plasmodium Falciparum infection.

Single doses of 100 mg, 200 mg and 500 mg were administered orally to participants in Cohort 1, Cohort 2 and Cohort 3 respectively.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
OZ439 100mg	Experimental	Drug: OZ439OZ439 100mg Powder for Oral Suspension
OZ439 200mg	Experimental	Drug: OZ439OZ439 200mg Powder for Oral Suspension
OZ439 500mg	Experimental	Drug: OZ439OZ439 500mg Powder for Oral Suspension

Who may qualify

Ages: 18 to 45 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (7 listed)

Volunteers will be adults (males or non pregnant females), aged between 18 and 45 years who do not live alone (from Day 1 until at least the end of the antimalarial drug treatment).
Volunteers must have a BMI within the range 18-30.
Volunteers must understand the procedures involved and agree to participate in the study by giving fully informed, written consent.
Be contactable and available for the duration of the trial (maximum of 4 weeks).
Volunteers must be non-smokers and in good health, as assessed during pre-study medical examination and by review of screening results.

Key exclusion criteria (13 listed)

History of malaria.
Travelled to or lived (2 weeks or more) in a malaria-endemic country during the past 12 months or planned travel to a malaria-endemic country during the course of the study.
Has evidence of increased cardiovascular disease risk (defined as greater than 10%, 5 year risk)
History of splenectomy.
History of a severe allergic reaction, anaphylaxis or convulsions following any vaccination or infusion.

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
OZ439OZ439 Powder for Oral Suspension	Drug	OZ439 100mg, OZ439 200mg, OZ439 500mg

Primary outcome

Individual Parasite Reduction Ratio (PRR)
Time frame: 48 hours
PRR estimates the efficacy of an anti-malarial treatment and is the ratio of the parasite density between admission and 48 hours post-treatment. Individual subject PRR and corresponding 95% CI were calculated using the slope and corresponding standard error of mean (SE) of the optimal regression model.
500mg Cohort Mean Parasite Reduction Ratio (PRR)
Time frame: 48 hours
OZ439 500mg individual subject PRR and corresponding 95% CI were used to calculate the OZ439 500mg cohort specific PRR and the corresponding 95% CI: the weighted average slope estimate and corresponding SE were calculated by the inverse-variance method.

2 secondary outcomes

OZ439 Cmax
Time frame: Pre-dose, and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose
OZ439 AUC(0-144)
Time frame: Pre-dose, and 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120 and 144 hours post-dose

Results and safety

Results posted to the registry on 13 Jul 2015, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
OZ439 100mg	8	8
OZ439 200mg	8	8
OZ439 500mg	8	8

Primary outcome: Individual Parasite Reduction Ratio (PRR)

Time frame: 48 hours. Number (95% Confidence Interval). Unit: none (ratio)

Measure	OZ439 500mg - R017 n = 1	OZ439 500mg - R018 n = 1	OZ439 500mg - R019 n = 1	OZ439 500mg - R020 n = 1	OZ439 500mg - R021 n = 1	OZ439 500mg - R022 n = 1	OZ439 500mg - R023 n = 1	OZ439 500mg - R024 n = 1
Value	1132 (357 to 3587)	217646 (21471 to 2206216)	314040 (42823 to 2302975)	8021 (147 to 438967)	8227 (2665 to 25403)	13557 (3113 to 59037)	13560 (3320 to 55381)	21924 (1486 to 323346)

Population analysed: As the doses of 100 mg and 200 mg of OZ439 in Cohorts 1 and 2 were inadequate to eliminate the parasites and regrowth occurred, PRR calculations were only undertaken for subjects receiving 500mg of OZ439 in Cohort 3.

Primary outcome: 500mg Cohort Mean Parasite Reduction Ratio (PRR)

Time frame: 48 hours. Mean (95% Confidence Interval). Unit: none (ratio)

Measure	OZ439 500mg Arm n = 7
Value	10176 (5757 to 17986)

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: 144 hours. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
OZ439 100mg	0 of 8 (0%)	1 of 8 (12.5%)	Not reported
OZ439 200mg	0 of 8 (0%)	3 of 8 (37.5%)	Not reported
OZ439 500mg	0 of 8 (0%)	1 of 8 (12.5%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 17 Aug 2015.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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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.

James McCarthy, Pr principal investigator

Q-Pharm Pty Limited

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing OZ439 in people with Malaria, run by Medicines for Malaria Venture at 1 site in Australia.

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 13 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 17 Aug 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Australia. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 13 Jul 2015). 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?

Individual Parasite Reduction Ratio (PRR) (time frame: 48 hours). The study lists 2 primary outcomes in all. 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 NCT02453581.

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 17 Aug 2015.