Plasmodium Falciparum MalariaPhase 1NCT02543086
Effectiveness of KAE609 in Reducing Asexual & Sexual Blood-stage P.Falciparum Infection & Infectivity to Mosquitos
A Phase 1 study testing KAE609 and Piperaquine Phosphate in people with Plasmodium Falciparum Malaria, run by Novartis Pharmaceuticals at 1 site in Australia.
Trial summary
This is a single-center open label study conducted in multiple sequential cohorts using Induced Blood Stage Malaria infection in healthy volunteers to characterize the effectiveness of KAE609 against sexual and asexual blood stage forms of Plasmodium falciparum. This study is divided in 2 parts (Part A and part B). Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Plasmodium Falciparum Malaria
- What is being tested?
- KAE609 and Piperaquine Phosphate
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteAustralia
- Study dates
- Jul 2015to Sep 2015
- Phase
- Phase 1
- 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 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Written informed consent must be obtained before any assessment is performed.
- Male and females participants between 18 and 55 years of age. Female participants between 18 and 55 years of age have to be of non-child bearing potential.
- Body weight, minimum 50.0 kg, body mass index (BMI) between 18.0 and 32.0 kg/m2, inclusive.
- Certified as healthy by a comprehensive clinical assessment.
- Normal standard 12-lead electrocardiogram (ECG).
- Laboratory parameters within the normal range.
Who cannot join
- Any history of malaria or participation to a previous malaria challenge study
- Spent more than four weeks in a malaria-endemic country during the past 12 months or planned travel to a malaria endemic area during the course of the study
- Has evidence of increased cardiovascular disease risk
- History of splenectomy
- Presence or history of drug hypersensitivity, or allergic disease diagnosed
- Presence of current or suspected serious chronic diseases
Show all 18Show fewer
- History of malignancy of any organ system
- Presence of acute infectious disease or fever (e.g., sub-lingual temperature
- 38.5°C) within the five days prior to inoculation with malaria parasites.
- Participation in any investigational product study within the 12 weeks preceding the study.
- Participant who has ever received a blood transfusion.
- History or presence of alcohol abuse
- Any vaccination within the last 28 days.
- Any corticosteroids, anti-inflammatory drugs, immunomodulators or anticoagulants.
- Any recent (< 1 month) or current systemic therapy with an antibiotic or drug with potential antimalarial activity (including chloroquine, piperaquine, tetracycline, azithromycin, clindamycin, hydroxychloroquine,).
- Medicinal products that are known to prolong the QTc interval.
- Positive result on any of the following tests: hepatitis B surface (HBs Ag) antigen, antihepatitis B core antibodies (anti-HBc Ab), anti-hepatitis C virus (anti-HCV) antibodies, anti-human immunodeficiency virus 1 and 2 antibodies (anti-HIV1 and anti HIV2 Ab).
- Known severe reaction to mosquito bites other than local itching and redness
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase1 Interventional Sequential Single Site Study to Characterize the Effectiveness of Oral KAE609 in Reducing Asexual & Sexual Blood-stage P. Falciparum Following Inoculation in Healthy-volunteers & Subsequent Infectivity to Mosquitoes
This is a single-center open label study conducted in multiple sequential cohorts using Induced Blood Stage Malaria infection in healthy volunteers to characterize the effectiveness of KAE609 against sexual and asexual blood stage forms of Plasmodium falciparum. This study is divided in 2 parts (Part A and part B). A total of 8 healthy volunteers per cohort will be enrolled. Based on the results of Part A, Part B will be undertaken to evaluate the effect of KAE609 following pretreatment with Piperaquine on sexual stage/gametocytemia and its activity as an inhibitor of onward transmission to mosquito vectors using experimental mosquito feeding assays.
Read the detailed description
This is single center multiple sequential Cohort study divided in 2 parts (Part A and part B). A total of 8 healthy volunteers per cohort will be enrolled in Part A, which will focus on characterizing the antiparasitic activity of KAE609 after single dose administration in the human Induced Blood Stage Malaria model. Once Part A is completed, Part B will evaluate the effect of KAE609 following pre-treatment with Piperaquine on sexual stage/gametocytemia and its activity as an inhibitor of onward transmission to mosquito vectors using experimental mosquito feeding assays.
For Part A the threshold for commencement of treatment for an individual subject will occur if Quantitative-Polymerase Chain Reaction quantification of all participants in that Cohort is ≥ 1,000 parasites/mL or if Quantitative-Polymerase Chain Reaction quantification of any participant is ≥ 5,000 parasites/mL, and there is clinical evidence of malaria, as defined by a Clinical symptom score ≥6. The First cohort will be dosed with a single dose of KAE609. During Part A, an additional second single-dose of KAE609 for subsequent cohorts may be tested (~15 days after first dose of KAE609 but may vary) if sexual parasitemia is identified. Subsequent cohorts of part A (An) will be dosed based on the results of first cohort (A1).
For Part B, the threshold for commencement of treatment for an individual subject will be when Polymerase Chain Reaction quantification of all participants is ≥ 5,000 parasites/mL or if the Polymerase Chain Reaction quantification of any participant is ≥ 5,000 parasites/mL and is accompanied by a clinical symptom score ≥6, before all participants have reached the treatment threshold (PCR quantification of ≥ 5,000), then treatment of that participant will begin within a 24 h period. Cohort B will receive a pre-treatment with Piperaquine (480 mg) followed by KAE609 (~15 days) after Piperaquine.
Following initial treatment with KAE609 (Part A) or Piperaquine (Part B) on Day 1, participants will be followed up as in-subjects for at least 72 hours to ensure tolerance of the treatment and clinical response. If subjects are clinically well as per judgment of the Investigator, they will be discharged and will be monitored on an outpatient basis for safety and clearance of malaria parasites via Quantitative-Polymerase Chain Reaction. If any study subjects in a cohort in Part A show evidence of gametocytemia after initial treatment with KAE609, a second single-dose of KAE609 will be administered to those subjects as out patient. In part B where significant gametocytemia is expected because the initial Piperaquine treatment is not expected to clear gametocytes, a single dose of KAE609 will be administered at the time of peak gametocytemia. The KAE609 dose for Part B will be selected during the study, based on Pharmacokinetic/Pharmacodynamic and safety analysis of Part A. If recrudescent asexual parasitemia is identified, compulsory commencement of rescue medication will be used. Treatment for recrudescence will be a single dose of Piperaquine only for Part A. In addition, compulsory terminal curative treatment will be administered to all participants at the end of study. Participants will be monitored for three days to ensure adherence to the rescue medication therapy. Adverse events will be monitored via telephone monitoring, within the clinical research unit, and on out-subject review after malaria challenge inoculation and antimalarial study drug administration. Blood samples for safety evaluation, malaria monitoring, and red blood cell antibodies will be drawn at screening and/ or baseline and at nominated times after malaria challenge.
- Conditions
- Plasmodium Falciparum Malaria
- Being tested
- KAE609, Piperaquine Phosphate
- Keywords
- Phase 1, malaria, inoculum, P. falciparum, KAE609, Piperaquine
- Medical subject headings
- Malaria, Falciparum, Malaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KAE609Drug
Study drug
Piperaquine PhosphateDrug
Pre-administration of Piperaquine Phosphate will be done to eliminate the asexual form of the parasite and induce gametocytaemia before characterizing the activity of KAE609 in clearing sexual blood stage parasites from the blood of healthy subjects in the Induced Blood Stage Malaria Challenge model in Part B of study
| Study group | Role | What they receive |
|---|---|---|
| Multiple Sequential Cohort | Experimental | This study is divided in 2 parts (Part A and part B). Each participant in each of the cohorts will be inoculated with viable parasites of Plasmodium falciparum-infected human erythrocytes administered intravenously. For Part A \& Part B, commencement of treatment will be determined by Quantitative-Polymerase Chain Reaction results.
The First cohort of Part A (A1) will be dosed with a single dose of KAE609. During Part A, an additional second single-dose of KAE609 may be tested (~15 days after first dose of KAE609 but may vary) if sexual parasitemia is identified. Subsequent cohorts of part A (An) will be dosed based on the results of first cohort (A1).
Subjects enrolled in Cohort B will receive a pre-treatment with Piperaquine followed by KAE609 (~15 days). Receives: Drug: KAE609; Drug: Piperaquine Phosphate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Parasitic count in blood by Polymerase Chain Reaction
Clearance of Plasmodium falciparum asexual and sexual blood stage parasites from the blood of healthy subjects in the Induced Blood Stage Malaria Challenge model
Measured: 36 days
Secondary outcomes (2)
Plasma Pharmacokinetics (PK) of KAE609: Area Under the Plasma Concentration-time Curve (AUC)
It will be measured by Area Under the Concentration-Time Curve (AUC) from the time of dosing to the last quantifiable concentration
Measured: Day 1: 0, 1, 2, 3, 4, 8, 12, 16 hours, then 24, 36, 48, 72, 96 and 120 hours post dose Days 2 to 6, Day 15 0, 12 hours post dose then 24, 48, 72, 96 and 120 hours post dose Day 16 to Day 20
Safety and Tolerability as measured by adverse events (including serious) for incidence, KAE609 (and inoculum) relatedness and severity
Adverse events (including serious) will be recorded during the study and will be rated according to incidence, relation to study drug (inoculum) and severity
Measured: From day of screening until end of study (day 36)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Sep 2015 (estimated)
- Study startJul 2015
- Primary completionSep 2015
- Study completionSep 2015
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 Plasmodium Falciparum MalariaStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Medicine for Malaria Venture
- Responsible party
- Sponsor
- Investigators
- James McCarthy, MD FRACP, Principal investigator, Q-Pharm Pty Limited
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02543086
- Sponsor's protocol ID
- CKAE609A2109
- Status last verified
- Jul 2019
- First submitted
- 23 Jul 2015
- Last updated
- 23 Jul 2019
- Results posted
- No
- Data monitoring committee
- No
Publications
McCarthy JS, Abd-Rahman AN, Collins KA, Marquart L, Griffin P, Kummel A, Fuchs A, Winnips C, Mishra V, Csermak-Renner K, Jain JP, Gandhi P. Defining the Antimalarial Activity of Cipargamin in Healthy Volunteers Experimentally Infected with Blood-Stage Plasmodium falciparum. Antimicrob Agents Chemother. 2021 Jan 20;65(2):e01423-20. doi: 10.1128/AAC.01423-20. Print 2021 Jan 20.
PubMed 33199389
Study at a glance
From the registry record, last updated by the sponsor on 23 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase1 Interventional Sequential Single Site Study to Characterize the Effectiveness of Oral KAE609 in Reducing Asexual & Sexual Blood-stage P. Falciparum Following Inoculation in Healthy-volunteers & Subsequent Infectivity to Mosquitoes
- ClinicalTrials.gov ID
- NCT02543086
- Acronym / sponsor ID
- CKAE609A2109
- Conditions
- Plasmodium Falciparum Malaria
- Keywords
- Phase 1, malaria, inoculum, P. falciparum, KAE609, Piperaquine
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Collaborators
- Medicine for Malaria Venture
- Study start
- Jul 2015
- Primary completion
- Sep 2015 (actual)
- Study completion
- Sep 2015 (actual)
- First posted
- 7 Sep 2015 (estimated)
- 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 is a single-center open label study conducted in multiple sequential cohorts using Induced Blood Stage Malaria infection in healthy volunteers to characterize the effectiveness of KAE609 against sexual and asexual blood stage forms of Plasmodium falciparum. This study is divided in 2 parts (Part A and part B). A total of 8 healthy volunteers per cohort will be enrolled. Based on the results of Part A, Part B will be undertaken to evaluate the effect of KAE609 following pretreatment with Piperaquine on sexual stage/gametocytemia and its activity as an inhibitor of onward transmission to mosquito vectors using experimental mosquito feeding assays.
Detailed description
This is single center multiple sequential Cohort study divided in 2 parts (Part A and part B). A total of 8 healthy volunteers per cohort will be enrolled in Part A, which will focus on characterizing the antiparasitic activity of KAE609 after single dose administration in the human Induced Blood Stage Malaria model. Once Part A is completed, Part B will evaluate the effect of KAE609 following pre-treatment with Piperaquine on sexual stage/gametocytemia and its activity as an inhibitor of onward transmission to mosquito vectors using experimental mosquito feeding assays.
For Part A the threshold for commencement of treatment for an individual subject will occur if Quantitative-Polymerase Chain Reaction quantification of all participants in that Cohort is ≥ 1,000 parasites/mL or if Quantitative-Polymerase Chain Reaction quantification of any participant is ≥ 5,000 parasites/mL, and there is clinical evidence of malaria, as defined by a Clinical symptom score ≥6. The First cohort will be dosed with a single dose of KAE609. During Part A, an additional second single-dose of KAE609 for subsequent cohorts may be tested (~15 days after first dose of KAE609 but may vary) if sexual parasitemia is identified. Subsequent cohorts of part A (An) will be dosed based on the results of first cohort (A1).
For Part B, the threshold for commencement of treatment for an individual subject will be when Polymerase Chain Reaction quantification of all participants is ≥ 5,000 parasites/mL or if the Polymerase Chain Reaction quantification of any participant is ≥ 5,000 parasites/mL and is accompanied by a clinical symptom score ≥6, before all participants have reached the treatment threshold (PCR quantification of ≥ 5,000), then treatment of that participant will begin within a 24 h period. Cohort B will receive a pre-treatment with Piperaquine (480 mg) followed by KAE609 (~15 days) after Piperaquine.
Following initial treatment with KAE609 (Part A) or Piperaquine (Part B) on Day 1, participants will be followed up as in-subjects for at least 72 hours to ensure tolerance of the treatment and clinical response. If subjects are clinically well as per judgment of the Investigator, they will be discharged and will be monitored on an outpatient basis for safety and clearance of malaria parasites via Quantitative-Polymerase Chain Reaction. If any study subjects in a cohort in Part A show evidence of gametocytemia after initial treatment with KAE609, a second single-dose of KAE609 will be administered to those subjects as out patient. In part B where significant gametocytemia is expected because the initial Piperaquine treatment is not expected to clear gametocytes, a single dose of KAE609 will be administered at the time of peak gametocytemia. The KAE609 dose for Part B will be selected during the study, based on Pharmacokinetic/Pharmacodynamic and safety analysis of Part A. If recrudescent asexual parasitemia is identified, compulsory commencement of rescue medication will be used. Treatment for recrudescence will be a single dose of Piperaquine only for Part A. In addition, compulsory terminal curative treatment will be administered to all participants at the end of study. Participants will be monitored for three days to ensure adherence to the rescue medication therapy. Adverse events will be monitored via telephone monitoring, within the clinical research unit, and on out-subject review after malaria challenge inoculation and antimalarial study drug administration. Blood samples for safety evaluation, malaria monitoring, and red blood cell antibodies will be drawn at screening and/ or baseline and at nominated times after malaria challenge.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Multiple Sequential Cohort | Experimental | Drug: KAE609, Drug: Piperaquine PhosphateThis study is divided in 2 parts (Part A and part B). Each participant in each of the cohorts will be inoculated with viable parasites of Plasmodium falciparum-infected human erythrocytes administered intravenously. For Part A \& Part B, commencement of treatment will be determined by Quantitative-Polymerase Chain Reaction results. The First cohort of Part A (A1) will be dosed with a single dose of KAE609. During Part A, an additional second single-dose of KAE609 may be tested (~15 days after first dose of KAE609 but may vary) if sexual parasitemia is identified. Subsequent cohorts of part A (An) will be dosed based on the results of first cohort (A1). Subjects enrolled in Cohort B will receive a pre-treatment with Piperaquine followed by KAE609 (~15 days). |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Written informed consent must be obtained before any assessment is performed.
- Male and females participants between 18 and 55 years of age. Female participants between 18 and 55 years of age have to be of non-child bearing potential.
- Body weight, minimum 50.0 kg, body mass index (BMI) between 18.0 and 32.0 kg/m2, inclusive.
- Certified as healthy by a comprehensive clinical assessment.
- Normal standard 12-lead electrocardiogram (ECG).
Key exclusion criteria (18 listed)
- Any history of malaria or participation to a previous malaria challenge study
- Spent more than four weeks in a malaria-endemic country during the past 12 months or planned travel to a malaria endemic area during the course of the study
- Has evidence of increased cardiovascular disease risk
- History of splenectomy
- Presence or history of drug hypersensitivity, or allergic disease diagnosed
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 |
|---|---|---|
| KAE609Study drug | Drug | Multiple Sequential Cohort |
| Piperaquine PhosphatePre-administration of Piperaquine Phosphate will be done to eliminate the asexual form of the parasite and induce gametocytaemia before characterizing the activity of KAE609 in clearing sexual blood stage parasites from the blood of healthy subjects in the Induced Blood Stage Malaria Challenge model in Part B of study | Drug | Multiple Sequential Cohort |
Primary outcome
Parasitic count in blood by Polymerase Chain Reaction
Time frame: 36 days
Clearance of Plasmodium falciparum asexual and sexual blood stage parasites from the blood of healthy subjects in the Induced Blood Stage Malaria Challenge model
2 secondary outcomes
Plasma Pharmacokinetics (PK) of KAE609: Area Under the Plasma Concentration-time Curve (AUC)
Time frame: Day 1: 0, 1, 2, 3, 4, 8, 12, 16 hours, then 24, 36, 48, 72, 96 and 120 hours post dose Days 2 to 6, Day 15 0, 12 hours post dose then 24, 48, 72, 96 and 120 hours post dose Day 16 to Day 20
Safety and Tolerability as measured by adverse events (including serious) for incidence, KAE609 (and inoculum) relatedness and severity
Time frame: From day of screening until end of study (day 36)
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jul 2019.
- Derived from this study: PubMed 33199389McCarthy JS, Abd-Rahman AN, Collins KA, Marquart L, Griffin P, Kummel A, Fuchs A, Winnips C, Mishra V, Csermak-Renner K, Jain JP, Gandhi P. Defining the Antimalarial Activity of Cipargamin in Healthy Volunteers Experimentally Infected with Blood-Stage Plasmodium falciparum. Antimicrob Agents Chemother. 2021 Jan 20;65(2):e01423-20. doi: 10.1128/AAC.01423-20. Print 2021 Jan 20.
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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, MD FRACP 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 KAE609 and Piperaquine Phosphate in people with Plasmodium Falciparum Malaria, run by Novartis Pharmaceuticals 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 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: stopped early, as of the sponsor's last update on 23 Jul 2019. 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?
The study was stopped early. 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?
Parasitic count in blood by Polymerase Chain Reaction (time frame: 36 days). 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 NCT02543086, 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 23 Jul 2019.