MalariaPhase 2NCT01753323

Efficacy, Safety, Tolerability and Pharmacokinetics of KAF156 in Adult Patients With Acute, Uncomplicated Plasmodium Falciparum or Vivax Malaria Mono-infection

A Phase 2 study testing KAF156 in people with Malaria, run by Novartis Pharmaceuticals at 5 sites in 2 countries.

Completed

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

Trial summary

This study will assess efficacy, safety , tolerability and PK in uncomplicated adult malaria patients with P. vivax or P. falciparum infection after 3 day dosing with KAF156 at 400 mg/day (Part 1) and single dosing with KAF156 at 800mg (Part 2) Read more about this study

Who is it for?: Ages 20 to 60 years
Conditions the study is for: Malaria
What is being tested?: KAF156
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 43 participants
Where: 5 sitesin 2 countries
Study dates: Mar 2013to Aug 2014
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 20 to 60 years
All sexes
No healthy volunteers
Adult

Who may be able to join

-Male and female patients aged 20 to 60 years;Presence of mono-infection of P. falciparum or P. vivax; Weight between 40 kg to 90 kg.

Who cannot join

Patients with signs and symptoms of severe/complicated malaria
Infection with more than one parasite species
Women of child-bearing potential; pregnant or nursing women
Those who have taken any anti-malarial treatment in the preceding 14 days or other investigational drugs within 30 days or 5 half-lives

Trial locations and contacts

5 sites in 2 countries.

Country

City, postcode or hospital

5 sites in 2 countries

Thailand4 sites

Novartis Investigative Site
Bangkok, 10400
Novartis Investigative Site
Si Sa Ket, 33140
Novartis Investigative Site
Tak, 63110
Novartis Investigative Site
Tak, 63140

Other trials in Thailand

Vietnam1 site

Novartis Investigative Site
Hanoi, 10000

Other trials in Vietnam

About this study

Official title: A Proof-of-concept, Open Label Study to Assess Efficacy, Safety, Tolerability and Pharmacokinetics of KAF156 in Adult Patients With Acute, Uncomplicated Plasmodium Falciparum or Vivax Malaria Mono-infection

Conditions: Malaria
Being tested: KAF156
Keywords: acute malaria, KAF156
Medical subject headings: Malaria, Acute malaria

What participants receive

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

KAF156Drug
KAF156 was supplied as tablets for oral use.

Study groups in NCT01753323
Study group	Role	What they receive
Part 1 - Cohort 1: P. vivax: KAF156 400mg QD	Experimental	Participants with Plasmodium vivax malaria received KAF156 400 mg once a day for three days. Receives: Drug: KAF156
Part 1 - Cohort 2: P. falciparum: KAF156 400mg QD	Experimental	Participants with Plasmodium falciparum malaria received KAF156 400mg once a day for three days. Receives: Drug: KAF156
Part 2 - Cohort 3: P. falciparum: KAF156 800mg single dose	Experimental	Participants with Plasmodium falciparum malaria received a single dose of KAF156 800mg. Receives: Drug: KAF156

What is being measured

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

Time to Parasite Clearance
Parasite clearance was determined by assessing the parasite count in blood, using thin film, thick film and blood density assessments.
Measured: Day 5
28-day Cure Rate - Part 2
28-day cure rate was defined as the percentage of participants with blood parasite count of zero after 28 days of treatment.
Measured: Day 28

Secondary outcomes (18)

Area Under the Curve (AUC)0-24h - Part 1
AUC0-24h was analyzed using parent drug in plasma samples. On Day 1, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours post dose. The 24h sampling of first post dose was taken before the second dose. On Day 3, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, and 192 hours post dose.
Measured: Days 1 and 3
Maximum Concentration (Cmax) - Part 1
Cmax was analyzed using parent drug in plasma samples. On Day 1, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours post dose. The 24h sampling of first post dose should be taken before the second dose. On Day 3, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, and 192 hours post dose.
Measured: Days 1 and 3
Time to Maximum Concentration (Tmax) - Part 1
Tmax was analyzed using parent drug in plasma samples. On Day 1, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours post dose. The 24h sampling of first post dose should be taken before the second dose. On Day 3, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, and 192 hours post dose.
Measured: Days 1 and 3
Area Under the Curve (AUC)Last - Part 1
AUClast was analyzed using parent drug in plasma samples. On Day 3, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, and 192 hours post dose.
Measured: Day 3
Area Under the Curve (AUC)Inf - Part 1
AUCinf was analyzed using parent drug in plasma samples. On Day 3, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, and 192 hours post dose.
Measured: Day 3
Half-life (T1/2) - Part 1
T1/2 was analyzed using parent drug in plasma samples. On day 3, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, and 192 hours post dose.
Measured: Day 3
Clearance (CL/F ) - Part 1
CL/F was analyzed using parent drug in plasma samples. On day 3, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, and 192 hours post dose.
Measured: Day 3
Apparent Volume of Distribution During the Terminal Elimination Phase Following Extravascular Administration (Vz/F) - Part 1
Vz/F was analyzed using parent drug in plasma samples. On Day 3, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, and 192 hours post dose.
Measured: Day 3
Accumulation Ratio (Racc) (=AUC0-24h, day3/AUC0-24h, day1) - Part 1
Racc was analyzed using parent drug in plasma samples. On day 3, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, and 192 hours post dose.
Measured: Day 3
AUC0-24h - Part 2
AUC0-24h was analyzed using parent drug in plasma samples. On Day 1, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours post dose.
Measured: Day 1
AUC0-48h - Part 2
AUC0-48h was analyzed using parent drug in plasma samples. On Day 1, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, and 192 hours post dose.
Measured: Day 1
AUClast - Part 2
AUClast was analyzed using parent drug in plasma samples. On Day 1, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, and 192 hours post dose
Measured: Day 1
AUCinf - Part 2
AUCinf was analyzed using parent drug in plasma samples. On Day 1, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, and 192 hours post dose
Measured: Day 1
Cmax - Part 2
Cmax was analyzed using parent drug in plasma samples. On Day 1, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours post dose.
Measured: Day 1
Tmax - Part 2
Tmax was analyzed using parent drug in plasma samples. On Day 1, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours post dose.
Measured: Day 1
T1/2 - Part 2
T1/2 was analyzed using parent drug in plasma samples. On Day 1, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, and 192 hours post dose.
Measured: Day 1
CL/F - Part 2
CL/F was analyzed using parent drug in plasma samples. On Day 1, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, and 192 hours post dose.
Measured: Day 1
Vz/F - Part 2
Vz/F was analyzed using parent drug in plasma samples. On Day 1, samples were taken at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 96, 144, and 192 hours post dose.
Measured: Day 1

Timeline

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

Mar 2013Aug 2014

First posted20 Dec 2012 (estimated)
Study startMar 2013
Primary completionAug 2014
Study completionAug 2014

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 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 2
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Enrolment: 43 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01753323
Sponsor's protocol ID: CKAF156X2201
Status last verified: Jun 2018
First submitted: 17 Dec 2012
Last updated: 7 Jun 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

White NJ, Duong TT, Uthaisin C, Nosten F, Phyo AP, Hanboonkunupakarn B, Pukrittayakamee S, Jittamala P, Chuthasmit K, Cheung MS, Feng Y, Li R, Magnusson B, Sultan M, Wieser D, Xun X, Zhao R, Diagana TT, Pertel P, Leong FJ. Antimalarial Activity of KAF156 in Falciparum and Vivax Malaria. N Engl J Med. 2016 Sep 22;375(12):1152-60. doi: 10.1056/NEJMoa1602250.
PubMed 27653565

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 7 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Proof-of-concept, Open Label Study to Assess Efficacy, Safety, Tolerability and Pharmacokinetics of KAF156 in Adult Patients With Acute, Uncomplicated Plasmodium Falciparum or Vivax Malaria Mono-infection
ClinicalTrials.gov ID: NCT01753323
Acronym / sponsor ID: CKAF156X2201
Conditions: Malaria
Keywords: acute malaria, KAF156
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 43 participants (actual)
Lead sponsor: Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
Study start: Mar 2013
Primary completion: Aug 2014 (actual)
Study completion: Aug 2014 (actual)
First posted: 20 Dec 2012 (estimated)
Results: Posted 19 Aug 2015

Clinical summary

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

Study design

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

Arm	Type	Receives
Part 1 - Cohort 1: P. vivax: KAF156 400mg QD	Experimental	Drug: KAF156Participants with Plasmodium vivax malaria received KAF156 400 mg once a day for three days.
Part 1 - Cohort 2: P. falciparum: KAF156 400mg QD	Experimental	Drug: KAF156Participants with Plasmodium falciparum malaria received KAF156 400mg once a day for three days.
Part 2 - Cohort 3: P. falciparum: KAF156 800mg single dose	Experimental	Drug: KAF156Participants with Plasmodium falciparum malaria received a single dose of KAF156 800mg.

Who may qualify

Ages: 20 to 60 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (1 listed)

-Male and female patients aged 20 to 60 years;Presence of mono-infection of P. falciparum or P. vivax; Weight between 40 kg to 90 kg.

Key exclusion criteria (4 listed)

Patients with signs and symptoms of severe/complicated malaria
Infection with more than one parasite species
Women of child-bearing potential; pregnant or nursing women
Those who have taken any anti-malarial treatment in the preceding 14 days or other investigational drugs within 30 days or 5 half-lives

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
KAF156KAF156 was supplied as tablets for oral use.	Drug	Part 1 - Cohort 1: P. vivax: KAF156 400mg QD, Part 1 - Cohort 2: P. falciparum: KAF156 400mg QD, Part 2 - Cohort 3: P. falciparum: KAF156 800mg single dose

Primary outcome

Time to Parasite Clearance
Time frame: Day 5
Parasite clearance was determined by assessing the parasite count in blood, using thin film, thick film and blood density assessments.
28-day Cure Rate - Part 2
Time frame: Day 28
28-day cure rate was defined as the percentage of participants with blood parasite count of zero after 28 days of treatment.

18 secondary outcomes

Area Under the Curve (AUC)0-24h - Part 1
Time frame: Days 1 and 3
Maximum Concentration (Cmax) - Part 1
Time frame: Days 1 and 3
Time to Maximum Concentration (Tmax) - Part 1
Time frame: Days 1 and 3
Area Under the Curve (AUC)Last - Part 1
Time frame: Day 3
Area Under the Curve (AUC)Inf - Part 1
Time frame: Day 3
Half-life (T1/2) - Part 1
Time frame: Day 3
Clearance (CL/F ) - Part 1
Time frame: Day 3
Apparent Volume of Distribution During the Terminal Elimination Phase Following Extravascular Administration (Vz/F) - Part 1
Time frame: Day 3
Accumulation Ratio (Racc) (=AUC0-24h, day3/AUC0-24h, day1) - Part 1
Time frame: Day 3
AUC0-24h - Part 2
Time frame: Day 1
AUC0-48h - Part 2
Time frame: Day 1
AUClast - Part 2
Time frame: Day 1
AUCinf - Part 2
Time frame: Day 1
Cmax - Part 2
Time frame: Day 1
Tmax - Part 2
Time frame: Day 1
T1/2 - Part 2
Time frame: Day 1
CL/F - Part 2
Time frame: Day 1
Vz/F - Part 2
Time frame: Day 1

Results and safety

Results posted to the registry on 19 Aug 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
Part 1 - Cohort 1: P. Vivax: KAF156 400mg QD	11	10
Part 1 - Cohort 2: P. Falciparum: KAF156 400mg QD	10	10
Part 2 - Cohort 3: P. Falciparum: KAF156 800mg Single Dose	22	13

Primary outcome: Time to Parasite Clearance

Time frame: Day 5. Median (95% Confidence Interval). Unit: Hours

Measure	Part 1 - Cohort 1: P. Vivax: KAF156 400mg QD n = 10	Part 1 - Cohort 2: P. Falciparum: KAF156 400mg QD n = 10	Part 2 - Cohort 3: P. Falciparum: KAF156 800mg Single Dose n = 21
Value	23.63 (16.00 to 30.02)	44.97 (36.25 to 47.98)	48.75 (42.00 to 53.95)

Population analysed: Pharmacodynamic (PD) analysis set for Cohorts 1, 2 and 3: The PD set included all participants who received at least one dose of study medication except for 1 participant from Cohort 1, who was excluded due to a protocol deviation, and 1 participant from Cohort 3, who was withdrawn on Day 1.

Primary outcome: 28-day Cure Rate - Part 2

Time frame: Day 28. Number. Unit: Percentage of participants

Measure	Part 2 - Cohort 3: P. Falciparum: KAF156 800mg Single Dose n = 22
Value	63.6

Population analysed: Intent-to-treat analysis set: the intent-to-treat analysis set included all randomized participants who received at least one dose of study medication.

18 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 1% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Part 1 - Cohort 1: P. Vivax: KAF156 400mg QD	0 of 11 (0%)	5 of 11 (45.5%)	Not reported
Part 1 - Cohort 2: P. Falciparum: KAF156 400mg QD	0 of 10 (0%)	8 of 10 (80%)	Not reported
Part 2 - Cohort 3: P. Falciparum: KAF156 800mg Single Dose	0 of 22 (0%)	22 of 22 (100%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 7 Jun 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 27653565White NJ, Duong TT, Uthaisin C, Nosten F, Phyo AP, Hanboonkunupakarn B, Pukrittayakamee S, Jittamala P, Chuthasmit K, Cheung MS, Feng Y, Li R, Magnusson B, Sultan M, Wieser D, Xun X, Zhao R, Diagana TT, Pertel P, Leong FJ. Antimalarial Activity of KAF156 in Falciparum and Vivax Malaria. N Engl J Med. 2016 Sep 22;375(12):1152-60. doi: 10.1056/NEJMoa1602250.

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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.

Novartis Pharmaceuticals study director

Novartis Pharmaceuticals

5 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing KAF156 in people with Malaria, run by Novartis Pharmaceuticals at 5 sites in 2 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 1 inclusion and 4 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 7 Jun 2018. 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 Thailand, Vietnam. 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 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 19 Aug 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?

Time to Parasite Clearance (time frame: Day 5). 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 NCT01753323, 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 7 Jun 2018.