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MalariaPhase 1NCT04072302

Safety and Causal Prophylactic Efficacy of KAF156 in a Controlled Human Malaria Challenge Model

A Phase 1 study testing KAF156 in people with Malaria, run by Novartis Pharmaceuticals at 1 site in United States.

Completed

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

Official record
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Trial summary

This study is designed to investigate the safety and causal prophylactic efficacy of KAF156 in healthy subjects using a controlled human malaria infection model. Read more about this study

Who is it for?
Ages 18 to 40 years, men onlyHealthy volunteers can take part
Conditions the study is for
Malaria
What is being tested?
KAF156
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
86 participants
Where
1 siteUnited States
Study dates
15 Sep 2014to 29 Nov 2017
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 40 years
  • Men only
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • Healthy male subjects,aged 18 to 40 years of age included and in good health as determined by past medical history, physical examination, vital signs, ECG, and laboratory tests

Who cannot join

  • History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes.
  • Known history or current clinically significant ECG abnormalities or arrhythmias.
  • Symptoms, physical signs and laboratory values suggestive of systemic disorders including renal, hepatic, cardiovascular, pulmonary, skin, immunodeficiency, psychiatric, or other conditions which could interfere with the interpretation of the study results or compromise the health of the subjects.
  • Sexually active males must use a condom during intercourse while taking drug and for al least 4 weeks after stopping study medication and should not father a child during this period.
  • History of malaria or residence in a malaria-endemic area over a period of 6 months before study entry. - Any condition that would, in the opinion of the site investigator, place the subject at an unacceptable risk or render the subject unable to meet requirements of the protocol.
  • Other protocol-defined inclusion/exclusion criteria may apply.

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Novartis Investigative Site

    Seattle, Washington, 98109

Other trials in United States

About this study

Official title: A Two-part, Randomized, Double-blind, Placebo-controlled, Single-center Study to Evaluate the Safety and Causal Prophylactic Efficacy of KAF156 in a Controlled Human Malaria Challenge Model

This study is designed to investigate the safety and causal prophylactic efficacy of KAF156 in healthy subjects using a controlled human malaria infection model.

Conditions
Malaria
Being tested
KAF156, Placebo
Keywords
Malaria, KAF156, P. falciparum
Medical subject headings
Malaria

What participants receive

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

  • KAF156Drug

    100 mg tablet, 20 mg tablet, 50 mg tablet

  • PlaceboDrug

    100 mg tablet, 20 mg tablet, 50 mg tablet

Study groups in NCT04072302
Study groupRoleWhat they receive
KAF156 800 mg pre-challengeExperimentalSingle dose 800 mg KAF156 oral administration in healthy subjects, prior to exposure to P. falciparum sporozoite-infected mosquitos
Receives: Drug: KAF156
Placebo 800 mg pre-challengePlacebo comparatorSingle dose 800 mg placebo oral administration in healthy subjects, prior to exposure to P. falciiparum sporozoite-infected mosquitos
Receives: Drug: Placebo
KAF156 800 mg post-challengeExperimentalSingle dose 800 mg KAF156 oral administration in heatlhy subjects, after exposure to P. falciparum sporozoite-infected mosquitos
Receives: Drug: KAF156
Placebo 800 mg post-challengePlacebo comparatorSingle dose 800 mg placebo oral administration in heatlhy subjects, after exposure to P. falciparum sporozoite-infected mosquitos
Receives: Drug: Placebo
KAF156 300 mg post-challengeExperimentalSingle dose 300 mg KAF156 oral administration in heatlhy subjects, after exposure to P. falciparum sporozoite-infected mosquitos
Receives: Drug: KAF156
Placebo 300 mg post-challengePlacebo comparatorSingle dose 300 mg placebo oral administration in heatlhy subjects, after exposure to P. falciparum sporozoite-infected mosquitos
Receives: Drug: Placebo
KAF156 100 mg post-challengeExperimentalSingle dose 100 mg KAF156 oral administration in heatlhy subjects, after exposure to P. falciparum sporozoite-infected mosquitos
Receives: Drug: KAF156
Placebo 100 mg post-challengePlacebo comparatorSingle dose 100 mg placebo oral administration in heatlhy subjects, after exposure to P. falciparum sporozoite-infected mosquitos
Receives: Drug: Placebo
KAF156 20 mg post-challengeExperimentalSingle dose 20 mg KAF156 oral administration in heatlhy subjects, after exposure to P. falciparum sporozoite-infected mosquitos
Receives: Drug: KAF156
Placebo 20 mg post-challengePlacebo comparatorSingle dose 20 mg Placebo oral administration in heatlhy subjects, after exposure to P. falciparum sporozoite-infected mosquitos
Receives: Drug: Placebo
KAF156 50 mg post-challengeExperimentalSingle dose 50 mg KAF156 oral administration in heatlhy subjects, after exposure to P. falciparum sporozoite-infected mosquitos
Receives: Drug: KAF156
Placebo 50 mg post-challengePlacebo comparatorSingle dose 50 mg Placebo oral administration in heatlhy subjects, after exposure to P. falciparum sporozoite-infected mosquitos
Receives: Drug: Placebo

What is being measured

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

  1. Number of subjects with parasitemia after single dose oral administration of KAF156 either prior to, or following, exposure to P. falciparum sporozoite-infected mosquitoes

    The number of subjects that became infected with malaria at each dose

    Measured: From Day 1 to Day 43

  2. Relationship between pharmacokinetics (i.e., Maximum Plasma Concentration [Cmax], Area Under Curve [AUC]) of KAF156 and number of subjects with parasitemia, after oral administration of single descending doses of KAF156 in healthy subjects with CHMI

    The exposure-response relationship of KAF156 was explored in a PK/PD model to relate drug exposure to prophylactic efficacy using standard statistical methods such as CART or non-linear regression. Summary statistics were also provided for the malaria incidence rate by cohort and treatment arm

    Measured: From Day 1 to Day 43

Secondary outcomes (10)
  1. Number of subjects with adverse events, serious adverse events, and death

    All information obtained on adverse events will be displayed by arm, treatment, and subject. The number and percentage of subjects with adverse events will be tabulated by body system and preferred term with a breakdown by cohort and treatment.

    Measured: From screening to Day 43

  2. Pharmacokinetics of KAF156: Area under the plasma concentration-time curve from time zero to infinity (AUCinf)

    KAF156 plasma concentration data will be listed by arm, subject, and sampling time point.

    Descriptive summary statistics will be provided by arm and sampling time point. These values will be used to calculate AUCinf

    Measured: Pre-dose, and Post-dose: 1 hour, 3 hours, 6 hours, 9 hours, 12 hours, 24 hours, 96 hours, 144 hours, 110 hours, 216 hours, 240 hours

  3. Pharmacokinetics of KAF156: Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast)

    KAF156 plasma concentration data will be listed by arm, subject, and sampling time point.

    Descriptive summary statistics will be provided by arm and sampling time point. These values will be used to calculate AUClast

    Measured: Pre-dose, and Post-dose: 1 hour, 3 hours, 6 hours, 9 hours, 12 hours, 24 hours, 96 hours, 144 hours, 110 hours, 216 hours, 240 hours

  4. Pharmacokinetics of KAF156: Area under teh plasma concentration-time curve from time zero to time 24 h (AUC0-24)

    KAF156 plasma concentration data will be listed by arm, subject, and sampling time point.

    Descriptive summary statistics will be provided by arm and sampling time point. These values will be used to calculate AUC0-24

    Measured: Pre-dose, and Post-dose: 1 hour, 3 hours, 6 hours, 9 hours, 12 hours, 24 hours, 96 hours, 144 hours, 110 hours, 216 hours, 240 hours

  5. Pharmacokinetics of KAF156: Terminal elimination half life (T1/2)

    KAF156 plasma concentration data will be listed by arm, subject, and sampling time point.

    Descriptive summary statistics will be provided by arm and sampling time point. These values will be used to calculate T1/2.

    Measured: Pre-dose, and Post-dose: 1 hour, 3 hours, 6 hours, 9 hours, 12 hours, 24 hours, 96 hours, 144 hours, 110 hours, 216 hours, 240 hours

  6. Pharmacokinetics of KAF156: Apparent systemic clearance from plasma following oral administration (CL/F)

    KAF156 plasma concentration data will be listed by arm, subject, and sampling time point.

    Descriptive summary statistics will be provided by arm and sampling time point. These values will be used to calculate CL/F

    Measured: Pre-dose, and Post-dose: 1 hour, 3 hours, 6 hours, 9 hours, 12 hours, 24 hours, 96 hours, 144 hours, 110 hours, 216 hours, 240 hours

  7. Pharmacokinetics of KAF156: Apparent volume of distribution during the terminal phase following oral administration (Vz/F)

    KAF156 plasma concentration data will be listed by arm, subject, and sampling time point.

    Descriptive summary statistics will be provided by arm and sampling time point. These values will be used to calculate Vz/F

    Measured: Pre-dose, and Post-dose: 1 hour, 3 hours, 6 hours, 9 hours, 12 hours, 24 hours, 96 hours, 144 hours, 110 hours, 216 hours, 240 hours

  8. Pharmacokinetics of KAF156: Observed maximum plasma concentration (Cmax)

    KAF156 plasma concentration data will be listed by arm, subject, and sampling time point.

    Descriptive summary statistics will be provided by arm and sampling time point. These values will be used to calculate Cmax

    Measured: Pre-dose, and Post-dose: 1 hour, 3 hours, 6 hours, 9 hours, 12 hours, 24 hours, 96 hours, 144 hours, 110 hours, 216 hours, 240 hours

  9. Pharmacokinetics of KAF156: Time to reach the maximum concentration (Tmax)

    KAF156 plasma concentration data will be listed by arm, subject, and sampling time point.

    Descriptive summary statistics will be provided by arm and sampling time point. These values will be used to calculate Tmax

    Measured: Pre-dose, and Post-dose: 1 hour, 3 hours, 6 hours, 9 hours, 12 hours, 24 hours, 96 hours, 144 hours, 110 hours, 216 hours, 240 hours

  10. Parasite growth Kinetics by qRT-PCR

    Parasitemia levels as measured by qRT-PCR will be summarized and displayed graphically over time.

    Measured: Pre-dose, days 7-23, Day 29, Day 43

Timeline

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

  1. First posted28 Aug 2019
  2. Study start15 Sep 2014
  3. Primary completion29 Nov 2017
  4. Study completion29 Nov 2017

Resources

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
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
86 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04072302
Sponsor's protocol ID
CKAF156X2202
Status last verified
Aug 2019
First submitted
20 Aug 2019
Last updated
28 Aug 2019
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Kublin JG, Murphy SC, Maenza J, Seilie AM, Jain JP, Berger D, Spera D, Zhao R, Soon RL, Czartoski JL, Potochnic MA, Duke E, Chang M, Vaughan A, Kappe SHI, Leong FJ, Pertel P, Prince WT; KAF156 Study Team. Safety, Pharmacokinetics, and Causal Prophylactic Efficacy of KAF156 in a Plasmodium falciparum Human Infection Study. Clin Infect Dis. 2021 Oct 5;73(7):e2407-e2414. doi: 10.1093/cid/ciaa952.

    PubMed 32644127

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing KAF156 in people with Malaria, run by Novartis Pharmaceuticals at 1 site in United States.

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 6 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 28 Aug 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 United States. 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. Some participants in this study may receive a placebo. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Number of subjects with parasitemia after single dose oral administration of KAF156 either prior to, or following, exposure to P. falciparum sporozoite-infected mosquitoes (time frame: From Day 1 to Day 43). 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 NCT04072302, 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 28 Aug 2019.

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