AzTrials
AzTrials

MalariaPhase 1NCT04321252

Study to Assess Safety, Tolerability and Phamacokinetics of KAE609 Administered Intravenously in Healthy Subjects

A Phase 1 study testing KAE609 in people with Malaria, run by Novartis Pharmaceuticals at 1 site in Belgium.

Completed

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

Official record
Search all trials

Trial summary

This was a randomized, subject and investigator-blinded, placebo-controlled, single and multiple ascending intravenous (iv) dose study in healthy subjects to assess the safety and tolerability of KAE609 given in the vein. Read more about this study

Who is it for?
Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for
Malaria
What is being tested?
KAE609
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
57 participants
Where
1 siteBelgium
Study dates
22 Jul 2020to 10 Nov 2020
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 55 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • Healthy male and female subjects 18 to 55 years of age inclusive, and in good health as determined by past medical history, physical examination, vital signs, electrocardiogram, and laboratory tests.
  • Subjects must weigh at least 50 kg to participate in the study, and must have a body mass index (BMI) within the range of 18.0 - 30.0 kg/m2.

Who cannot join

  • Use of other investigational drugs within 5 half-lives of Screening, or within 30 days of dosing, whichever is longer; or longer if required by local regulations.
  • Significant illness which has not resolved within two (2) weeks prior to initial dosing.
  • Pregnant or nursing (lactating) women.
  • Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant.
  • Sexually active males unwilling to use a condom during intercourse while taking investigational drug and for at least 2 weeks after last dose of investigational drug.

Trial locations and contacts

1 site in 1 country.

Belgium1 site
  • Novartis Investigative Site

    Antwerp, B-2060

Other trials in Belgium

About this study

Official title: A Randomized, Subject and Investigator-blinded, Placebo Controlled, Single and Multiple Ascending Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of KAE609 Administered Intravenously in Healthy Subjects

This was a randomized, subject and investigator-blinded, placebo-controlled, single and multiple ascending intravenous (iv) dose study in healthy subjects to assess the safety and tolerability of KAE609 given in the vein.

Read the detailed description

The study consisted of 2 parts: single-ascending dose (SAD) part and multiple ascending dose (MAD) part.

In Part A (Single-ascending dose (SAD) part), it was planned to recruit 6 active, 2 placebo subjects in each cohort:

  • Cohort A1: 10.5 mg/placebo
  • Cohort A2: 30 mg/placebo
  • Cohort A3: 75 mg/placebo
  • Cohort A4: 120 mg/placebo
  • Cohort A5: 210 mg/placebo

In Part B (Multiple-ascending dose (MAD) part), Subjects were assigned to one of the following treatment arms in a ratio of 2:1 (6 active, 3 placebo):

  • Cohort B1: 60 mg/placebo, every 24 hours (q24h) × 5 days
  • Cohort B2: 120 mg/placebo, every 24 hours (q24h) × 5 days

Eligible subjects were randomized to receive a single or q24h x 5 doses of either KAE609 or placebo. Safety, tolerability and pharmacokinetics were assessed over the period of 8 days for single dose and 12 days for multiple dose up to end of study visit for each subject.

Conditions
Malaria
Being tested
KAE609, Placebo
Keywords
safety, tolerability, pharmacokinetics, healthy volunteers, phase 1, malaria, intravenous, iv, KAE609, Placebo
Medical subject headings
Malaria

What participants receive

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

  • KAE609Drug

    • iv bolus administration over approximately 2 min for doses < 75 mg (Cohorts A1, A2 and B1)
    • iv infusion over approximately 10 min for doses ≥ 75 mg (Cohorts A3, A4, A5 and B2)
  • PlaceboDrug

    matching placeo for iv administration

Study groups in NCT04321252
Study groupRoleWhat they receive
Cohort A1: 10.5 mg/placeboExperimentalSingle iv bolus dose of KAE609 or placebo administered at the clinical site by the study personnel.
Receives: Drug: KAE609; Drug: Placebo
Cohort A2: 30 mg/placeboExperimentalSingle iv bolus dose of KAE609 or placebo administered at the clinical site by the study personnel.
Receives: Drug: KAE609; Drug: Placebo
Cohort A3: 75 mg/placeboExperimentalSingle iv infusion dose of KAE609 or placebo administered at the clinical site by the study personnel.
Receives: Drug: KAE609; Drug: Placebo
Cohort A4: 120 mg/placeboExperimentalSingle iv infusion dose of KAE609 or placebo administered at the clinical site by the study personnel.
Receives: Drug: KAE609; Drug: Placebo
Cohort A5: 210 mg/placeboExperimentalSingle iv infusion dose of KAE609 or placebo administered at the clinical site by the study personnel.
Receives: Drug: KAE609; Drug: Placebo
Cohort B1: 60 mg/placebo, every 24 hours (q24h) × 5 daysExperimentalMultiple iv bolus doses of KAE609 or placebo administered at the clinical site by the study personnel.
Receives: Drug: KAE609; Drug: Placebo
Cohort B2: 120 mg/placebo, every 24 hours (q24h) × 5 daysExperimentalMultiple iv infusion doses of KAE609 or placebo administered at the clinical site by the study personnel.
Receives: Drug: KAE609; Drug: Placebo

What is being measured

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

  1. Number of Participants With On-Treatments Adverse Events, Serious Adverse Events, and Deaths

    The distribution of adverse events was done via the analysis of frequencies for Adverse Event (AEs), Serious Adverse Event (SAEs) and Deaths, through the monitoring of relevant clinical and laboratory safety parameters.

    Measured: From study treatment start date till 30 days safety follow-up, assessed for up to 4 months

Secondary outcomes (15)
  1. Part A - Pharmacokinetic of KAE609: Maximum Observed Plasma Concentration (Cmax)

    Venous whole blood samples were collected for activity-based pharmacokinetics characterization. Cmax was calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.

    Measured: Day 1 (-1 hr, 2 min, 10 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr)

  2. Part A - Pharmacokinetic of KAE609: Time to Reach the Maximum Concentration After Drug Administration (Tmax)

    Venous whole blood samples were collected for activity-based pharmacokinetics characterization. Tmax was calculated from plasma concentration-time data using non-compartmental methods based on the actual time of sample collection and summarized using descriptive statistics.

    Measured: Day 1 (-1 hr, 2 min, 10 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr)

  3. Part A - Pharmacokinetic of KAE609: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast)

    Venous whole blood samples were collected for activity-based pharmacokinetics characterization. AUClast was calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.

    Measured: Day 1 (-1 hr, 2 min, 10 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr)

  4. Part A - Pharmacokinetic of KAE609: Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf)

    Venous whole blood samples were collected for activity-based pharmacokinetics characterization. AUCinf was calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.

    Measured: Day 1 (-1 hr, 2 min, 10 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr)

  5. Part A - Pharmacokinetic of KAE609: Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC0-24hrs)

    Venous whole blood samples were collected for activity-based pharmacokinetics characterization. AUC0-24hrs was calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.

    Measured: Day 1 (-1 hr, 2 min, 10 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr)

  6. Part A - Pharmacokinetic of KAE609: Terminal Elimination Half-life (T1/2)

    Venous whole blood samples were collected for activity-based pharmacokinetics characterization. T1/2 was calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.

    Measured: Day 1 (-1 hr, 2 min, 10 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr)

  7. Part A - Pharmacokinetic of KAE609: Clearance From Plasma (CL) Following Drug Administration

    Venous whole blood samples were collected for activity-based pharmacokinetics characterization. CL was calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.

    Measured: Day 1 (-1 hr, 2 min, 10 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr)

  8. Part A - Pharmacokinetic of KAE609: Apparent Volume of Distribution During Terminal Phase (Vz)

    Venous whole blood samples were collected for activity-based pharmacokinetics characterization. Vz was calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.

    Measured: Day 1 (-1 hr, 2 min, 10 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr)

  9. Part B - Pharmacokinetic of KAE609: Maximum Observed Plasma Concentration (Cmax)

    Venous whole blood samples were collected for activity-based pharmacokinetics characterization. Cmax was calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.

    Measured: Days 1 and 5 (-1 hr, 2 min, 10 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr)

  10. Part B - Pharmacokinetic of KAE609: Time to Reach the Maximum Concentration After Drug Administration (Tmax)

    Venous whole blood samples were collected for activity-based pharmacokinetics characterization. Tmax was calculated from plasma concentration-time data using non-compartmental methods based on the actual time of sample collection and summarized using descriptive statistics.

    Measured: Days 1 and 5 (-1 hr, 2 min, 10 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr)

  11. Part B - Pharmacokinetic of KAE609: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast)

    Venous whole blood samples were collected for activity-based pharmacokinetics characterization. AUClast was calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.

    Measured: Day 5 (-1 hr, 2 min, 10 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr)

  12. Part B - Pharmacokinetic of KAE609: Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC0-24hrs)

    Venous whole blood samples were collected for activity-based pharmacokinetics characterization. AUC0-24hrs was calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.

    Measured: Days 1 and 5 (-1 hr, 2 min, 10 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr)

  13. Part B - Pharmacokinetic of KAE609: Terminal Elimination Half-life (T1/2)

    Venous whole blood samples were collected for activity-based pharmacokinetics characterization. T1/2 was calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.

    Measured: Days 1 and 5 (-1 hr, 2 min, 10 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr)

  14. Part B - Pharmacokinetic of KAE609: Clearance From Plasma (CL) Following Drug Administration

    Venous whole blood samples were collected for activity-based pharmacokinetics characterization. CL was calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.

    Measured: Day 5 (-1 hr, 2 min, 10 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr)

  15. Part B - Pharmacokinetic of KAE609: Apparent Volume of Distribution During Terminal Phase (Vz)

    Venous whole blood samples were collected for activity-based pharmacokinetics characterization. Vz was calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.

    Measured: Day 5 (-1 hr, 2 min, 10 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr)

Timeline

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

  1. First posted25 Mar 2020
  2. Study start22 Jul 2020
  3. Primary completion10 Nov 2020
  4. Study completion10 Nov 2020

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
Other
Allocation
Randomised
Intervention model
Sequential
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
57 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04321252
Sponsor's protocol ID
CKAE609X2111
Other IDs
2019-000405-71, 217692/Z/19/Z, 2019
Status last verified
Oct 2021
First submitted
23 Mar 2020
Last updated
13 Dec 2021
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Venishetty VK, Lecot J, Nguyen A, Zhang J, Prince WT. First-in-human, randomized, double-blind, placebo-controlled, single and multiple ascending doses clinical study to assess the safety, tolerability, and pharmacokinetics of cipargamin administered intravenously in healthy adults. Antimicrob Agents Chemother. 2024 Sep 4;68(9):e0128723. doi: 10.1128/aac.01287-23. Epub 2024 Jul 26.

    PubMed 39058022

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing KAE609 in people with Malaria, run by Novartis Pharmaceuticals at 1 site in Belgium.

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 2 inclusion and 5 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 13 Dec 2021. 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 Belgium. 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 Dec 2021). 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?

Number of Participants With On-Treatments Adverse Events, Serious Adverse Events, and Deaths (time frame: From study treatment start date till 30 days safety follow-up, assessed for up to 4 months). 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 NCT04321252, 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 13 Dec 2021.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in