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Completed

NCT Number: NCT04321252

Study to Assess Safety, Tolerability and Phamacokinetics 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.

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Key information

Conditions

Malaria Infections Mosquito-Borne Diseases Parasitic Diseases Protozoan Infections Vector Borne Diseases

Age range

18 year–55 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Novartis Investigative Site

Antwerp, B-2060, Belgium

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Key Inclusion Criteria:

  • 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.

Key Exclusion Criteria:

  • 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.

Treatment and study plan

KAE609

Drug
  • 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)

Placebo

Drug

matching placeo for iv administration

Primary outcomes

  1. 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

    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.

Secondary outcomes

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

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

    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.

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

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

    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.

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

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

    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.

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

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

    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.

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

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

    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.

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

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

    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.

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

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

    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.

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

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

    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.

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

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

    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.

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

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

    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.

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

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

    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.

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

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

    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.

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

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

    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.

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

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

    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.

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

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

    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.

Sponsors and collaborators

Lead sponsor

Novartis Pharmaceuticals

Industry

Collaborators

  • Wellcome Trust

Registry information

Official study 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

Important dates

Study start
2020
Primary completion
2020
Study completion
2020
First posted
Mar 25, 2020
Registry last updated
Dec 13, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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