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

Primary Purpose

Malaria

Status
Completed
Phase
Phase 1
Locations
Belgium
Study Type
Interventional
Intervention
KAE609
Placebo
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Malaria focused on measuring safety, tolerability, pharmacokinetics, healthy volunteers, phase 1, malaria, intravenous, iv, KAE609, Placebo

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

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

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

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

Arm Description

Single iv bolus dose of KAE609 or placebo administered at the clinical site by the study personnel.

Single iv bolus dose of KAE609 or placebo administered at the clinical site by the study personnel.

Single iv infusion dose of KAE609 or placebo administered at the clinical site by the study personnel.

Single iv infusion dose of KAE609 or placebo administered at the clinical site by the study personnel.

Single iv infusion dose of KAE609 or placebo administered at the clinical site by the study personnel.

Multiple iv bolus doses of KAE609 or placebo administered at the clinical site by the study personnel.

Multiple iv infusion doses of KAE609 or placebo administered at the clinical site by the study personnel.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.

Full Information

First Posted
March 23, 2020
Last Updated
October 27, 2021
Sponsor
Novartis Pharmaceuticals
Collaborators
Wellcome Trust
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1. Study Identification

Unique Protocol Identification Number
NCT04321252
Brief Title
Study to Assess Safety, Tolerability and Phamacokinetics of KAE609 Administered Intravenously in Healthy Subjects
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2021
Overall Recruitment Status
Completed
Study Start Date
July 22, 2020 (Actual)
Primary Completion Date
November 10, 2020 (Actual)
Study Completion Date
November 10, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals
Collaborators
Wellcome Trust

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malaria
Keywords
safety, tolerability, pharmacokinetics, healthy volunteers, phase 1, malaria, intravenous, iv, KAE609, Placebo

7. Study Design

Primary Purpose
Other
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
57 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cohort A1: 10.5 mg/placebo
Arm Type
Experimental
Arm Description
Single iv bolus dose of KAE609 or placebo administered at the clinical site by the study personnel.
Arm Title
Cohort A2: 30 mg/placebo
Arm Type
Experimental
Arm Description
Single iv bolus dose of KAE609 or placebo administered at the clinical site by the study personnel.
Arm Title
Cohort A3: 75 mg/placebo
Arm Type
Experimental
Arm Description
Single iv infusion dose of KAE609 or placebo administered at the clinical site by the study personnel.
Arm Title
Cohort A4: 120 mg/placebo
Arm Type
Experimental
Arm Description
Single iv infusion dose of KAE609 or placebo administered at the clinical site by the study personnel.
Arm Title
Cohort A5: 210 mg/placebo
Arm Type
Experimental
Arm Description
Single iv infusion dose of KAE609 or placebo administered at the clinical site by the study personnel.
Arm Title
Cohort B1: 60 mg/placebo, every 24 hours (q24h) × 5 days
Arm Type
Experimental
Arm Description
Multiple iv bolus doses of KAE609 or placebo administered at the clinical site by the study personnel.
Arm Title
Cohort B2: 120 mg/placebo, every 24 hours (q24h) × 5 days
Arm Type
Experimental
Arm Description
Multiple iv infusion doses of KAE609 or placebo administered at the clinical site by the study personnel.
Intervention Type
Drug
Intervention Name(s)
KAE609
Intervention Description
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)
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
matching placeo for iv administration
Primary Outcome Measure Information:
Title
Number of Participants With On-Treatments Adverse Events, Serious Adverse Events, and Deaths
Description
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.
Time Frame
From study treatment start date till 30 days safety follow-up, assessed for up to 4 months
Secondary Outcome Measure Information:
Title
Part A - Pharmacokinetic of KAE609: Maximum Observed Plasma Concentration (Cmax)
Description
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.
Time Frame
Day 1 (-1 hr, 2 min, 10 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr)
Title
Part A - Pharmacokinetic of KAE609: Time to Reach the Maximum Concentration After Drug Administration (Tmax)
Description
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.
Time Frame
Day 1 (-1 hr, 2 min, 10 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr)
Title
Part A - Pharmacokinetic of KAE609: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast)
Description
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.
Time Frame
Day 1 (-1 hr, 2 min, 10 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr)
Title
Part A - Pharmacokinetic of KAE609: Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf)
Description
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.
Time Frame
Day 1 (-1 hr, 2 min, 10 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr)
Title
Part A - Pharmacokinetic of KAE609: Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC0-24hrs)
Description
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.
Time Frame
Day 1 (-1 hr, 2 min, 10 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr)
Title
Part A - Pharmacokinetic of KAE609: Terminal Elimination Half-life (T1/2)
Description
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.
Time Frame
Day 1 (-1 hr, 2 min, 10 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr)
Title
Part A - Pharmacokinetic of KAE609: Clearance From Plasma (CL) Following Drug Administration
Description
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.
Time Frame
Day 1 (-1 hr, 2 min, 10 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr)
Title
Part A - Pharmacokinetic of KAE609: Apparent Volume of Distribution During Terminal Phase (Vz)
Description
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.
Time Frame
Day 1 (-1 hr, 2 min, 10 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr)
Title
Part B - Pharmacokinetic of KAE609: Maximum Observed Plasma Concentration (Cmax)
Description
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.
Time Frame
Days 1 and 5 (-1 hr, 2 min, 10 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr)
Title
Part B - Pharmacokinetic of KAE609: Time to Reach the Maximum Concentration After Drug Administration (Tmax)
Description
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.
Time Frame
Days 1 and 5 (-1 hr, 2 min, 10 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr)
Title
Part B - Pharmacokinetic of KAE609: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast)
Description
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.
Time Frame
Day 5 (-1 hr, 2 min, 10 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr)
Title
Part B - Pharmacokinetic of KAE609: Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC0-24hrs)
Description
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.
Time Frame
Days 1 and 5 (-1 hr, 2 min, 10 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr)
Title
Part B - Pharmacokinetic of KAE609: Terminal Elimination Half-life (T1/2)
Description
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.
Time Frame
Days 1 and 5 (-1 hr, 2 min, 10 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr)
Title
Part B - Pharmacokinetic of KAE609: Clearance From Plasma (CL) Following Drug Administration
Description
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.
Time Frame
Day 5 (-1 hr, 2 min, 10 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr)
Title
Part B - Pharmacokinetic of KAE609: Apparent Volume of Distribution During Terminal Phase (Vz)
Description
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.
Time Frame
Day 5 (-1 hr, 2 min, 10 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Antwerpen
ZIP/Postal Code
B-2060
Country
Belgium

12. IPD Sharing Statement

Plan to Share IPD
No

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

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