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

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Primary Purpose

Status

Completed

Phase

Phase 1

Locations

Belgium

Study Type

Interventional

Intervention

KAE609

Placebo

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

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 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

NCT ID

NCT04321252

First Posted

March 23, 2020

Last Updated

October 27, 2021

Sponsor

Novartis Pharmaceuticals

Collaborators

Wellcome Trust

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