Clinical Trial Results:
A randomized, controlled, evaluator-blinded, multi-center study to evaluate LYS228 pharmacokinetics, clinical response, safety, and tolerability in patients with complicated intra-abdominal infection
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Summary
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EudraCT number |
2017-003130-90 |
Trial protocol |
CZ DE |
Global end of trial date |
24 Sep 2018
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Results information
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Results version number |
v1(current) |
This version publication date |
04 Oct 2019
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First version publication date |
04 Oct 2019
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
CLYS228X2202
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03354754 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Novartis Pharma AG
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Sponsor organisation address |
CH-4002, Basel, Switzerland,
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Public contact |
Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, Novartis.email@novartis.com
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Scientific contact |
Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, Novartis.email@novartis.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
24 Sep 2018
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
24 Sep 2018
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
To evaluate the plasma pharmacokinetics of LYS228 in patients with cIAI and to evaluate the clinical response to LYS228 in combination with vancomycin and metronidazole compared to standard of care antibiotics for treating patients with cIAI
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Protection of trial subjects |
The study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
15 May 2018
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United States: 3
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Worldwide total number of subjects |
3
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EEA total number of subjects |
0
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
3
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Approximately 60 patients were planned to be randomized to LYS228 or a comparator (standard of care therapy preferably piperacillin/tazobactam) in a 2:1 ratio. | |||||||||
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Pre-assignment
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Screening details |
Due to the study being terminated early, only 3 patients were enrolled and randomized. | |||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | |||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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LYS228 | |||||||||
Arm description |
IV infusion every 6 hours for at least 5 days | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
LYS228
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Investigational medicinal product code |
LYS228
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Other name |
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Pharmaceutical forms |
Infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
2000 mg every 6 Hours or 3000 mg every 6 hours administered intravenously in normal saline solution.
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Arm title
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Standard of care | |||||||||
Arm description |
IV infusion of standard of care antibiotics for at least 5 days | |||||||||
Arm type |
Active comparator | |||||||||
Investigational medicinal product name |
Standard of care
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Investigational medicinal product code |
Standard of care
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Other name |
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Pharmaceutical forms |
Infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Patients were dosed according to local practices
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Baseline characteristics reporting groups
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Reporting group title |
LYS228
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Reporting group description |
IV infusion every 6 hours for at least 5 days | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Standard of care
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Reporting group description |
IV infusion of standard of care antibiotics for at least 5 days | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
LYS228
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Reporting group description |
IV infusion every 6 hours for at least 5 days | ||
Reporting group title |
Standard of care
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Reporting group description |
IV infusion of standard of care antibiotics for at least 5 days | ||
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End point title |
Clinical Success at Day 28 [1] | |||||||||
End point description |
Clinical success is defined as resolution, or substantial improvement (i.e. reduction of severity of all baseline signs and symptoms and worsening of none) of all or most baseline signs and symptoms of cIAI infection without the need for additional antibiotic therapy other than any oral antibiotics given to complete treatment at home following discontinuation of Study Drug and no drainage or surgical reintervention required 96 hours after the start of Study Drug.
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End point type |
Primary
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End point timeframe |
Day 28
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analyses as trial terminated after three patients |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Plasma Pharmacokinetics (PK) of LYS228: Area Under the Plasma Concentration-time Curve from time zero to the end of the dosing interval tau (AUCtau) [2] | ||||||||||||
End point description |
Calculated based on LYS228 concentration in blood at different time points following drug administration on Day 5
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End point type |
Primary
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End point timeframe |
Day 5
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| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analyses as trial terminated after three patients |
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| Notes [3] - PK analysis not conducted as per protocol the first analysis required 8 patients [4] - PK analysis was not planned to be conducted for patients that received Standard of Care |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Plasma Pharmacokinetics (PK) of LYS228: The observed maximum plasma concentration following drug administration (Cmax) [5] | ||||||||||||
End point description |
Calculated based on LYS228 concentration in blood at different time points following drug administration on Day 5
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End point type |
Primary
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End point timeframe |
Day 5
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| Notes [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analyses as trial terminated after three patients |
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| Notes [6] - PK analysis not conducted as per protocol the first analysis required 8 patients [7] - PK analysis was not planned to be conducted for patients that received Standard of Care |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Plasma Pharmacokinetics (PK) of LYS228: The time to reach the maximum concentration after drug administration (Tmax) [8] | ||||||||||||
End point description |
Calculated based on LYS228 concentration in blood at different time points following drug administration on Day 5
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End point type |
Primary
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End point timeframe |
Day 5
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| Notes [8] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analyses as trial terminated after three patients |
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| Notes [9] - PK analysis not conducted as per protocol the first analysis required 8 patients [10] - PK analysis was not planned to be conducted for patients that received Standard of Care |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Plasma Pharmacokinetics (PK) of LYS228: The systemic (or total body) clearance from plasma following intravenous administration (CL) [11] | ||||||||||||
End point description |
Calculated based on LYS228 concentration in blood at different time points following drug administration on Day 5
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End point type |
Primary
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End point timeframe |
Day 5
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| Notes [11] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analyses as trial terminated after three patients |
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| Notes [12] - PK analysis not conducted as per protocol the first analysis required 8 patients [13] - PK analysis was not planned to be conducted for patients that received Standard of Care |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Plasma Pharmacokinetics (PK) of LYS228: The volume of distribution at steady state following intravenous administration (Vss) [14] | ||||||||||||
End point description |
Calculated based on LYS228 concentration in blood at different time points following drug administration on Day 5
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End point type |
Primary
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End point timeframe |
Day 5
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| Notes [14] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analyses as trial terminated after three patients |
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| Notes [15] - PK analysis not conducted as per protocol the first analysis required 8 patients [16] - PK analysis was not planned to be conducted for patients that received Standard of Care |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Plasma Pharmacokinetics (PK) of LYS228: The terminal elimination half-life (T1/2) [17] | ||||||||||||
End point description |
Calculated based on LYS228 concentration in blood at different time points following drug administration on Day 5
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End point type |
Primary
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End point timeframe |
Day 5
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| Notes [17] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analyses as trial terminated after three patients |
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| Notes [18] - PK analysis not conducted as per protocol the first analysis required 8 patients [19] - PK analysis was not planned to be conducted for patients that received Standard of Care |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Number of patients with Adverse Events | |||||||||
End point description |
Number of patients with at least one Adverse Event
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End point type |
Secondary
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End point timeframe |
Daily
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| No statistical analyses for this end point | ||||||||||
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End point title |
Microbiological Response at Day 28 | |||||||||
End point description |
Microbiologic success at 28 days after randomization determined by microbial growth in culture from the intra-abdominal focus of infection when available or presumed eradication based on clinical success
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End point type |
Secondary
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End point timeframe |
Day 28
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| Notes [20] - Assessment not performed |
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| No statistical analyses for this end point | ||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Adverse events were collected from first dose of study treatment until day 28.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
21.0
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Reporting groups
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Reporting group title |
LYS228
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Reporting group description |
IV infusion every 6 hours for at least 5 days | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Standard of care
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Reporting group description |
IV infusion of standard of care antibiotics for at least 5 days | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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02 Nov 2017 |
The purpose of this amendment was to collect additional pharmacokinetics (PK) samples in order to better characterize LYS228 PK parameters in patients during the treatment course. |
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11 Jun 2018 |
The purpose of this amendment was to specify a preferred and alternative choice of standard of care antibiotics used as controls. Additional details on planned interim analysis were added. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| Due to the study being terminated early, only 3 patients were enrolled and randomized. | |||
