Trial Outcomes & Findings for LYS228 PK, Clinical Response, Safety and Tolerability in Patients With Complicated Intra-abdominal Infection (cIAI) (NCT NCT03354754)

NCT ID: NCT03354754

Last Updated: 2021-10-11

Results Overview

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.

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 3 participants
• Primary outcome timeframe: Day 28
• Results posted on: 2021-10-11

Participant Flow

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.

Participant milestones

Measure	LYS228 IV infusion every 6 hours for at least 5 days	Standard of Care IV infusion of standard of care antibiotics for at least 5 days
Overall Study STARTED	2	1
Overall Study COMPLETED	2	1
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

LYS228 PK, Clinical Response, Safety and Tolerability in Patients With Complicated Intra-abdominal Infection (cIAI)

Baseline characteristics by cohort

Measure	LYS228 n=2 Participants IV infusion every 6 hours for at least 5 days	Standard of Care n=1 Participants IV infusion of standard of care antibiotics for at least 5 days	Total n=3 Participants Total of all reporting groups
Age, Continuous	63.5 years n=93 Participants	63 years n=4 Participants	63 years n=27 Participants
Sex: Female, Male Female	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Sex: Female, Male Male	2 Participants n=93 Participants	1 Participants n=4 Participants	3 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Black or African American	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) White	2 Participants n=93 Participants	1 Participants n=4 Participants	3 Participants n=27 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants

PRIMARY outcome

Timeframe: Day 28

Population: All patients

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.

Outcome measures

Measure	LYS228 n=2 Participants IV infusion every 6 hours for at least 5 days	Standard of Care n=1 Participants IV infusion of standard of care antibiotics for at least 5 days
Clinical Success at Day 28	2 Participants	0 Participants

PRIMARY outcome

Timeframe: Day 5

Population: PK analysis for the 2 patients enrolled that received LYS228 was not conducted as per protocol the first analysis required 8 patients.

Calculated based on LYS228 concentration in blood at different time points following drug administration on Day 5

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Day 5

Population: PK analysis for the 2 patients enrolled that received LYS228 was not conducted as per protocol the first analysis required 8 patients

Calculated based on LYS228 concentration in blood at different time points following drug administration on Day 5

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Day 5

Population: PK analysis for the 2 patients enrolled that received LYS228 was not conducted as per protocol the first analysis required 8 patients

Calculated based on LYS228 concentration in blood at different time points following drug administration on Day 5

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Day 5

Population: PK analysis for the 2 patients enrolled that received LYS228 was not conducted as per protocol the first analysis required 8 patients

Calculated based on LYS228 concentration in blood at different time points following drug administration on Day 5

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Day 5

Population: PK analysis for the 2 patients enrolled that received LYS228 was not conducted as per protocol the first analysis required 8 patients

Calculated based on LYS228 concentration in blood at different time points following drug administration on Day 5

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Day 5

Population: PK analysis for the 2 patients enrolled that received LYS228 was not conducted as per protocol the first analysis required 8 patients

Calculated based on LYS228 concentration in blood at different time points following drug administration on Day 5

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Daily

Population: All patients

Number of patients with at least one Adverse Event

Outcome measures

Measure	LYS228 n=2 Participants IV infusion every 6 hours for at least 5 days	Standard of Care n=1 Participants IV infusion of standard of care antibiotics for at least 5 days
Number of Patients With Adverse Events	2 Participants	1 Participants

SECONDARY outcome

Timeframe: Day 28

Population: All patients with a microbiological response assessment

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

Outcome measures

Measure	LYS228 n=2 Participants IV infusion every 6 hours for at least 5 days	Standard of Care IV infusion of standard of care antibiotics for at least 5 days
Microbiological Response at Day 28	2 Participants	0 Participants

Adverse Events

LYS228

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Standard of Care

Serious events: 1 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Measure	LYS228 n=2 participants at risk IV infusion every 6 hours for at least 5 days	Standard of Care n=1 participants at risk IV infusion of standard of care antibiotics for at least 5 days
Infections and infestations Appendicitis perforated	0.00% 0/2 • Adverse events were collected from first dose of study treatment until day 28.	100.0% 1/1 • Adverse events were collected from first dose of study treatment until day 28.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/2 • Adverse events were collected from first dose of study treatment until day 28.	100.0% 1/1 • Adverse events were collected from first dose of study treatment until day 28.
Vascular disorders Deep vein thrombosis	0.00% 0/2 • Adverse events were collected from first dose of study treatment until day 28.	100.0% 1/1 • Adverse events were collected from first dose of study treatment until day 28.

Other adverse events

Measure	LYS228 n=2 participants at risk IV infusion every 6 hours for at least 5 days	Standard of Care n=1 participants at risk IV infusion of standard of care antibiotics for at least 5 days
Blood and lymphatic system disorders Anaemia	50.0% 1/2 • Adverse events were collected from first dose of study treatment until day 28.	0.00% 0/1 • Adverse events were collected from first dose of study treatment until day 28.
Gastrointestinal disorders Constipation	50.0% 1/2 • Adverse events were collected from first dose of study treatment until day 28.	0.00% 0/1 • Adverse events were collected from first dose of study treatment until day 28.
Gastrointestinal disorders Diarrhoea	50.0% 1/2 • Adverse events were collected from first dose of study treatment until day 28.	0.00% 0/1 • Adverse events were collected from first dose of study treatment until day 28.
Gastrointestinal disorders Dyspepsia	50.0% 1/2 • Adverse events were collected from first dose of study treatment until day 28.	0.00% 0/1 • Adverse events were collected from first dose of study treatment until day 28.
Infections and infestations Oral candidiasis	0.00% 0/2 • Adverse events were collected from first dose of study treatment until day 28.	100.0% 1/1 • Adverse events were collected from first dose of study treatment until day 28.
Investigations Alanine aminotransferase increased	0.00% 0/2 • Adverse events were collected from first dose of study treatment until day 28.	100.0% 1/1 • Adverse events were collected from first dose of study treatment until day 28.
Investigations Aspartate aminotransferase increased	0.00% 0/2 • Adverse events were collected from first dose of study treatment until day 28.	100.0% 1/1 • Adverse events were collected from first dose of study treatment until day 28.
Investigations Blood alkaline phosphatase increased	0.00% 0/2 • Adverse events were collected from first dose of study treatment until day 28.	100.0% 1/1 • Adverse events were collected from first dose of study treatment until day 28.
Investigations Blood magnesium decreased	50.0% 1/2 • Adverse events were collected from first dose of study treatment until day 28.	0.00% 0/1 • Adverse events were collected from first dose of study treatment until day 28.
Investigations Blood phosphorus decreased	50.0% 1/2 • Adverse events were collected from first dose of study treatment until day 28.	0.00% 0/1 • Adverse events were collected from first dose of study treatment until day 28.
Investigations Blood potassium decreased	50.0% 1/2 • Adverse events were collected from first dose of study treatment until day 28.	0.00% 0/1 • Adverse events were collected from first dose of study treatment until day 28.
Investigations Gamma-glutamyltransferase increased	0.00% 0/2 • Adverse events were collected from first dose of study treatment until day 28.	100.0% 1/1 • Adverse events were collected from first dose of study treatment until day 28.
Psychiatric disorders Anxiety	50.0% 1/2 • Adverse events were collected from first dose of study treatment until day 28.	0.00% 0/1 • Adverse events were collected from first dose of study treatment until day 28.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/2 • Adverse events were collected from first dose of study treatment until day 28.	100.0% 1/1 • Adverse events were collected from first dose of study treatment until day 28.
Vascular disorders Hypertension	50.0% 1/2 • Adverse events were collected from first dose of study treatment until day 28.	0.00% 0/1 • Adverse events were collected from first dose of study treatment until day 28.
Vascular disorders Hypotension	50.0% 1/2 • Adverse events were collected from first dose of study treatment until day 28.	0.00% 0/1 • Adverse events were collected from first dose of study treatment until day 28.

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Email: Novartis.email@novartis.com

Results disclosure agreements

• Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
• Publication restrictions are in place

Restriction type: OTHER