Trial Outcomes & Findings for A Study of SYN-004 for the Prevention of C.Diff in Patients With a LRTI (NCT NCT02563106)

Last Updated: 2018-11-27

Results Overview

Percentage of subjects with CDI, based on the protocol definition of CDI (defined as 3 or more unformed stools per 24 hour period and a stool sample being positive for C. difficile toxin A and/or B \[or their respective genes, tcdA and/or tcdB\], based on the clinical site local laboratory results) from Day 1 to the 4-week Follow-up Visit in the SYN-004 treatment group compared to the placebo group, imputing early termination without CDI as not being treatment failures.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

413 participants

Primary outcome timeframe

Day 1 to the 4 week Follow-up Visit.

Results posted on

2018-11-27

Participant Flow

Participant milestones

Participant milestones
Measure	SYN-004 SYN-004 150 mg	Placebo Placebo (no active drug)
Overall Study STARTED	206	207
Overall Study COMPLETED	172	178
Overall Study NOT COMPLETED	34	29

Reasons for withdrawal

Reasons for withdrawal
Measure	SYN-004 SYN-004 150 mg	Placebo Placebo (no active drug)
Overall Study Withdrawal by Subject	7	8
Overall Study Adverse Event	17	15
Overall Study Protocol Violation	1	0
Overall Study Use of non-permitted concurrent therapy	1	2
Overall Study Lost to Follow-up	3	2
Overall Study Physician Decision	3	1
Overall Study Other reason - not specified	2	1

Baseline Characteristics

A Study of SYN-004 for the Prevention of C.Diff in Patients With a LRTI

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	SYN-004 n=206 Participants SYN-004 150 mg	Placebo n=206 Participants Matching Placebo	Total n=412 Participants Total of all reporting groups
Age, Continuous	68.8 years STANDARD_DEVIATION 9.37 • n=99 Participants	69.7 years STANDARD_DEVIATION 9.37 • n=107 Participants	69.2 years STANDARD_DEVIATION 9.37 • n=206 Participants
Sex: Female, Male Female	73 Participants n=99 Participants	80 Participants n=107 Participants	153 Participants n=206 Participants
Sex: Female, Male Male	133 Participants n=99 Participants	126 Participants n=107 Participants	259 Participants n=206 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Asian	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Black or African American	0 Participants n=99 Participants	1 Participants n=107 Participants	1 Participants n=206 Participants
Race (NIH/OMB) White	206 Participants n=99 Participants	205 Participants n=107 Participants	411 Participants n=206 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Region of Enrollment Europe	203 Participants n=99 Participants	201 Participants n=107 Participants	404 Participants n=206 Participants
Region of Enrollment North America	3 Participants n=99 Participants	4 Participants n=107 Participants	7 Participants n=206 Participants

PRIMARY outcome

Timeframe: Day 1 to the 4 week Follow-up Visit.

Population: The Modified Intent-to-Treat (mITT) analysis set included randomized subjects who received at least 1dose of study drug. Number of subjects with CDI, imputing early termination without CDI as not being treatment failures.

Outcome measures

Outcome measures
Measure	SYN-004 n=206 Participants SYN-004 150 mg	Placebo n=206 Participants Matching placebo
Percentage of Patients With Clostridium Difficile Infection at 4- Weeks of Follow-up.	2 Participants	7 Participants

Adverse Events

SYN-004

Serious events: 33 serious events

Other events: 59 other events

Deaths: 11 deaths

Placebo

Serious events: 21 serious events

Other events: 59 other events

Deaths: 5 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	SYN-004 n=206 participants at risk SYN-004 150 mg	Placebo n=206 participants at risk Matching Placebo
Vascular disorders Hypertension	3.4% 7/206 • Number of events 7 • 6 weeks. The "Total" reported in the "Other (Not Including Serious) Adverse Events (AEs) Section" for SYN-004 and Placebo indicate the total number of AEs. The number of subjects "Affected" by those AEs is 42 for SYN-004 and 46 for Placebo. The frequency threshold of 1% for non-serious adverse events is reported as the # of subjects w/ AEs (excluding Serious Adverse Events (SAEs)) in each group, based on # of subjects w/ AEs \>1% in the SYN-004 group \& the corresponding AE categories for Placebo group.	4.9% 10/206 • Number of events 13 • 6 weeks. The "Total" reported in the "Other (Not Including Serious) Adverse Events (AEs) Section" for SYN-004 and Placebo indicate the total number of AEs. The number of subjects "Affected" by those AEs is 42 for SYN-004 and 46 for Placebo. The frequency threshold of 1% for non-serious adverse events is reported as the # of subjects w/ AEs (excluding Serious Adverse Events (SAEs)) in each group, based on # of subjects w/ AEs \>1% in the SYN-004 group \& the corresponding AE categories for Placebo group.
Gastrointestinal disorders Constipation	3.4% 7/206 • Number of events 10 • 6 weeks. The "Total" reported in the "Other (Not Including Serious) Adverse Events (AEs) Section" for SYN-004 and Placebo indicate the total number of AEs. The number of subjects "Affected" by those AEs is 42 for SYN-004 and 46 for Placebo. The frequency threshold of 1% for non-serious adverse events is reported as the # of subjects w/ AEs (excluding Serious Adverse Events (SAEs)) in each group, based on # of subjects w/ AEs \>1% in the SYN-004 group \& the corresponding AE categories for Placebo group.	2.9% 6/206 • Number of events 7 • 6 weeks. The "Total" reported in the "Other (Not Including Serious) Adverse Events (AEs) Section" for SYN-004 and Placebo indicate the total number of AEs. The number of subjects "Affected" by those AEs is 42 for SYN-004 and 46 for Placebo. The frequency threshold of 1% for non-serious adverse events is reported as the # of subjects w/ AEs (excluding Serious Adverse Events (SAEs)) in each group, based on # of subjects w/ AEs \>1% in the SYN-004 group \& the corresponding AE categories for Placebo group.
Nervous system disorders Insomnia	1.9% 4/206 • Number of events 4 • 6 weeks. The "Total" reported in the "Other (Not Including Serious) Adverse Events (AEs) Section" for SYN-004 and Placebo indicate the total number of AEs. The number of subjects "Affected" by those AEs is 42 for SYN-004 and 46 for Placebo. The frequency threshold of 1% for non-serious adverse events is reported as the # of subjects w/ AEs (excluding Serious Adverse Events (SAEs)) in each group, based on # of subjects w/ AEs \>1% in the SYN-004 group \& the corresponding AE categories for Placebo group.	4.4% 9/206 • Number of events 9 • 6 weeks. The "Total" reported in the "Other (Not Including Serious) Adverse Events (AEs) Section" for SYN-004 and Placebo indicate the total number of AEs. The number of subjects "Affected" by those AEs is 42 for SYN-004 and 46 for Placebo. The frequency threshold of 1% for non-serious adverse events is reported as the # of subjects w/ AEs (excluding Serious Adverse Events (SAEs)) in each group, based on # of subjects w/ AEs \>1% in the SYN-004 group \& the corresponding AE categories for Placebo group.
Nervous system disorders Headache	2.4% 5/206 • Number of events 5 • 6 weeks. The "Total" reported in the "Other (Not Including Serious) Adverse Events (AEs) Section" for SYN-004 and Placebo indicate the total number of AEs. The number of subjects "Affected" by those AEs is 42 for SYN-004 and 46 for Placebo. The frequency threshold of 1% for non-serious adverse events is reported as the # of subjects w/ AEs (excluding Serious Adverse Events (SAEs)) in each group, based on # of subjects w/ AEs \>1% in the SYN-004 group \& the corresponding AE categories for Placebo group.	2.9% 6/206 • Number of events 7 • 6 weeks. The "Total" reported in the "Other (Not Including Serious) Adverse Events (AEs) Section" for SYN-004 and Placebo indicate the total number of AEs. The number of subjects "Affected" by those AEs is 42 for SYN-004 and 46 for Placebo. The frequency threshold of 1% for non-serious adverse events is reported as the # of subjects w/ AEs (excluding Serious Adverse Events (SAEs)) in each group, based on # of subjects w/ AEs \>1% in the SYN-004 group \& the corresponding AE categories for Placebo group.
Gastrointestinal disorders Diarrhoea	4.4% 9/206 • Number of events 9 • 6 weeks. The "Total" reported in the "Other (Not Including Serious) Adverse Events (AEs) Section" for SYN-004 and Placebo indicate the total number of AEs. The number of subjects "Affected" by those AEs is 42 for SYN-004 and 46 for Placebo. The frequency threshold of 1% for non-serious adverse events is reported as the # of subjects w/ AEs (excluding Serious Adverse Events (SAEs)) in each group, based on # of subjects w/ AEs \>1% in the SYN-004 group \& the corresponding AE categories for Placebo group.	5.3% 11/206 • Number of events 11 • 6 weeks. The "Total" reported in the "Other (Not Including Serious) Adverse Events (AEs) Section" for SYN-004 and Placebo indicate the total number of AEs. The number of subjects "Affected" by those AEs is 42 for SYN-004 and 46 for Placebo. The frequency threshold of 1% for non-serious adverse events is reported as the # of subjects w/ AEs (excluding Serious Adverse Events (SAEs)) in each group, based on # of subjects w/ AEs \>1% in the SYN-004 group \& the corresponding AE categories for Placebo group.
Gastrointestinal disorders Nausea	2.4% 5/206 • Number of events 5 • 6 weeks. The "Total" reported in the "Other (Not Including Serious) Adverse Events (AEs) Section" for SYN-004 and Placebo indicate the total number of AEs. The number of subjects "Affected" by those AEs is 42 for SYN-004 and 46 for Placebo. The frequency threshold of 1% for non-serious adverse events is reported as the # of subjects w/ AEs (excluding Serious Adverse Events (SAEs)) in each group, based on # of subjects w/ AEs \>1% in the SYN-004 group \& the corresponding AE categories for Placebo group.	1.5% 3/206 • Number of events 3 • 6 weeks. The "Total" reported in the "Other (Not Including Serious) Adverse Events (AEs) Section" for SYN-004 and Placebo indicate the total number of AEs. The number of subjects "Affected" by those AEs is 42 for SYN-004 and 46 for Placebo. The frequency threshold of 1% for non-serious adverse events is reported as the # of subjects w/ AEs (excluding Serious Adverse Events (SAEs)) in each group, based on # of subjects w/ AEs \>1% in the SYN-004 group \& the corresponding AE categories for Placebo group.
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.9% 4/206 • Number of events 4 • 6 weeks. The "Total" reported in the "Other (Not Including Serious) Adverse Events (AEs) Section" for SYN-004 and Placebo indicate the total number of AEs. The number of subjects "Affected" by those AEs is 42 for SYN-004 and 46 for Placebo. The frequency threshold of 1% for non-serious adverse events is reported as the # of subjects w/ AEs (excluding Serious Adverse Events (SAEs)) in each group, based on # of subjects w/ AEs \>1% in the SYN-004 group \& the corresponding AE categories for Placebo group.	1.9% 4/206 • Number of events 5 • 6 weeks. The "Total" reported in the "Other (Not Including Serious) Adverse Events (AEs) Section" for SYN-004 and Placebo indicate the total number of AEs. The number of subjects "Affected" by those AEs is 42 for SYN-004 and 46 for Placebo. The frequency threshold of 1% for non-serious adverse events is reported as the # of subjects w/ AEs (excluding Serious Adverse Events (SAEs)) in each group, based on # of subjects w/ AEs \>1% in the SYN-004 group \& the corresponding AE categories for Placebo group.
Cardiac disorders Atrial Fibrillation	1.5% 3/206 • Number of events 3 • 6 weeks. The "Total" reported in the "Other (Not Including Serious) Adverse Events (AEs) Section" for SYN-004 and Placebo indicate the total number of AEs. The number of subjects "Affected" by those AEs is 42 for SYN-004 and 46 for Placebo. The frequency threshold of 1% for non-serious adverse events is reported as the # of subjects w/ AEs (excluding Serious Adverse Events (SAEs)) in each group, based on # of subjects w/ AEs \>1% in the SYN-004 group \& the corresponding AE categories for Placebo group.	0.97% 2/206 • Number of events 2 • 6 weeks. The "Total" reported in the "Other (Not Including Serious) Adverse Events (AEs) Section" for SYN-004 and Placebo indicate the total number of AEs. The number of subjects "Affected" by those AEs is 42 for SYN-004 and 46 for Placebo. The frequency threshold of 1% for non-serious adverse events is reported as the # of subjects w/ AEs (excluding Serious Adverse Events (SAEs)) in each group, based on # of subjects w/ AEs \>1% in the SYN-004 group \& the corresponding AE categories for Placebo group.
Infections and infestations Oral Candidiasis	1.5% 3/206 • Number of events 3 • 6 weeks. The "Total" reported in the "Other (Not Including Serious) Adverse Events (AEs) Section" for SYN-004 and Placebo indicate the total number of AEs. The number of subjects "Affected" by those AEs is 42 for SYN-004 and 46 for Placebo. The frequency threshold of 1% for non-serious adverse events is reported as the # of subjects w/ AEs (excluding Serious Adverse Events (SAEs)) in each group, based on # of subjects w/ AEs \>1% in the SYN-004 group \& the corresponding AE categories for Placebo group.	1.5% 3/206 • Number of events 3 • 6 weeks. The "Total" reported in the "Other (Not Including Serious) Adverse Events (AEs) Section" for SYN-004 and Placebo indicate the total number of AEs. The number of subjects "Affected" by those AEs is 42 for SYN-004 and 46 for Placebo. The frequency threshold of 1% for non-serious adverse events is reported as the # of subjects w/ AEs (excluding Serious Adverse Events (SAEs)) in each group, based on # of subjects w/ AEs \>1% in the SYN-004 group \& the corresponding AE categories for Placebo group.
Hepatobiliary disorders Cholelithiasis	1.5% 3/206 • Number of events 3 • 6 weeks. The "Total" reported in the "Other (Not Including Serious) Adverse Events (AEs) Section" for SYN-004 and Placebo indicate the total number of AEs. The number of subjects "Affected" by those AEs is 42 for SYN-004 and 46 for Placebo. The frequency threshold of 1% for non-serious adverse events is reported as the # of subjects w/ AEs (excluding Serious Adverse Events (SAEs)) in each group, based on # of subjects w/ AEs \>1% in the SYN-004 group \& the corresponding AE categories for Placebo group.	0.97% 2/206 • Number of events 2 • 6 weeks. The "Total" reported in the "Other (Not Including Serious) Adverse Events (AEs) Section" for SYN-004 and Placebo indicate the total number of AEs. The number of subjects "Affected" by those AEs is 42 for SYN-004 and 46 for Placebo. The frequency threshold of 1% for non-serious adverse events is reported as the # of subjects w/ AEs (excluding Serious Adverse Events (SAEs)) in each group, based on # of subjects w/ AEs \>1% in the SYN-004 group \& the corresponding AE categories for Placebo group.
Respiratory, thoracic and mediastinal disorders Pleural Effusion	1.5% 3/206 • Number of events 3 • 6 weeks. The "Total" reported in the "Other (Not Including Serious) Adverse Events (AEs) Section" for SYN-004 and Placebo indicate the total number of AEs. The number of subjects "Affected" by those AEs is 42 for SYN-004 and 46 for Placebo. The frequency threshold of 1% for non-serious adverse events is reported as the # of subjects w/ AEs (excluding Serious Adverse Events (SAEs)) in each group, based on # of subjects w/ AEs \>1% in the SYN-004 group \& the corresponding AE categories for Placebo group.	0.49% 1/206 • Number of events 1 • 6 weeks. The "Total" reported in the "Other (Not Including Serious) Adverse Events (AEs) Section" for SYN-004 and Placebo indicate the total number of AEs. The number of subjects "Affected" by those AEs is 42 for SYN-004 and 46 for Placebo. The frequency threshold of 1% for non-serious adverse events is reported as the # of subjects w/ AEs (excluding Serious Adverse Events (SAEs)) in each group, based on # of subjects w/ AEs \>1% in the SYN-004 group \& the corresponding AE categories for Placebo group.
Skin and subcutaneous tissue disorders Erythema	1.5% 3/206 • Number of events 3 • 6 weeks. The "Total" reported in the "Other (Not Including Serious) Adverse Events (AEs) Section" for SYN-004 and Placebo indicate the total number of AEs. The number of subjects "Affected" by those AEs is 42 for SYN-004 and 46 for Placebo. The frequency threshold of 1% for non-serious adverse events is reported as the # of subjects w/ AEs (excluding Serious Adverse Events (SAEs)) in each group, based on # of subjects w/ AEs \>1% in the SYN-004 group \& the corresponding AE categories for Placebo group.	0.49% 1/206 • Number of events 1 • 6 weeks. The "Total" reported in the "Other (Not Including Serious) Adverse Events (AEs) Section" for SYN-004 and Placebo indicate the total number of AEs. The number of subjects "Affected" by those AEs is 42 for SYN-004 and 46 for Placebo. The frequency threshold of 1% for non-serious adverse events is reported as the # of subjects w/ AEs (excluding Serious Adverse Events (SAEs)) in each group, based on # of subjects w/ AEs \>1% in the SYN-004 group \& the corresponding AE categories for Placebo group.
Respiratory, thoracic and mediastinal disorders Pneumonia	1.5% 3/206 • Number of events 3 • 6 weeks. The "Total" reported in the "Other (Not Including Serious) Adverse Events (AEs) Section" for SYN-004 and Placebo indicate the total number of AEs. The number of subjects "Affected" by those AEs is 42 for SYN-004 and 46 for Placebo. The frequency threshold of 1% for non-serious adverse events is reported as the # of subjects w/ AEs (excluding Serious Adverse Events (SAEs)) in each group, based on # of subjects w/ AEs \>1% in the SYN-004 group \& the corresponding AE categories for Placebo group.	0.49% 1/206 • Number of events 1 • 6 weeks. The "Total" reported in the "Other (Not Including Serious) Adverse Events (AEs) Section" for SYN-004 and Placebo indicate the total number of AEs. The number of subjects "Affected" by those AEs is 42 for SYN-004 and 46 for Placebo. The frequency threshold of 1% for non-serious adverse events is reported as the # of subjects w/ AEs (excluding Serious Adverse Events (SAEs)) in each group, based on # of subjects w/ AEs \>1% in the SYN-004 group \& the corresponding AE categories for Placebo group.

Additional Information

Michael Kaleko, MD

Synthetic Biologics

Phone: (240) 238-3862

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Investigators do not see trial results ahead of public disclosure unless it is under CDA. Investigators will not be allowed to publish or disclose any study results prior to sponsor communicating it to the public.
Publication restrictions are in place

Restriction type: OTHER