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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02563106
Recruitment Status : Completed
First Posted : September 29, 2015
Results First Posted : March 12, 2018
Last Update Posted : November 27, 2018
Sponsor:
Information provided by (Responsible Party):
Synthetic Biologics Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Prevention
Conditions Clostridium Difficile
Clostridium Infections
Interventions Drug: SYN-004
Drug: Placebo
Enrollment 413
Recruitment Details  
Pre-assignment Details  
Arm/Group Title SYN-004 Placebo
Hide Arm/Group Description SYN-004 150 mg Placebo (no active drug)
Period Title: Overall Study
Started 206 207
Completed 172 178
Not Completed 34 29
Reason Not Completed
Withdrawal by Subject             7             8
Adverse Event             17             15
Protocol Violation             1             0
Use of non-permitted concurrent therapy             1             2
Lost to Follow-up             3             2
Physician Decision             3             1
Other reason - not specified             2             1
Arm/Group Title SYN-004 Placebo Total
Hide Arm/Group Description SYN-004 150 mg Matching Placebo Total of all reporting groups
Overall Number of Baseline Participants 206 206 412
Hide Baseline Analysis Population Description
One subject in the placebo group was randomized but never dosed. The subject withdrew consent prior to dosing, therefore they are not included in the analysis population.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 206 participants 206 participants 412 participants
68.8  (9.37) 69.7  (9.37) 69.2  (9.37)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 206 participants 206 participants 412 participants
Female
73
  35.4%
80
  38.8%
153
  37.1%
Male
133
  64.6%
126
  61.2%
259
  62.9%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 206 participants 206 participants 412 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
1
   0.5%
1
   0.2%
White
206
 100.0%
205
  99.5%
411
  99.8%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 206 participants 206 participants 412 participants
Europe
203
  98.5%
201
  97.6%
404
  98.1%
North America
3
   1.5%
4
   1.9%
7
   1.7%
1.Primary Outcome
Title Percentage of Patients With Clostridium Difficile Infection at 4- Weeks of Follow-up.
Hide Description 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.
Time Frame Day 1 to the 4 week Follow-up Visit.
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title SYN-004 Placebo
Hide Arm/Group Description:
SYN-004 150 mg
Matching placebo
Overall Number of Participants Analyzed 206 206
Measure Type: Count of Participants
Unit of Measure: Participants
2
   1.0%
7
   3.4%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection SYN-004, Placebo
Comments The Modified Intent-to-Treat (mITT) analysis set included randomized subjects who received at least 1 dose of study drug. Number of subjects with CDI, imputing early termination without CDI as not being treatment failures.
Type of Statistical Test Other
Comments The analysis of the primary endpoint was based on the mITT analysis set. Per-protocol and worse case analyses were performed as sensitivity analyses.The P-value was based on a one-sided z-test for the comparison of the treatment difference between the SYN-004 group and the Placebo group.
Statistical Test of Hypothesis P-Value 0.045
Comments Study was designed to provide 80% power to detect treatment effect with one-sided alpha = 0.05 on the primary endpoint. Based on the pre-specified z-test the one-sided P=0.045.
Method z-test
Comments 1-sided P=0.045.
Method of Estimation Estimation Parameter Relative Risk Reduction (%)
Estimated Value 71.4
Confidence Interval (2-Sided) 95%
-35.9 to 94.0
Estimation Comments Relative Risk Reduction in SYN-004 group compared to Placebo group.
Time Frame 6 weeks.
Adverse Event Reporting Description

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.

 
Arm/Group Title SYN-004 Placebo
Hide Arm/Group Description SYN-004 150 mg Matching Placebo
All-Cause Mortality
SYN-004 Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   11/206 (5.34%)      5/206 (2.43%)    
Hide Serious Adverse Events
SYN-004 Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   33/206 (16.02%)      21/206 (10.19%)    
Blood and lymphatic system disorders     
Anemia of Chronic Disease   0/206 (0.00%)  1/206 (0.49%) 
Iron Deficiency Anemia   1/206 (0.49%)  0/206 (0.00%) 
Cardiac disorders     
Acute coronary syndrome   1/206 (0.49%)  0/206 (0.00%) 
Angina unstable   1/206 (0.49%)  0/206 (0.00%) 
Atrial fibrillation   2/206 (0.97%)  0/206 (0.00%) 
Cardiac arrest   1/206 (0.49%)  0/206 (0.00%) 
Cardiac failure   1/206 (0.49%)  2/206 (0.97%) 
Cardiac failure acute   0/206 (0.00%)  1/206 (0.49%) 
Cardiac failure congestive   1/206 (0.49%)  0/206 (0.00%) 
Cardio-respiratory arrest   1/206 (0.49%)  0/206 (0.00%) 
Cardiomyopathy   0/206 (0.00%)  2/206 (0.97%) 
Cardiopulmonary failure   1/206 (0.49%)  0/206 (0.00%) 
Myocardial infarction   1/206 (0.49%)  0/206 (0.00%) 
Myocardial ischaemia   0/206 (0.00%)  1/206 (0.49%) 
Gastrointestinal disorders     
Abdominal pain   0/206 (0.00%)  1/206 (0.49%) 
Diarrhoea   1/206 (0.49%)  0/206 (0.00%) 
Upper gastrointestinal haemorrhage   0/206 (0.00%)  1/206 (0.49%) 
Infections and infestations     
Bronchopneumonia   2/206 (0.97%)  0/206 (0.00%) 
Clostridium difficile colitis   1/206 (0.49%)  1/206 (0.49%) 
Empyema   1/206 (0.49%)  0/206 (0.00%) 
Lobar pneumonia   1/206 (0.49%)  0/206 (0.00%) 
Pneumonia   4/206 (1.94%)  5/206 (2.43%) 
Pseudomembranous colitis   0/206 (0.00%)  1/206 (0.49%) 
Respiratory tract infection   1/206 (0.49%)  0/206 (0.00%) 
Investigations     
International normalised ratio abnormal   0/206 (0.00%)  1/206 (0.49%) 
Metabolism and nutrition disorders     
Diabetes mellitus inadequate control   1/206 (0.49%)  0/206 (0.00%) 
Hypokalaemia   1/206 (0.49%)  0/206 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Chronic lymphocytic leukaemia recurrent   0/206 (0.00%)  1/206 (0.49%) 
Lung neoplasm   1/206 (0.49%)  1/206 (0.49%) 
Lung neoplasm malignant   1/206 (0.49%)  1/206 (0.49%) 
Ovarian cancer   0/206 (0.00%)  1/206 (0.49%) 
Nervous system disorders     
Syncope   1/206 (0.49%)  0/206 (0.00%) 
Psychiatric disorders     
Mental status changes   1/206 (0.49%)  0/206 (0.00%) 
Renal and urinary disorders     
Haematuria   2/206 (0.97%)  0/206 (0.00%) 
Renal failure   0/206 (0.00%)  1/206 (0.49%) 
Tubulointerstitial nephritis   1/206 (0.49%)  0/206 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Acute respiratory failure   0/206 (0.00%)  1/206 (0.49%) 
Asthma   1/206 (0.49%)  0/206 (0.00%) 
Bronchospasm   0/206 (0.00%)  1/206 (0.49%) 
Chronic obstructive pulmonary disease   4/206 (1.94%)  2/206 (0.97%) 
Chronic respiratory failure   2/206 (0.97%)  0/206 (0.00%) 
Idiopathic pulmonary fibrosis   1/206 (0.49%)  0/206 (0.00%) 
Pleural effusion   1/206 (0.49%)  0/206 (0.00%) 
Pulmonary oedema   0/206 (0.00%)  3/206 (1.46%) 
Respiratory failure   3/206 (1.46%)  4/206 (1.94%) 
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 1%
SYN-004 Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   59/206 (28.64%)      59/206 (28.64%)    
Cardiac disorders     
Atrial Fibrillation   3/206 (1.46%)  3 2/206 (0.97%)  2
Gastrointestinal disorders     
Constipation   7/206 (3.40%)  10 6/206 (2.91%)  7
Diarrhoea   9/206 (4.37%)  9 11/206 (5.34%)  11
Nausea   5/206 (2.43%)  5 3/206 (1.46%)  3
Hepatobiliary disorders     
Cholelithiasis   3/206 (1.46%)  3 2/206 (0.97%)  2
Infections and infestations     
Oral Candidiasis   3/206 (1.46%)  3 3/206 (1.46%)  3
Nervous system disorders     
Insomnia   4/206 (1.94%)  4 9/206 (4.37%)  9
Headache   5/206 (2.43%)  5 6/206 (2.91%)  7
Respiratory, thoracic and mediastinal disorders     
Dyspnoea   4/206 (1.94%)  4 4/206 (1.94%)  5
Pleural Effusion   3/206 (1.46%)  3 1/206 (0.49%)  1
Pneumonia   3/206 (1.46%)  3 1/206 (0.49%)  1
Skin and subcutaneous tissue disorders     
Erythema   3/206 (1.46%)  3 1/206 (0.49%)  1
Vascular disorders     
Hypertension   7/206 (3.40%)  7 10/206 (4.85%)  13
Indicates events were collected by systematic assessment
A safety assessment conducted by an independent third party to evaluate SAEs and fatal events confirmed that they were related to the subjects' underlying health, medical history, and comorbidities and not to study drug administration.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Michael Kaleko, MD
Organization: Synthetic Biologics
Phone: (240) 238-3862
EMail: mkaleko@syntheticbiologics.com
Layout table for additonal information
Responsible Party: Synthetic Biologics Inc.
ClinicalTrials.gov Identifier: NCT02563106    
Other Study ID Numbers: SB-2-004-005
First Submitted: September 28, 2015
First Posted: September 29, 2015
Results First Submitted: February 12, 2018
Results First Posted: March 12, 2018
Last Update Posted: November 27, 2018