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A Phase 2b Parallel-Group, Double-Blind, Placebo-Controlled, Multicenter Study of SYN-004 Compared to Placebo for the Prevention of Clostridium difficile Infection (CDI) in Hospitalized Patients receiving IV ceftriaxone with a Diagnosis of a Lower Respiratory Tract Infection (LRTI).
This is a Phase 2b, randomized, double-blind, placebo controlled, parallel-group, multi-center proof-of-concept study to assess the potential of SYN-004 in the prevention of CDI and the unwanted side effects of IV antibiotic treatment in at risk patients who are hospitalized for LRTI and receiving IV ceftriaxone alone or in combination with a macrolide. Subjects will be 50 years or older. The entire duration of the study may be up to 59 days. All patients will be evaluated for the occurrence of CDI and AAD by testing according to local diagnostic standards and monitoring for diarrhea (3 or more unformed stools per 24 hour period).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| SYN-004 | Experimental | SYN-004 150 mg |
|
| Placebo | Placebo Comparator | Matching placebo |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| SYN-004 | Drug |
| ||
| Placebo |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Patients With Clostridium Difficile Infection at 4- Weeks of Follow-up. | 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. | Day 1 to the 4 week Follow-up Visit. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Michael Kaleko, MD | Synthetic Biologics | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Synthetic Biologics Investigational Site | Little Rock | Arkansas | 72205 | United States | ||
| Synthetic Biologics Investigational Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30885591 | Derived | Kokai-Kun JF, Roberts T, Coughlin O, Le C, Whalen H, Stevenson R, Wacher VJ, Sliman J. Use of ribaxamase (SYN-004), a beta-lactamase, to prevent Clostridium difficile infection in beta-lactam-treated patients: a double-blind, phase 2b, randomised placebo-controlled trial. Lancet Infect Dis. 2019 May;19(5):487-496. doi: 10.1016/S1473-3099(18)30731-X. Epub 2019 Mar 15. |
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| ID | Title | Description |
|---|---|---|
| FG000 | SYN-004 | SYN-004 150 mg |
| FG001 | Placebo | Placebo (no active drug) |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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|
| Torrance |
| California |
| 90502 |
| United States |
| Synthetic Biologics Investigational Site | DeLand | Florida | 32720 | United States |
| Synthetic Biologics Investigational Site | Będzin | Louisiana | 71457 | United States |
| Synthetic Biologics Investigational Site | Debrecen | Louisiana | 71457 | United States |
| Synthetic Biologics Investigational SIte | Natchitoches | Louisiana | 71457 | United States |
| Synthetic Biologics Investigational Site | Gabrovo | Bulgaria |
| Synthetic Biologics Investigational Site | Kyustendil | Bulgaria |
| Synthetic Biologics Investigational Site | Lovech | Bulgaria |
| Synthetic Biologics Investigational Site | Multiple Locations | Bulgaria |
| Synthetic Biologics Investigational Site | Rousse | Bulgaria |
| Synthetic Biologics Investigational Site | Sevlievo | Bulgaria |
| Synthetic Biologics Investigational Site | Sofia | Bulgaria |
| Synthetic Biologics Investigational Site | Targovishte | Bulgaria |
| Synthetic Biologics Investigational Site | Sherbrooke | Canada |
| Synthetic Biologics Investigational Site | Toronto | Canada |
| Synthetic Biologics Investigational Site | Balassagyarmat | Hungary |
| Synthetic Biologics Investigational Site | Budapest | Hungary |
| Synthetic Biologics Investigational Site | Veszprém | Hungary |
| Synthetic Biologics Investigational Site | Bialystok | Poland |
| Synthetic Biologics Investigational Site | Bochnia | Poland |
| Synthetic Biologics Investigational Site | Bydgoszcz | Poland |
| Synthetic Biologics Investigational Site | Chodzież | Poland |
| Synthetic Biologics Investigational Site | Lodz | Poland |
| Synthetic Biologics Investigational Site | Oława | Poland |
| Synthetic Biologics Investigational Site | Pomorskie | Poland |
| Synthetic Biologics Investigational Site | Siedlce | Poland |
| Synthetic Biologics Investigational Site | Tarnów | Poland |
| SyntheticBiologics Investigational Site | Tychy | Poland |
| Synthetic Biologics Investigational Site | Warszawice | Poland |
| Synthetic Biologics Investigational Site | Arad | Romania |
| Synthetic Biologics Investigational Site | Brasov | Romania |
| Synthetic Biologics Investigational SIte | Bucharest | Romania |
| Synthetic Biologics Investigational Site | Cluj-Napoca | Romania |
| Synthetic Biologics Investigational Site | Oradea | Romania |
| Synthetic Biologics Investigational Site | Otopeni | Romania |
| Synthetic Biologics Investigational Site | Timișoara | Romania |
| Synthetic Biologics Investigational Site | Belgrade | Serbia |
| Synthetic Biologics Investigational Site | Čačak | Serbia |
| Synthetic Biologics Investigational Site | Gornji Matejevac | Serbia |
| Synthetic Biologics Investigational Site | Kragujevac | Serbia |
| Synthetic Biologics Investigational Site | Novi Sad | Serbia |
| Synthetic Biologics Investigational Site | Užice | Serbia |
| COMPLETED |
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| NOT COMPLETED |
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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.
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| ID | Title | Description |
|---|---|---|
| BG000 | SYN-004 | SYN-004 150 mg |
| BG001 | Placebo | Matching Placebo |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percentage of Patients With Clostridium Difficile Infection at 4- Weeks of Follow-up. | 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. | 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. | Posted | Count of Participants | Participants | Day 1 to the 4 week Follow-up Visit. |
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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.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | SYN-004 | SYN-004 150 mg | 11 | 206 | 33 | 206 | 59 | 206 |
| EG001 | Placebo | Matching Placebo | 5 | 206 | 21 | 206 | 59 | 206 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anemia of Chronic Disease | Blood and lymphatic system disorders | Systematic Assessment |
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| Iron Deficiency Anemia | Blood and lymphatic system disorders | Systematic Assessment |
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| Acute coronary syndrome | Cardiac disorders | Systematic Assessment |
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| Angina unstable | Cardiac disorders | Systematic Assessment |
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| Atrial fibrillation | Cardiac disorders | Systematic Assessment |
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| Cardiac arrest | Cardiac disorders | Systematic Assessment |
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| Cardiac failure | Cardiac disorders | Systematic Assessment |
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| Cardiac failure acute | Cardiac disorders | Systematic Assessment |
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| Cardiac failure congestive | Cardiac disorders | Systematic Assessment |
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| Cardio-respiratory arrest | Cardiac disorders | Systematic Assessment |
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| Cardiomyopathy | Cardiac disorders | Systematic Assessment |
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| Cardiopulmonary failure | Cardiac disorders | Systematic Assessment |
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| Myocardial infarction | Cardiac disorders | Systematic Assessment |
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| Myocardial ischaemia | Cardiac disorders | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | Systematic Assessment |
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| Upper gastrointestinal haemorrhage | Gastrointestinal disorders | Systematic Assessment |
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| Bronchopneumonia | Infections and infestations | Systematic Assessment |
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| Clostridium difficile colitis | Infections and infestations | Systematic Assessment |
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| Empyema | Infections and infestations | Systematic Assessment |
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| Lobar pneumonia | Infections and infestations | Systematic Assessment |
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| Pneumonia | Infections and infestations | Systematic Assessment |
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| Pseudomembranous colitis | Infections and infestations | Systematic Assessment |
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| Respiratory tract infection | Infections and infestations | Systematic Assessment |
| ||
| International normalised ratio abnormal | Investigations | Systematic Assessment |
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| Diabetes mellitus inadequate control | Metabolism and nutrition disorders | Systematic Assessment |
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| Hypokalaemia | Metabolism and nutrition disorders | Systematic Assessment |
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| Chronic lymphocytic leukaemia recurrent | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
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| Lung neoplasm | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
| ||
| Lung neoplasm malignant | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
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| Ovarian cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
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| Syncope | Nervous system disorders | Systematic Assessment |
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| Mental status changes | Psychiatric disorders | Systematic Assessment |
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| Haematuria | Renal and urinary disorders | Systematic Assessment |
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| Renal failure | Renal and urinary disorders | Systematic Assessment |
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| Tubulointerstitial nephritis | Renal and urinary disorders | Systematic Assessment |
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| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Asthma | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Bronchospasm | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Chronic respiratory failure | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Idiopathic pulmonary fibrosis | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Pleural effusion | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Pulmonary oedema | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Respiratory failure | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hypertension | Vascular disorders | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | Systematic Assessment |
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| Insomnia | Nervous system disorders | Systematic Assessment |
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| Headache | Nervous system disorders | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | Systematic Assessment |
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| Dyspnoea | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Atrial Fibrillation | Cardiac disorders | Systematic Assessment |
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| Oral Candidiasis | Infections and infestations | Systematic Assessment |
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| Cholelithiasis | Hepatobiliary disorders | Systematic Assessment |
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| Pleural Effusion | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Erythema | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Pneumonia | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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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.
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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Michael Kaleko, MD | Synthetic Biologics | (240) 238-3862 | mkaleko@syntheticbiologics.com |
| ID | Term |
|---|---|
| D003015 | Clostridium Infections |
| ID | Term |
|---|---|
| D016908 | Gram-Positive Bacterial Infections |
| D001424 | Bacterial Infections |
| D001423 | Bacterial Infections and Mycoses |
| D007239 | Infections |
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| ID | Term |
|---|---|
| C000613271 | SYN-004 |
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| Male |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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| North America |
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| Other |
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. |