Ignite Creation Date:
2024-05-06 @ 3:36 PM
Last Modification Date:
2024-10-26 @ 1:53 PM
Study NCT ID:
NCT04692181
Status:
RECRUITING
Last Update Posted:
2023-10-13
First Post:
2020-12-28
Brief Title:
SYN-004 Safety and Tolerability in Allo-HCT Subjects
Sponsor:
Theriva Biologics Inc
Organization:
Theriva Biologics Inc
Study Overview
Official Title:
Phase 1b2a Evaluation of the Safety and Tolerability of SYN-004 in Adult Allogeneic Hematopoietic Cell Transplantation Allo-HCT Recipients
Status:
RECRUITING
Status Verified Date:
2023-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Study Objectives
1 To evaluate the safety and tolerability of oral SYN-004 in adult allogeneic HCT allo-HCT recipients who develop fever after conditioning therapy and are treated with IV β-lactam antibiotics meropenem MER piperacillin tazobactam PIPTAZO or cefepime FEP
2 To evaluate potential absorption of oral SYN-004 into the systemic circulation of allo-HCT recipients and potential SYN-004-mediated alterations to systemic levels and efficacy of IV MER PIPTAZO or FEP
3 To evaluate potential protective effects of SYN-004 on the intestinal microbiome of allo-HCT recipients treated with IV MER PIPTAZO or FEP
4 To obtain preliminary information on potential therapeutic benefits and patient outcomes of SYN-004 in allo-HCT recipients treated with IV MER PIPTAZO or FEP
1 To evaluate the safety and tolerability of oral SYN-004 in adult allogeneic HCT allo-HCT recipients who develop fever after conditioning therapy and are treated with IV β-lactam antibiotics meropenem MER piperacillin tazobactam PIPTAZO or cefepime FEP
2 To evaluate potential absorption of oral SYN-004 into the systemic circulation of allo-HCT recipients and potential SYN-004-mediated alterations to systemic levels and efficacy of IV MER PIPTAZO or FEP
3 To evaluate potential protective effects of SYN-004 on the intestinal microbiome of allo-HCT recipients treated with IV MER PIPTAZO or FEP
4 To obtain preliminary information on potential therapeutic benefits and patient outcomes of SYN-004 in allo-HCT recipients treated with IV MER PIPTAZO or FEP
Detailed Description:
Study Design
This is a single-center placebo controlled double blinded Phase 1b2a study to assess the safety tolerability and potential efficacy of orally administered SYN-004 in adult allo-HCT recipients Participants will be randomized 21 to SYN-004 or placebo in blocks of three stratified in three cohorts based on study assigned antibiotic MER piperacillintazobactam PIPTAZO FEP to be administered if the treating clinicians determine initiation of broad-spectrum antibiotics is indicated As such there will be six groups based on antibiotic cohort and randomized assignment of study drug
Group 1 Placebo IV MER n4 MER control Group 2 SYN-004 IV MER n8 MER treatment Group 3 Placebo IV PIPTAZO n4 PIPTAZO control Group 4 SYN-004 IV PIPTAZO n8 PIPTAZO treatment Group 5 Placebo IV FEP n4 FEP control Group 6 SYN-004 IV FEP n8 FEP treatment Study-assigned antibiotics will be dosed as follows adjusted for renal function as needed MER 1 gram every 8 hours PIPTAZO 45 grams every 6 hours FEP 1 gram every 8 hours SYN-004 treated participants Groups 2 4 and 6 will be compared to control participants who receive placebo Groups 1 3 and 5 respectively The study will be conducted in stages commencing with Groups 1 and 2 who will be assigned to receive MER if antibiotics are indicated MER is the first cohort because anti-infective efficacy of MER is not anticipated to be affected if SYN-004 is absorbed systemically Accrual for Groups 3 and 4 PIPTAZO cohort will begin only after review of the data from Groups 1 and 2 by the Data and Safety Monitoring Committee DSMC and agreement to proceed PIPTAZO is the next cohort because TAZO is a beta-lactamase inhibitor As such in the unlikely event of SYN-004 systemic absorption TAZO systemic concentrations should be sufficient to inhibit any absorbed SYN-004 Accrual for the FEP cohort will begin after approval by the DSMCs review of results from groups 3 and 4
Patients planned to receive an allo-HCT will be eligible for enrollment in the study and can be enrolled anytime from when it is known they will undergo HCT until day 1 after HCT day of study drug start Written informed consent will be obtained by all patients To count towards the enrollment goal of 36 participants a study participant must receive at least 80 of scheduled study drug doses from initiation of study assigned antibiotics through the second antibiotic pharmacokinetic assessment 7-9 days of concomitant study drug and study assigned antibiotic Additional participants will be enrolled to replace participants who do not meet criteria to count towards the goal study enrollment until the goal enrollment is achieved
This Phase 1b2a study will use the SYN-004 dosing regimen 150 mg PO q6h used in previous Phase 1 and Phase 2 clinical trials in healthy volunteers and patents with LRTIs The first dose of study drug will be administered at day 1 after HCT and will be continued until Criteria for Discontinuation of Study Drug are met
The study will consist of two periods the Treatment Period and the Follow-up Period
1 The Treatment Period will be defined as the time from first dose of study drug until the last dose For participants who do not meet criteria for early discontinuation study drug will be continued for 72 hours after last dose of MER PIPTAZO or FEP
2 The Follow-up Period begins after cessation of study drug dosing and is split into three parts
Part A up to 30 days after study drug was discontinued
Part B from end of Part A to day 180 after HCT
Part C from end of Part B to day 365 after HCT Patients enrolled in the study will receive conditioning and HCT according to their treatment plan Fever and time of antibiotic start will be defined per local standard of care of patients Cessation of antibiotic therapy andor changes to antibiotic therapy will be at the discretion of the treating physician
All participants will be evaluated as outlined in the Schedule of Assessments At predetermined points during the study as outlined in the SOA blood samples urine samples fecal swabs and fecal samples will be collected for the indicated analyses
This is a single-center placebo controlled double blinded Phase 1b2a study to assess the safety tolerability and potential efficacy of orally administered SYN-004 in adult allo-HCT recipients Participants will be randomized 21 to SYN-004 or placebo in blocks of three stratified in three cohorts based on study assigned antibiotic MER piperacillintazobactam PIPTAZO FEP to be administered if the treating clinicians determine initiation of broad-spectrum antibiotics is indicated As such there will be six groups based on antibiotic cohort and randomized assignment of study drug
Group 1 Placebo IV MER n4 MER control Group 2 SYN-004 IV MER n8 MER treatment Group 3 Placebo IV PIPTAZO n4 PIPTAZO control Group 4 SYN-004 IV PIPTAZO n8 PIPTAZO treatment Group 5 Placebo IV FEP n4 FEP control Group 6 SYN-004 IV FEP n8 FEP treatment Study-assigned antibiotics will be dosed as follows adjusted for renal function as needed MER 1 gram every 8 hours PIPTAZO 45 grams every 6 hours FEP 1 gram every 8 hours SYN-004 treated participants Groups 2 4 and 6 will be compared to control participants who receive placebo Groups 1 3 and 5 respectively The study will be conducted in stages commencing with Groups 1 and 2 who will be assigned to receive MER if antibiotics are indicated MER is the first cohort because anti-infective efficacy of MER is not anticipated to be affected if SYN-004 is absorbed systemically Accrual for Groups 3 and 4 PIPTAZO cohort will begin only after review of the data from Groups 1 and 2 by the Data and Safety Monitoring Committee DSMC and agreement to proceed PIPTAZO is the next cohort because TAZO is a beta-lactamase inhibitor As such in the unlikely event of SYN-004 systemic absorption TAZO systemic concentrations should be sufficient to inhibit any absorbed SYN-004 Accrual for the FEP cohort will begin after approval by the DSMCs review of results from groups 3 and 4
Patients planned to receive an allo-HCT will be eligible for enrollment in the study and can be enrolled anytime from when it is known they will undergo HCT until day 1 after HCT day of study drug start Written informed consent will be obtained by all patients To count towards the enrollment goal of 36 participants a study participant must receive at least 80 of scheduled study drug doses from initiation of study assigned antibiotics through the second antibiotic pharmacokinetic assessment 7-9 days of concomitant study drug and study assigned antibiotic Additional participants will be enrolled to replace participants who do not meet criteria to count towards the goal study enrollment until the goal enrollment is achieved
This Phase 1b2a study will use the SYN-004 dosing regimen 150 mg PO q6h used in previous Phase 1 and Phase 2 clinical trials in healthy volunteers and patents with LRTIs The first dose of study drug will be administered at day 1 after HCT and will be continued until Criteria for Discontinuation of Study Drug are met
The study will consist of two periods the Treatment Period and the Follow-up Period
1 The Treatment Period will be defined as the time from first dose of study drug until the last dose For participants who do not meet criteria for early discontinuation study drug will be continued for 72 hours after last dose of MER PIPTAZO or FEP
2 The Follow-up Period begins after cessation of study drug dosing and is split into three parts
Part A up to 30 days after study drug was discontinued
Part B from end of Part A to day 180 after HCT
Part C from end of Part B to day 365 after HCT Patients enrolled in the study will receive conditioning and HCT according to their treatment plan Fever and time of antibiotic start will be defined per local standard of care of patients Cessation of antibiotic therapy andor changes to antibiotic therapy will be at the discretion of the treating physician
All participants will be evaluated as outlined in the Schedule of Assessments At predetermined points during the study as outlined in the SOA blood samples urine samples fecal swabs and fecal samples will be collected for the indicated analyses
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None