Enteric HyperoxaluriaEarly Phase 1NCT05377112
Safety, Tolerability, and Pharmacodynamics of SYNB8802v1 in Subjects With History of Gastric Bypass Surgery or Short-bowel Syndrome
A Early Phase 1 study testing SYNB8802v1 in people with Enteric Hyperoxaluria, run by Synlogic at 1 site in United States.
Trial summary
Study SYNB8802-CP-002 is designed to assess safety, tolerability, and oxalate lowering, in subjects with a history of gastric bypass surgery or short-bowel syndrome. In addition, this study will explore other PD effects relative to baseline as well as predictors of efficacy and tolerability. Read more about this study
- Who is it for?
- Ages 18 to 74 years
- Conditions the study is for
- Enteric Hyperoxaluria
- What is being tested?
- SYNB8802v1
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- 29 Mar 2022to 7 Dec 2022
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 74 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 to ≤ 74 years.
- Able and willing to voluntarily complete the informed consent process.
- Available for, and agree to, all study procedures, including fixed diet, feces, urine, and blood
- collection, follow-up visits, and compliance with all study procedures.
- History of gastric bypass surgery (at least 12 months prior to Day 1) or short-bowel
- syndrome.
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- If taking probiotic supplements (enriched foods excluded), has been on a stable, well tolerated dose for at least 2 weeks prior to Day 1.
- Women of childbearing potential must have a negative pregnancy test (human chorionic
- gonadotropin) at screening and at baseline prior to the start of IMP.
- Screening laboratory evaluations (e.g., chemistry panel, complete blood count with
- differential, prothrombin time, urinalysis) and electrocardiogram (ECG) must be within
- normal limits or judged not to be clinically significant by the investigator. Subjects with
- known diabetes should be well controlled and have an A1c of ≤ 8% within 3 months prior to Day 1.
- Agree to abstain from tobacco/nicotine use for the duration of the inpatient stay.
- Subjects who are HIV positive, on therapy with normal CD4 counts and undetectable viral loads, can be included.
Who cannot join
- Acute or chronic medical (including COVID-19 infection), surgical, psychiatric, or social condition or laboratory abnormality (except those that can be explained by malabsorption) that may increase subject risk associated with study participation, compromise adherence to study procedures and requirements, or may confound interpretation of results and, in the judgment of the investigator, would make the subject inappropriate for enrollment.
- Estimated glomerular filtration rate < 45 mL/min/1.73 m2.
- History of kidney stones.
- Subjects taking supplements that contain vitamin C should continue to use their supplements at a constant dose throughout the study, having maintained a constant dose for 2 weeks prior to screening.
- Known primary hyperoxaluria.
- Pregnant or lactating.
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- Administration or ingestion of any type of systemic (e.g., oral or intravenous) antibiotic within 5 half-lives of the agent prior to Day 1. Exception: topical antibiotics are allowed.
- Any co-morbid condition that may necessitate antibiotic use or disrupt the controlled diet during the study period.
- Intolerance of, or allergic reaction to, EcN, all PPIs, or any of the ingredients in SYNB8802v1 or placebo formulations.
- Dependence on alcohol or drugs of abuse.
- Current, immunodeficiency disorder including autoimmune, except for controlled HIV (see inclusion Criterion #9). disorders.
- Administration or ingestion of an investigational drug within 30 days or 5 half-lives, whichever is longer, prior to screening visit, or current enrollment in an investigational study.
- History of inflammatory bowel disease.
Trial locations and contacts
1 site in 1 country.
United States1 site
PPD, part of Thermo Fisher Scientific
Austin, Texas, 78744
About this study
Official title: A Double-Blind, Randomized, Placebo-controlled Study to Assess the Safety, Tolerability, and Pharmacodynamics of SYNB8802v1 in Subjects With History of Gastric Bypass Surgery or Short-bowel Syndrome
Study SYNB8802-CP-002 is designed to assess safety, tolerability, and oxalate lowering, in subjects with a history of gastric bypass surgery or short-bowel syndrome. In addition, this study will explore other PD effects relative to baseline as well as predictors of efficacy and tolerability.
Read the detailed description
This is a double-blind (sponsor-open), randomized (3:2), placebo-controlled, inpatient study evaluating the safety and tolerability of SYNB8802v1 in subjects with a history of gastric bypass surgery or short-bowel syndrome. An interim analysis of results by an unblinded statistician will be performed after 10 subjects.
The study includes the following periods:
- Screening period (27 days)
- Diet run in (3 days)
- Dosing Period (12 days)
- Safety follow-up (28 days)
The maximum duration of the inpatient stay will be 17 days (Day -4 to Day 13). Subjects will report to the clinical research unit (CRU) on Day -4 and will complete a 3-day diet run-in period (Days -3 to -1) during which they will consume an AOLC diet (refer to Diet Manual for details). Dietary oxalate and calcium will be distributed across 3 meals per day, and subjects will maintain this diet until the end of the dosing period. A proton pump inhibitor (PPI, esomeprazole) will be administered once daily (QD), 60-90 minutes before breakfast, from the start of the diet run-in period (Day -3) until the end of the dosing period (Day 12).
On Day 1, subjects will be randomly assigned to treatment with SYNB8802v1 or placebo (collectively referred to as investigational medicinal product [IMP]). The dosing period consists of 12 days following a dose escalation plan from 1 × 1011 live cells QD to 3 × 1011 live cells TID; the dosing period for each dose level includes a 2-day dose ramp and a 3-day steady-state period. During the dose ramp, placebo will be administered such that all subjects receive IMP dosing TID. On the morning of the first day of the run-in period (Day -3), a forced void urine sample will be collected to completely empty the bladder before the first placebo dose administration. A 24-hour urine collection will then be started and will continue throughout the in-patient period. In addition, daily 24-hour fecal samples will be collected. Subjects will be released from the CRU upon the completion of safety assessments on Day 13 (the day after the last dose of IMP). Safety follow-up visits (calls) will occur every 7 (±2) days until 28 (±2) days after the last dose of IMP.
- Conditions
- Enteric Hyperoxaluria
- Being tested
- SYNB8802v1, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SYNB8802v1Drug
SYNB8802v1 is an orally administered, non-systemically absorbed live biotherapeutic developed for the treatment of EH. The strain converts oxalate to formate and CO2, two naturally occurring GI metabolites.
SYNB8802 was developed by engineering a pathway for oxalate degradation in a probiotic strain of Escherichia coli Nissle 1917 (EcN). It is intended to act within the GI tract to reduce the oxalate levels in patients with EH by converting oxalate to formate and CO2, two naturally occurring GI metabolites.
PlaceboOther
placebo powder will be aliquoted into high density polyethylene (HDPE) bottles and diluted in the same formulation buffer as SYNB8802v1 lyophilized powder. The placebo consists of corn starch and dyes to color match the placebo to the SYNB8802v1 powder for oral suspension
| Study group | Role | What they receive |
|---|---|---|
| SYNB8802v1 | Experimental | Dose ramp to 1 × 1011 QD and then dose ramp to 3 × 1011 TID SYNB8802v1 live cells Receives: Drug: SYNB8802v1 |
| Placebo | Placebo comparator | Placebo will be administered during the dose ramp such that all subjects receive IMP dosing TID Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability of SYNB8802v1, as assessed by measuring of vital signs
Vital Signs Resting vital signs will be collected as specified in the protocol. Subjects are required to remain in the sitting position for at least 5 minutes prior to obtaining vital signs. A symptom-directed physical examination will be performed by trained medical personnel as specified in the protocol.
Measured: 17 days
Safety and tolerability of SYNB8802v1 by assessing clinical laboratory tests
The clinical laboratory tests listed in the protocol will be performed at the time points specified in the protocol's schedule of assessments.
Measured: 17 days
Safety and tolerability of SYNB8802v1, as assessed by AEs, clinical laboratory tests, and vital sign measurements
Adverse events will be assessed continuously by direct observation and subject event recording and interviews. The severity of AEs will be evaluated using the NCI CTCAE, version 5.0 criteria.
Measured: 43 days
Secondary outcomes (1)
Change from baseline in 24-hour excreted UOx among SYNB8802v1-treated subjects versus those treated with placebo.
Urinary oxalate will be determined from 24-hour urine sample collections to be completed at the points specified in the Schedule of Assessments.
Measured: 17 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 May 2022
- Study start29 Mar 2022
- Primary completion7 Dec 2022
- Study completion7 Dec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Enteric HyperoxaluriaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Placebo control (3:2 \[active: placebo\]) is included for a better understanding of the safety and tolerability of SYNB8802v1.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Synlogic
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05377112
- Sponsor's protocol ID
- SYNB8802-CP-002
- Status last verified
- Mar 2023
- First submitted
- 15 Apr 2022
- Last updated
- 17 Mar 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-Blind, Randomized, Placebo-controlled Study to Assess the Safety, Tolerability, and Pharmacodynamics of SYNB8802v1 in Subjects With History of Gastric Bypass Surgery or Short-bowel Syndrome
- ClinicalTrials.gov ID
- NCT05377112
- Acronym / sponsor ID
- SYNB8802-CP-002
- Conditions
- Enteric Hyperoxaluria
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- SynlogicIndustry (pharma, biotech, devices)
- Study start
- 29 Mar 2022 (actual)
- Primary completion
- 7 Dec 2022 (actual)
- Study completion
- 7 Dec 2022 (actual)
- First posted
- 17 May 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Study SYNB8802-CP-002 is designed to assess safety, tolerability, and oxalate lowering, in subjects with a history of gastric bypass surgery or short-bowel syndrome. In addition, this study will explore other PD effects relative to baseline as well as predictors of efficacy and tolerability.
Detailed description
This is a double-blind (sponsor-open), randomized (3:2), placebo-controlled, inpatient study evaluating the safety and tolerability of SYNB8802v1 in subjects with a history of gastric bypass surgery or short-bowel syndrome. An interim analysis of results by an unblinded statistician will be performed after 10 subjects.
The study includes the following periods:
- Screening period (27 days)
- Diet run in (3 days)
- Dosing Period (12 days)
- Safety follow-up (28 days)
The maximum duration of the inpatient stay will be 17 days (Day -4 to Day 13). Subjects will report to the clinical research unit (CRU) on Day -4 and will complete a 3-day diet run-in period (Days -3 to -1) during which they will consume an AOLC diet (refer to Diet Manual for details). Dietary oxalate and calcium will be distributed across 3 meals per day, and subjects will maintain this diet until the end of the dosing period. A proton pump inhibitor (PPI, esomeprazole) will be administered once daily (QD), 60-90 minutes before breakfast, from the start of the diet run-in period (Day -3) until the end of the dosing period (Day 12).
On Day 1, subjects will be randomly assigned to treatment with SYNB8802v1 or placebo (collectively referred to as investigational medicinal product [IMP]). The dosing period consists of 12 days following a dose escalation plan from 1 × 1011 live cells QD to 3 × 1011 live cells TID; the dosing period for each dose level includes a 2-day dose ramp and a 3-day steady-state period. During the dose ramp, placebo will be administered such that all subjects receive IMP dosing TID. On the morning of the first day of the run-in period (Day -3), a forced void urine sample will be collected to completely empty the bladder before the first placebo dose administration. A 24-hour urine collection will then be started and will continue throughout the in-patient period. In addition, daily 24-hour fecal samples will be collected. Subjects will be released from the CRU upon the completion of safety assessments on Day 13 (the day after the last dose of IMP). Safety follow-up visits (calls) will occur every 7 (±2) days until 28 (±2) days after the last dose of IMP.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- Placebo control (3:2 [active: placebo]) is included for a better understanding of the safety and tolerability of SYNB8802v1.
| Arm | Type | Receives |
|---|---|---|
| SYNB8802v1 | Experimental | Drug: SYNB8802v1Dose ramp to 1 × 1011 QD and then dose ramp to 3 × 1011 TID SYNB8802v1 live cells |
| Placebo | Placebo comparator | Other: PlaceboPlacebo will be administered during the dose ramp such that all subjects receive IMP dosing TID |
Who may qualify
- Ages
- 18 to 74 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Age ≥ 18 to ≤ 74 years.
- Able and willing to voluntarily complete the informed consent process.
- Available for, and agree to, all study procedures, including fixed diet, feces, urine, and blood
- collection, follow-up visits, and compliance with all study procedures.
- History of gastric bypass surgery (at least 12 months prior to Day 1) or short-bowel
Key exclusion criteria (13 listed)
- Acute or chronic medical (including COVID-19 infection), surgical, psychiatric, or social condition or laboratory abnormality (except those that can be explained by malabsorption) that may increase subject risk associated with study participation, compromise adherence to study procedures and requirements, or may confound interpretation of results and, in the judgment of the investigator, would make the subject inappropriate for enrollment.
- Estimated glomerular filtration rate < 45 mL/min/1.73 m2.
- History of kidney stones.
- Subjects taking supplements that contain vitamin C should continue to use their supplements at a constant dose throughout the study, having maintained a constant dose for 2 weeks prior to screening.
- Known primary hyperoxaluria.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SYNB8802v1SYNB8802v1 is an orally administered, non-systemically absorbed live biotherapeutic developed for the treatment of EH. The strain converts oxalate to formate and CO2, two naturally occurring GI metabolites. SYNB8802 was developed by engineering a pathway for oxalate degradation in a probiotic strain of Escherichia coli Nissle 1917 (EcN). It is intended to act within the GI tract to reduce the oxalate levels in patients with EH by converting oxalate to formate and CO2, two naturally occurring GI metabolites. | Drug | SYNB8802v1 |
| Placeboplacebo powder will be aliquoted into high density polyethylene (HDPE) bottles and diluted in the same formulation buffer as SYNB8802v1 lyophilized powder. The placebo consists of corn starch and dyes to color match the placebo to the SYNB8802v1 powder for oral suspension | Other | Placebo |
Primary outcome
Safety and tolerability of SYNB8802v1, as assessed by measuring of vital signs
Time frame: 17 days
Vital Signs Resting vital signs will be collected as specified in the protocol. Subjects are required to remain in the sitting position for at least 5 minutes prior to obtaining vital signs. A symptom-directed physical examination will be performed by trained medical personnel as specified in the protocol.
Safety and tolerability of SYNB8802v1 by assessing clinical laboratory tests
Time frame: 17 days
The clinical laboratory tests listed in the protocol will be performed at the time points specified in the protocol's schedule of assessments.
Safety and tolerability of SYNB8802v1, as assessed by AEs, clinical laboratory tests, and vital sign measurements
Time frame: 43 days
Adverse events will be assessed continuously by direct observation and subject event recording and interviews. The severity of AEs will be evaluated using the NCI CTCAE, version 5.0 criteria.
1 secondary outcome
Change from baseline in 24-hour excreted UOx among SYNB8802v1-treated subjects versus those treated with placebo.
Time frame: 17 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Mar 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing SYNB8802v1 in people with Enteric Hyperoxaluria, run by Synlogic at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and tolerability of SYNB8802v1, as assessed by measuring of vital signs (time frame: 17 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Mar 2023.