CirrhosisPhase 1/2NCT03447730
Safety, Tolerability and Pharmacodynamics of SYNB1020
A Phase 1/2 study testing SYNB1020 in people with Cirrhosis, run by Synlogic at 5 sites in United States.
Trial summary
This Phase 1b/2a, randomized, double-blind, placebo-controlled study was designed to evaluate the safety, tolerability, and pharmacodynamics of SYNB1020 in hepatic insufficiency and cirrhosis patients with hyperammonemia, with dosing of the investigational medicinal product (IMP) administered in an inpatient unit and… Read more about this study
- Who is it for?
- Ages 18 to 74 years
- Conditions the study is for
- Cirrhosis
- What is being tested?
- SYNB1020
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 23 participants
- Where
- 5 sitesUnited States
- Study dates
- 19 Mar 2018to 19 Jul 2019
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 < 75 years
- Females must have been of non-childbearing potential
- Able and willing to complete informed consent process
- Available for and agreed to all study procedures
- Screening laboratory evaluations within defined acceptable limits or judged to be not clinically significant by the Investigator
- Diagnosis of chronic, stable, hepatic insufficiency with features of cirrhosis due to any etiology
- Evidence of elevated portal hypertension by either liver stiffness measurement, the presence of abdominal or esophageal varices, splenomegaly or ascites (Part 2 only)
- Elevated venous ammonia (Part 2 only)
Who cannot join
- Body mass index < 18.5 or ≥ 40 kg/m^2
- Administration or ingestion of an investigational drug within 8 weeks or 5 half-lives, whichever was longer, prior to screening or current enrollment in an investigational study
- Allergy to ranitidine or intolerance to any of the excipients (glycerol, CS Health Easy Fiber)
- Any condition, prescription medication or over-the-counter product that may possibly have affected absorption of medications or nutrients
- Dependence on drugs of abuse
- Apart from chronic liver disease, any acute or chronic medical, surgical, psychiatric, or social condition including history of cerebrovascular disease (stroke, transient ischemic attack) or dementia, or laboratory abnormality that may have increased the subject risk associated with study participation, compromised adherence to study procedures and requirements, confounded interpretation of the safety, kinetics, or PD results, and, in the judgment of the Investigator, made the subject inappropriate for enrollment
Show all 9Show fewer
- Current or past hepatic encephalopathy of Grade 2 or higher requiring hospitalization
- Child-Turcotte-Pugh score > 9
- History of liver transplant
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Medical University of South Carolina
Charleston, South Carolina, 29425
Southern California Research Center
Coronado, California, 92118
Inland Empire Liver Foundation
Rialto, California, 92377
McGuire VA Medical Center
Richmond, Virginia, 23249
Texas Liver Institute
San Antonio, Texas, 78006
About this study
Official title: A Randomized, Double-blind, Placebo-controlled Study to Assess the Safety, Tolerability, and Pharmacodynamics of SYNB1020 in Hepatic Insufficiency and Cirrhosis Patients
This Phase 1b/2a, randomized, double-blind, placebo-controlled study was designed to evaluate the safety, tolerability, and pharmacodynamics of SYNB1020 in hepatic insufficiency and cirrhosis patients with hyperammonemia, with dosing of the investigational medicinal product (IMP) administered in an inpatient unit and subsequent outpatient follow-up for SYNB1020 clearance in two study parts.
Read the detailed description
In Part 1, a sentinel open-label cohort of subjects with cirrhosis and Model for End-Stage Liver Disease (MELD) score <12 was admitted to an inpatient facility for a run-in diet, baseline assessments, IMP administration, safety monitoring, and collection of blood, urine, and stool samples for evaluation of safety, tolerability, and pharmacokinetic (PK) and pharmacodynamic (PD) evaluations. Subjects in Part 1 were enrolled sequentially to receive SYNB1020. Once the safety and tolerability were established in Part 1, enrollment was opened to subjects in Part 2.
Part 2 comprised a randomized, double-blind, placebo-controlled study in subjects with cirrhosis and hyperammonemia. Subjects were permitted to be pre-screened for eligibility based on medical history and a single fasting spot venous ammonia measurement. Eligible subjects with elevated fasting spot venous ammonia then underwent full screening within 7 days of pre-screening. Eligible subjects were admitted to an inpatient facility for a run-in diet and 24-hour ammonia profile, and those with an elevated 24-hour ammonia area under the curve (AUC) (>1.2 × the upper limit of normal [ULN]) proceeded with computer-generated randomization in a 1:1 ratio to receive either SYNB1020 or matching placebo. Randomization was followed by IMP administration, safety monitoring, and collection of blood, urine, and stool samples for PK and PD evaluations.
- Conditions
- Cirrhosis
- Being tested
- SYNB1020, Placebo
- Medical subject headings
- Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SYNB1020Drug
SYNB1020 was supplied at a concentration of approximately 1 × 10^11 CFU/mL in a buffered solution in 5 mL cryovials with a nominal 5 mL fill volume, administered with 100 mL of masking buffer solution.
PlaceboOther
Subjects received placebo orally in a chilled buffered solution (100 mL).
| Study group | Role | What they receive |
|---|---|---|
| Part 1: SYNB1020 | Experimental | Part 1 comprised a sentinel open-label cohort of subjects enrolled sequentially to receive SYNB1020, which was administered orally at a dose of 5 × 10^11 colony-forming units (CFU) 3 times daily (TID) given immediately after meals from Days 1 through 6. Receives: Drug: SYNB1020 |
| Part 2: SYNB1020 | Experimental | Subjects randomized to receive SYNB1020 in Part 2 received SYNB1020 administered orally at a dose of 5 × 10^11 CFU TID given immediately after meals from Days 1 through 6. Receives: Drug: SYNB1020 |
| Part 2: Placebo | Placebo comparator | Subjects randomized to receive control in Part 2 received matching placebo (100 mL masking solution) administered orally TID given immediately after meals from Days 1 through 6. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Treatment-Emergent Adverse Events
Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.03, as follows: Grade 1 (mild/asymptomatic; no intervention); Grade 2 (moderate; minimal intervention); Grade 3 (severe/medically significant; hospitalization indicated; disabling); Grade 4 (life-threatening; urgent intervention required). Adverse events (AEs) were reported based on clinical laboratory tests, vital sign and weight measurements, physical examinations, and any other medically indicated assessments, including subject interviews, from the time informed consent was signed through the end of the safety follow-up period. AEs were considered to be treatment emergent adverse events (TEAEs) if they occurred or worsened in severity after the first dose of study treatment. TEAEs were considered treatment-related if relationship to study drug was possibly related, probably related, definitely related, or a missing relationship.
Measured: Up to 70 days
Secondary outcomes (2)
Number of Participants With Clearance of SYNB1020 From Feces
SYNB1020 transit through the gastrointestinal tract was measured with qualitative and quantitative polymerase chain reaction (PCR) fecal assays from fecal samples collected at baseline, daily during the dosing period (Days 1 through 6), at the time of discharge from the inpatient unit (Day 7), and at follow-up visits beginning 7±1 days after the last dose and continuing biweekly until a subject had a negative SYNB1020 fecal test. SYNB1020 clearance reflects a test value of below the limit of quantitation (BLQ) occurring after the indicated number of days following the last dose of study treatment.
Measured: Up to 65 days
Daily Fasting Spot Venous Ammonia
Fasting spot venous ammonia was collected at baseline (Day -2) and at the time of discharge from the inpatient unit (Day 7).
Measured: Up to 9 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Feb 2018
- Study start19 Mar 2018
- Primary completion19 Jul 2019
- Study completion19 Jul 2019
Why it stopped: Interim futility analyses identified a lack of SYNB1020 efficacy.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for CirrhosisStudies 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
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Synlogic
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03447730
- Sponsor's protocol ID
- SYNB1020-CP-002
- Status last verified
- May 2021
- First submitted
- 16 Feb 2018
- Last updated
- 13 May 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-blind, Placebo-controlled Study to Assess the Safety, Tolerability, and Pharmacodynamics of SYNB1020 in Hepatic Insufficiency and Cirrhosis Patients
- ClinicalTrials.gov ID
- NCT03447730
- Acronym / sponsor ID
- SYNB1020-CP-002
- Conditions
- Cirrhosis
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Interim futility analyses identified a lack of SYNB1020 efficacy.
- Enrolment
- 23 participants (actual)
- Lead sponsor
- SynlogicIndustry (pharma, biotech, devices)
- Study start
- 19 Mar 2018 (actual)
- Primary completion
- 19 Jul 2019 (actual)
- Study completion
- 19 Jul 2019 (actual)
- First posted
- 27 Feb 2018 (actual)
- Results
- Posted 14 Oct 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This Phase 1b/2a, randomized, double-blind, placebo-controlled study was designed to evaluate the safety, tolerability, and pharmacodynamics of SYNB1020 in hepatic insufficiency and cirrhosis patients with hyperammonemia, with dosing of the investigational medicinal product (IMP) administered in an inpatient unit and subsequent outpatient follow-up for SYNB1020 clearance in two study parts.
Detailed description
In Part 1, a sentinel open-label cohort of subjects with cirrhosis and Model for End-Stage Liver Disease (MELD) score <12 was admitted to an inpatient facility for a run-in diet, baseline assessments, IMP administration, safety monitoring, and collection of blood, urine, and stool samples for evaluation of safety, tolerability, and pharmacokinetic (PK) and pharmacodynamic (PD) evaluations. Subjects in Part 1 were enrolled sequentially to receive SYNB1020. Once the safety and tolerability were established in Part 1, enrollment was opened to subjects in Part 2.
Part 2 comprised a randomized, double-blind, placebo-controlled study in subjects with cirrhosis and hyperammonemia. Subjects were permitted to be pre-screened for eligibility based on medical history and a single fasting spot venous ammonia measurement. Eligible subjects with elevated fasting spot venous ammonia then underwent full screening within 7 days of pre-screening. Eligible subjects were admitted to an inpatient facility for a run-in diet and 24-hour ammonia profile, and those with an elevated 24-hour ammonia area under the curve (AUC) (>1.2 × the upper limit of normal [ULN]) proceeded with computer-generated randomization in a 1:1 ratio to receive either SYNB1020 or matching placebo. Randomization was followed by IMP administration, safety monitoring, and collection of blood, urine, and stool samples for PK and PD evaluations.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Part 1: SYNB1020 | Experimental | Drug: SYNB1020Part 1 comprised a sentinel open-label cohort of subjects enrolled sequentially to receive SYNB1020, which was administered orally at a dose of 5 × 10^11 colony-forming units (CFU) 3 times daily (TID) given immediately after meals from Days 1 through 6. |
| Part 2: SYNB1020 | Experimental | Drug: SYNB1020Subjects randomized to receive SYNB1020 in Part 2 received SYNB1020 administered orally at a dose of 5 × 10^11 CFU TID given immediately after meals from Days 1 through 6. |
| Part 2: Placebo | Placebo comparator | Other: PlaceboSubjects randomized to receive control in Part 2 received matching placebo (100 mL masking solution) administered orally TID given immediately after meals from Days 1 through 6. |
Who may qualify
- Ages
- 18 to 74 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Age ≥ 18 to < 75 years
- Females must have been of non-childbearing potential
- Able and willing to complete informed consent process
- Available for and agreed to all study procedures
- Screening laboratory evaluations within defined acceptable limits or judged to be not clinically significant by the Investigator
Key exclusion criteria (9 listed)
- Body mass index < 18.5 or ≥ 40 kg/m^2
- Administration or ingestion of an investigational drug within 8 weeks or 5 half-lives, whichever was longer, prior to screening or current enrollment in an investigational study
- Allergy to ranitidine or intolerance to any of the excipients (glycerol, CS Health Easy Fiber)
- Any condition, prescription medication or over-the-counter product that may possibly have affected absorption of medications or nutrients
- Dependence on drugs of abuse
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 |
|---|---|---|
| SYNB1020SYNB1020 was supplied at a concentration of approximately 1 × 10^11 CFU/mL in a buffered solution in 5 mL cryovials with a nominal 5 mL fill volume, administered with 100 mL of masking buffer solution. | Drug | Part 1: SYNB1020, Part 2: SYNB1020 |
| PlaceboSubjects received placebo orally in a chilled buffered solution (100 mL). | Other | Part 2: Placebo |
Primary outcome
Number of Participants With Treatment-Emergent Adverse Events
Time frame: Up to 70 days
Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.03, as follows: Grade 1 (mild/asymptomatic; no intervention); Grade 2 (moderate; minimal intervention); Grade 3 (severe/medically significant; hospitalization indicated; disabling); Grade 4 (life-threatening; urgent intervention required). Adverse events (AEs) were reported based on clinical laboratory tests, vital sign and weight measurements, physical examinations, and any other medically indicated assessments, including subject interviews, from the time informed consent was signed through the end of the safety follow-up period. AEs were considered to be treatment emergent adverse events (TEAEs) if they occurred or worsened in severity after the first dose of study treatment. TEAEs were considered treatment-related if relationship to study drug was possibly related, probably related, definitely related, or a missing relationship.
2 secondary outcomes
Number of Participants With Clearance of SYNB1020 From Feces
Time frame: Up to 65 days
Daily Fasting Spot Venous Ammonia
Time frame: Up to 9 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 May 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing SYNB1020 in people with Cirrhosis, run by Synlogic at 5 sites 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 8 inclusion and 9 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: stopped early, as of the sponsor's last update on 13 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Oct 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Participants With Treatment-Emergent Adverse Events (time frame: Up to 70 days). 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 13 May 2021.