A Phase 1/2 interventional study of SYNB1020 and Placebo in Cirrhosis, sponsored by Synlogic. Terminated at 5 sites in United States. Open to participants aged 18 Years to 74 Years. Per ClinicalTrials.gov, last updated 2021-05-13.
Sponsored by Synlogic · Phase 1/2, Interventional, and Treatment
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.
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.
1,270 studies on the registry are indexed under Fibrosis; 276 are open to participants now.
This study's enrollment of 23 is below the median of 63 across 840 interventional studies indexed under Fibrosis.
Browse Fibrosis studies →Synlogic is the lead sponsor of 10 studies on the registry; none are open to participants now.
Of its 10 completed or terminated interventional studies of FDA-regulated products, 3 (30%) have results posted.
Counted across the registry records on this site, refreshed daily.
Key Inclusion Criteria:
Key Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
A “mini-stroke”: temporary stroke-like symptoms caused by reduced blood flow to part of the brain, spinal cord or eye, without signs of a new stroke on a scan.
Stroke symptoms need emergency care at once, even if they go away.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
BMI (body mass index)
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Excipients
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
TIA (transient ischaemic attack)
A “mini-stroke”: temporary stroke-like symptoms caused by reduced blood flow to part of the brain, spinal cord or eye, without signs of a new stroke on a scan.
Stroke symptoms need emergency care at once, even if they go away.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Drug: SYNB1020
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.
Drug: SYNB1020
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.
Other: Placebo
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.
Subjects received placebo orally in a chilled buffered solution (100 mL).
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.
Time frame: Up to 70 days
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.
Time frame: 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).
Time frame: Up to 9 days
| Milestone | Part 1: SYNB1020 | Part 2: SYNB1020 | Part 2: Placebo |
|---|---|---|---|
| Started | 6 | 9 | 8 |
| Completed | 6 | 7 | 8 |
| Not completed | 0 | 2 | 0 |
| Withdrew: Adverse event | 0 | 2 | 0 |
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.
| participants | Part 1: SYNB1020 | Part 2: SYNB1020 | Part 2: Placebo |
|---|---|---|---|
| Any TEAE | 4 | 8 | 4 |
| Maximum TEAE severity Grade 1 | 3 | 3 | 1 |
| Maximum TEAE severity Grade 2 | 1 | 5 | 2 |
| Maximum TEAE severity Grade 3 | 0 | 0 | 1 |
| Treatment-related TEAE | 2 | 4 | 0 |
| TEAE leading to discontinuation | 0 | 2 | 0 |
| Treatment-related TEAE leading to discontinuation | 0 | 0 | 0 |
| Serious TEAE | 0 | 0 | 1 |
| Treatment-related Serious TEAE | 0 | 0 | 0 |
| TEAE leading to death | 0 | 0 | 0 |
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.
| Participants | Part 1: SYNB1020 | Part 2: SYNB1020 | Part 2: Placebo |
|---|---|---|---|
| Cleared by 25 days after last dose | 6 | 9 | 0 |
| SYNB1020 presence not detected | 0 | 0 | 8 |
Fasting spot venous ammonia was collected at baseline (Day -2) and at the time of discharge from the inpatient unit (Day 7).
| μmol/L | Part 1: SYNB1020 | Part 2: SYNB1020 | Part 2: Placebo |
|---|---|---|---|
| Baseline | 64.7 ± 25.00 | 82.0 ± 36.41 | 55.6 ± 18.18 |
| End of Study/Day 7 | 62.3 ± 27.57 | 97.7 ± 58.79 | 67.9 ± 42.69 |
Collected over All AEs occurring from the time a subject signs informed consent through the safety follow-up period (i.e.,up to 70 days) were documented, regardless of the causal relationship to study drug. AEs that occurred or worsened in severity after the first dose of study treatment were considered treatment emergent (i.e., TEAEs).. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Part 1: SYNB1020 | 0/6 (0%) | 0/6 (0%) | 4/6 (66.7%) |
| Part 2: SYNB1020 | 0/9 (0%) | 0/9 (0%) | 8/9 (88.9%) |
| Part 2: Placebo | 0/8 (0%) | 1/8 (12.5%) | 3/8 (37.5%) |
| Event | Part 1: SYNB1020 | Part 2: SYNB1020 | Part 2: Placebo |
|---|---|---|---|
| Oesophageal varices haemorrhageGastrointestinal disorders | 0/6 | 0/9 | 1/8 |
| Event | Part 1: SYNB1020 | Part 2: SYNB1020 | Part 2: Placebo |
|---|---|---|---|
| VomitingGastrointestinal disorders | 3/6 | 3/9 | 0/8 |
| ConstipationGastrointestinal disorders | 2/6 | 4/9 | 0/8 |
| NauseaGastrointestinal disorders | 2/6 | 4/9 | 0/8 |
| DiarrhoeaGastrointestinal disorders | 1/6 | 2/9 | 1/8 |
| DizzinessNervous system disorders | 1/6 | 2/9 | 0/8 |
| HeadacheNervous system disorders | 1/6 | 2/9 | 0/8 |
| Hepatic encephalopathyNervous system disorders | 0/6 | 2/9 | 0/8 |
| DehydrationMetabolism and nutrition disorders | 0/6 | 2/9 | 0/8 |
| Upper respiratory tract infectionInfections and infestations | 1/6 | 0/9 | 0/8 |
| InsomniaPsychiatric disorders | 1/6 | 0/9 | 0/8 |
All subjects who received at least 1 dose of study treatment
| Age, Continuous(years) | Part 1: SYNB1020 | Part 2: SYNB1020 | Part 2: Placebo | Total |
|---|---|---|---|---|
| Median | 54.5 (35.0 to 68.0) | 57.0 (38.0 to 74.0) | 59.5 (45.0 to 74.0) | 58.0 (35.0 to 74.0) |
| Sex: Female, Male(Participants) | Part 1: SYNB1020 | Part 2: SYNB1020 | Part 2: Placebo | Total |
|---|---|---|---|---|
| Female | 2 | 4 | 1 | 7 |
| Male | 4 | 5 | 7 | 16 |
| Ethnicity (NIH/OMB)(Participants) | Part 1: SYNB1020 | Part 2: SYNB1020 | Part 2: Placebo | Total |
|---|---|---|---|---|
| Hispanic or Latino | 3 | 4 | 6 | 13 |
| Not Hispanic or Latino | 3 | 5 | 2 | 10 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | Part 1: SYNB1020 | Part 2: SYNB1020 | Part 2: Placebo | Total |
|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 |
| Black or African American | 0 | 0 | 0 | 0 |
| White | 6 | 9 | 8 | 23 |
| More than one race | 0 | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 |
| Region of Enrollment(participants) | Part 1: SYNB1020 | Part 2: SYNB1020 | Part 2: Placebo | Total |
|---|---|---|---|---|
| United States | 6 | 9 | 8 | 23 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: No
Ran from Mar 2018 to primary completion in Jul 2019, 16 months.
Results were first posted in Oct 2020, 1 year 2 months after primary completion.
How these figures are worked out, and which studies are left out of them.
This study is terminated, as verified in May 2021. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Synlogic