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NCT03447730

Safety, Tolerability and Pharmacodynamics of SYNB1020

Terminated Phase 1, PHASE2 Results posted Last updated 13 May 2021
What this trial tests

Phase 1, PHASE2 trial testing SYNB1020 in Cirrhosis in 23 participants. Terminated before completion.

Timeline
19 March 2018
Primary endpoint
19 July 2019
19 July 2019

Quick facts

Lead sponsorSynlogic
PhasePhase 1, PHASE2
StatusTerminated
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment23
Start date19 March 2018
Primary completion19 July 2019
Estimated completion19 July 2019
Sites5 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Synlogic — full company profile →

Who can join

Adults 18 to 74, any sex, with Cirrhosis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With Treatment-Emergent Adverse Events Primary · 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 tim

Any TEAE
GroupValue95% CI
Part 1: SYNB10204
Part 2: SYNB10208
Part 2: Placebo4
Maximum TEAE severity Grade 1
GroupValue95% CI
Part 1: SYNB10203
Part 2: SYNB10203
Part 2: Placebo1
Maximum TEAE severity Grade 2
GroupValue95% CI
Part 1: SYNB10201
Part 2: SYNB10205
Part 2: Placebo2
Maximum TEAE severity Grade 3
GroupValue95% CI
Part 1: SYNB10200
Part 2: SYNB10200
Part 2: Placebo1
Treatment-related TEAE
GroupValue95% CI
Part 1: SYNB10202
Part 2: SYNB10204
Part 2: Placebo0
TEAE leading to discontinuation
GroupValue95% CI
Part 1: SYNB10200
Part 2: SYNB10202
Part 2: Placebo0
Treatment-related TEAE leading to discontinuation
GroupValue95% CI
Part 1: SYNB10200
Part 2: SYNB10200
Part 2: Placebo0
Serious TEAE
GroupValue95% CI
Part 1: SYNB10200
Part 2: SYNB10200
Part 2: Placebo1
Number of Participants With Clearance of SYNB1020 From Feces Secondary · Up to 65 days

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 treatm

GroupValue95% CI
Part 1: SYNB10206
Part 2: SYNB10209
Part 2: Placebo0
Part 1: SYNB10200
Part 2: SYNB10200
Part 2: Placebo8
Daily Fasting Spot Venous Ammonia Secondary · Up to 9 days

Fasting spot venous ammonia was collected at baseline (Day -2) and at the time of discharge from the inpatient unit (Day 7).

Baseline
GroupValue95% CI
Part 1: SYNB102064.7± 25.00
Part 2: SYNB102082.0± 36.41
Part 2: Placebo55.6± 18.18
End of Study/Day 7
GroupValue95% CI
Part 1: SYNB102062.3± 27.57
Part 2: SYNB102097.7± 58.79
Part 2: Placebo67.9± 42.69

Adverse events — posted to ClinicalTrials.gov

Time frame: 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).. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Part 1: SYNB1020
Serious: 0/6 (0%)
Deaths: 0/6
Part 2: SYNB1020
Serious: 0/9 (0%)
Deaths: 0/9
Part 2: Placebo
Serious: 1/8 (13%)
Deaths: 0/8

Serious adverse events (1 terms)

ReactionSystemPart 1: SYNB1020Part 2: SYNB1020Part 2: Placebo
Oesophageal varices haemorrhageGastrointestinal disorders
Other adverse events (19 terms — click to expand)

ReactionSystemPart 1: SYNB1020Part 2: SYNB1020Part 2: Placebo
ConstipationGastrointestinal disorders
NauseaGastrointestinal disorders
VomitingGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
DizzinessNervous system disorders
HeadacheNervous system disorders
Hepatic encephalopathyNervous system disorders
DehydrationMetabolism and nutrition disorders
Abdominal painGastrointestinal disorders
Abdominal pain upperGastrointestinal disorders
EructationGastrointestinal disorders
TremorNervous system disorders
NasopharyngitisInfections and infestations
Upper respiratory tract infectionInfections and infestations
Urinary tract infectionInfections and infestations
Limb injuryInjury, poisoning and procedural complications
Post-traumatic painInjury, poisoning and procedural complications
InsomniaPsychiatric disorders
RashSkin and subcutaneous tissue disorders

Most-reported serious reactions: Oesophageal varices haemorrhage.

Data from ClinicalTrials.gov NCT03447730 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. The gut-liver axis and gut microbiota in health and liver disease.
    Hsu CL, Schnabl B. · · 2023 · cited 425× · PMID 37316582 · DOI 10.1038/s41579-023-00904-3
  2. Microbiome and Human Health: Current Understanding, Engineering, and Enabling Technologies.
    Aggarwal N, Kitano S, Puah GRY, Kittelmann S, et al · · 2023 · cited 242× · PMID 36317983 · DOI 10.1021/acs.chemrev.2c00431
  3. Emerging strategies for engineering Escherichia coli Nissle 1917-based therapeutics.
    Lynch JP, Goers L, Lesser CF. · · 2022 · cited 146× · PMID 35232591 · DOI 10.1016/j.tips.2022.02.002
  4. Engineering probiotics as living diagnostics and therapeutics for improving human health.
    Zhou Z, Chen X, Sheng H, Shen X, et al · · 2020 · cited 74× · PMID 32131831 · DOI 10.1186/s12934-020-01318-z
  5. Engineered probiotics.
    Ma J, Lyu Y, Liu X, Jia X, et al · · 2022 · cited 72× · PMID 35477497 · DOI 10.1186/s12934-022-01799-0
  6. Molecular and Cellular Mediators of the Gut-Liver Axis in the Progression of Liver Diseases.
    Bruneau A, Hundertmark J, Guillot A, Tacke F. · · 2021 · cited 59× · PMID 34650994 · DOI 10.3389/fmed.2021.725390
  7. Microbial therapeutics: New opportunities for drug delivery.
    Jimenez M, Langer R, Traverso G. · · 2019 · cited 43× · PMID 31028093 · DOI 10.1084/jem.20190609
  8. Microbiome engineering: engineered live biotherapeutic products for treating human disease.
    Rutter JW, Dekker L, Owen KA, Barnes CP. · · 2022 · cited 34× · PMID 36185459 · DOI 10.3389/fbioe.2022.1000873

Verify or expand the search:

Other trials of SYNB1020

Trials testing the same drug.

Other recruiting trials for Cirrhosis

Currently open trials in the same condition.

Other Synlogic trials

Trials by the same sponsor.

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Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03447730.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing