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HomocystinuriaPhase 1HCUNCT05462132

Safety, Tolerability and Pharmacodynamics of SYNB1353 in Healthy Adult Volunteers

A Phase 1 study testing SYNB1353 in people with Homocystinuria, run by Synlogic at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is a Phase 1, double-blind (Sponsor-open), placebo-controlled, randomized, dose-escalation, inpatient study using a multiple-ascending dose (MAD) design to assess the safety, tolerability, and PD of SYNB1353 in HVs. Read more about this study

Who is it for?
Ages 18 to 64 yearsHealthy volunteers can take part
Conditions the study is for
Homocystinuria
What is being tested?
SYNB1353
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
31 participants
Where
1 siteUnited States
Study dates
7 Jul 2022to 27 Nov 2022
Phase
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 64 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • Age ≥ 18 to ≤ 64 years.
  • Able and willing to voluntarily complete the informed consent process.
  • Available for and agree to all study procedures, including feces, urine, and blood collection and adherence to diet control, inpatient monitoring, follow-up visits, and compliance with all study procedures.
  • Male subjects who are sexually abstinent or surgically sterilized (vasectomy), or those who are sexually active with a female partner(s) and agree to use an acceptable method of contraception (such as a condom with spermicide) combined with an acceptable method of contraception for their non-pregnant female partner(s) (as defined in Inclusion Criterion # 5) after informed consent, throughout the study, and for a minimum of 3 months after the last dose of IMP, and who do not intend to donate sperm in the period from Screening until 3 months following administration of the IMP.
  • Female subjects who meet 1 of the following:
  • Women of childbearing potential (WOCBP) must have a negative serum pregnancy test (human chorionic gonadotropin) at Screening and a negative urine pregnancy test at baseline prior to the start of IMP and must agree to use acceptable method(s) of contraception, combined with an acceptable method of contraception for their male partner(s) (as defined in Inclusion Criterion # 4) after informed consent, throughout the study and for a minimum of 3 months after the last dose of IMP. Acceptable methods of contraception include hormonal contraception, hormonal or non-hormonal intrauterine device, bilateral tubal occlusion, complete abstinence, and/or vasectomized partner with documented azoospermia 3 months after procedure.
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  • WOCBP must not be breastfeeding.
  • Premenopausal women with at least 1 of the following:
  • Documented hysterectomy ii. Documented bilateral salpingectomy iii. Documented bilateral oophorectomy iv. Documented tubal ligation/occlusion v. Sexual abstinence is preferred or usual lifestyle of the subject d. Postmenopausal women (12 months or more amenorrhea verified by follicle- stimulating hormone [FSH] assessment and over 45 years of age in the absence of other biological or physiological causes).

Who cannot join

  • Acute or chronic medical, surgical, psychiatric, or social condition or laboratory abnormality that may increase subject risk associated with study participation, compromise adherence to study procedures and requirements, or may confound interpretation of study safety or PD results and, in the judgment of the Investigator, would make the subject inappropriate for enrollment.
  • Body mass index < 18.5 or ≥ 35 kg/m2.
  • History of or current immunodeficiency disorder including human immunodeficiency virus (HIV) antibody positivity.
  • Hepatitis B surface antigen positivity (subjects with hepatitis B surface antibody positivity and hepatitis B core antibody positivity are not excluded, provided that the hepatitis B surface antigen is negative).
  • Hepatitis C antibody positivity, unless a hepatitis C virus ribonucleic acid test is performed, and the result is negative.
  • History of febrile illness, confirmed bacteremia, or other active infection deemed clinically significant by the Investigator within 30 days prior to the anticipated first dose of IMP.
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  • History of (within the past month) passage of 3 or more loose stools per day, where "loose stool" is defined as a Type 6 or Type 7 on the Bristol Stool Chart (see Appendix 1).
  • Inflammatory or irritable bowel disorder of any grade experienced within the previous 60 days.
  • Active or past history of GI bleeding within 60 days prior to the Screening Visit as confirmed by hospitalization-related event(s) or medical history of hematemesis or hematochezia.
  • Underlying cardiovascular disease or uncontrolled gastroesophageal reflux disease
  • Intolerance of or allergic reaction to EcN, esomeprazole and all other PPIs, or any of the ingredients in SYNB1353 or placebo formulations.
  • Allergy or intolerance to multiple antibiotics which would preclude use of antibiotics for eradication of SYNB1353 in case of colonization.
  • Currently taking or plans to take Methotrexate, Azuridine, Nitrous Oxide, Phenytoin, or Carbamazepine.
  • Currently taking or plans to take any type of systemic (e.g., oral or intravenous) antibiotic within 28 days prior to the first anticipated dose of IMP through final assessment, including planned surgery, hospitalizations, dental procedures, or interventional studies that are expected to require antibiotics. Exception: topical antibiotics are allowed.
  • Major surgery (an operation upon an organ within the cranium, chest, abdomen, or pelvic cavity) or inpatient hospital stay within the past 3 months prior to Screening.
  • Dependence on alcohol or drugs of abuse.
  • Administration or ingestion of an investigational drug within 30 days or 5 half-lives, whichever is longer, prior to the Screening Visit, or current enrollment in an investigational study.
  • Screening laboratory parameters (e.g., chemistry panel, hematology, coagulation) and ECG outside of the normal limits based on standard ranges or as judged to be clinically significant by the Investigator. A single repeat evaluation is acceptable.

Trial locations and contacts

1 site in 1 country.

United States1 site
  • High Point Clinical Trials Center

    High Point, North Carolina, 27265

Other trials in United States

About this study

Official title: A Phase 1, Dose-escalation, Randomized, Placebo-Controlled Study to Assess the Safety, Tolerability, and Pharmacodynamics of SYNB1353 in Healthy Volunteers

This is a Phase 1, double-blind (Sponsor-open), placebo-controlled, randomized, dose-escalation, inpatient study using a multiple-ascending dose (MAD) design to assess the safety, tolerability, and PD of SYNB1353 in HVs.

Read the detailed description

This study is evaluating the safety, tolerability and PD of SYNB1353 in up to 8 cohorts of HVs. In each cohort, HVs will be randomly assigned to investigational medicinal product (IMP), according to a MAD design, to receive either SYNB1353 or placebo (6 active:2 placebo per cohort). A methionine loading study will be performed on Day -1 and Day 7. At each IMP dose level, a dose of methionine will be evaluated. The methionine dose may increase if necessary to evaluate the PD of SYNB1353.

Conditions
Homocystinuria
Being tested
SYNB1353
Keywords
HCU, Amino acid metabolism, Inborn error of metabolism
Medical subject headings
Homocystinuria, Metabolism, Inborn Errors

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SYNB1353Drug

    SYNB1353 IMP is formulated as a nonsterile solution intended for oral administration. SYNB1353 is subsequently lyophilized to form the bulk drug product. The lyophilized product is sieved into powder form and filled into high-density polyethylene (HDPE) bottles. Placebo will be manufactured using an inactive powder that is color matched to the SYNB1353 drug product. L-Methionine will be supplied as dry powder and will be suspended in a diluent prior to use.

Study groups in NCT05462132
Study groupRoleWhat they receive
Cohort 1ExperimentalHV subjects receive doses 3 × 10^11 live cells of SYNB1353 and 30 mg/kg of methionine. Subjects will receive a single dose of SYNB1353 on the first day of dosing (Day 1), on Days 2 and 3 subjects will receive up to 2 doses of IMP (BID), and on Days 4 to 7 subjects will receive up to 3 doses of IMP (TID). A methionine loading study will be performed on Day -1 and Day 7 after an overnight fast. A dose of methionine of 30 mg/kg will be evaluated.
Receives: Drug: SYNB1353
Cohort 2ExperimentalHV subjects receive doses 3 × 10^11 live cells of SYNB1353 and up to 100 mg/kg of methionine. Subjects will receive a single dose of SYNB1353 on the first day of dosing (Day 1), on Days 2 and 3 subjects will receive up to 2 doses of IMP (BID), and on Days 4 to 7 subjects will receive up to 3 doses of IMP (TID). A methionine loading study will be performed on Day -1 and Day 7 after an overnight fast. A dose of methionine of up to 100 mg/kg will be evaluated.
Receives: Drug: SYNB1353
Cohort 3ExperimentalHV subjects receive doses 6 × 10^11 live cells of SYNB1353 and 30 mg/kg of methionine. Subjects will receive a single dose of SYNB1353 on the first day of dosing (Day 1), on Days 2 and 3 subjects will receive up to 2 doses of IMP (BID), and on Days 4 to 7 subjects will receive up to 3 doses of IMP (TID). A methionine loading study will be performed on Day -1 and Day 7 after an overnight fast. A dose of methionine of 30 mg/kg will be evaluated.
Receives: Drug: SYNB1353
Cohort 4ExperimentalHV subjects receive doses 6 × 10^11 live cells of SYNB1353 and up to 100 mg/kg of methionine. Subjects will receive a single dose of SYNB1353 on the first day of dosing (Day 1), on Days 2 and 3 subjects will receive up to 2 doses of IMP (BID), and on Days 4 to 7 subjects will receive up to 3 doses of IMP (TID). A methionine loading study will be performed on Day -1 and Day 7 after an overnight fast. A dose of methionine of up to 100 mg/kg will be evaluated.
Receives: Drug: SYNB1353
Cohort 5ExperimentalHV subjects receive doses 1 × 10^12 live cells of SYNB1353 and 30 mg/kg of methionine. Subjects will receive a single dose of SYNB1353 on the first day of dosing (Day 1), on Days 2 and 3 subjects will receive up to 2 doses of IMP (BID), and on Days 4 to 7 subjects will receive up to 3 doses of IMP (TID). A methionine loading study will be performed on Day -1 and Day 7 after an overnight fast. A dose of methionine of 30 mg/kg will be evaluated.
Receives: Drug: SYNB1353
Cohort 6ExperimentalHV subjects receive doses 1 × 10^12 live cells of SYNB1353 and up to 100 mg/kg of methionine. Subjects will receive a single dose of SYNB1353 on the first day of dosing (Day 1), on Days 2 and 3 subjects will receive up to 2 doses of IMP (BID), and on Days 4 to 7 subjects will receive up to 3 doses of IMP (TID). A methionine loading study will be performed on Day -1 and Day 7 after an overnight fast. A dose of methionine of up to 100 mg/kg will be evaluated.
Receives: Drug: SYNB1353
Cohort 7ExperimentalHV subjects receive doses less than or equal to 2 × 10^12 live cells of SYNB1353 and 30 mg/kg of methionine. Subjects will receive a single dose of SYNB1353 on the first day of dosing (Day 1), on Days 2 and 3 subjects will receive up to 2 doses of IMP (BID), and on Days 4 to 7 subjects will receive up to 3 doses of IMP (TID). A methionine loading study will be performed on Day -1 and Day 7 after an overnight fast. A dose of methionine of 30 mg/kg will be evaluated.
Receives: Drug: SYNB1353
Cohort 8ExperimentalHV subjects receive doses less than or equal to 2 × 10^12 live cells of SYNB1353 and up to 100 mg/kg of methionine. Subjects will receive a single dose of SYNB1353 on the first day of dosing (Day 1), on Days 2 and 3 subjects will receive up to 2 doses of IMP (BID), and on Days 4 to 7 subjects will receive up to 3 doses of IMP (TID). A methionine loading study will be performed on Day -1 and Day 7 after an overnight fast. A dose of methionine of up to 100 mg/kg will be evaluated.
Receives: Drug: SYNB1353

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of participants with abnormal laboratory values and/or adverse events

    Lab results outside of the central laboratory normal range parameters will be considered abnormal and reviewed for clinical significance and reported as AEs. AEs will be evaluated using the NCI CTCAE v5.0

    Measured: Day -2 through Day 8

Secondary outcomes (1)
  1. The rate at which the SYNB1353 strain clears

    Clearance is measured in feces by quantitative polymerase chain reaction (qPCR). A negative in fecal SYNB1353 qPCR is defined as a result below the limit of quantification.

    Measured: Up to 14 weeks following the last dose of IMP

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Jul 2022
  2. Study start7 Jul 2022
  3. Primary completion27 Nov 2022
  4. Study completion27 Nov 2022

Resources

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
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Sequential
Model description
Dose-escalation decisions will be made once at least 6 subjects in a cohort have received IMP and have had at least 24 hours of post-dose observation. Dose escalation will be up to approximately 3-fold per cohort.
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
31 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05462132
Sponsor's protocol ID
SYNB1353-CP-001
Acronym
HCU
Status last verified
Mar 2023
First submitted
7 Jul 2022
Last updated
17 Mar 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing SYNB1353 in people with Homocystinuria, 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 9 inclusion and 18 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. 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?

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.

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?

Number of participants with abnormal laboratory values and/or adverse events (time frame: Day -2 through Day 8). 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.

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