NCT04534842

Brief Summary

This Phase 2 study in patients with phenylketonuria (PKU) will be an open-label, dual-arm study of either a SYNB1618 or SYNB1934 dose-ramp regimen. All evaluations and assessments throughout this study may be conducted either at the clinical site or by a home healthcare professional at an alternative location (e.g., patient's home, hotel).

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
20

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Aug 2020

Geographic Reach
1 country

11 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 24, 2020

Completed
1 day until next milestone

Study Start

First participant enrolled

August 25, 2020

Completed
7 days until next milestone

First Posted

Study publicly available on registry

September 1, 2020

Completed
2.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 7, 2022

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

October 7, 2022

Completed
Last Updated

October 17, 2022

Status Verified

October 1, 2022

Enrollment Period

2.1 years

First QC Date

August 24, 2020

Last Update Submit

October 14, 2022

Conditions

Outcome Measures

Primary Outcomes (1)

  • Changes from baseline in labeled Phe (D5-Phe) in plasma

    The primary efficacy outcome will be assessed by measuring change from baseline in plasma D5-Phe AUC over 24 hours after D5-Phe administration

    Day 14

Secondary Outcomes (2)

  • Changes from baseline in fasting levels of plasma Phe

    Day 14

  • Incidence of Treatment-Emergent Adverse Events

    Day 43

Study Arms (2)

SYNB1618

EXPERIMENTAL

Dose ramp of SYNB1618

Drug: SYNB1618

SYNB1934

EXPERIMENTAL

Dose ramp of SYNB1934

Drug: SYNB1934

Interventions

15-day dose-ramp regimen (4 dose levels) of orally administered SYNB1618

SYNB1618

15-day dose-ramp regimen (4 dose levels) of orally administered SYNB1934

SYNB1934

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Age ≥ 18 years.
  • Able and willing to voluntarily complete the informed consent process.
  • Diagnosis of classic PKU based on medical history as assessed by the investigator (e.g., Phe concentration of \>1200 µmol/L at any time, low dietary Phe tolerance, or genetic diagnosis).
  • Blood Phe ≥ 600 µmol/L at Screening.
  • Stable diet including stable medical formula regimen (if used) for at least 1 month prior to Screening.
  • Available for and agree to all study procedures, including urine and blood collection, adherence to diet control, follow-up visits, and IMP ingestion compliance.
  • Female patients who meet one of the following criteria:
  • Premenopausal woman with one of the following:
  • i. 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 patient c. 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).
  • Screening laboratory evaluations (e.g., chemistry panel, complete blood count \[CBC\] with differential, urinalysis, creatinine clearance, CRP) within normal limits or judged to be not clinically significant by the investigator.

You may not qualify if:

  • Currently taking Palynziq® (pegvaliase-pqpz) (within 1 month of Screening).
  • Inflammatory or irritable bowel disorder of any grade.
  • History of or current immunodeficiency disorder.
  • Intolerance of or allergic reaction to E. coli Nissle or any of the ingredients in SYNB1618 formulation.
  • Any condition (e.g., celiac disease, gastrectomy, bypass surgery, ileostomy) or receiving prescription medication or an over-the-counter product that may possibly affect absorption of medications or nutrients.
  • Currently taking or plans to take any type of systemic (e.g., oral or intravenous) antibiotic within 28 days prior to the first dose of IMP through final safety assessment, including planned surgery, hospitalizations, dental procedures, or interventional studies that are expected to require antibiotics. Exception: topical antibiotics are allowed.
  • Within the 3 months prior to anticipated first dose, major surgery (an operation upon an organ within the cranium, chest, abdomen, or pelvic cavity) or inpatient hospital stay.
  • Dependence on alcohol or drugs of abuse.
  • Administration or ingestion of an investigational drug within the 30 days or 5 half-lives before Screening, whichever is longer, or cell/gene therapy prior to the Screening visit, or current enrollment in an investigational drug study.
  • Acute or chronic medical, surgical, psychiatric, or social condition or laboratory abnormality that may increase patient 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 patient inappropriate for enrollment.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (11)

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Excel Medical Clinical Trials, LLC

Boca Raton, Florida, 33434, United States

Location

University of Florida College of Medicine

Gainesville, Florida, 32608, United States

Location

Washington University in St Louis

St Louis, Missouri, 63110, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Oregon Health and Science University

Portland, Oregon, 97201, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15224, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

Location

PRA Health Sciences

Salt Lake City, Utah, 84124, United States

Location

University Hospital Adult Services

Salt Lake City, Utah, 84132, United States

Location

Related Publications (1)

  • Vockley J, Sondheimer N, Puurunen M, Diaz GA, Ginevic I, Grange DK, Harding C, Northrup H, Phillips JA 3rd, Searle S, Thomas JA, Zori R, Denney WS, Ernst SL, Humphreys K, McWhorter N, Kurtz C, Brennan AM. Efficacy and safety of a synthetic biotic for treatment of phenylketonuria: a phase 2 clinical trial. Nat Metab. 2023 Oct;5(10):1685-1690. doi: 10.1038/s42255-023-00897-6. Epub 2023 Sep 28.

MeSH Terms

Conditions

Phenylketonurias

Condition Hierarchy (Ancestors)

Brain Diseases, Metabolic, InbornBrain Diseases, MetabolicBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesAmino Acid Metabolism, Inborn ErrorsMetabolism, Inborn ErrorsGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesMetabolic DiseasesNutritional and Metabolic Diseases

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 24, 2020

First Posted

September 1, 2020

Study Start

August 25, 2020

Primary Completion

October 7, 2022

Study Completion

October 7, 2022

Last Updated

October 17, 2022

Record last verified: 2022-10

Locations