search
Back to results

Efficacy and Safety of SYNB1934 in Patients With PKU (SYNPHENY-3) (SYNPHENY-3)

Primary Purpose

Phenylketonuria

Status
Recruiting
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
SYNB1934v1
Placebo
Sponsored by
Synlogic
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Phenylketonuria focused on measuring PKU, Inborn error of Metabolism, Synpheny, Synlogic, Phe, Metabolic

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Age ≥ 18 years Able and willing to voluntarily complete the informed consent process. Diagnosis of PKU and failure to maintain recommended blood Phe levels on existing management (sapropterin, sepiapterin and/or Phe-restricted diet), demonstrated by uncontrolled blood Phe level ≥ 360 μmol/L on current therapy any time during screening and uncontrolled blood Phe level ≥ 360 μmol/L on current therapy when taking the average of the 3 most recent Phe levels from the participant's medical history (inclusive of any screening values). All screening values must be obtained more than 7 days apart, as determined by central or local laboratory. Females of childbearing potential must have a negative pregnancy test at screening and the end of DEP (in order to enter Part 2) and RWP (in order to enter Part 3) and be willing to have additional pregnancy tests during the study. Sexually active female participants of childbearing potential must be willing to use an acceptable method of contraception while participating in the study and for 2 weeks after the last dose. Stable diet including stable medical formula regimen (if used) for at least 1 month prior to screening. If using sapropterin or sepiapterin, must be on a stable dose for at least 3 months. Willing and able to continue current diet, sapropterin, sepiapterin and large neutral amino acids unchanged during screening, DEP, and RWP and to engage in all study activities. Exclusion Criteria: Currently taking Palynziq® (pegvaliase-pqpz) (within 1 month of screening). 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, and, in the judgment of the investigator, would make the patient inappropriate for enrollment. A known or suspected diagnosis of DNAJC12 deficiency, biopterin synthesis deficiency, or irritable bowel syndrome. Intolerance to or allergic reaction to E. coli Nissle or any of the ingredients in SYNB1934v1 formulation, or an allergy to cinnamon. Known intolerance to proton pump inhibitors and H2 blockers. 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 SYNB1934v1 through final safety assessment in RWP, including planned surgery, hospitalizations, dental procedures, or interventional studies that are expected to require antibiotics. Exception: topical antibiotics are allowed. Pregnant, planning to become pregnant, or breastfeeding. Current participation in any other investigational drug study or use of any investigational agent within 30 days or 5 half-lives (whichever is longer) prior to screening. Ever received gene therapy for treatment of PKU.

Sites / Locations

  • Science 37Recruiting
  • University of Colorado Children's HospitalRecruiting
  • Oregon Health and Science University Department of Molecular and Medical GeneticsRecruiting
  • UT Southwestern Medical CenterRecruiting
  • McGovern Medical School/Memorial Hermann HospitalRecruiting
  • MAGIC ClinicRecruiting
  • Hamilton Health Sciences CorporationRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

RWP (Part 2)

RWP/Part 2

Arm Description

Outcomes

Primary Outcome Measures

To assess the percentage change in blood phenylalanine (Phe) level
Dose Escalating, Open-Label Period (DEP; Part 1)
To evaluate efficacy of SYNB1934v1 versus placebo in the responder population through the change from baseline to Week 4 in blood Phe level.
Randomized Withdrawal Period (RWP; Part 2)

Secondary Outcome Measures

To assess the absolute change in Phe level
Dose Escalating, Open-Label Period (DEP; Part 1)
To assess proportion of participants with a ≥ 20% reduction in blood Phe level
Dose Escalating, Open-Label Period (DEP; Part 1)
To evaluate the efficacy of SYNB1934v1 versus placebo in the responder population with regard to the proportion of participants with a blood Phe level ≤ 360 μmol/L
Randomized Withdrawal Period (RWP; Part 2)
To evaluate the efficacy of SYNB1934v1 versus placebo in the responder population with regard to change from DEP baseline in blood Phe level
Randomized Withdrawal Period (RWP; Part 2)
To evaluate efficacy of SYNB1934v1 versus placebo in the responder population with regard to percent change from DEP baseline in blood Phe level at Week 4
Randomized Withdrawal Period (RWP; Part 2)

Full Information

First Posted
February 15, 2023
Last Updated
October 10, 2023
Sponsor
Synlogic
search

1. Study Identification

Unique Protocol Identification Number
NCT05764239
Brief Title
Efficacy and Safety of SYNB1934 in Patients With PKU (SYNPHENY-3)
Acronym
SYNPHENY-3
Official Title
A Phase 3, Double-blind, Placebo-controlled, Randomized Withdrawal Study to Evaluate the Efficacy and Safety of SYNB1934 in Patients With PKU (SYNPHENY-3)
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 5, 2023 (Actual)
Primary Completion Date
October 15, 2024 (Anticipated)
Study Completion Date
October 15, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Synlogic

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a 3-part, adaptive study consisting of a dose-escalating period (DEP) of up to 15 weeks (Part 1), followed by a 4-week, double-blind, placebo-controlled randomized withdrawal period (RWP) (Part 2), and an open-label extension (OLE) (Part 3) of up to 36 months.
Detailed Description
In the DEP, all enrolled participants will maintain a stable diet reflecting their baseline Phe intake and receive escalating doses of SYNB1934v1 from approximately 3 to 15 weeks to determine an individually titrated dose (iTD), which is defined as the highest dose the patient is able to tolerate. Participants who complete the DEP at their iTD for at least 3 weeks will enter a 4-week RWP. Participants will be randomized 1:1 to receive SYNB1934v1 at their iTD determined in the DEP or placebo 3 times daily (TID). Participants who complete the 4-week RWP may enter the OLE and receive SYNB1934v1 for up to 36 months. The primary determination of efficacy will be based on the comparison of SYNB1934v1 versus placebo in the RWP. Safety will be evaluated by scheduled monitoring of adverse events, vital signs, and clinical laboratory measurements.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Phenylketonuria
Keywords
PKU, Inborn error of Metabolism, Synpheny, Synlogic, Phe, Metabolic

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Sequential Assignment
Model Description
This is a phase 2b/3 adaptive study design.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
RWP/Part 2 of study will be double-blinded.
Allocation
Randomized
Enrollment
150 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
RWP (Part 2)
Arm Type
Experimental
Arm Title
RWP/Part 2
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
SYNB1934v1
Intervention Description
SYNB1934v1 IMP consists of powder for oral suspension packaged in sachets. During dose preparation, the powder will be resuspended in water or apple juice prior to administration.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
A placebo will be manufactured using an inactive powder that is color matched to the SYNB1934v1 drug product. In order to maintain study blinding during the RWP, placebo will be packaged, labeled, stored, and administered in an identical manner to SYNB1934v1.
Primary Outcome Measure Information:
Title
To assess the percentage change in blood phenylalanine (Phe) level
Description
Dose Escalating, Open-Label Period (DEP; Part 1)
Time Frame
up to 15 weeks
Title
To evaluate efficacy of SYNB1934v1 versus placebo in the responder population through the change from baseline to Week 4 in blood Phe level.
Description
Randomized Withdrawal Period (RWP; Part 2)
Time Frame
4 weeks
Secondary Outcome Measure Information:
Title
To assess the absolute change in Phe level
Description
Dose Escalating, Open-Label Period (DEP; Part 1)
Time Frame
up to 15 weeks
Title
To assess proportion of participants with a ≥ 20% reduction in blood Phe level
Description
Dose Escalating, Open-Label Period (DEP; Part 1)
Time Frame
up to 15 weeks
Title
To evaluate the efficacy of SYNB1934v1 versus placebo in the responder population with regard to the proportion of participants with a blood Phe level ≤ 360 μmol/L
Description
Randomized Withdrawal Period (RWP; Part 2)
Time Frame
4 weeks
Title
To evaluate the efficacy of SYNB1934v1 versus placebo in the responder population with regard to change from DEP baseline in blood Phe level
Description
Randomized Withdrawal Period (RWP; Part 2)
Time Frame
4 weeks
Title
To evaluate efficacy of SYNB1934v1 versus placebo in the responder population with regard to percent change from DEP baseline in blood Phe level at Week 4
Description
Randomized Withdrawal Period (RWP; Part 2)
Time Frame
4 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age ≥ 18 years Able and willing to voluntarily complete the informed consent process. Diagnosis of PKU and failure to maintain recommended blood Phe levels on existing management (sapropterin, sepiapterin and/or Phe-restricted diet), demonstrated by uncontrolled blood Phe level ≥ 360 μmol/L on current therapy any time during screening and uncontrolled blood Phe level ≥ 360 μmol/L on current therapy when taking the average of the 3 most recent Phe levels from the participant's medical history (inclusive of any screening values). All screening values must be obtained more than 7 days apart, as determined by central or local laboratory. Females of childbearing potential must have a negative pregnancy test at screening and the end of DEP (in order to enter Part 2) and RWP (in order to enter Part 3) and be willing to have additional pregnancy tests during the study. Sexually active female participants of childbearing potential must be willing to use an acceptable method of contraception while participating in the study and for 2 weeks after the last dose. Stable diet including stable medical formula regimen (if used) for at least 1 month prior to screening. If using sapropterin or sepiapterin, must be on a stable dose for at least 3 months. Willing and able to continue current diet, sapropterin, sepiapterin and large neutral amino acids unchanged during screening, DEP, and RWP and to engage in all study activities. Exclusion Criteria: Currently taking Palynziq® (pegvaliase-pqpz) (within 1 month of screening). 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, and, in the judgment of the investigator, would make the patient inappropriate for enrollment. A known or suspected diagnosis of DNAJC12 deficiency, biopterin synthesis deficiency, or irritable bowel syndrome. Intolerance to or allergic reaction to E. coli Nissle or any of the ingredients in SYNB1934v1 formulation, or an allergy to cinnamon. Known intolerance to proton pump inhibitors and H2 blockers. 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 SYNB1934v1 through final safety assessment in RWP, including planned surgery, hospitalizations, dental procedures, or interventional studies that are expected to require antibiotics. Exception: topical antibiotics are allowed. Pregnant, planning to become pregnant, or breastfeeding. Current participation in any other investigational drug study or use of any investigational agent within 30 days or 5 half-lives (whichever is longer) prior to screening. Ever received gene therapy for treatment of PKU.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Neal Sondheimer, M.D., Ph.D
Phone
(617) 401-9975
Email
Neal.Sondheimer@synlogictx.com
Facility Information:
Facility Name
Science 37
City
Culver City
State/Province
California
ZIP/Postal Code
90230
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
David Kudrow
Facility Name
University of Colorado Children's Hospital
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Janet Thomas
Facility Name
Oregon Health and Science University Department of Molecular and Medical Genetics
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Cary Harding
Facility Name
UT Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Markey McNutt
Facility Name
McGovern Medical School/Memorial Hermann Hospital
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hope Northrup
Facility Name
MAGIC Clinic
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2E 7Z4
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Aneal Khan
Facility Name
Hamilton Health Sciences Corporation
City
Hamilton
State/Province
Ontario
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Murray Potter

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Efficacy and Safety of SYNB1934 in Patients With PKU (SYNPHENY-3)

We'll reach out to this number within 24 hrs