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

NCT05764239 | Terminated Phase 3 Results DMC FDA Drug

• 1 other identifier: SYNB1934-CP-003
• Study Type: interventional
• Target: 35
• Locations: 4 countries
• Sites: 21

Brief Summary

SYNB1934-CP-003 was designed as a 3-part, adaptive study consisting of a dose-escalating, open-label period (DEP; Part 1) of up to 15 weeks, 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

Conditions

Phenylketonuria

Keywords

PKU; Inborn error of metabolism; Synpheny; Synlogic; Phe; Metabolic

Outcome Measures

Primary Outcomes (1)

• Mean Percent Change From DEP Baseline in Blood Phenylalanine (Phe) Level at Week 3 of iTD During the DEP

  Baseline for blood Phe level in the DEP was defined as the mean of the duplicate blood Phe level measurements obtained immediately prior to administration of the first dose in the DEP. If only 1 blood Phe level measurement was available, then that measure was used as baseline. The last measurement was the participant's last Week 3 blood Phe level at the iTD of SYNB1934v1.

  Up to 15 weeks

Secondary Outcomes (2)

• Absolute Change From DEP Baseline in Blood Phe Level at Week 3 of iTD During the DEP

  Up to 15 weeks

• Number of Participants With a ≥ 20% Reduction From Baseline in Blood Phe Level at Any Time in the DEP

  Up to 15 weeks

Study Arms (4)

DEP (Part 1, SYNB1934v1)

EXPERIMENTAL

Participants received SYNB1934v1 orally immediately after meals on the following dose-ramp regimen: Dose level 1 (Days 1-9): 3 × 10\^11 live cells partial dose up to 3 times daily (TID); Dose level 2 (Weeks 4-6): 6 × 10\^11 live cells up to TID; Dose level 3 (Weeks 7-9): 1 × 10\^12 live cells up to TID.

Drug: SYNB1934v1

RWP (Part 2, SYNB1934v1)

EXPERIMENTAL

Participants who completed the DEP were randomized 1:1 to receive SYNB1934v1 at their iTD established in the DEP orally immediately after meals. Participants remained on this dose of SYNB1934v1 for the duration of the RWP; doses of SYNB1934v1 were not permitted to be modified during the RWP.

Drug: SYNB1934v1

RWP (Part 2, Placebo)

PLACEBO COMPARATOR

Participants who completed the DEP were randomized 1:1 to receive placebo orally immediately after meals. Participants remained on the same dose of placebo for the duration of the RWP; doses of placebo were not permitted to be modified during the RWP.

Drug: Placebo

OLE (Part 3, SYNB1934v1)

EXPERIMENTAL

Participants completed a dose ramp to their iTD guided by tolerability, as described for the DEP, including the full dose-ramp schedule. The iTD in the OLE may have been different from the iTD in the DEP or RWP. The investigator may have escalated the dose of SYNB1934v1 up to 1 × 10\^12 live cells based on tolerability; multiple attempts to escalate to a higher dose level were permitted per investigator discretion.

Drug: SYNB1934v1

Interventions

SYNB1934v1 DRUG

SYNB1934v1 consisted of powder for oral suspension packaged in sachets. During dose preparation, the powder was resuspended in water or apple juice prior to administration.

DEP (Part 1, SYNB1934v1); OLE (Part 3, SYNB1934v1); RWP (Part 2, SYNB1934v1)

Placebo DRUG

Placebo was manufactured using an inactive powder that was color matched to the SYNB1934v1 drug product. In order to maintain study blinding during the RWP, placebo was packaged, labeled, stored, and administered in an identical manner to SYNB1934v1.

RWP (Part 2, Placebo)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years.
• Able and willing to voluntarily complete the informed consent process.
• Diagnosis of phenylketonuria (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 have been obtained more than 7 days apart, as determined by central or local laboratory.
• Females of childbearing potential must have had a negative pregnancy test at screening and at the end of the DEP (in order to enter the RWP) and RWP (in order to enter the OLE) and been willing to have additional pregnancy tests during the study.
• Sexually active female participants of childbearing potential must have been 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 have been 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.

You may not qualify if:

• Currently taking Palynziq® (pegvaliase-pqpz) (within 1 month of screening).
• Acute or chronic medical, surgical, psychiatric, or social condition or laboratory abnormality that may have increased participant risk associated with study participation, compromised adherence to study procedures and requirements, and, in the judgment of the investigator, would have made the participant inappropriate for enrollment.
• A known or suspected diagnosis of DNAJC12 deficiency, biopterin synthesis deficiency, or irritable bowel syndrome.
• Intolerance to or allergic reaction to Escherichia coli Nissle or any of the ingredients in SYNB1934v1 formulation, or an allergy to cinnamon. Known intolerance to proton pump inhibitors and H2 blockers, since one or the other must have been used.
• 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 the RWP, including planned surgery, hospitalizations, dental procedures, or interventional studies that were expected to require antibiotics. Exception: topical antibiotics were 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 was longer) prior to screening.
• Ever received gene therapy for treatment of PKU.

Sponsors & Collaborators

• Synlogic: lead

Study Sites (21)

Science 37

Culver City, California, 90230, United States

Location

Children's Hospital Orange County

Orange, California, 92868, United States

Location

Stanford University, Department of Pediatrics

Palo Alto, California, 94304, United States

Location

University of Colorado Children's Hospital

Aurora, Colorado, 80045, United States

Location

University of Florida - Gainesville

Gainesville, Florida, 32610, United States

Location

Ann & Robert H. Lurie Children's Hospital of Chicago, Pediatrics

Chicago, Illinois, 60611-2991, United States

Location

Massachusetts General Hospital, Department of Pediatrics

Boston, Massachusetts, 02114, United States

Location

Oregon Health and Science University Department of Molecular and Medical Genetics

Portland, Oregon, 97239, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pittsburgh Medical Center - Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15224, United States

Location

Medical University of South Carolina, Pediatrics

Charleston, South Carolina, 29425, United States

Location

Division of Medical Genetics-Pediatrics, Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

McGovern Medical School/Memorial Hermann Hospital

Houston, Texas, 77030, United States

Location

MAGIC Clinic

Calgary, Alberta, T2E 7Z4, Canada

Location

Hamilton Health Sciences Corporation

Hamilton, Ontario, L8N 3Z5, Canada

Location

Children's Hospital of Eastern Ontario

Ottawa, Ontario, K1H 8L1, Canada

Location

University Health Network

Toronto, Ontario, M5T 3L9, Canada

Location

Medical Genetics and Laboratory Diagnostics Center

Tbilisi, 0159, Georgia

Location

Gazi Üniversitesi Hastanesi

Yenimahalle, Ankara, 06560, Turkey (Türkiye)

Location

Dokuz Eylül Üniversitesi Araştırma ve Uygulama Hastanesi

Balçova, İzmir, 35340, Turkey (Türkiye)

Location

MeSH Terms

Conditions

Phenylketonurias; Metabolism, Inborn Errors

Condition Hierarchy (Ancestors)

Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Amino Acid Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Limitations and Caveats

Early termination leading to small numbers of participants analyzed

Results Point of Contact

• Title: Clinical Operations
• Organization: Synlogic

info@synlogictx.com

(617) 401-9975

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The DEP (Part 1) and OLE (Part 3) were open label, and the RWP (Part 2) was double blinded.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This was a Phase 2b/3 adaptive study design.

Study Record Dates

• First Submitted: February 15, 2023
• First Posted: March 10, 2023
• Study Start: July 5, 2023
• Primary Completion: March 15, 2024
• Study Completion: March 15, 2024
• Last Updated: June 20, 2024
• Results First Posted: June 20, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

TU (2); CA (4); US (14); GE (1)