TerminatedNCT05764239SYNPHENY-3Updated Jun 20, 2024Results posted

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

A Phase 3 interventional study of SYNB1934v1 and Placebo in Phenylketonuria, sponsored by Synlogic. Terminated at 21 sites in 4 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-06-20.

Sponsored by Synlogic · Phase 3, Interventional, and Treatment

Why this study was terminated

Based on a review of interim data from participants in the dose-escalation phase, it was determined that the study was unlikely to meet the primary endpoint.

Phase: Phase 3
Study type: Interventional
Enrollment: 35
Allocation: Randomized
Ages: 18 Years and older
Sex: All

Study 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

Read the detailed description

In the DEP, all enrolled participants maintained a stable diet reflecting their baseline phenylalanine (Phe) intake and received escalating doses of SYNB1934v1 from approximately 3 to 15 weeks to determine an individually titrated dose (iTD), which was defined as the highest dose the participant was able to tolerate. A participant was defined as having reached an iTD if they tolerated 3 weeks at a dose, regardless of whether other doses were tolerated.

Blood Phe level was measured at each dose level after 3 weeks at that level. A responder was defined as a participant who achieved a ≥ 20% reduction in blood Phe level compared to DEP baseline on SYNB1934v1.

Participants who completed at least 3 weeks at their iTD during the DEP entered a 4-week RWP in which they were randomized 1:1 to receive SYNB1934v1 at their iTD determined in the DEP or placebo TID. Randomization was stratified on screening Phe level. Participants remained on their assigned dose (iTD of SYNB1934v1 or matching placebo) for the duration of the RWP, unless they developed intolerance or met other discontinuation criteria, and remained on the same diet they consumed during the DEP. Blood Phe level was measured at Weeks 1, 3, and 4 of the RWP.

Participants who completed the 4-week RWP may have entered the OLE and received SYNB1934v1 for up to 36 months. During the OLE, participants completed a dose ramp to their iTD over time guided by tolerability. The iTD in the OLE may have been different from the iTD in the DEP. The investigator may have escalated the SYNB1934v1 dose up to 1 × 10\^12 live cells based on tolerability. Participants were allowed to modify their standard diet, with guidance from the investigator, if their blood Phe level was \< 240 µmol/L.

Conditions studied

Phenylketonuria

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Keywords

PKU
Inborn error of metabolism
Synpheny
Synlogic
Phe
Metabolic

In context

Phenylketonurias

191 studies on the registry are indexed under Phenylketonurias; 40 are open to participants now.

This study's enrollment of 35 is above the median of 27 across 122 interventional studies indexed under Phenylketonurias.

Browse Phenylketonurias studies →

Lead sponsor

Synlogic is the lead sponsor of 10 studies on the registry; none are open to participants now.

Of its 10 completed or terminated interventional studies of FDA-regulated products, 3 (30%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Male and female participants were enrolled.

Inclusion criteria

Inclusion Criteria:

Age ≥ 18 years.
Able and willing to voluntarily complete the 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 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 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.

Exclusion criteria

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 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 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.

Terms in these criteria, in plain language(4)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

Childbearing potential

Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).

Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.

Contraception

Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.

Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.

Investigational drug or device

A drug or device being studied in a clinical trial.

It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.

Study design

Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Sequential assignment
Masking: Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment: 35 participants (actual)

Study arms

Experimental
DEP (Part 1, SYNB1934v1)
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
Experimental
RWP (Part 2, SYNB1934v1)
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
Placebo comparator
RWP (Part 2, Placebo)
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
Experimental
OLE (Part 3, SYNB1934v1)
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

DrugSYNB1934v1
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.
DrugPlacebo
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.

What researchers measure

Primary outcomes

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.
Time frame: Up to 15 weeks

Secondary outcomes

Absolute Change From DEP Baseline in Blood 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.
Time frame: Up to 15 weeks
Number of Participants With a ≥ 20% Reduction From Baseline in Blood Phe Level at Any Time in 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. Blood Phe level was measured at each dose level after 3 weeks at that level.
Time frame: Up to 15 weeks

Results

Posted Jun 20, 2024

Limitations and caveats

Early termination leading to small numbers of participants analyzed

Participant flow

DEP (Part 1)

Participant flow — DEP (Part 1)
Milestone	All Participants
Started	35
Completed dep	17
Completed	0
Not completed	35
Withdrew: Study terminated by sponsor	28
Withdrew: Withdrawal by subject	3
Withdrew: Non-compliance with study drug	2
Withdrew: Adverse event	1
Withdrew: Lost to follow-up	1

RWP (Part 2, SYNB1934v1)

Participant flow — RWP (Part 2, SYNB1934v1)
Milestone	All Participants
Started	9
Completed rwp	9
Completed	0
Not completed	9
Withdrew: Study terminated by sponsor	7
Withdrew: Non-compliance with study drug	2

RWP (Part 2, Placebo)

Participant flow — RWP (Part 2, Placebo)
Milestone	All Participants
Started	8
Completed rwp	8
Completed	0
Not completed	8
Withdrew: Study terminated by sponsor	8

OLE (Part 3)

Participant flow — OLE (Part 3)
Milestone	All Participants
Started	10
Completed	0
Not completed	10
Withdrew: Study terminated by sponsor	10

Outcome measures

PrimaryMean 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.

Time frame:: Up to 15 weeks
Reported as:: Median · percent change

Mean Percent Change From DEP Baseline in Blood Phenylalanine (Phe) Level at Week 3 of iTD During the DEP
percent change	iTD of 3 x 10^11 Live Cells	iTD of 6 x 10^11 Live Cells	iTD of 1 x 10^12 Live Cells	Overall DEP
Mean Percent Change From DEP Baseline in Blood Phenylalanine (Phe) Level at Week 3 of iTD During the DEP	—	-3.85 (0 to -3.85)	5.33 (-37.2 to 59.3)	3.35 (-37.2 to 59.3)

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

Time frame:: Up to 15 weeks
Reported as:: Median · µmol/L

Absolute Change From DEP Baseline in Blood Phe Level at Week 3 of iTD During the DEP
µmol/L	iTD of 3 x 10^11 Live Cells	iTD of 6 x 10^11 Live Cells	iTD of 1 x 10^12 Live Cells	Overall DEP
Absolute Change From DEP Baseline in Blood Phe Level at Week 3 of iTD During the DEP	—	-55.00 (0 to -55.00)	55.25 (-227.0 to 406.5)	30.50 (-227.0 to 406.5)

SecondaryNumber of Participants With a ≥ 20% Reduction From Baseline in Blood Phe Level at Any Time in 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. Blood Phe level was measured at each dose level after 3 weeks at that level.

Time frame:: Up to 15 weeks
Reported as:: Count of participants · Participants

Number of Participants With a ≥ 20% Reduction From Baseline in Blood Phe Level at Any Time in the DEP
Participants	iTD of 3 x 10^11 Live Cells	iTD of 6 x 10^11 Live Cells	iTD of 1 x 10^12 Live Cells	Overall DEP
Number of Participants With a ≥ 20% Reduction From Baseline in Blood Phe Level at Any Time in the DEP	0	0	6	6

Adverse events

Collected over All AEs occurring from the time a participant signed the informed consent form through the safety follow-up period and at least 1 month following the last dose of IMP were documented, regardless of causal assessment to IMP.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
DEP (Part 1, SYNB1934v1)	0/35 (0%)	0/35 (0%)	23/35 (65.7%)
RWP (Part 2, SYNB1934v1)	0/9 (0%)	0/9 (0%)	3/9 (33.3%)
RWP (Part 2, Placebo)	0/8 (0%)	0/8 (0%)	5/8 (62.5%)
OLE (Part 3, SYNB1934v1)	0/10 (0%)	0/10 (0%)	2/10 (20%)

Most frequent other events

Showing 10 of 41

Most frequent other events
Event	DEP (Part 1, SYNB1934v1)	RWP (Part 2, SYNB1934v1)	RWP (Part 2, Placebo)	OLE (Part 3, SYNB1934v1)
NauseaGastrointestinal disorders	11/35	0/9	0/8	1/10
FlatulenceGastrointestinal disorders	9/35	0/9	1/8	0/10
Influenza like illnessGeneral disorders	1/35	2/9	1/8	0/10
Abdominal distensionGastrointestinal disorders	7/35	0/9	0/8	1/10
DiarrhoeaGastrointestinal disorders	7/35	0/9	0/8	1/10
HeadacheNervous system disorders	3/35	0/9	0/8	2/10
Abdominal painGastrointestinal disorders	5/35	0/9	0/8	1/10
ConstipationGastrointestinal disorders	5/35	0/9	0/8	0/10
NasopharyngitisInfections and infestations	5/35	0/9	0/8	0/10
GastroenteritisInfections and infestations	1/35	0/9	1/8	0/10

Baseline characteristics

All participants who took at least 1 dose of SYNB1934v1 in the indicated study period (DEP or OLE) or who were randomized into the RWP.

Age, Categorical
Age, Categorical(Participants)	All Participants
<=18 years	0
Between 18 and 65 years	35
>=65 years	0

Age, Continuous
Age, Continuous(years)	All Participants
Median	31.0 (18 to 64)

Sex: Female, Male
Sex: Female, Male(Participants)	All Participants
Female	11
Male	24

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	All Participants
Hispanic or Latino	1
Not Hispanic or Latino	33
Unknown or Not Reported	1

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	All Participants
American Indian or Alaska Native	0
Asian	2
Native Hawaiian or Other Pacific Islander	0
Black or African American	2
White	30
More than one race	0
Unknown or Not Reported	1

Region of Enrollment
Region of Enrollment(participants)	All Participants
Canada	10
United States	25

Study locations

21 sites

Science 37
Culver City, California 90230, United States
Children's Hospital Orange County
Orange, California 92868, United States
Stanford University, Department of Pediatrics
Palo Alto, California 94304, United States
University of Colorado Children's Hospital
Aurora, Colorado 80045, United States
University of Florida - Gainesville
Gainesville, Florida 32610, United States
Ann & Robert H. Lurie Children's Hospital of Chicago, Pediatrics
Chicago, Illinois 60611-2991, United States
Massachusetts General Hospital, Department of Pediatrics
Boston, Massachusetts 02114, United States
Oregon Health and Science University Department of Molecular and Medical Genetics
Portland, Oregon 97239, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania 19104, United States
University of Pittsburgh Medical Center - Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania 15224, United States
Medical University of South Carolina, Pediatrics
Charleston, South Carolina 29425, United States
Division of Medical Genetics-Pediatrics, Vanderbilt University Medical Center
Nashville, Tennessee 37232, United States
UT Southwestern Medical Center
Dallas, Texas 75390, United States
McGovern Medical School/Memorial Hermann Hospital
Houston, Texas 77030, United States
MAGIC Clinic
Calgary, Alberta T2E 7Z4, Canada
Hamilton Health Sciences Corporation
Hamilton, Ontario L8N 3Z5, Canada
Children's Hospital of Eastern Ontario
Ottawa, Ontario K1H 8L1, Canada
University Health Network
Toronto, Ontario M5T 3L9, Canada
Medical Genetics and Laboratory Diagnostics Center
Tbilisi, 0159, Georgia
Gazi Üniversitesi Hastanesi
Yenimahalle, Ankara 06560, Turkey
Dokuz Eylül Üniversitesi Araştırma ve Uygulama Hastanesi
Balçova, Izmir 35340, Turkey

References and documents

Study documents

Study protocol ↗ · Jul 1, 2023
Statistical analysis plan ↗ · Oct 5, 2023

PDFs hosted by the registry, ClinicalTrials.gov.

Individual participant data

Plan to share: No

Timeline

Tracking since Sep 25, 2026

ElapsedEstimatedEstimated, not yet reached

Ran from Jul 2023 to primary completion in Mar 2024, 8 months.

Results were first posted in Jun 2024, 3 months after primary completion.

How these figures are worked out, and which studies are left out of them.

Registered: Feb 15, 2023
First posted: Mar 10, 2023
StartActual: Jul 5, 2023
Primary completionActual: Mar 15, 2024
CompletionActual: Mar 15, 2024
Results first posted: Jun 20, 2024
Last update: Jun 20, 2024

What these dates mean

Start.: When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.: When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.: When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.: Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.

No changes since tracking began. The registry record was last updated on Jun 20, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT05764239
Lead sponsor: Synlogic
Responsible party: Sponsor
First posted: Mar 10, 2023
Start date: Jul 5, 2023
Primary completion: Mar 15, 2024
Completion: Mar 15, 2024
Results posted: Jun 20, 2024
Last update: Jun 20, 2024

Oversight

Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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