PhenylketonuriaPhase 1/2PKUNCT03516487
Safety and Tolerability of SYNB1618 in Healthy Adult Volunteers and Adult Subjects With Phenylketonuria
A Phase 1/2 study testing SYNB1618 in people with Phenylketonuria and Healthy, run by Synlogic at 4 sites in United States.
Trial summary
This Phase 1/2a, first-in-human, oral single and multiple dose-escalation, randomized, double-blinded, placebo-controlled study is evaluating SYNB1618 in healthy volunteers (HV) and subjects diagnosed with phenylketonuria (PKU), a rare inherited metabolic disorder that occurs in people who are missing an enzyme that… Read more about this study
- Who is it for?
- Ages 18 to 64 yearsHealthy volunteers can take part
- Conditions the study is for
- Phenylketonuria, Healthy
- What is being tested?
- SYNB1618
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 70 participants
- Where
- 4 sitesUnited States
- Study dates
- 17 Apr 2018to 21 Jun 2019
- Phase
- Phase 1/2
- 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 (subject or subject's representative).
- Available for and agrees to all study procedures, including feces, urine, and blood collection and adherence to diet control, inpatient monitoring, follow-up visits, and IP ingestion compliance.
- 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 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 90 days after the last dose of IP, and who do not intend to donate sperm in the period from screening until 3 months following administration of the investigational medical product.
- Female subjects that meet one of the following:
- Women of childbearing potential must have a negative serum pregnancy test (human chorionic gonadotropin [HCG]) at screening and at baseline prior to the start of IP 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 90 days after the last dose of IP. Acceptable methods of contraception include hormonal contraception, hormonal or non-hormonal intrauterine device, bilateral tubal occlusion, complete abstinence, vasectomized partner with documented azoospermia 90 days after procedure, diaphragm with spermicide, cervical cap with spermicide, vaginal sponge with spermicide, or male or female condom with or without spermicide.
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- 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 subject.
- Postmenopausal woman (12 months or more amenorrhea verified by follicle stimulating hormone 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 with differential, prothrombin time/activated partial thromboplastin time, urinalysis, C reactive protein, creatinine clearance) and electrocardiogram must be within normal limits or judged to be not clinically significant by the Investigator.
- Stable diet including protein intake for at least 60 days prior to screening assessments.
- Able to produce at least 2 bowel movements per week on average without the assistance of laxatives.
- In addition to the above criteria for HV, inclusion criteria for PKU subjects are as noted below.
- Diagnosis of classic PKU by either medical history of blood Phe concentration of >1200 µmol/L at any time OR genetic diagnosis.
- Blood Phe concentration of ≥ 600 µmol/L at Screening.
- Stable diet including stable medical formula regimen (if used) for 60 days prior to screening assessments.
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 confound interpretation of study safety or pharmacodynamic results and, in the judgment of the Investigator, make the subject inappropriate for enrollment.
- Body mass index < 18.5 or ≥ 30 kg/m^2 (> 40 kg/m^2 for PKU subjects).
- History of or current immunodeficiency disorder including autoimmune disorders and human immunodeficiency virus 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 within 30 days prior to the anticipated first dose of IP.
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- History of active or chronic passage of 3 or more loose stools per day.
- Active laxative use within 30 days prior to the anticipated first dose of IP.
- Active inflammatory or irritable bowel disorder of any grade.
- Active or past history of gastrointestinal bleeding within 60 days prior to the Screening Visit as confirmed via hospitalization-related event(s) or medical history of hematemesis or hematochezia.
- Intolerance of or allergic reaction to E. coli Nissle or any of the ingredients in SYNB1618 or placebo formulations.
- Any condition, prescription medication, or over-the-counter product that may possibly affect absorption of medications or nutrients (e.g., celiac disease, gastrectomy, bypass surgery, ileostomy).
- Currently taking or plans to take any type of systemic (e.g., oral or intravenous) antibiotic within 28 days prior to the anticipated first dose of IP through the final outpatient follow-up. 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 3 months prior to the anticipated first dose of IP.
- Planned surgery, hospitalizations, dental, or interventional studies between screening and last anticipated visit that might require antibiotics.
- Taking or planning to take probiotic supplements (enriched foods excluded) within 28 days prior to the anticipated first dose of IP and for the duration of participation and follow-up.
- Dependence on drugs of abuse.
- Regular alcohol consumption in excess of 14 standard drinks/week for men and in excess of 7 standard drinks/week for women and/or any evidence of binge or heavy drinking (according to National Institute on Alcohol Abuse and Alcoholism guidelines). One drink is equivalent to 12 g of alcohol: 12 oz (360 mL) of beer, 5 oz (150 mL) of wine or 1.5 oz (45 mL) of 80 proof distilled spirits.
- Administration or ingestion of an investigational drug within 60 days or 5 half-lives, whichever is longer, prior to the Screening Visit or current enrollment in an investigational study. (PKU subjects who participate in the PKU SAD cohort may be eligible for screening for the PKU MAD cohort ≥ 30 days after the last dose of IP.)
- Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular (including stable coronary artery disease/angina or prior cardiac stent), hepatic, neurologic, or allergic disease including drug allergies.
- Screening laboratory parameters within the acceptable range.
- In addition to the above criteria for HV, exclusion criteria for PKU subjects are as noted below.
- Currently taking (within 1 week prior to screening) sapropterin (KUVAN®).
- Currently taking (within 6 months prior to screening) pegylated recombinant phenylalanine ammonia lyase (PALYNZIQ™).
- History of a severe immune reaction based on National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) after administration of pegylated recombinant phenylalanine ammonia lyase (PALYNZIQ).
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Boston Children's Hospital
Boston, Massachusetts, 02115
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224
PRA Health Sciences
Salt Lake City, Utah, 84124
About this study
Official title: A Phase 1/2a, First-in-human, Oral Single and Multiple Dose-escalation, Randomized, Double-blinded, Placebo-controlled Study of SYNB1618 in Healthy Adult Volunteers and Adult Subjects With Phenylketonuria to Evaluate Safety, Tolerability, Kinetics, and Pharmacodynamics
This Phase 1/2a, first-in-human, oral single and multiple dose-escalation, randomized, double-blinded, placebo-controlled study is evaluating SYNB1618 in healthy volunteers (HV) and subjects diagnosed with phenylketonuria (PKU), a rare inherited metabolic disorder that occurs in people who are missing an enzyme that the body needs to use phenylalanine (Phe). Eligible subjects receive investigational product (IP) in the clinic and undergo safety monitoring, evaluations, and subsequent follow-up after IP administration.
Read the detailed description
This study is evaluating the safety, tolerability, kinetics, and pharmacodynamics of SYNB1618 within the following 2 study parts:
Part 1 comprises a single-ascending dose (SAD) study conducted over 4 days in HV male and female subjects in up to 6 dose cohorts (3 treated:1 placebo) to identify the maximum tolerated dose (MTD) within the single-dose range studied. Up to 24 HV subjects are planned for enrollment in this part of the study. Following attainment of the MTD in HV, a SAD cohort of up to 4 subjects (male and female, ≥ 18 years old) previously diagnosed with PKU will be enrolled (3 treated:1 placebo).
Part 2 comprises a multiple-ascending dose (MAD) study conducted in an inpatient setting (6 treated:2 placebo) over 10 days in HV male and female subjects in up to 4 cohorts at doses not exceeding the MTD from the SAD part of the study to identify the MTD of SYNB1618 within the multiple-dose range studied. Up to 32 HV subjects are planned for enrollment in this part of the study. Once the highest MAD cohort and the SAD PKU cohort are completed, a multiple-dose cohort of male and female subjects (≥ 18 years old) previously diagnosed with PKU are evaluated. Up to 20 subjects with PKU are planned for enrollment in the MAD PKU cohort (12 treated:8 placebo).
- Conditions
- Phenylketonuria, Healthy
- Being tested
- SYNB1618, Placebo
- Keywords
- PKU
- Medical subject headings
- Phenylketonurias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SYNB1618Drug
SYNB1618 is supplied in a buffered solution in 5 mL polypropylene cryovials with a nominal 5 mL fill volume, administered with 100 mL of masking buffer solution.
PlaceboDrug
Subjects receive placebo orally in a chilled buffered solution (100 mL).
| Study group | Role | What they receive |
|---|---|---|
| SAD HV: SYNB1618 (1 x 10^10 CFU) | Experimental | HV subjects receive a single oral dose of SYNB1618 (1 x 10^10 colony-forming units [CFU]) in a chilled buffered solution on Day 1 in the SAD study (Part 1). Receives: Drug: SYNB1618 |
| SAD HV: SYNB1618 (5 x 10^10 CFU) | Experimental | HV subjects receive a single oral dose of SYNB1618 (5 x 10^10 CFU) in a chilled buffered solution on Day 1 in the SAD study (Part 1). Receives: Drug: SYNB1618 |
| SAD HV: SYNB1618 (1 x 10^11 CFU) | Experimental | HV subjects receive a single oral dose of SYNB1618 (1 x 10^11 CFU) in a chilled buffered solution on Day 1 in the SAD study (Part 1). Receives: Drug: SYNB1618 |
| SAD HV SB: SYNB1618 (1 x 10^11 CFU) | Experimental | HV subjects receive a single oral dose of SYNB1618 (1 x 10^11 CFU) in a chilled buffered solution on Day 1 in the SAD study (Part 1). On Day 1, subjects in this cohort receive a solid breakfast (SB) that contains approximately the same amount of calories and protein as the meal supplement shake given to subjects in the other SAD cohorts. Receives: Drug: SYNB1618 |
| SAD HV: SYNB1618 (2 x 10^11 CFU) | Experimental | HV subjects receive a single oral dose of SYNB1618 (2 x 10^11 CFU) in a chilled buffered solution on Day 1 in the SAD study (Part 1). Receives: Drug: SYNB1618 |
| SAD HV: SYNB1618 (5 x 10^11 CFU) | Experimental | HV subjects receive a single oral dose of SYNB1618 (5 x 10^11 CFU) in a chilled buffered solution on Day 1 in the SAD study (Part 1). Receives: Drug: SYNB1618 |
| SAD HV: Placebo | Placebo comparator | HV subjects receive a single oral dose of placebo in a chilled buffered solution on Day 1 in the SAD study (Part 1). Receives: Drug: Placebo |
| SAD PKU: SYNB1618 (7 x 10^10 CFU) | Experimental | Subjects with PKU receive a single oral dose of SYNB1618 (7 x 10^10 CFU) in a chilled buffered solution on Day 1 in the SAD study (Part 1). Receives: Drug: SYNB1618 |
| SAD PKU: Placebo | Placebo comparator | HV subjects receive a single oral dose of placebo in a chilled buffered solution on Day 1 in the SAD study (Part 1). Receives: Drug: Placebo |
| MAD HV: SYNB1618 (1 x 10^10 CFU) | Experimental | HV subjects receive oral SYNB1618 (1 x 10^10 CFU) in a chilled buffered solution 3 times per day (TID) for 7 days in the MAD study (Part 2). Receives: Drug: SYNB1618 |
| MAD HV: SYNB1618 (5 x 10^10 CFU) | Experimental | HV subjects receive oral SYNB1618 (5 x 10^10 CFU) in a chilled buffered solution TID for 7 days in the MAD study (Part 2). Receives: Drug: SYNB1618 |
| MAD HV: SYNB1618 (7 x 10^10 CFU) | Experimental | HV subjects receive oral SYNB1618 (7 x 10^10 CFU) in a chilled buffered solution TID for 7 days in the MAD study (Part 2). Receives: Drug: SYNB1618 |
| MAD HV: SYNB1618 (1 x 10^11 CFU) | Experimental | HV subjects receive oral SYNB1618 (1 x 10^11 CFU) in a chilled buffered solution TID for 7 days in the MAD study (Part 2). Receives: Drug: SYNB1618 |
| MAD HV: Placebo | Placebo comparator | HV subjects receive oral placebo in a chilled buffered solution TID for 7 days in the MAD study (Part 2). Receives: Drug: Placebo |
| MAD PKU: SYNB1618 (7 x 10^10 CFU) | Experimental | Subjects with PKU receive oral SYNB1618 (7 x 10^10 CFU) in a chilled buffered solution TID for 7 days in the MAD study (Part 2). Receives: Drug: SYNB1618 |
| MAD PKU: Placebo | Placebo comparator | Subjects with PKU receive oral placebo in a chilled buffered solution TID for 7 days in the MAD study (Part 2). Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Subjects With Treatment-Emergent Adverse Events
Toxicity is graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.03. Adverse events (AEs) are reported based on clinical laboratory tests, vital sign and weight measurements, physical examinations, electrocardiograms, and any other medically indicated assessments, including subject interviews, from the time informed consent is signed through the end of the safety follow-up period.
AEs are considered to be treatment emergent (TEAE) if they occur or worsen in severity after the first dose of study treatment. TEAEs are considered treatment-related if relationship to study drug is possibly related, probably related, or definitely related.
Measured: Up to 4 months
Secondary outcomes (1)
Clearance of SYNB1618 From Feces
SYNB1618 transit through the gastrointestinal tract is measured with fecal quantitative polymerase chain reaction (qPCR) assays from fecal samples collected at baseline, daily during the dosing period, at the time of discharge from the inpatient unit, and weekly thereafter for up to 8 weeks after the last dose of investigational product (IP) until a subject has a negative SYNB1618 fecal test. SYNB1618 clearance reflects a test value of below the limit of quantitation (BLQ) occurring after the indicated number of days following the last dose of IP.
Measured: Up to 4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 May 2018
- Study start17 Apr 2018
- Primary completion21 Jun 2019
- Study completion21 Jun 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for PhenylketonuriaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Model description
- Dose-escalating, randomized, double-blinded, placebo-controlled
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 70 participants (actual)
Sponsor and investigators
- Lead sponsor
- Synlogic
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03516487
- Sponsor's protocol ID
- SYNB1618-CP-001
- Acronym
- PKU
- Status last verified
- May 2021
- First submitted
- 11 Apr 2018
- Last updated
- 13 May 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Puurunen MK, Vockley J, Searle SL, Sacharow SJ, Phillips JA 3rd, Denney WS, Goodlett BD, Wagner DA, Blankstein L, Castillo MJ, Charbonneau MR, Isabella VM, Sethuraman VV, Riese RJ, Kurtz CB, Brennan AM. Safety and pharmacodynamics of an engineered E. coli Nissle for the treatment of phenylketonuria: a first-in-human phase 1/2a study. Nat Metab. 2021 Aug;3(8):1125-1132. doi: 10.1038/s42255-021-00430-7. Epub 2021 Jul 22.
PubMed 34294923Charbonneau MR, Denney WS, Horvath NG, Cantarella P, Castillo MJ, Puurunen MK, Brennan AM. Development of a mechanistic model to predict synthetic biotic activity in healthy volunteers and patients with phenylketonuria. Commun Biol. 2021 Jul 22;4(1):898. doi: 10.1038/s42003-021-02183-1.
PubMed 34294862
Study at a glance
From the registry record, last updated by the sponsor on 13 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2a, First-in-human, Oral Single and Multiple Dose-escalation, Randomized, Double-blinded, Placebo-controlled Study of SYNB1618 in Healthy Adult Volunteers and Adult Subjects With Phenylketonuria to Evaluate Safety, Tolerability, Kinetics, and Pharmacodynamics
- ClinicalTrials.gov ID
- NCT03516487
- Acronym / sponsor ID
- PKU / SYNB1618-CP-001
- Conditions
- Phenylketonuria, Healthy
- Keywords
- PKU
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 70 participants (actual)
- Lead sponsor
- SynlogicIndustry (pharma, biotech, devices)
- Study start
- 17 Apr 2018 (actual)
- Primary completion
- 21 Jun 2019 (actual)
- Study completion
- 21 Jun 2019 (actual)
- First posted
- 4 May 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This Phase 1/2a, first-in-human, oral single and multiple dose-escalation, randomized, double-blinded, placebo-controlled study is evaluating SYNB1618 in healthy volunteers (HV) and subjects diagnosed with phenylketonuria (PKU), a rare inherited metabolic disorder that occurs in people who are missing an enzyme that the body needs to use phenylalanine (Phe). Eligible subjects receive investigational product (IP) in the clinic and undergo safety monitoring, evaluations, and subsequent follow-up after IP administration.
Detailed description
This study is evaluating the safety, tolerability, kinetics, and pharmacodynamics of SYNB1618 within the following 2 study parts:
Part 1 comprises a single-ascending dose (SAD) study conducted over 4 days in HV male and female subjects in up to 6 dose cohorts (3 treated:1 placebo) to identify the maximum tolerated dose (MTD) within the single-dose range studied. Up to 24 HV subjects are planned for enrollment in this part of the study. Following attainment of the MTD in HV, a SAD cohort of up to 4 subjects (male and female, ≥ 18 years old) previously diagnosed with PKU will be enrolled (3 treated:1 placebo).
Part 2 comprises a multiple-ascending dose (MAD) study conducted in an inpatient setting (6 treated:2 placebo) over 10 days in HV male and female subjects in up to 4 cohorts at doses not exceeding the MTD from the SAD part of the study to identify the MTD of SYNB1618 within the multiple-dose range studied. Up to 32 HV subjects are planned for enrollment in this part of the study. Once the highest MAD cohort and the SAD PKU cohort are completed, a multiple-dose cohort of male and female subjects (≥ 18 years old) previously diagnosed with PKU are evaluated. Up to 20 subjects with PKU are planned for enrollment in the MAD PKU cohort (12 treated:8 placebo).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 16
- Model description
- Dose-escalating, randomized, double-blinded, placebo-controlled
| Arm | Type | Receives |
|---|---|---|
| SAD HV: SYNB1618 (1 x 10^10 CFU) | Experimental | Drug: SYNB1618HV subjects receive a single oral dose of SYNB1618 (1 x 10^10 colony-forming units [CFU]) in a chilled buffered solution on Day 1 in the SAD study (Part 1). |
| SAD HV: SYNB1618 (5 x 10^10 CFU) | Experimental | Drug: SYNB1618HV subjects receive a single oral dose of SYNB1618 (5 x 10^10 CFU) in a chilled buffered solution on Day 1 in the SAD study (Part 1). |
| SAD HV: SYNB1618 (1 x 10^11 CFU) | Experimental | Drug: SYNB1618HV subjects receive a single oral dose of SYNB1618 (1 x 10^11 CFU) in a chilled buffered solution on Day 1 in the SAD study (Part 1). |
| SAD HV SB: SYNB1618 (1 x 10^11 CFU) | Experimental | Drug: SYNB1618HV subjects receive a single oral dose of SYNB1618 (1 x 10^11 CFU) in a chilled buffered solution on Day 1 in the SAD study (Part 1). On Day 1, subjects in this cohort receive a solid breakfast (SB) that contains approximately the same amount of calories and protein as the meal supplement shake given to subjects in the other SAD cohorts. |
| SAD HV: SYNB1618 (2 x 10^11 CFU) | Experimental | Drug: SYNB1618HV subjects receive a single oral dose of SYNB1618 (2 x 10^11 CFU) in a chilled buffered solution on Day 1 in the SAD study (Part 1). |
| SAD HV: SYNB1618 (5 x 10^11 CFU) | Experimental | Drug: SYNB1618HV subjects receive a single oral dose of SYNB1618 (5 x 10^11 CFU) in a chilled buffered solution on Day 1 in the SAD study (Part 1). |
| SAD HV: Placebo | Placebo comparator | Drug: PlaceboHV subjects receive a single oral dose of placebo in a chilled buffered solution on Day 1 in the SAD study (Part 1). |
| SAD PKU: SYNB1618 (7 x 10^10 CFU) | Experimental | Drug: SYNB1618Subjects with PKU receive a single oral dose of SYNB1618 (7 x 10^10 CFU) in a chilled buffered solution on Day 1 in the SAD study (Part 1). |
| SAD PKU: Placebo | Placebo comparator | Drug: PlaceboHV subjects receive a single oral dose of placebo in a chilled buffered solution on Day 1 in the SAD study (Part 1). |
| MAD HV: SYNB1618 (1 x 10^10 CFU) | Experimental | Drug: SYNB1618HV subjects receive oral SYNB1618 (1 x 10^10 CFU) in a chilled buffered solution 3 times per day (TID) for 7 days in the MAD study (Part 2). |
| MAD HV: SYNB1618 (5 x 10^10 CFU) | Experimental | Drug: SYNB1618HV subjects receive oral SYNB1618 (5 x 10^10 CFU) in a chilled buffered solution TID for 7 days in the MAD study (Part 2). |
| MAD HV: SYNB1618 (7 x 10^10 CFU) | Experimental | Drug: SYNB1618HV subjects receive oral SYNB1618 (7 x 10^10 CFU) in a chilled buffered solution TID for 7 days in the MAD study (Part 2). |
| MAD HV: SYNB1618 (1 x 10^11 CFU) | Experimental | Drug: SYNB1618HV subjects receive oral SYNB1618 (1 x 10^11 CFU) in a chilled buffered solution TID for 7 days in the MAD study (Part 2). |
| MAD HV: Placebo | Placebo comparator | Drug: PlaceboHV subjects receive oral placebo in a chilled buffered solution TID for 7 days in the MAD study (Part 2). |
| MAD PKU: SYNB1618 (7 x 10^10 CFU) | Experimental | Drug: SYNB1618Subjects with PKU receive oral SYNB1618 (7 x 10^10 CFU) in a chilled buffered solution TID for 7 days in the MAD study (Part 2). |
| MAD PKU: Placebo | Placebo comparator | Drug: PlaceboSubjects with PKU receive oral placebo in a chilled buffered solution TID for 7 days in the MAD study (Part 2). |
Who may qualify
- Ages
- 18 to 64 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (15 listed)
- Age ≥ 18 to ≤ 64 years.
- Able and willing to voluntarily complete the informed consent process (subject or subject's representative).
- Available for and agrees to all study procedures, including feces, urine, and blood collection and adherence to diet control, inpatient monitoring, follow-up visits, and IP ingestion compliance.
- 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 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 90 days after the last dose of IP, and who do not intend to donate sperm in the period from screening until 3 months following administration of the investigational medical product.
- Female subjects that meet one of the following:
Key exclusion criteria (25 listed)
- 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 confound interpretation of study safety or pharmacodynamic results and, in the judgment of the Investigator, make the subject inappropriate for enrollment.
- Body mass index < 18.5 or ≥ 30 kg/m^2 (> 40 kg/m^2 for PKU subjects).
- History of or current immunodeficiency disorder including autoimmune disorders and human immunodeficiency virus 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SYNB1618SYNB1618 is supplied in a buffered solution in 5 mL polypropylene cryovials with a nominal 5 mL fill volume, administered with 100 mL of masking buffer solution. | Drug | MAD HV: SYNB1618 (1 x 10^10 CFU), MAD HV: SYNB1618 (1 x 10^11 CFU), MAD HV: SYNB1618 (5 x 10^10 CFU), MAD HV: SYNB1618 (7 x 10^10 CFU), MAD PKU: SYNB1618 (7 x 10^10 CFU), SAD HV SB: SYNB1618 (1 x 10^11 CFU), SAD HV: SYNB1618 (1 x 10^10 CFU), SAD HV: SYNB1618 (1 x 10^11 CFU), SAD HV: SYNB1618 (2 x 10^11 CFU), SAD HV: SYNB1618 (5 x 10^10 CFU), SAD HV: SYNB1618 (5 x 10^11 CFU), SAD PKU: SYNB1618 (7 x 10^10 CFU) |
| PlaceboSubjects receive placebo orally in a chilled buffered solution (100 mL). | Drug | MAD HV: Placebo, MAD PKU: Placebo, SAD HV: Placebo, SAD PKU: Placebo |
Primary outcome
Number of Subjects With Treatment-Emergent Adverse Events
Time frame: Up to 4 months
Toxicity is graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.03. Adverse events (AEs) are reported based on clinical laboratory tests, vital sign and weight measurements, physical examinations, electrocardiograms, and any other medically indicated assessments, including subject interviews, from the time informed consent is signed through the end of the safety follow-up period. AEs are considered to be treatment emergent (TEAE) if they occur or worsen in severity after the first dose of study treatment. TEAEs are considered treatment-related if relationship to study drug is possibly related, probably related, or definitely related.
1 secondary outcome
Clearance of SYNB1618 From Feces
Time frame: Up to 4 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 May 2021.
- Derived from this study: PubMed 34294923Puurunen MK, Vockley J, Searle SL, Sacharow SJ, Phillips JA 3rd, Denney WS, Goodlett BD, Wagner DA, Blankstein L, Castillo MJ, Charbonneau MR, Isabella VM, Sethuraman VV, Riese RJ, Kurtz CB, Brennan AM. Safety and pharmacodynamics of an engineered E. coli Nissle for the treatment of phenylketonuria: a first-in-human phase 1/2a study. Nat Metab. 2021 Aug;3(8):1125-1132. doi: 10.1038/s42255-021-00430-7. Epub 2021 Jul 22.
- Derived from this study: PubMed 34294862Charbonneau MR, Denney WS, Horvath NG, Cantarella P, Castillo MJ, Puurunen MK, Brennan AM. Development of a mechanistic model to predict synthetic biotic activity in healthy volunteers and patients with phenylketonuria. Commun Biol. 2021 Jul 22;4(1):898. doi: 10.1038/s42003-021-02183-1.
- Individual participant dataSharing planned: No
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A Study of MZE782 in Adults With PKU
Phenylketonuria (PKU)
RecruitingPhase 3
A Study of Sepiapterin in Participants With Phenylketonuria (PKU)
Phenylketonuria
Recruiting
Impact of Phenylalanine Elevations on Brain and Cognition in Adult PKU Carriers
Carrier of Phenylketonuria, Healthy
RecruitingPhase 3
A Study of JNT-517 in Participants With Phenylketonuria (PKU)
Phenylketonuria
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing SYNB1618 in people with Phenylketonuria and Healthy, run by Synlogic at 4 sites 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 15 inclusion and 25 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 13 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 Subjects With Treatment-Emergent Adverse Events (time frame: Up to 4 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03516487, which also lists 2 linked publications.
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 13 May 2021.