| Eligibility |
Inclusion Criteria:
1. Age = 18 years.
2. Able and willing to voluntarily complete the informed consent process.
3. 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).
4. Blood Phe = 600 µmol/L at Screening.
5. Stable diet including stable medical formula regimen (if used) for at least 1 month
prior to Screening.
6. Available for and agree to all study procedures, including urine and blood collection,
adherence to diet control, follow-up visits, and IMP ingestion compliance.
7. Male patients who are sexually abstinent or surgically sterilized (vasectomy), or
those who are sexually active with a female partner(s) and agree to use an effective
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 #8 below) after informed consent, throughout the study, and for a
minimum of 3 months after the last dose of IMP, and who do not intend to donate sperm
in the period from Screening until 3 months following administration of the IMP.
8. Female patients who meet one of the following criteria:
1. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test
(human chorionic gonadotropin) at Screening and a negative urine pregnancy test
at Baseline prior to the start of IMP 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 #7 above) after informed
consent, throughout the study, and for a minimum of 3 months after the last dose
of IMP. Acceptable methods of contraception include hormonal contraception,
hormonal or non-hormonal intrauterine device, bilateral tubal occlusion, complete
abstinence, vasectomized partner with documented azoospermia 3 months after
procedure, diaphragm with spermicide, cervical cap with spermicide, vaginal
sponge with spermicide, or male or female condom with or without spermicide.
2. 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).
9. 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.
Exclusion Criteria:
1. Currently taking Palynziq® (pegvaliase-pqpz) (within 1 month of Screening).
2. Inflammatory or irritable bowel disorder of any grade.
3. History of or current immunodeficiency disorder.
4. Intolerance of or allergic reaction to E. coli Nissle or any of the ingredients in
SYNB1618 formulation.
5. 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.
6. 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.
7. 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.
8. Dependence on alcohol or drugs of abuse.
9. 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.
10. 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.
|
