NCT03516487

Safety and Tolerability of SYNB1618 in Healthy Adult Volunteers and Adult Subjects With Phenylketonuria

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

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 70 (actual)
• Sponsor: Synlogic · Industry
• Sex: All
• Age: 18 Years – 64 Years
• Healthy volunteers: Accepted

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 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).

Conditions

• Phenylketonuria
• Healthy

Interventions

Type	Name	Description
DRUG	SYNB1618	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.
DRUG	Placebo	Subjects receive placebo orally in a chilled buffered solution (100 mL).

Timeline

• Start date: 2018-04-17
• Primary completion: 2019-06-21
• Completion: 2019-06-21
• First posted: 2018-05-04
• Last updated: 2021-05-13

Locations

4 sites across 1 country: United States

Regulatory

• FDA-regulated drug study