Phenylketonuria (PKU) Clinical Trials

Experimental: Palynziq naïve

Individuals with uncontrolled blood phenylalanine (Phe) \> 600 μmol/L on existing management who have never been treated with Palynziq. Participants will have a 4-week Screening Period, followed by a 4-week MTX Tolerability Period during which only MTX will be administered. If MTX is tolerated during the MTX Tolerability Period, the participant will then enter the 24-week Combination Treatment Period during which MTX + Palynziq will be administered concurrently. After completion of Week 24 (Combination Treatment Period), MTX will be discontinued for both cohorts and Palynziq only will continue for another 24 weeks (to Week 49).

Experimental: Palynziq experienced

Individuals who have uncontrolled blood Phe \> 600 μmol/L after ≥ 24 consecutive weeks of treatment with Palynziq, are on a current dose of ≥ 20mg/day and are unable to further dose escalate (Palynziq experienced). Participants will have a 4-week Screening Period. Participants will then have 24 weeks of concurrent MTX + Palynziq treatment (Combination Treatment Period): participants will be assessed for MTX tolerability during the first 4 weeks of MTX + Palynziq (MTX Tolerability Period) and then receive another 20 weeks of MTX + Palynziq. After completion of Week 24 (Combination Treatment Period), MTX will be discontinued for both cohorts and Palynziq only will continue for another 24 weeks (to Week 49).