Immune Modulation During Palynziq® Treatment in Adults (IMPALA)
ConditionPhenylketonuria
Trial statusRecruiting
Trial phasePhase 4
Trial typeInterventional
Biological sexAll
Age18-65
SponsorBioMarin Pharmaceutical
About this trial
Study 165-401 is a Phase 4, open-label study designed to examine the concomitant use of methotrexate (MTX) to suppress immune responses to Palynziq and improve tolerability and efficacy in adults with PKU.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Adults between 18 and 65 years old
Have a confirmed diagnosis of phenylketonuria (PKU)
Are in generally good health based on medical evaluation
Are willing and medically eligible to receive Palynziq and methotrexate (MTX) Cohort A: Have never taken Palynziq before and are willing to start it during the study Cohort B: Have blood > 600 μmol/L after taking Palynziq for at least 24 weeks, are on a daily dose of at least 20mg and unable to increase the dose further
Disqualifiers
Pregnant, breastfeeding, planning to become pregnant, planning to father a child, or not using effective birth control if applicable
Have a known severe allergy or hypersensitivity reaction to methotrexate (MTX), Palynziq, or other PEG-containing medications
Have a serious active infection or a history of severe or recurrent infections
Have significant medical conditions that may affect safety or participation (such as serious heart, lung, liver, kidney, immune, neurological, psychiatric, or cancer-related conditions)
Trial design
Design model
Parallel
Treatments tested in this trial
Pegvaliase
Biological/VaccinePegvaliase (Palynziq) administered by subcutaneous injection. Dosing follows U.S. Prescribing Information and investigator judgement.
Methotrexate
DrugOral methotrexate 15 mg administered once weekly during the Tolerability Period and the Combination Treatment Period.
Treatment groups
12 Participants
are divided into 2 treatment groupsGroup A: Palynziq naïveExperimental treatment 2 interventions
Group B: Palynziq experiencedExperimental treatment 2 interventions
Trial outcomes
Primary outcomes
1
Change in blood Phe levels from baseline to Week 25 and Week 49
To evaluate blood Phe response in adults with PKU co-administered Palynziq with MTX for 6 months
Time frame
Baseline to Week 25 and Baseline to Week 492
Anti-PEG IgG, IgM, anti-PAL IgG, IgM levels at Weeks 5, 9, 25, and 49
To evaluate the ability of MTX to modulate the immune response to Palynziq in adults with PKU
Time frame
Baseline to Week 5, Week 9, Week 25, and Week 49Secondary outcomes
1
Incidence of TEAEs
To evaluate the safety of co-administration of Palynziq with MTX in adults with PKU. A TEAE is defined as any AE that newly appeared, increased in frequency, or worsened in severity following initiation of the study drugs (MTX or Palynziq) administration. Incidence of TEAEs will be defined as (number of TEAEs)/(total exposure time in person-years) \*100
Time frame
Baseline through Week 492
Trough Palynziq plasma PK
To characterize the PK of Palynziq during co-administration with MTX in adults with PKU
Time frame
Baseline through Week 49Other outcomes
1
Change in IgG-C3d CIC, C3, C4 levels from baseline to Weeks 9, 25, and 49
To evaluate formation of CIC and activation of complement pathway. Change from baseline to time t for each participant will be defined as (blood level at time t) - (blood level at baseline)
Time frame
Baseline to Weeks 9, 25, and 492
Percentage of participants in Cohort B that have escalated from dose at enrollment
To evaluate ability to dose escalate in Cohort B participants following co-administration of Palynziq with MTX
Time frame
Baseline to Week 24 and Week 48Sponsors and contacts
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Source ClinicalTrials.gov