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NCT00924703

Long-Term Extension of Previous rAvPAL-PEG Protocols in Subjects With PKU (PAL-003)

Completed Phase 2 Results posted Last updated 12 October 2021
What this trial tests

Phase 2 trial testing rAvPAL-PEG in Phenylketonuria in 68 participants. Completed in 31 January 2019.

Timeline
13 January 2010
Primary endpoint
31 January 2019
31 January 2019

Quick facts

Lead sponsorBioMarin Pharmaceutical
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment68
Start date13 January 2010
Primary completion31 January 2019
Estimated completion31 January 2019
Sites14 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

BioMarin Pharmaceutical — full company profile →

Who can join

Adults 16 to 55, any sex, with Phenylketonuria. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Baseline in the Blood Phenylalanine (Phe) Concentration Primary · At Baseline and Change from Baseline to Week 48, Week 96, Week 144, Week 216, and Week 240

Blood Phe Concentration (Change from Baseline) and Daily Dose in PAL-003 Subjects by Disposition (PAL-003 Population)

Baseline
GroupValue95% CI
rAvPAL-PEG1022.4± 530.39
Change from Baseline to Week 48
GroupValue95% CI
rAvPAL-PEG-553.5± 652.95
Change from Baseline to Week 96
GroupValue95% CI
rAvPAL-PEG-653.3± 637.81
Change from Baseline to Week 144
GroupValue95% CI
rAvPAL-PEG-672.3± 621.06
Change from Baseline to Week 216
GroupValue95% CI
rAvPAL-PEG-535.9± 573.08
Change from Baseline to Week 240
GroupValue95% CI
rAvPAL-PEG-574.9± 549.90
Pharmacokinetics-Plasma Pegvaliase Concentration Secondary · At Baseline, Week 48, Week 96, Week 144, Week 216 and Week 240

Steady-state Pharmacokinetics (PK) of pegvaliase was measured in subjects who have achieved and maintained target blood Phe

At Baseline
GroupValue95% CI
rAvPAL-PEG961.5± 3013.43
Week 48
GroupValue95% CI
rAvPAL-PEG4127.3± 6116.72
Week 96
GroupValue95% CI
rAvPAL-PEG7457.7± 10685.02
Week 144
GroupValue95% CI
rAvPAL-PEG7196.1± 11678.89
Week 216
GroupValue95% CI
rAvPAL-PEG7764.4± 9292.34
Week 240
GroupValue95% CI
rAvPAL-PEG6557.8± 9220.95
Number of Subjects With Treatment Emergent Adverse Events (TEAEs) Secondary · Up to 109 months.

A treatment-emergent AE was defined as any adverse event (AE) newly appearing or worsened in severity following initiation of study drug until 4 weeks after last dose of pegvaliase (PAL-003)

Subjects with any adverse event
GroupValue95% CI
rAvPAL-PEG68
Subjects with any serious adverse events
GroupValue95% CI
rAvPAL-PEG12
Subjects with any treatment-related adverse event
GroupValue95% CI
rAvPAL-PEG65
Any treatment-related serious adverse event
GroupValue95% CI
rAvPAL-PEG6
Death
GroupValue95% CI
rAvPAL-PEG0
Percentage of Participants With Positive PEG IgG Antibody Secondary · At Baseline and Change from Baseline to Week 24, Week 52, Week 104 and Week 156

The presence of IgG Antibodies against PEG (polyethylene glycol) is measured overtime

Baseline
GroupValue95% CI
rAvPAL-PEG29
Change from Baseline to Week 24
GroupValue95% CI
rAvPAL-PEG24
Change from Baseline to Week 52
GroupValue95% CI
rAvPAL-PEG14
Change from Baseline to Week 104
GroupValue95% CI
rAvPAL-PEG2
Change from Baseline to Week 156
GroupValue95% CI
rAvPAL-PEG7
Percentage of Participants With Positive PAL IgG Antibody Secondary · At Baseline and Change from Baseline to Week 24, Week 52, Week 104 and Week 156

The presence of IgG Antibodies against PAL (phenylalanine ammonia lyase) is measured overtime

Baseline
GroupValue95% CI
rAvPAL-PEG10
Change from Baseline to Week 24
GroupValue95% CI
rAvPAL-PEG63
Change from Baseline to Week 52
GroupValue95% CI
rAvPAL-PEG60
Change from Baseline to Week 104
GroupValue95% CI
rAvPAL-PEG48
Change from Baseline to Week 156
GroupValue95% CI
rAvPAL-PEG45

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 109 months.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

rAvPAL-PEG
Serious: 12/68 (18%)
Deaths: 0/68

Serious adverse events (21 terms)

ReactionSystemrAvPAL-PEG
AsthmaRespiratory, thoracic and mediastinal disorders
HypersensitivityImmune system disorders
Abortion inducedSurgical and medical procedures
Anaphylactic reactionImmune system disorders
AppendicitisInfections and infestations
ArthralgiaMusculoskeletal and connective tissue disorders
BacteraemiaInfections and infestations
Bacterial infectionInfections and infestations
Bone marrow failureBlood and lymphatic system disorders
Diarrhoea infectiousInfections and infestations
HyponatraemiaMetabolism and nutrition disorders
HypotensionVascular disorders
Injection related reactionInjury, poisoning and procedural complications
LymphadenopathyBlood and lymphatic system disorders
Neuropathy peripheralNervous system disorders
NeutropeniaBlood and lymphatic system disorders
PanniculitisSkin and subcutaneous tissue disorders
Postoperative wound complicationInjury, poisoning and procedural complications
Staphylococcal infectionInfections and infestations
Suicide attemptPsychiatric disorders
UrticariaSkin and subcutaneous tissue disorders
Other adverse events (132 terms — click to expand)

ReactionSystemrAvPAL-PEG
NasopharyngitisInfections and infestations
HeadacheNervous system disorders
RashSkin and subcutaneous tissue disorders
ArthralgiaMusculoskeletal and connective tissue disorders
Injection site reactionGeneral disorders
Injection site erythemaGeneral disorders
Injection site bruisingGeneral disorders
Upper respiratory tract infectionInfections and infestations
UrticariaSkin and subcutaneous tissue disorders
CoughRespiratory, thoracic and mediastinal disorders
Oropharyngeal painRespiratory, thoracic and mediastinal disorders
NauseaGastrointestinal disorders
VomitingGastrointestinal disorders
Back painMusculoskeletal and connective tissue disorders
PruritusSkin and subcutaneous tissue disorders
DiarrhoeaGastrointestinal disorders
DizzinessNervous system disorders
PyrexiaGeneral disorders
Pain in extremityMusculoskeletal and connective tissue disorders
SinusitisInfections and infestations
ContusionInjury, poisoning and procedural complications
Injection site pruritusGeneral disorders
Nasal congestionRespiratory, thoracic and mediastinal disorders
MyalgiaMusculoskeletal and connective tissue disorders
Abdominal painGastrointestinal disorders
Injection site painGeneral disorders
Injection site urticariaGeneral disorders
Neck painMusculoskeletal and connective tissue disorders
FatigueGeneral disorders
Injection site swellingGeneral disorders
Rash erythematousSkin and subcutaneous tissue disorders
PainGeneral disorders
Sinus congestionRespiratory, thoracic and mediastinal disorders
MigraineNervous system disorders
InsomniaPsychiatric disorders
ErythemaSkin and subcutaneous tissue disorders
Urinary tract infectionInfections and infestations
ToothacheGastrointestinal disorders
DepressionPsychiatric disorders
InfluenzaInfections and infestations

Most-reported serious reactions: Asthma, Hypersensitivity, Abortion induced, Anaphylactic reaction, Appendicitis, Arthralgia, Bacteraemia, Bacterial infection.

Data from ClinicalTrials.gov NCT00924703 adverse events section.

Sponsor's own description

This study is an extension of previous rAvPAL-PEG studies. Administration of rAvPAL-PEG will be continued to assess whether long-term dosing of rAvPAL-PEG is safe and can maintain reduced blood Phe concentrations in PKU subjects.

Publications & conference data

7 peer-reviewed publications reference this trial (live from Europe PMC):

  1. A Comprehensive Review of Pegvaliase, an Enzyme Substitution Therapy for the Treatment of Phenylketonuria.
    Hydery T, Coppenrath VA. · · 2019 · cited 38× · PMID 31258325 · DOI 10.1177/1177392819857089
  2. Evaluation of orally administered PEGylated phenylalanine ammonia lyase in mice for the treatment of Phenylketonuria.
    Sarkissian CN, Kang TS, Gámez A, Scriver CR, et al · · 2011 · cited 33× · PMID 21803624 · DOI 10.1016/j.ymgme.2011.06.016
  3. Long-term safety and efficacy of pegvaliase for the treatment of phenylketonuria in adults: combined phase 2 outcomes through PAL-003 extension study.
    Longo N, Zori R, Wasserstein MP, Vockley J, et al · · 2018 · cited 26× · PMID 29973227 · DOI 10.1186/s13023-018-0858-7
  4. Pegvaliase for the treatment of phenylketonuria: Results of the phase 2 dose-finding studies with long-term follow-up.
    Burton BK, Longo N, Vockley J, Grange DK, et al · · 2020 · cited 24× · PMID 32593547 · DOI 10.1016/j.ymgme.2020.06.006
  5. Long-term comparative effectiveness of pegvaliase versus standard of care comparators in adults with phenylketonuria.
    Zori R, Ahring K, Burton B, Pastores GM, et al · · 2019 · cited 24× · PMID 31439512 · DOI 10.1016/j.ymgme.2019.07.018
  6. Pharmacokinetic, pharmacodynamic, and immunogenic rationale for optimal dosing of pegvaliase, a PEGylated bacterial enzyme, in adult patients with phenylketonuria.
    Qi Y, Patel G, Henshaw J, Gupta S, et al · · 2021 · cited 16× · PMID 34057292 · DOI 10.1111/cts.13043
  7. Pegvaliase for the treatment of phenylketonuria: Final results of a long-term phase 3 clinical trial program.
    Harding CO, Longo N, Northrup H, Sacharow S, et al · · 2024 · cited 12× · PMID 38694233 · DOI 10.1016/j.ymgmr.2024.101084

Verify or expand the search:

Other recruiting trials for Phenylketonuria

Currently open trials in the same condition.

Other BioMarin Pharmaceutical trials

Trials by the same sponsor.

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing