Pegvaliase for Phenylketonuria

(PEGASUS Trial)

Recruiting at 21 trial locations

Overseen By Trial Specialist

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: BioMarin Pharmaceutical

Must not be taking: PKU treatments, PEG injectables

Disqualifiers: Organ transplant, HIV, Hepatitis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 72 weeks

55 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you must stop any PKU treatments and certain injectable drugs before starting the study. If you're on medication for ADHD, depression, or other psychiatric disorders, you can continue as long as the dose is stable.

What data supports the effectiveness of the drug Pegvaliase for treating Phenylketonuria?

Research shows that Pegvaliase effectively reduces blood phenylalanine levels in adults with phenylketonuria, with about 70% of patients achieving significant reductions. It also allows patients to consume a normal protein diet without needing special medical foods. ^{1 2 3 4 5}

Is Pegvaliase safe for humans?

Pegvaliase has been studied for safety in adults with phenylketonuria (PKU), and while it can help lower certain blood levels, it may cause immune reactions and hypersensitivity (allergic) responses. Long-term studies have been conducted to assess its safety, but careful patient selection is important due to potential harmful effects. ^{3 4 5 6 7}

How does the drug Pegvaliase differ from other treatments for phenylketonuria?

Pegvaliase is unique because it is an enzyme replacement therapy that uses a modified enzyme to break down phenylalanine, a substance that builds up in people with phenylketonuria. Unlike other treatments, it allows patients to consume a normal protein diet without relying on special medical foods. ^{2 3 4 5 6}

What is the purpose of this trial?

This trial is testing pegvaliase injections in adolescents with PKU. The goal is to see if these injections are safe and effective. Pegvaliase helps the body break down a harmful substance that people with PKU cannot process on their own. Pegvaliase is a newer treatment for PKU, following earlier treatments like dietary restriction and sapropterin.

Research Team

Study Director

Principal Investigator

BioMarin Pharmaceutical

Eligibility Criteria

This trial is for adolescents aged 12-17 in the US (or 12-15 in the EU) with Phenylketonuria (PKU) who haven't been able to control their blood Phe levels through current treatments. They must be stable on any psychiatric meds, willing to follow a diet plan, and have an adult supervisor during treatment. Sexually active participants need to use two forms of contraception.

Inclusion Criteria

I am using two forms of birth control and do not plan to get pregnant or father a child while in the study.

I've been on a stable dose of my psychiatric medication for at least 8 weeks and can keep it steady.

I am able to understand and sign the consent form.

Exclusion Criteria

Your creatinine levels in your blood are higher than 1.5 times the normal upper limit.

I haven't used any PEG-containing injectable drugs recently, except for COVID-19 vaccines.

I have had an organ transplant or am on long-term immune-weakening medication.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive daily pegvaliase injections or manage PKU with diet alone

72 weeks

Crossover Treatment

Participants in the diet-only control arm initiate pegvaliase treatment

143 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Pegvaliase

Trial Overview The study tests Pegvaliase injections against a diet-only approach in managing PKU. It's an open-label Phase 3 trial where about 54 young people are randomly assigned to either get the drug or stick with dietary management to see which is safer and works better.

Participant Groups

Group I: Pegvaliase Experimental Treatment 1 Intervention

Group II: Drug: Diet Only Experimental Treatment 1 Intervention

Participants will be managing their PKU with diet alone. Participants in the diet-only control arm will be required to maintain and adjust dietary and medical protein food intake through Week 72, initiating pegvaliase treatment beginning Week 73 and, from Weeks 73 through 215.

Who Is Running the Clinical Trial?

BioMarin Pharmaceutical

Lead Sponsor

Trials

162

Recruited

115,000+

Alexander Hardy

BioMarin Pharmaceutical

Chief Executive Officer since 2023

MBA from INSEAD

Greg Friberg

BioMarin Pharmaceutical

Chief Medical Officer

MD from New York Medical College

Findings from Research

Pegvaliase, an injectable enzyme therapy for phenylketonuria (PKU), can cause Type III hypersensitivity reactions, particularly during the initial induction and titration phases, but these reactions tend to decrease over time with continued treatment due to factors like antibody affinity maturation.

To manage hypersensitivity adverse events (HAEs) effectively, it is recommended to use a slow induction and titration regimen, premedication with H1-receptor antagonists, and to ensure patients carry auto-injectable adrenaline, which can improve tolerability and safety during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pegvaliase: Immunological profile and recommendations for the clinical management of hypersensitivity reactions in patients with phenylketonuria treated with this enzyme substitution therapy. Hausmann, O., Daha, M., Longo, N., et al.[2020]

References

1. United States pubmed.ncbi.nlm.nih.gov

First 1.5 years of pegvaliase clinic: Experiences and outcomes. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

Nutrition status of adults with phenylketonuria treated with pegvaliase. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Case-control study about the acceptance of Pegvaliase in Phenylketonuria. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Pegvaliase for the treatment of phenylketonuria: Results of the phase 2 dose-finding studies with long-term follow-up. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Long-term safety and efficacy of pegvaliase for the treatment of phenylketonuria in adults: combined phase 2 outcomes through PAL-003 extension study. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Pegvaliase for the treatment of phenylketonuria: A pivotal, double-blind randomized discontinuation Phase 3 clinical trial. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Pegvaliase: Immunological profile and recommendations for the clinical management of hypersensitivity reactions in patients with phenylketonuria treated with this enzyme substitution therapy. [2020]