A Phase 3 Multi-Center Study to Evaluate the Safety and Efficacy of Subcutaneous Injections of Pegvaliase in Adolescent Subjects (Ages 12- 17) with Phenylketonuria

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Biomarin Pharmaceutical Inc.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

Trial duration

25 Oct 2022 → ongoing

Decision date (initial)

2024-07-04

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

BioMarin Pharmaceutical Inc., United States

External identifiers

EU CT number

2024-510875-39-00

EudraCT number

2021-005058-27

WHO UTN

U1111-1304-1217

ClinicalTrials.gov

NCT05270837

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacokinetic, Therapy, Safety

1 - To evaluate the efficacy of pegvaliase in adolescent participants with PKU
2 - To evaluate the safety of pegvaliase in adolescent participants with PKU

Secondary objectives 2

1. To characterize total dietary protein intake in adolescent participants with PKU after pegvaliase treatment
2. To characterize the pharmacokinetics (PK) of pegvaliase in adolescent participants with PKU

Conditions and MedDRA coding

Phenylketonuria (PKU)

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-001951-PIP01-16

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Is 12 to 17 years old (US), inclusive, and 12 to 15 years old, (ex-US), inclusive, at the start of the Screening / Run in Period (Day 28).
2. Diagnosis of PKU and failure to maintain recommended blood Phe levels on existing management (defined as failed both sapropterin dihydrochloride treatment and Phe-restricted diet) demonstrated by 2 blood Phe concentration measurements > 600 µmol/L during the Screening/Run-in Period (7 to 10 days in between blood Phe assessments) and average blood Phe concentration > 600 µmol/L over the past 12 months (per available data).
3. Willing and able to maintain and adjust dietary and medical protein food intake according to the study protocol and under the supervision of study dietician or adequately trained designee per investigator during study participation.
4. If on medication for ADHD, depression, or other psychiatric disorder, stable dose of medication for ≥ 8 weeks prior to enrollment and willing to maintain stable dose unless a change is medically indicated.
5. An adult (≥ 18 years of age) has been identified who is willing and competent to observe the participant during study drug administration and for a minimum of 1 hour following administration.
6. Able and willing to comply with all study procedures.
7. Generally in good health, as evidenced by physical examination, clinical laboratory evaluations (hematology, chemistry, and urinalysis), and electrocardiogram (ECG) tests performed at Screening.
8. Males and females are eligible to participate in this clinical study.
9. Females with childbearing potential must have a negative pregnancy test at Screening/Run-in and be willing to have additional pregnancy tests during the study.

Exclusion criteria 6

1. Have a history of a severe systemic hypersensitivity reaction or recurrence of a mild to moderate acute systemic hypersensitivity reaction to any of the excipients or another PEGylated medicinal product.
2. Taking any of the prohibited medications outlined in Section 6.8.1.
3. Previous treatment with pegvaliase.
4. Use of any medication that is intended to treat PKU, including the use of large neutral amino acids, within 14 days prior to the administration of study drug on Day 1.
5. Use or planned use of any injectable drugs containing polyethylene glycol (PEG; other than pegvaliase), including medroxyprogesterone injection, within 3 months prior to the start of Screening/Run-in and during study participation with the exception of COVID-19 vaccinations (Section 6.8.1).
6. A history of organ transplantation or on chronic immunosuppressive therapy.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Safety will be evaluated by assessment of AEs, SAEs, laboratory test results (chemistry, hematology, and urinalysis), vital signs physical examination, ECG and anti-BMN165 immunogenicity test results

Secondary endpoints 2

1. Change from baseline in total dietary protein intake (ie, medical food and/or intact food).
2. Plasma sample for trough PK

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Biomarin Pharmaceutical Inc.

Sponsor organisation

Biomarin Pharmaceutical Inc.

Address

105 Digital Drive

City

Novato

Postcode

94949-8703

Country

United States

Scientific contact point

Organisation

Biomarin Pharmaceutical Inc.

Contact name

Clinical Trial Information Desk

Public contact point

Organisation

Biomarin Pharmaceutical Inc.

Contact name

Clinical Trial Information Desk

Third parties 8

Locations

1 EU/EEA country · 3 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 18 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications