A Phase 1/2 study to evaluate the safety and efficacy of BMN 307 gene therapy in patients with phenylketonuria

• Register: EUCTR
• Last refreshed on: 4 May 2020
• Main ID: EUCTR2019-001878-28-GB
• Date of registration: 21/11/2019
• Prospective Registration: Yes
• Primary sponsor: BioMarin Pharmaceutical Inc.
• Public title: A Phase 1/2 study to evaluate the safety and efficacy of BMN 307 gene therapy in patients with phenylketonuria
• Scientific title: A Phase 1/2 Open-Label, Dose Escalation Study to Determine the Safety and Efficacy of BMN 307, an Adeno-Associated Virus Vector-Mediated Gene Transfer of Human Phenylalanine Hydroxylase in Subjects with Phenylketonuria and Plasma Phe Levels > 600 µmol/L - A Phase 1/2 study to evaluate the safety and efficacy of BMN 307
• Date of first enrolment: 17/12/2019
• Target sample size: 100
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2019-001878-28
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no
• Phase: Human pharmacology (Phase I): yes Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Germany, Italy, Spain, Taiwan, Turkey, United Kingdom, United States

Contacts

• Name: Clinical Trials Information
• Affiliation: BioMarin Pharmaceutical Inc.

• Name: Clinical Trials Information
• Affiliation: BioMarin Pharmaceutical Inc.

Key inclusion & exclusion criteria

Inclusion criteria:
1. age 15 or 18 years and older at Screening
2. Diagnosis of PKU which is a condition characterized by PAH deficiency
3. Average of two plasma Phe levels > 600 µmol/L during the Screening period
4. Ability and willingness to maintain dietary protein intake consistent with baseline intake for the duration of the study unless otherwise directed.

Are the trial subjects under 18? yes
Number of subjects for this age range: 8
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 100
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

Exclusion criteria:
1. Subjects with primary BH4 deficiency or other forms of BH4 metabolism deficiency.
2. Clinically significant liver disease as assessed by ultrasound at Screening.
3. Prior treatment with gene therapy.
4. Detectable antibodies to the AAV5 capsid at Screening.
5. Contraindication to use of corticosteroids (CS) or history of condition that could worsen with CS therapy.
6. Hemoglobin A1C = 8.0% or glucose = 250 mg/dL at Screening.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Phenylketonuria
MedDRA version: 20.0 Level: PT Classification code 10034872 Term: Phenylketonuria System Organ Class: 10010331 - Congenital, familial and genetic disorders

Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

Intervention(s)

Product Code: BMN 307
Pharmaceutical Form: Solution for infusion
Current Sponsor code: BMN 307
Concentration unit: Other
Concentration type: equal
Concentration number: 6E13-

Primary Outcome(s)

Secondary Objective: - Determine the efficacy of a single administration of BMN 307 on changing plasma Phe level over time
- Assess the change in dietary protein intake post-infusion following a single administration of BMN 307
- Assess changes in dietary Phe and protein intake over time following a single administration of BMN 307

Timepoint(s) of evaluation of this end point: Week 10 - 12

Primary end point(s): - Change in mean plasma Phe levels

Main Objective: - Determine safe, effective, and tolerable dose of BMN 307
- Determine the efficacy of a single administration of BMN 307

Secondary Outcome(s)

Secondary end point(s): - Change in mean plasma Phe levels
- Proportion of subjects achieving plasma Phe milestones
- Change in dietary protein intake from intact food
- Proportion of subjects consuming protein from intact food while maintaining plasma Phe

Timepoint(s) of evaluation of this end point: Week 22 - 24, Week 24, Week 48, Week 96

Secondary ID(s)

307-201

Source(s) of Monetary Support

BioMarin Pharmaceutical Inc.

Ethics review

Status: Approved
Approval date: 13/12/2019
Contact: