A Phase 3b, Open-Label, Single Arm, Multi-Centre Study to Assess the Safety and Efficacy of Pegvaliase (BMN 165) Treatment in adults With Phenylketonuria Not Controlled With Current Management

• Register: EUCTR
• Last refreshed on: 25 November 2019
• Main ID: EUCTR2018-000648-25-NL
• Date of registration: 13/11/2018
• Prospective Registration: Yes
• Primary sponsor: BioMarin Pharmaceutical Inc.
• Public title: A Phase 3b, Open-Label, Single Arm, Multi-Centre Study to Assess the Safety and Efficacy of Pegvaliase (BMN 165) Treatment in adults With Phenylketonuria Not Controlled With Current Management
• Scientific title: A Phase 3b, Open-Label, Single Arm, Multi-Centre Study to Assess the Safety and Efficacy of Pegvaliase (BMN 165) Treatment in adults With Phenylketonuria Not Controlled With Current Management - OPTIC Study
• Target sample size: 85
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2018-000648-25
• 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; Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Austria, France, Germany, Italy, Netherlands, Spain, Turkey

Contacts

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

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

Key inclusion & exclusion criteria

Inclusion criteria:
1. Aged = 18 years of age at the time of Screening.
2. A current diagnosis of PKU with both of the following:
a. Average Phe concentration of > 600 µmol/L at Screening Visits 1 and 2.
b. Average blood Phe concentration of > 600 µmol/L over the past 6 months (per available data).
3. Has identified a competent person or persons = 18 years of age who can observe the subject during study drug administration and for a minimum of 1 hour following administration for at least the first 6 months of self-administration. A home healthcare nurse may perform the study drug observations.
4. For females of childbearing potential, must have a negative pregnancy test at Screening and be willing to have additional pregnancy tests during the study. (Females are considered not to have childbearing potential if they have been in menopause for at least 2 years, have had a tubal ligation at least 1 year prior to Screening, or have had a total hysterectomy).
5. If sexually active, must be willing to use two acceptable methods of contraception while participating in the study and 4 weeks after completion of the study:
a. Acceptable methods of contraception may include: (1) primary forms: hormonal (combination hormone-containing pills, patch, vaginal ring, or intrauterine device) or non-hormonal (copper-containing intrauterine device); (2) secondary forms: include barrier forms and other forms of birth control and must include spermicide (eg, male condom; female condom is not an acceptable secondary form).
b. Males (including partners) post vasectomy for 2 years with no known pregnancies do not need to use any other forms of contraception during the study.
c. Females (including partners) who have been in menopause for at least 2 years, have had a tubal ligation at least 1 year prior to Screening, or have had a total hysterectomy do not need to use any other forms of contraception during the study.
6. Is willing and able to provide written, signed informed consent after the nature of the study has been explained and prior to any research-related procedures.
7. Is willing and able to comply with all study procedures.
8. Is in generally good health, as evidenced by physical examination.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 85
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. In the judgment of the investigator, is likely to be able to achieve control of blood Phe below 600 µmol/L with MNT (basis of judgment documented).
2. In the judgment of the investigator, is likely to be able to achieve control of blood Phe below 600 µmol/L with sapropterin (Kuvan) (basis of judgment documented).
3. Use of any medication that is intended to treat PKU including the use of sapropterin (Kuvan), within 14 days prior to administration of study drug (Day 1; first dose of pegvaliase).
4. Not willing or unlikely to be able to perform independent self-administration (or to allow carer administration) or not have the ability to recognise the signs and symptoms of acute systemic hypersensitivity reactions (ASHRs).
5. Not willing or unlikely to be able to use adrenaline/epinephrine injection device (auto injector or prefilled syringe) and have them readily available at all times throughout pegvaliase treatment.
6. Not willing or unlikely to be able to maintain their diet in accordance with dietary information presented in the protocol.
7. Based on the clinical judgement of the investigator, does not have the neurocognitive and linguistic capacities to comprehend and answer the patient-reported outcome questionnaires.
8. Not willing or unlikely to be able to complete the study diary.
9. Use or planned use of any injectable drugs containing PEG (other than pegvaliase), including medroxyprogesterone injection, within 3 months prior to Screening and during study participation.
10. Concurrent disease or condition that would interfere with study participation or safety.
11. Alanine aminotransferase (ALT) concentration = 2 times the upper limit of normal (ULN).
12. Subjects with known renal pathology, persistent albuminuria (elevated urine albumin creatinine ratio above the ULN measured on first morning void, confirmed on a repeat measurement), or creatinine > 1.5 times the ULN.
13. Pregnant or breastfeeding at Screening or planning to become pregnant (subject or partner of subject) or breastfeed at any time during the study.
14. Use of any investigational product or investigational medical device within 30 days prior to Screening or requirement for any investigational agent prior to completion of all scheduled study assessments.
15. Previous exposure to pegvaliase.
16. Any condition that, in the view of the investigator, places the subject at high risk of poor treatment compliance or terminating early from study.


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

Health Condition(s) or Problem(s) studied

Phenylketonuria (PKU)
MedDRA version: 20.0 Level: LLT Classification code 10034873 Term: Phenylketonuria (PKU) System Organ Class: 100000004850

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

Intervention(s)

Product Name: Pegvaliase
Pharmaceutical Form: Solution for injection
INN or Proposed INN: PEGVALIASE
CAS Number: 1585984-95-7
Current Sponsor code: pegvaliase, rAvPAL-PEG, PEG-PAL, PAL-PEG
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2.5-

Product Name: Pegvaliase
Pharmaceutical Form: Solution for injection
INN or Proposed INN: PEGVALIASE
CAS Number: 1585984-95-7
Current Sponsor code: pegvaliase, rAvPAL-PEG, PEG-PAL, PAL-PEG
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-

Product Name: Pegvaliase
Pharmaceutical Form: Solution for injection
INN or Proposed INN: PEGVALIASE
CAS Number: 1585984-95-7
Current Sponsor code: pegvaliase, rAvPAL-PEG, PEG-PAL, PAL-PEG
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-

Primary Outcome(s)

Secondary Objective: To evaluate whether treatment with pegvaliase can enable reduction or discontinuation of medical food protein intake and increase of intact (natural, complete) protein intake using a prospectively defined algorithm, whilst still maintaining blood Phe control (= 600 µmol/L).

Timepoint(s) of evaluation of this end point: A subject is considered to have achieved Phe concentration = 600 µmol/L by Week 60 if they have at least 2 consecutive blood Phe assessments = 600 µmol/L at or prior to Week 60.

Main Objective: To evaluate in adult subjects with PKU, the efficacy of pegvaliase when administered through an Induction/Titration /Maintenance dose regimen.

Primary end point(s): The primary efficacy endpoint is the percentage of subjects with blood Phe concentration = 600 µmol/L by Week 60.

Secondary Outcome(s)

Secondary end point(s): The secondary efficacy endpoint is assessed in subjects who were either on medical food or had < 1 x RDI for total protein at baseline, as the percentage of subjects who met both of the following criteria:
• At Week 60, have either a reduction in protein intake from medical food from baseline and/or an increase in intact protein intake from baseline*
• At Week 60, have a blood Phe concentration = 600 µmol/L

* A limited number of specific scenarios that that are not considered to represent a clinical improvement in nutritional status will be defined in the Statistical Analysis Plan (SAP), and these subjects will be excluded from the analysis

Timepoint(s) of evaluation of this end point: At Week 60

Secondary ID(s)

165-502

2018-000648-25-DE

Source(s) of Monetary Support

BioMarin Pharmaceutical Inc.