Safety and Tolerability Study of rAvPAL-PEG to Treat Phenylketonuria

NCT00634660 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: PAL-001
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 8

Brief Summary

The purpose of this study is to assess the safety and tolerability of injections of rAvPAL-PEG in subjects with PKU.

Conditions

Phenylketonuria

Outcome Measures

Primary Outcomes (1)

• • To assess the incidence of treatment-emergent adverse events of a single, subcutaneous (SC) injections of rAvPAL-PEG in subjects with PKU.

  Specifically, safety was to be assessed by examining the incidence of all treatment-emergent adverse events reported during the study period and clinically significant changes in vital signs and clinical laboratory results, including development of rAvPAL-PEG antibodies.

  6 weeks

Secondary Outcomes (2)

• • To evaluate the pharmacokinetics (PK) of single, SC injections of rAvPAL-PEG administered at escalating doses, in subjects with PKU.

  6 weeks

• • To evaluate the effect of different dose levels of rAvPAL-PEG on blood Phe concentrations in subjects with PKU.

  6 weeks

Study Arms (7)

0.001 mg/kg

ACTIVE COMPARATOR

One subcutaneous injection of 0.001 mg/kg of rAvPAL-PEG.

Drug: rAvPAL-PEG

0.003 mg/kg

ACTIVE COMPARATOR

One subcutaneous injection of 0.003 mg/kg of rAvPAL-PEG.

Drug: rAvPAL-PEG

0.01 mg/kg

ACTIVE COMPARATOR

One subcutaneous injection of 0.01 mg/kg of rAvPAL-PEG.

Drug: rAvPAL-PEG

0.03 mg/kg

ACTIVE COMPARATOR

One subcutaneous injection of 0.03 mg/kg of rAvPAL-PEG.

Drug: rAvPAL-PEG

0.1 mg/kg

ACTIVE COMPARATOR

One subcutaneous injection of 0.1 mg/kg of rAvPAL-PEG.

Drug: rAvPAL-PEG

0.3 mg/kg

ACTIVE COMPARATOR

One subcutaneous injection of 0.3 mg/kg of rAvPAL-PEG.

Drug: rAvPAL-PEG

1.0 mg/kg

ACTIVE COMPARATOR

One subcutaneous injection of 1.0 mg/kg of rAvPAL-PEG.

Drug: rAvPAL-PEG

Interventions

rAvPAL-PEG DRUG

rAvPAL-PEG will be administered as a single, SC injection at dose levels of 0.001, 0.003, 0.01, 0.03, 0.1, 0.3, and 1.0 mg/kg. The duration of treatment is a single dose of study drug with 42 days (6 weeks) of follow-up.

0.001 mg/kg; 0.003 mg/kg; 0.01 mg/kg; 0.03 mg/kg; 0.1 mg/kg; 0.3 mg/kg; 1.0 mg/kg

Eligibility Criteria

• Age: 16 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Diagnosis of PKU with both of the following:
• Current blood Phe concentration of ≥600 µmol/L at Screening.
• Average blood Phe concentration of ≥600 µmol/L over the past 3 years, using available data.
• Willing and able to provide written, signed informed consent, or, in the case of participants under the age of 18, provide written assent (if required) and written informed consent by a parent or legal guardian, after the nature of the study has been explained, and prior to any research-related procedures.
• Willing and able to comply with all study procedures.
• Between the ages of 16 and 50 years, inclusive.
• Females of childbearing potential must have a negative pregnancy test at Screening and be willing to have additional pregnancy tests during the study. Females considered not of childbearing potential include those who have been in menopause at least 2 years, or had tubal ligation at least 1 year prior to Screening, or who have had total hysterectomy.
• Sexually active subjects must be willing to use an acceptable method of contraception while participating in the study.
• Stable diet with no significant modifications during the 4 weeks preceding the administration of study drug.
• In generally good health as evidenced by physical examination, clinical laboratory evaluations (hematology, chemistry, and urinalysis), and electrocardiogram (ECG) at Screening.

You may not qualify if:

• 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.
• Pregnant or breastfeeding at Screening or planning to become pregnant (self or partner) or to breastfeed at any time during the study.
• Concurrent disease or condition that would interfere with study participation or safety (eg, history or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurological, oncologic, or psychiatric disease).
• Any condition that, in the view of the Principal Investigator (PI), places the subject at high risk of poor treatment compliance or of not completing the study.
• Known hypersensitivity to rAvPAL PEG or its excipients.
• Alanine aminotransferase (ALT) concentration \> 2 times the upper limit of normal.
• Creatinine above the upper limit of normal.
• Donation of blood or plasma within 30 days prior to the administration of study drug.
• Use of any over-the-counter (OTC) medication, including vitamins, within 7 days prior to the administration of study drug, without evaluation and approval by the Investigator.
• Use of any prescription medication within 14 days prior to the administration of study drug without evaluation and approval by the Investigator.
• Treatment with any drug known to affect hepatic enzyme activity, including (but not limited to) barbiturates, phenothiazines, cimetidine, or carbamazepine, within 30 days prior to study drug administration.
• Use of any tobacco products within 60 days prior to study drug administration.
• Positive urine screen for use of nicotine (cotinine) or drugs of abuse (amphetamines, barbiturates, benzodiazepines, cocaine, cannabinoids, and opiates).
• Positive test or has been treated for hepatitis B, hepatitis C, or human immunodeficiency virus (HIV).

Sponsors & Collaborators

• BioMarin Pharmaceutical: lead

Study Sites (8)

Children's Memorial Hospital

Chicago, Illinois, 60614, United States

Location

University of Minnesota Medical Center-Fairview

Minneapolis, Minnesota, 55455, United States

Location

Washington University Center for Applied Research Sciences

St Louis, Missouri, 63110, United States

Location

Mount Sinai Medical Center

New York, New York, 10029, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

University of Utah Hospital

Salt Lake City, Utah, 84132, United States

Location

University of Wisconsin

Madison, Wisconsin, 53705, United States

Location

MeSH Terms

Conditions

Phenylketonurias

Interventions

pegvaliase

Condition Hierarchy (Ancestors)

Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Amino Acid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Celeste Decker, MD

  BioMarin Pharmaceutical

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 6, 2008
• First Posted: March 13, 2008
• Study Start: May 1, 2008
• Primary Completion: April 1, 2009
• Study Completion: October 1, 2009
• Last Updated: February 1, 2017

Record last verified: 2017-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (8)