A safety and efficacy study in MPS 7 patients receiving enzyme (UX003) replacement by intravenous injection

• Register: EUCTR
• Last refreshed on: 3 October 2016
• Main ID: EUCTR2013-001152-35-ES
• Date of registration: 04/07/2014
• Prospective Registration: Yes
• Primary sponsor: Ultragenyx Pharmaceutical Inc.
• Public title: A safety and efficacy study in MPS 7 patients receiving enzyme (UX003) replacement by intravenous injection
• Scientific title: An Open-Label Phase 1/2 Study to Assess the Safety, Efficacy and Dose of UX003 rhGUS Enzyme Replacement Therapy in Patients with MPS 7
• Date of first enrolment: 21/08/2014
• Target sample size: 5
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-001152-35
• 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): yes Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Spain, United Kingdom

Contacts

• Name: Clinical Operation
• Affiliation: Ultragenyx Pharmaceutical Inc.

• Name: Clinical Operation
• Affiliation: Ultragenyx Pharmaceutical Inc.

Key inclusion & exclusion criteria

Inclusion criteria:
Individuals eligible to participate in this study must meet all of the following inclusion criteria:
-Confirmed diagnosis of MPS 7 based on leukocyte or fibroblast glucuronidase enzyme assay or genetic testing confirming diagnosis.
-Elevated uGAG excretion at a minimum of 2-fold over the mean normal for age.
-Between 5 and 30 years of age, inclusive.
-Willing and able to provide written, signed informed consent, or in the case of subjects under the age of 18 (or 16 years, depending on the region), provide written assent (if required) and written informed consent by a legally authorized representative after the nature of the study has been explained, and prior to any research-related procedures.
-Sexually active subjects must be willing to use an acceptable method of contraception while participating in the study.
-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 had total hysterectomy, have been in menopause for at least two years, or have had tubal ligation at least one year prior to Screening.
Are the trial subjects under 18? yes
Number of subjects for this age range: 5
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 2
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

Exclusion criteria:
Individuals who meet any of the following exclusion criteria will not be eligible to participate in the study:
-Has undergone a successful bone marrow or stem cell transplant or has any degree of detectable chimaerism with donor cells.
-Any hypersensitivity to rhGUS or its excipients that, in the judgment of the Investigator, place the subject at increased risk for adverse effects.
-Pregnant or breastfeeding at Screening or planning to become pregnant (self or partner) at any time during the study.
-Use of any investigational product (drug or device or combination product) within 30 days prior to Screening, or requirement for any investigational agent prior to completion of all scheduled study assessments at any time during the study.
-Has a condition of such severity and acuity, in the opinion of the Investigator, that it warrants immediate surgical intervention or other treatment or may not allow safe study participation.
-Has a concurrent disease or condition that, in the view of the Investigator, places the subject at high risk of poor treatment compliance or of not completing the study, or would interfere with study participation or affect safety.


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

Health Condition(s) or Problem(s) studied

Mucopolysaccharidosis type 7 (MPS 7, Sly syndrome)

Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Intervention(s)

Product Name: Recombinant human beta-glucuronidase
Product Code: UX003
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Not available
Current Sponsor code: UX003
Other descriptive name: RECOMBINANT HUMAN BETA GLUCURONIDASE; RHGUS
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 2-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: -Safety: Assessed up to Week 72. Serious adverse events (SAEs) will be recorded beginning at the time the subject signs the informed consent form (ICF) through 30 days following the last study visit. Non-serious AEs will be recorded from the time of signing the ICF through the last study visit.
-Efficacy (total urinary GAG excretion): Urine samples will be collected every other week up to Week 36 and at Weeks 48, 60 and 72 in the extension phase, and 2 samples will be collected during the baseline week. The primary efficacy analysis will evaluate the mean change in urinary GAG excretion from Week 0 to Week 12.

Main Objective: The primary objectives of the study are to evaluate:
-Safety and tolerability of UX003 exposure.
-Efficacy as determined by the reduction of total urinary GAG (uGAG) excretion.

Secondary Objective: The secondary objectives of the study are to evaluate the effect of rhGUS on:
-Total uGAG excretion to assess the optimal dose using a forced dose titration regimen.
-Walking capacity as measured by the 6 Minute Walk Test (6MWT).
-Stair climbing capacity as measured by the 3 Minute Stair Climb Test (3MSCT).
-Pulmonary function as measured by forced vital capacity (FVC), forced expiratory volume in one second (FEV1) and maximum voluntary ventilation in one minute (MVV1).
-Height and weight growth velocity compared to estimated pretreatment growth rate velocity from medical records (prepubertal pediatric patients only).
-Shoulder range of motion as measured by goniometry.

Primary end point(s): The primary endpoints of this study are:
-Safety of UX003 as measured by the incidence and frequency of AEs and serious adverse events (SAEs), including clinically significant changes from Baseline to scheduled time points in Medical history, Physical examination findings, Vital signs, Clinical laboratory evaluations, Concomitant medications, Pregnancy testing/pregnancy of partner, IgG antibodies to rhGUS, Complement C3, C4 and CH50 (or CH100) levels.
-Efficacy of UX003 as determined by mean change in total urinary glycosaminoglycan (uGAG) excretion from Week 0.

Secondary Outcome(s)

Secondary end point(s): The secondary endpoints of this study are:
-Walking capacity as measured by the 6 Minute Walk Test (6MWT).
-Stair climbing capacity as measured by the 3 Minute Stair Climb Test (3MSCT).
-Pulmonary function testing (spirometry) as measured by Forced Vital Capacity(FVC), Forced Expiratory Volume (FEV1) and Maximal Voluntary Ventilation (MVV1).
-Growth velocity for height and weight as calculated from anthropometric measurements (standing height, either measured or derived from ulnar length measures and weight) and compared with pretreatment growth velocity when available.
-Shoulder range of motion as measured by goniometry.
-Optimal dose as determined by total urinary GAG excretion using a forced dose titration regimen.

Timepoint(s) of evaluation of this end point: -6MWT: Assessed at 0, 6, 12, 22, 30, 36, 48, 60, 72 Weeks.
-3MSCT: Assessed at 0, 6, 12, 22, 30, 36, 48, 60, 72 Weeks.
-Pulmonary function testing (spirometry): Assessed at 0, 6, 12, 22, 30, 36, 48, 60, 72 Weeks.
-Growth velocity for height and weight anthropometric measurements (standing height, either measured or derived from ulnar length measures and weight): Assessed at 0, 12, 22, 30, 36, 48, 60, 72 Weeks.
-Shoulder range of motion as measured by goniometry: Assessed at 0, 6, 12, 22, 30, 36, 48, 60, 72 Weeks.
-Optimal dose as determined by total uGAG excretion using a forced dose titration regimen up to Week 36.

Secondary ID(s)

NCT01856218

UX003-CL201

2013-001152-35-GB

Source(s) of Monetary Support

Ultragenyx Pharmaceutical Inc.