E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
XLH is a rare, genetic disorder that is serious, chronically debilitating and represents an
unmet medical need. This genetic deficiency is estimated to occur in about 1:20,000 live
births (Burnett et al. 1964), (Imel et al. 2005). XLH is the most common inherited form of
rickets and the most common inherited defect in renal tubular phosphate transport. XLH is
transmitted as an X-linked dominant disorder (Dixon et al. 1998). |
|
E.1.1.1 | Medical condition in easily understood language |
Inheritable form of rickets |
|
E.1.1.2 | Therapeutic area | Body processes [G] - Bones and nerves physological processes [G11] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10016206 |
E.1.2 | Term | Familial hypophosphataemic rickets |
E.1.2 | System Organ Class | 100000004850 |
|
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To continue to evaluate the long-term efficacy and safety of burosumab as a treatment for adult
patients with XLH and to provide continued treatment for subjects previously enrolled in
UX023-CL303 and UX023-CL304 clinical trials. |
|
E.2.2 | Secondary objectives of the trial |
The objectives are to assess the efficacy and
safety of burosumab administered via subcutaneous (SC) injections every 4 weeks and to allow
subjects continued access to burosumab up until December 2019 or until commercially available, with
no cost to the patient, in each individual country.
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Subjects who provide written informed consent after the nature of the study has been
explained, and prior to any research-related procedures.
2) Subject who successfully completed Study UX023-CL303 or UX023-CL304. Subjects should have completed the study up to and including the final study visit.Subjects who were prematurely discontinued due to adverse events, Sponsor's decision or Investigator's decision will not be enrolled in this study. Subjects' enrolment is not dependent on any response to Primary or Secondary endpoints in studies UX023-CL303 or UX023CL304.or those which did not complete the studies for reasons other than serious adverse events or protocol deviations may be considered on a case by case basis.
3) Willing to provide access to prior medical records for the collection of historical growth,
biochemical and radiographic data, and disease history.
4) Must, in the opinion of the investigator, be willing and able to complete all aspects of the
study, adhere to the study visit schedule and comply with the assessments.
5) Females of child-bearing potential must have a negative urine pregnancy test at Screening and
be willing to have additional pregnancy tests during the study. Females considered not to be of
child-bearing potential include those who have been in menopause for at least two years prior
to Screening, or have had tubal ligation at least one year prior to Screening, or have had a total
hysterectomy or bilateral salpingo-oophorectomy. If sexually active, male and female subjects
must be willing to use one highly effective method of contraception for the duration of the
study. |
|
E.4 | Principal exclusion criteria |
1) Hypocalcemia or hypercalcemia, defined as serum calcium levels outside the age-adjusted
normal limits and deemed as clinically significant in the opinion of the investigator.
2) Presence of a concurrent disease or condition that would interfere with study participation
or affect safety in the opinion of the investigator or Sponsor.
3) Use of any investigational product other than burosumab or investigational medical device
within 30 days prior to Screening, or requirement for any investigational agent prior to
completion of all scheduled study assessments.
4) Subjects with major protocol deviations in Study UX023-CL303 or UX023-CL304 which
in the view of the investigator places the subject at high risk of poor treatment compliance or of not completing the study. Or higher than a grade 3 treatment related hypersensitivity reaction or burosumab related hypersensitivity reaction reported as a SAE will be excluded. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Primary efficacy objective: Establish the effect of burosumab treatment on maintaining serum
phosphorous levels to within normal range in adults with XLH. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Until December 2021or reimbursed commercially available product is supplied |
|
E.5.2 | Secondary end point(s) |
Key secondary objectives: Evaluate the effect of burosumab treatment in adults with XLH on:
o Pre-existing (identified during UX023-CL303 or UX023-CL304) pseudofracture
healing and enthesopathy
o Patient impression of their improvement (compared to baseline in this study and
previous UGX023 study)
o Walking ability as measured by Six Minute Walk Test (6MWT)
o Mobility as measured by Timed Up and Go (TUG) test completion time
o Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Brief
Pain Inventory (BPI) and Brief Fatigue Inventory (BFI)
o Pharmacodynamic:
Serum phosphorus
Serum 1,25-dihydroxyvitamin D (1,25(OH) 2 D)
Urinary phosphorus
hosphate reabsorption: ratio of renal tubular maximum reabsorption rate of phosphate to glomerular filtration rate (TmP/GFR).
Carboxy-terminal cross-linked telopeptide of type I collagen (CTx), procollagen type 1 N-propeptide (P1NP), bone alkaline phosphatase and alkaline phosphatase
Safety Objectives:
Establish the long-term safety and tolerability profile of burosumab in the treatment of
adults with XLH including adverse events (AEs), ectopic mineralization risk, cardiovascular effects and immunogenicity profile.
Assess impact of burosumab on pre- and post-prandial serum
concentrations of phosphorus and calcium in a subset of study subjects. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |