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).
Conditions
Interventions
Trade Name: CRYSVITA
Product Name: recombinant human igG1 monoclonal antibody to fibrolblast growth facttor23 (FGF-23)
Product Code: KRN23
Pharmaceutica
Sponsors
Kyowa Kirin Pharmaceutical Development Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
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) Subjects 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 UX023-CL304. 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. 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 40 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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. ; Secondary Objective: 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. ; 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. ;Timepoint(s) of evaluation of this end point: Until December 2019 or reimbursed commercially available product is supplied | — |
Secondary
| Measure | Time frame |
|---|---|
| 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 Phosphate 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. ;Timepoint(s) of evaluation of this end point: not applicable | — |
Countries
France, Ireland, Italy, United Kingdom
Contacts
Public ContactRegulatory Affairs
Icon Clinical Research Ltd
Outcome results
None listed