Effectiveness and safety of burosumab in an Early Access Program: a study of UK adults with X-linked hypophosphataemia
| ISRCTN | ISRCTN13102817 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN13102817 |
| IRAS number | 321609 |
| Secondary identifying numbers | 2021-66-UK-CRY , IRAS 321609, CPMS 54855 |
- Submission date
- 31/07/2023
- Registration date
- 01/08/2023
- Last edited
- 06/11/2023
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Genetic Diseases
Plain English summary of protocol
Background and study aims
X-linked hypophosphataemia (XLH) is a rare, severe, lifelong disease where phosphate is lost from the blood via the kidneys in the urine, and is at lower levels than the body requires for healthy bone and muscle development. Patients can have slowed growth, short stature, limb deformities, pain and other health problems despite conventional treatment with phosphate and vitamin D. Consequently, their quality of life can be very bad. However, a recently available treatment (burosumab) can help; this medicine was made available to patients in an Early Access Program in the UK. Because it was the first time that adult patients had been given burosumab outside a clinical trial, this is a good opportunity to see how well the medicine works and learn about symptoms, medications and side effects that patients may experience.
Who can participate?
Patients aged 18 years or over who received burosumab through the Kyowa Kirin Early Access Programme for the treatment of XLH
What does the study involve?
Participants' medical records will be reviewed and relevant information collected by their normal care team. This includes basic patient details, medical history and medications, as well as information about their XLH symptoms and blood test results during the time they were taking burosumab. No change is made to patients' care as part of this study, the period being studied is in the past. Participants will be informed about the study beforehand and given the opportunity to opt out, but all participants from the burosumab Early Access Programme can take part in this study.
What are the possible benefits and risks of participating?
There are no benefits or additional risks for participants in this study compared to their usual care, their care teams are collecting the study data.
Where is the study run from?
Bionical Emas Ltd (UK)
When is the study starting and how long is it expected to run for?
April 2021to September 2023
Who is funding the study?
Kyowa Kirin Ltd (UK)
Who is the main contact?
Gillian Logan, gillian.logan@kyowakirin.com
Contact information
Public
92 Street Lane
Leeds
LS27 7HY
United Kingdom
 ORCID ID |
0000-0002-7646-6515 |
|---|---|
| Phone | +44 (0)7880728152 |
| daniel.stevens@bionicalemas.com |
Scientific
92 Street Lane
Leeds
LS27 7HY
United Kingdom
| Phone | +44 (0)7880728152 |
|---|---|
| daniel.stevens@bionicalemas.com |
Principal Investigator
Royal National Orthopaedic Hospital
Brockley Hill
Stanmore
HA7 4LP
United Kingdom
| Phone | +44 (0)20 3947 0056 |
|---|---|
| judith.bubbear@nhs.net |
Study information
| Study design | Multicentre single-arm retrospective longitudinal observational study |
|---|---|
| Primary study design | Observational |
| Secondary study design | Longitudinal study |
| Study setting(s) | Hospital |
| Study type | Quality of life, Treatment, Safety |
| Scientific title | Early Access experience with burosumab in adults with X-linked hypophosphataemia in the UK: real-world clinical and patient-reported outcomes |
| Study objectives | This is a retrospective observational study of patients enrolled in an Early Access Program. This cohort is the first group of adult UK patients to receive burosumab outside a clinical trial. As such it is an opportunity to gain insight into the effectiveness and safety of the medicine in patients under normal clinical care. |
| Ethics approval(s) |
Approved 09/05/2023, East Midlands - Leicester South Research Ethics Committee (Equinox House City Link, Nottingham, NG2 4LA, United Kingdom; +44 (0)207 104 8193; leicestersouth.rec@hra.nhs.uk), ref: 23/EM/0078 |
| Health condition(s) or problem(s) studied | X-linked hypophosphataemia (XLH) |
| Intervention | UK centres with patients enrolled in the burosumab Early Access Program are sites in this observational study. Investigators collect data from patients' medical records, including patient-reported outcomes, that were recorded during participants' normal clinical care. No additional tests or instruments were used for the purposes of this study. Key parameters that will be abstracted, if available, from medical records include: 1. Patient characteristics, demographics and relevant medical history 2. Medications, including analgesics, and treatment history 3. Serum phosphate, alkaline phosphatase, parathyroid hormone, calcium and vitamin D 4. Patient-reported outcomes including Brief Pain Inventory Short Form (BPI), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and EQ-5D-5L 5. Burosumab exposure and adverse events |
| Intervention type | Other |
| Primary outcome measure | The proportion of adults receiving burosumab for XLH achieving serum phosphate level above the lower limit of normal (according to local reference ranges) in a real-world clinical setting after 6 months’ treatment, assessed locally and recorded in medical record |
| Secondary outcome measures | 1. Population and clinical characteristics at baseline, including patient-reported outcomes (PROs), recorded in and abstracted from medical records 2. The proportion of adults receiving burosumab for XLH who achieved a serum phosphate level above the lower limit of normal (according to local reference ranges) in a real-world clinical setting at any time, assessed (including vs local reference ranges), recorded in and abstracted from medical records 3. Patient-reported outcomes (where available) change from baseline (start of treatment with burosumab) to 6 months of treatment and 6-monthly thereafter: 3.1. Pain intensity measured by BPI Short Form Q3 (Worst Pain) score 3.2. WOMAC stiffness, pain, difficulty performing daily activities, total scores in most bothersome joint 3.3. EuroQOL-5-dimension 5 level (EQ-5D-5L) 4. Baseline distribution and changes in the following biochemical measures versus baseline over time: 4.1. Serum phosphate, creatinine, alkaline phosphatase (ALP), parathyroid hormone (PTH), calcium, 1,25 dihydroxyvitamin D: routine blood tests carried out during patients’ usual clinical care, abstracted from medical records as/when available 4.2. Urine calcium and ratio of tubular maximum reabsorption of phosphate to glomerular filtration rate (TmP/GFR): routine urinalysis carried out during patients’ usual clinical care, abstracted from medical records as/when available 5. The number and percentage of participants taking opioid, or any pain medication will be summarised at baseline and at 6-monthly intervals. Changes to opioid dose over time will be described. Data from medications/dosing information abstracted from participants’ medical records. 6. Impact on ability to work/study will be summarised at baseline and at 6-monthly intervals. Data abstracted from participants’ medical records by direct care team, as and when routine care visits happened. 7. Burosumab dosing at baseline, changes over time and total burosumab treatment duration, abstracted from participants’ medical records 8. Real-world time to treatment discontinuation (rwTTTD) and description of the reasons, abstracted from participants’ medical records, with further information on reasons taken from adverse event reports collected during the Early Access Program. |
| Overall study start date | 08/04/2021 |
| Completion date | 31/10/2023 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 144 |
| Total final enrolment | 142 |
| Key inclusion criteria | All participants enrolled in the burosumab early access programme (EAP) will be considered for inclusion |
| Key exclusion criteria | Participants opting out will not have their clinical data collected |
| Date of first enrolment | 18/07/2023 |
| Date of final enrolment | 31/10/2023 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centres
Stanmore
HA7 4LP
United Kingdom
Marlborough Street
Bristol
BS1 3NU
United Kingdom
Herries Road
Sheffield
S5 7AU
United Kingdom
London
NW1 2PG
United Kingdom
Hills Road
Cambridge
CB2 0QQ
United Kingdom
Sponsor information
Industry
Galabank Business Park
Galashiels
TD1 1QH
Scotland
United Kingdom
| Phone | +44 (0)7741664277 |
|---|---|
| gillian.logan@kyowakirin.com | |
| Website | https://international.kyowa-kirin.com/uk/ |
"ROR" |
https://ror.org/017hh7b56 |
Funders
Funder type
Industry
Private sector organisation / For-profit companies (industry)
- Alternative name(s)
- Kyowa Kirin Farmaceutica SLU, Kyowa Kirin Farmaceutica SL, Kyowa Kirin Farmacéutica S.L.U., ProStrakan, Kyowa Kirin Farmacéutica, S.L.U.
- Location
- Spain
Results and Publications
| Intention to publish date | 31/10/2024 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | Planned publication in a high-impact peer-reviewed journal |
| IPD sharing plan | The data-sharing plans for the current study are unknown and will be made available at a later date |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Other files | Patient optout letter version 1.2 |
01/08/2023 | No | No |
Additional files
- 44034_PatientOptout_Letter_V1.2.pdf
- Patient optout letter
Editorial Notes
06/11/2023: Total final enrolment added.
05/09/2023: Internal review.
17/08/2023: The following changes were made to the study record:
1. The recruitment end date was changed from 31/08/2023 to 31/10/2023.
2. The overall study end date was changed from 30/09/2023 to 31/10/2023.
3. The intention to publish date was changed from 30/09/2024 to 31/10/2024.
01/08/2023: Study's existence confirmed by the East Midlands - Leicester South Research Ethics Committee.
