X-linked Hypophosphatemia (XLH)Phase 4NCT04842019
Study to Assess the Safety, Pharmacokinetics and Efficacy of KRN23 in Adult Chinese Patients With XLH
A Phase 4 study testing KRN23 in people with X-linked Hypophosphatemia (XLH), run by Kyowa Kirin Co., Ltd. at 5 sites in China.
Trial summary
The purpose of this study is to assess the safety, pharmacokinetics and efficacy of KRN23 in adult Chinese patients with XLH Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- X-linked Hypophosphatemia (XLH)
- What is being tested?
- KRN23
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 5 sitesChina
- Study dates
- 28 Sep 2021to 17 Aug 2023
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female Chinese patients, aged 18 to 65 years (inclusive) at the time of signing the ICF
- Diagnosis of XLH supported by classic clinical features of adult XLH (such as short stature or bowed legs) and at least either of the following at screening:
- Confirmed PHEX mutation (prior to the study with historic record) in the patient or a directly related family member with appropriate X linked inheritance
- Serum iFGF23 level ≥30 pg/mL by the Kainos assay at Screening
- Biochemical findings consistent with XLH following overnight fasting (≥8 hours) at Screening:
- Serum phosphorus <2.5 mg/dL (0.81 mmol/L). Serum phosphorus level may be re tested (once only) at least 7 days after discontinuation of therapy, if applicable.
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- TmP/GFR of <2.5 mg/dL
- Presence of skeletal pain attributed to XLH/osteomalacia, as defined by a score of ≥4 on the BPI Worst Pain question at Screening (Skeletal pain that, in the opinion of the investigator or subinvestigator, is attributed solely to causes other than XLH/osteomalacia [e.g., back pain or joint pain in the presence of severe osteoarthritis by radiograph in that anatomical location] in the absence of any skeletal pain likely attributed to XLH/osteomalacia should not be considered for eligibility)
- Patients who are taking chronic pain medications (including narcotic pain medications/opioids) must be on a stable regimen for at least 21 days before signing the ICF and be willing to maintain the medications at the same stable dose(s) and schedule throughout the study. The dose must not exceed 60 mg oral morphine equivalents/day
- Able to receive conventional therapy (oral phosphate and pharmacologic vitamin D [or metabolites/analogs])
- Written informed consent provided after the nature of the study has been explained and prior to any research related procedures
- Willing to provide access to prior medical records for the collection of biochemical and radiographic data and disease history
- Have a negative pregnancy test at Screening and be willing to have additional pregnancy tests during the study (female patients of child-bearing potential only)
- Be willing to use an effective method of contraception while participating in the study (sexually active patients of child bearing potential) and for 12 weeks after last dose of study drug. Women of non child bearing potential are defined as permanently sterile (i.e. due to hysterectomy or bilateral oophorectomy) or postmenopausal (defined as at least 12 months postcessation of menses without an alternative medical cause). Postmenopausal status of female patients will be confirmed with a Screening serum follicle stimulating hormone (FSH) level >40 mIU/mL
- Be willing and able to complete all aspects of the study, adhere to the study visit schedule, and comply with the assessments, as judged by the investigator or subinvestigator
- Have completed entries for ≥4 of 7 consecutive days of the patient diaries before Week -14
Who cannot join
- Use of a pharmacologic vitamin D, its metabolites, or analogs, and oral phosphate for treatment of XLH within 14 days prior to Screening.
- Use of aluminum hydroxide antacids, acetazolamide, thiazide diuretics and/or systemic corticosteroids within 14 days prior to Week -14
- Corrected serum calcium level ≥10.8 mg/dL (2.69 mmol/L) at Screening
- Plasma iPTH ≥2.5 times the upper limit of normal at Screening
- Uncontrolled diabetes mellitus, defined as HbA1c >7.5% at Screening
- Use of medication to suppress PTH (e.g., Sensipar®, cinacalcet, calcimimetics) within 60 days before signing the ICF
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- Use of oral bisphosphonates in the 2 years before signing the ICF
- Planned or recommended orthopedic surgery within the clinical trial period
- History of traumatic fracture or orthopedic surgery within 6 months before signing the ICF
- Use of KRN23, or any other therapeutic mAb within 90 days before signing the ICF
- Use of any investigational product or investigational medical device within 30 days before signing the ICF, or requirement for any investigational agent prior to completion of all scheduled study assessments
- Pregnant or breastfeeding at Screening or Week -14, or intention to become pregnant (the patient or partner) at any time during the study
- Unable or unwilling to withhold prohibited medications throughout the study
- Presence or history of any hypersensitivity, or allergic or anaphylactic reactions to any mAb or KRN23 excipients that, in the judgment of the investigator or subinvestigator, places the patient at increased risk for adverse effects
- Positive for human immunodeficiency virus (HIV) antibody, hepatitis B surface antigen (HBsAg), and/or hepatitis C virus (HCV) antibody at Screening, or prior history of positive test
- History of recurrent infection or predisposition to infection, or of known immunodeficiency
- Presence of malignant neoplasm (except basal cell carcinoma)
- Presence of a concurrent disease or condition that would interfere with study participation or affect safety
- Presence or history of any condition that, in the view of the investigator or subinvestigator, places the patient at high risk of poor treatment compliance or of not completing the study
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
China5 sites
Peking Union Medical College Hospital
Beijing
The First Medical Center of Chinese People's Liberation Army General Hospital
Beijing
Nanfang Hospital
Guangzhou
The Second Affiliated Hospital of Zhejiang University
Hangzhou
Shanghai 6th Hospital
Shanghai
About this study
Official title: An Open-label, Multi-center, Single-cohort, Post-marketing Phase 4 Study to Evaluate the Efficacy, Pharmacodynamics, and Safety of the Anti-FGF23 Antibody, KRN23, in Adult Chinese Patients With X-linked Hypophosphatemic Rickets/Osteomalacia
The purpose of this study is to assess the safety, pharmacokinetics and efficacy of KRN23 in adult Chinese patients with XLH
- Conditions
- X-linked Hypophosphatemia (XLH)
- Being tested
- KRN23
- Medical subject headings
- Familial Hypophosphatemic Rickets
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KRN23Drug
Also called Burosumab, Crysvita
KRN23 is a sterile clear colourless and preservative free solution supplied in single use 5 mL vials containing 1 mL of KRN23 at a concentration of 30mg/mL
| Study group | Role | What they receive |
|---|---|---|
| KRN23 | Experimental | KRN23 1 mg/kg administered subcutaneously (SC) every 4 weeks for 48 weeks. Before KRN23 treatment, all patients will receive oral phosphate and vitamin D analogs for 12 weeks of Run-in period. Receives: Drug: KRN23 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from Baseline (CFB) in mean serum phosphorus level at the end of the dose cycle
Measured: Weeks 4, 8, 12, 16, 20, 24, 36, and 48
Secondary outcomes (13)
Change in Brief Pain Inventory (BPI) Worst Pain score over time
Change from baseline to post-baseline visits in BPI-Q3 (Worst Pain) score as averaged from daily diary scores recorded over 1 week and the study visit score. The BPI evaluates the condition of all pain over the previous 24 hours. Two dimensions are measured: pain severity (worst, least, average, and now) and the impact of pain on functioning (pain interference with general activity, walking, work, mood, enjoyment of life, relations with others, and sleep). Question 3 of the short-form BPI (BPI-Q3) asks subjects to rate their pain at its worst in the last 24 hours on a scale of 0 (no pain) to 10 (pain as bad as you can imagine).
Measured: Weeks 0, 12, 24, 36, and 48
Change in BPI Pain Severity score and Pain Interference score over time
Change from baseline to post-baseline visits in BPI pain severity score as averaged from daily diary scores recorded over 1 week and the study visit score. The BPI evaluates the condition of all pain over the previous 24 hours. Two dimensions are measured: pain severity (worst, least, average, and now) and the impact of pain on functioning (pain interference with general activity, walking, work, mood, enjoyment of life, relations with others, and sleep). The severity of pain in the last 24 hours is rated on a scale of 0 (no pain) to 10 (pain as bad as you can imagine).
Measured: Weeks 0, 12, 24, 36, and 48
Change in BPI Pain Interference score over time
Change from baseline to post-baseline visits in BPI pain interference score as recorded on the day of the study visit. The BPI evaluates the condition of all pain over the previous 24 hours. Two dimensions are measured: pain severity (worst, least, average, and now) and the impact of pain on functioning (pain interference with general activity, walking, work, mood, enjoyment of life, relations with others, and sleep). Pain interference in the last 24 hours is rated on a scale of 0 (does not interfere) to 10 (completely interferes).
Measured: Weeks 0, 12, 24, 36, and 48
Change in the Stiffness and Physical Function domains of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) over time
The WOMAC is a 24-item participant-reported questionnaire with two domains, Stiffness (2 questions) and Physical Function (17 questions) over the previous 48 hours. The WOMAC is administered in a 5-point Likert-scale format using descriptors of none, mild, moderate, severe, and extreme corresponding to an ordinal scale of 0-4. Higher scores on the WOMAC indicate worse stiffness and functional limitations. Scores are normalized to a 0-100 metric where 0 was the best health state and 100 the worst.
Measured: Weeks 0, 12, 24, 36, and 48
Change in the health related QOL assessment by Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function over time
The PROMIS was developed by the National Institutes of Health and uses domain-specific measures to assess patient well-being (Broderick et al. 2013), (NIH 2015). It uses a T-score metric in which 50 is the mean of a relevant reference population and 10 is the standard deviation (SD) of that population. For the Physical Function Domain, increases indicate greater mobility.
Measured: Weeks 0, 12, 24, 36, and 48
The proportion of subjects achieving mean serum phosphorus levels above the lower limit of normal (LLN; 2.5 mg/dL [0.81 mmol/L]) at the end of the dosing cycle
Measured: Weeks 4, 8, 12, 16, 20, 24, 36, and 48
The proportion of subjects achieving mean serum phosphorus levels above the LLN (2.5 mg/dL [0.81 mmol/L]) at the mid-point of dosing cycle
Measured: Weeks 2, 6, 10, 14, 18 and 22
CFB in mean serum phosphorus level at the mid-time point of dosing cycle
Measured: Weeks 2, 6, 10, 14, 18 and 22
Mean percent CFB in serum phosphorus levels averaged at the end of dose cycles
Measured: Baseline to Week 48
Cumulative exposure: area under curve (AUC) of serum phosphorus
Measured: Baseline to Week 48
Change in serum 1,25(OH)2D over time
Measured: Baseline to Week 48
Change in urinary phosphorus over time
Measured: Baseline to Week 48
Change in ratio of renal tubular maximum reabsorption rate of phosphate to glomerular filtration rate (TmP/GFR; algorithm method) over time
Measured: Baseline to Week 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Apr 2021
- Study start28 Sep 2021
- Primary completion17 Aug 2023
- Study completion17 Aug 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for X-linked Hypophosphatemia (XLH)Studies of the same condition, open and under way.
- More trials run by Kyowa Kirin Co., Ltd.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kyowa Kirin Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04842019
- Sponsor's protocol ID
- KRN23-CN005
- Other IDs
- CTR20210506
- Status last verified
- Jul 2024
- First submitted
- 30 Mar 2021
- Last updated
- 9 Jul 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Multi-center, Single-cohort, Post-marketing Phase 4 Study to Evaluate the Efficacy, Pharmacodynamics, and Safety of the Anti-FGF23 Antibody, KRN23, in Adult Chinese Patients With X-linked Hypophosphatemic Rickets/Osteomalacia
- ClinicalTrials.gov ID
- NCT04842019
- Acronym / sponsor ID
- KRN23-CN005
- Conditions
- X-linked Hypophosphatemia (XLH)
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Kyowa Kirin Co., Ltd.Industry (pharma, biotech, devices)
- Study start
- 28 Sep 2021 (actual)
- Primary completion
- 17 Aug 2023 (actual)
- Study completion
- 17 Aug 2023 (actual)
- First posted
- 12 Apr 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to assess the safety, pharmacokinetics and efficacy of KRN23 in adult Chinese patients with XLH
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| KRN23 | Experimental | Drug: KRN23KRN23 1 mg/kg administered subcutaneously (SC) every 4 weeks for 48 weeks. Before KRN23 treatment, all patients will receive oral phosphate and vitamin D analogs for 12 weeks of Run-in period. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Male or female Chinese patients, aged 18 to 65 years (inclusive) at the time of signing the ICF
- Diagnosis of XLH supported by classic clinical features of adult XLH (such as short stature or bowed legs) and at least either of the following at screening:
- Biochemical findings consistent with XLH following overnight fasting (≥8 hours) at Screening:
- Presence of skeletal pain attributed to XLH/osteomalacia, as defined by a score of ≥4 on the BPI Worst Pain question at Screening (Skeletal pain that, in the opinion of the investigator or subinvestigator, is attributed solely to causes other than XLH/osteomalacia [e.g., back pain or joint pain in the presence of severe osteoarthritis by radiograph in that anatomical location] in the absence of any skeletal pain likely attributed to XLH/osteomalacia should not be considered for eligibility)
- Patients who are taking chronic pain medications (including narcotic pain medications/opioids) must be on a stable regimen for at least 21 days before signing the ICF and be willing to maintain the medications at the same stable dose(s) and schedule throughout the study. The dose must not exceed 60 mg oral morphine equivalents/day
Key exclusion criteria (19 listed)
- Use of a pharmacologic vitamin D, its metabolites, or analogs, and oral phosphate for treatment of XLH within 14 days prior to Screening.
- Use of aluminum hydroxide antacids, acetazolamide, thiazide diuretics and/or systemic corticosteroids within 14 days prior to Week -14
- Corrected serum calcium level ≥10.8 mg/dL (2.69 mmol/L) at Screening
- Plasma iPTH ≥2.5 times the upper limit of normal at Screening
- Uncontrolled diabetes mellitus, defined as HbA1c >7.5% at Screening
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| KRN23Also: Burosumab, CrysvitaKRN23 is a sterile clear colourless and preservative free solution supplied in single use 5 mL vials containing 1 mL of KRN23 at a concentration of 30mg/mL | Drug | KRN23 |
Primary outcome
Change from Baseline (CFB) in mean serum phosphorus level at the end of the dose cycle
Time frame: Weeks 4, 8, 12, 16, 20, 24, 36, and 48
13 secondary outcomes
Change in Brief Pain Inventory (BPI) Worst Pain score over time
Time frame: Weeks 0, 12, 24, 36, and 48
Change in BPI Pain Severity score and Pain Interference score over time
Time frame: Weeks 0, 12, 24, 36, and 48
Change in BPI Pain Interference score over time
Time frame: Weeks 0, 12, 24, 36, and 48
Change in the Stiffness and Physical Function domains of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) over time
Time frame: Weeks 0, 12, 24, 36, and 48
Change in the health related QOL assessment by Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function over time
Time frame: Weeks 0, 12, 24, 36, and 48
The proportion of subjects achieving mean serum phosphorus levels above the lower limit of normal (LLN; 2.5 mg/dL [0.81 mmol/L]) at the end of the dosing cycle
Time frame: Weeks 4, 8, 12, 16, 20, 24, 36, and 48
The proportion of subjects achieving mean serum phosphorus levels above the LLN (2.5 mg/dL [0.81 mmol/L]) at the mid-point of dosing cycle
Time frame: Weeks 2, 6, 10, 14, 18 and 22
CFB in mean serum phosphorus level at the mid-time point of dosing cycle
Time frame: Weeks 2, 6, 10, 14, 18 and 22
Mean percent CFB in serum phosphorus levels averaged at the end of dose cycles
Time frame: Baseline to Week 48
Cumulative exposure: area under curve (AUC) of serum phosphorus
Time frame: Baseline to Week 48
Change in serum 1,25(OH)2D over time
Time frame: Baseline to Week 48
Change in urinary phosphorus over time
Time frame: Baseline to Week 48
Change in ratio of renal tubular maximum reabsorption rate of phosphate to glomerular filtration rate (TmP/GFR; algorithm method) over time
Time frame: Baseline to Week 48
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jul 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing KRN23 in people with X-linked Hypophosphatemia (XLH), run by Kyowa Kirin Co., Ltd. at 5 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from Baseline (CFB) in mean serum phosphorus level at the end of the dose cycle (time frame: Weeks 4, 8, 12, 16, 20, 24, 36, and 48). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jul 2024.