X-linked Hypophosphatemia (XLH)Phase 4NCT04842032
Study to Assess the Safety, Pharmacokinetics and Efficacy of KRN23 in Pediatric 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 pediatric Chinese patients with XLH Read more about this study
- Who is it for?
- Ages 1 year to 12 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
- 28 participants
- Where
- 5 sitesChina
- Study dates
- 1 Nov 2021to 18 Dec 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 1 year to 12 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Male or female Chinese patients, aged 1 to ≤12 years at ICF signature with radiographic evidence of rickets
- Diagnosis of XLH supported by either of the following:
- Confirmed PHEX mutation (prior to the study with historic record) in the patient or a directly related family member with approximate X linked inheritance
- Serum intact FGF23 level ≥30 pg/mL by Kainos assay at Screening
- Able to receive conventional therapy (oral phosphate and pharmacologic vitamin D)
- Biochemical findings associated with XLH: Serum phosphorus <3.0 mg/dL (0.97 mmol/L). Serum phosphorus may be re tested (once only) at least 7 days after discontinuation of therapy, if applicable ([see Section 3.1])
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- Serum creatinine within age-adjusted normal range (based on overnight fasting [minimum 4 hours] values collected at Screening)
- Serum 25(OH)D above or equal to the lower limit of normal (≥16 ng/mL) at Screening. If 25(OH)D levels are below the normal range, 25(OH)D supplementation will be prescribed. Assuming a patient meets all other eligibility requirements, the patient may be re tested for serum 25(OH)D after a minimum of 7 days of treatment
- Willing to provide access to prior medical records for the collection of historical growth and radiographic data and disease history
- Written or verbal assent (as appropriate for the patient and region) by the patient and written informed consent by legally authorized representatives provided after the nature of the study has been explained, and prior to any research-related procedures
- 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
- Female patients who have reached menarche must have a negative pregnancy test at Screening and be willing to have additional pregnancy testing during the study. If sexually active, male and female patients must be willing to use an effective method of contraception for the duration of the study and for 12 weeks after the last dose of IP
Who cannot join
- Positive for human immunodeficiency virus (HIV) antibody, hepatitis B surface antigen (HBsAg), and/or hepatitis C virus (HCV) antibody at Screening
- Tanner stage 4 or higher through physical examination
- Height percentile >50% based on country specific norms
- Use of a pharmacologic vitamin D, its metabolites, or analogs, oral phosphate for treatment of XLH, aluminum hydroxide antacids, acetazolamide, thiazide diuretics, and/or systemic corticosteroids within 7 days prior to Week -14
- Current or prior use of leuprorelin, triptorelin, goserelin, or other drugs known to delay puberty
- Use of growth hormone therapy within 12 months before ICF signature
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- Have uncontrolled diabetes mellitus, defined as glycated hemoglobin (HbA1c) >8.5% at Screening
- Presence of nephrocalcinosis on renal ultrasound Grade 4 based on the following scale:
- Planned or recommended orthopedic surgery (implantation or removal), including staples, 8 plates, or osteotomy, within the first 40 weeks of the study
- Hypocalcemia or hypercalcemia, defined as serum calcium levels outside the age adjusted normal limits (based on overnight fasting [minimum 4 hours] values collected at the Screening)
- Evidence of hyperparathyroidism (parathyroid hormone [PTH] levels 2.5 × ULN)
- Use of medication to suppress PTH (e.g., Sensipar®, cinacalcet, calcimimetics) within 2 months prior to ICF signature
- Presence or history of any condition that, in the view of the investigator or subinvestigator, places the subject at high risk of poor treatment compliance or of not completing the study
- Presence of a concurrent disease or condition that would interfere with study participation or affect safety
- History of recurrent infection or predisposition to infection, or of known immunodeficiency
- Use of therapeutic mAb within 90 days prior to ICF signature or history of allergic or anaphylactic reactions to any mAb
- Presence or history of any hypersensitivity to KRN23 excipients that, in the judgment of the investigator or subinvestigator, places the patient at increased risk for adverse effects
- Use of any investigational product or investigational medical device within 30 days prior to ICF signature, or need for the use of any investigational agent prior to completion of all scheduled study assessments
- Other patients who are considered to be ineligible for the study by the investigator or subinvestigator for reasons other than the above
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
China5 sites
Peking Union Medical College Hospital
Beijing
Guangzhou Women and Children Medical Center
Guangzhou
Shanghai 6th Hospital
Shanghai
Shanghai Xinhua Hopsital
Shanghai
Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology
Wuhan
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 Pediatric Chinese Patients With X-linked Hypophosphatemic Rickets/Osteomalacia (XLH)
The purpose of this study is to assess the safety, pharmacokinetics and efficacy of KRN23 in pediatric 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 0.8 mg/kg starting dose, administered Q2W by SC injection up to Week 64. 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 2, 4, 8, 12, 16, 24, 32, 40, 52, and 64
Secondary outcomes (17)
Change in rickets at Weeks 40 and 64 as examined by the Radiograph Global Impression of Change (RGI-C) global score
Changes in the severity of rickets and bowing were assessed using a disease specific qualitative RGI-C scoring system. The RGI-C is a 7-point ordinal scale with possible values: +3 = very much better (complete or near complete healing of rickets), +2 = much better (substantial healing of rickets), +1 = minimally better (i.e., minimal healing of rickets), 0 = unchanged, -1 = minimally worse (minimal worsening of rickets), -2 = much worse (moderate worsening of rickets), -3 = very much worse (severe worsening of rickets).
Measured: Weeks 40 and 64
Change in Rickets Severity Score (RSS) total score at Weeks 40 and 64
The RSS system is a 10-point radiographic scoring method that was developed to assess the severity of nutritional rickets in the wrists and knees based on the degree of metaphyseal fraying, cupping, lucency, separation, and the proportion of the growth plate affected. Scores are assigned for the unilateral wrist and knee X-rays deemed by the rater to be the more severe of the bilateral images. The maximum total score on the RSS is 10 points and the minimum score is 0, with a total possible score of 4 points for the wrists and 6 points for the knees (the total score is the sum of the wrist and knee score). Higher scores indicate greater rickets severity.
Measured: Weeks 40 and 64
Change in lower extremity skeletal abnormalities, including genu varum and genu valgus, as determined by the RGI-C long leg score at Weeks 40 and 64
Changes in the severity of lower extremity skeletal abnormalities, including genu varum and genu valgus, were assessed using a disease specific qualitative RGI-C scoring system. The RGI-C is a 7-point ordinal scale with possible values: +3 = very much better (complete or near complete healing), +2 = much better (substantial healing), +1 = minimally better (i.e., minimal healing), 0 = unchanged, -1 = minimally worse (minimal worsening), -2 = much worse (moderate worsening), -3 = very much worse (severe worsening).
Measured: Weeks 40 and 64
Change in serum phosphorus over time
Measured: Weeks 0, 1, 2, 4, 8, 12, 16, 24, 32, 40, 52, 64, and 74
Change in serum 1,25-dihydroxyvitamin D (1,25(OH)2D) over time
Measured: Weeks 0, 1, 2, 4, 8, 12, 16, 24, 32, 40, 52, 64, and 74
Change in alkaline phosphatase (ALP) over time
Measured: Weeks 0, 1, 2, 4, 8, 12, 16, 24, 32, 40, 52, 64, and 74
Change in urinary phosphorus over time
Measured: Weeks 0, 1, 2, 4, 8, 12, 16, 24, 32, 40, 52, 64, and 74
Change in ratio of renal tubular maximum reabsorption rate of phosphate to glomerular filtration rate (TmP/GFR; algorithm method) over time
Measured: Weeks 0, 1, 2, 4, 8, 12, 16, 24, 32, 40, 52, 64, and 74
Change in recumbent length/standing height in cm, height for age z scores
Measured: Weeks 0, 24, 40 and 64
Change in growth velocity from pre-treatment and post-treatment over time
Measured: Weeks 0, 24, 40 and 64
Change in growth velocity z scores from pre-treatment and post-treatment over time
Measured: Weeks 0, 24, 40 and 64
Six-minute walking test (6MWT) results to examine walking ability (total distance; patients ≥5 years at the time of signing the ICF only)
Measured: Weeks 0, 24, 40 and 64
Six-minute walking test (6MWT) results to examine walking ability (percent of predicted normal; patients ≥5 years at the time of signing the ICF only)
Measured: Weeks 0, 24, 40 and 64
Ten-item Short Form Health Survey for Children (SF-10) physical domain scores to examine health-related Quality of Life
The SF-10 is a brief, 10-item, guardian-completed assessment designed to measure the physical and psychosocial functioning of children. The physical functioning (PHS) domain includes 5 questions that assess limitations in physical activities because of health problems. The PHS domain score was calculated using norm-based scoring so that 50 is the average score and the standard deviation equals 10. Higher scores are associated with better functioning/quality of life; a positive change from Baseline score indicates an improvement.
Measured: Weeks 0, 24, 40 and 64
Ten-item Short Form Health Survey for Children (SF-10) Psychosocial scores to examine health-related Quality of Life
The SF-10 is a brief, 10-item, guardian-completed assessment designed to measure the physical and psychosocial functioning of children. The Psychosocial functioning (PSS) domain includes 5 questions that assess limitations in psychosocial activities because of health problems. The PHS domain score was calculated using norm-based scoring so that 50 is the average score and the standard deviation equals 10. Higher scores are associated with better functioning/quality of life; a positive change from Baseline score indicates an improvement.
Measured: Weeks 0, 24, 40 and 64
Face Pain Scale-Revised (FPS-R) scores to examine health-related Quality of Life
The FPS-R is a dimensionless 10 point Likert scale used to assess self-reported pain intensity on a scale from 0 (no pain) to 10 (most pain you can imagine). Greater pain scores are indicative of more severe pain.
Measured: Weeks 0, 24, 40 and 64
Patient-Reported Outcomes Measurement Information System (PROMIS) scores to examine health-related Quality of Life
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 Pain Interference Domain, decreases indicate less pain, for the Physical Function Mobility Domain, increases indicate greater mobility and for the Fatigue Domain, decreases indicate less fatigue.
Measured: Weeks 0, 24, 40 and 64
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 start1 Nov 2021
- Primary completion18 Dec 2023
- Study completion18 Dec 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
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kyowa Kirin Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- KRN23 Study Director, Study director, Kyowa Kirin Co., Ltd.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04842032
- Sponsor's protocol ID
- KRN23-CN006
- Other IDs
- CTR20210505
- 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 Pediatric Chinese Patients With X-linked Hypophosphatemic Rickets/Osteomalacia (XLH)
- ClinicalTrials.gov ID
- NCT04842032
- Acronym / sponsor ID
- KRN23-CN006
- Conditions
- X-linked Hypophosphatemia (XLH)
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- Kyowa Kirin Co., Ltd.Industry (pharma, biotech, devices)
- Study start
- 1 Nov 2021 (actual)
- Primary completion
- 18 Dec 2023 (actual)
- Study completion
- 18 Dec 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 pediatric 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 0.8 mg/kg starting dose, administered Q2W by SC injection up to Week 64. Before KRN23 treatment, all patients will receive oral phosphate and vitamin D analogs for 12 weeks of Run-in period. |
Who may qualify
- Ages
- 1 year to 12 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (12 listed)
- Male or female Chinese patients, aged 1 to ≤12 years at ICF signature with radiographic evidence of rickets
- Diagnosis of XLH supported by either of the following:
- Able to receive conventional therapy (oral phosphate and pharmacologic vitamin D)
- Biochemical findings associated with XLH: Serum phosphorus <3.0 mg/dL (0.97 mmol/L). Serum phosphorus may be re tested (once only) at least 7 days after discontinuation of therapy, if applicable ([see Section 3.1])
- Serum creatinine within age-adjusted normal range (based on overnight fasting [minimum 4 hours] values collected at Screening)
Key exclusion criteria (19 listed)
- Positive for human immunodeficiency virus (HIV) antibody, hepatitis B surface antigen (HBsAg), and/or hepatitis C virus (HCV) antibody at Screening
- Tanner stage 4 or higher through physical examination
- Height percentile >50% based on country specific norms
- Use of a pharmacologic vitamin D, its metabolites, or analogs, oral phosphate for treatment of XLH, aluminum hydroxide antacids, acetazolamide, thiazide diuretics, and/or systemic corticosteroids within 7 days prior to Week -14
- Current or prior use of leuprorelin, triptorelin, goserelin, or other drugs known to delay puberty
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 2, 4, 8, 12, 16, 24, 32, 40, 52, and 64
17 secondary outcomes
Change in rickets at Weeks 40 and 64 as examined by the Radiograph Global Impression of Change (RGI-C) global score
Time frame: Weeks 40 and 64
Change in Rickets Severity Score (RSS) total score at Weeks 40 and 64
Time frame: Weeks 40 and 64
Change in lower extremity skeletal abnormalities, including genu varum and genu valgus, as determined by the RGI-C long leg score at Weeks 40 and 64
Time frame: Weeks 40 and 64
Change in serum phosphorus over time
Time frame: Weeks 0, 1, 2, 4, 8, 12, 16, 24, 32, 40, 52, 64, and 74
Change in serum 1,25-dihydroxyvitamin D (1,25(OH)2D) over time
Time frame: Weeks 0, 1, 2, 4, 8, 12, 16, 24, 32, 40, 52, 64, and 74
Change in alkaline phosphatase (ALP) over time
Time frame: Weeks 0, 1, 2, 4, 8, 12, 16, 24, 32, 40, 52, 64, and 74
Change in urinary phosphorus over time
Time frame: Weeks 0, 1, 2, 4, 8, 12, 16, 24, 32, 40, 52, 64, and 74
Change in ratio of renal tubular maximum reabsorption rate of phosphate to glomerular filtration rate (TmP/GFR; algorithm method) over time
Time frame: Weeks 0, 1, 2, 4, 8, 12, 16, 24, 32, 40, 52, 64, and 74
Change in recumbent length/standing height in cm, height for age z scores
Time frame: Weeks 0, 24, 40 and 64
Change in growth velocity from pre-treatment and post-treatment over time
Time frame: Weeks 0, 24, 40 and 64
Change in growth velocity z scores from pre-treatment and post-treatment over time
Time frame: Weeks 0, 24, 40 and 64
Six-minute walking test (6MWT) results to examine walking ability (total distance; patients ≥5 years at the time of signing the ICF only)
Time frame: Weeks 0, 24, 40 and 64
Six-minute walking test (6MWT) results to examine walking ability (percent of predicted normal; patients ≥5 years at the time of signing the ICF only)
Time frame: Weeks 0, 24, 40 and 64
Ten-item Short Form Health Survey for Children (SF-10) physical domain scores to examine health-related Quality of Life
Time frame: Weeks 0, 24, 40 and 64
Ten-item Short Form Health Survey for Children (SF-10) Psychosocial scores to examine health-related Quality of Life
Time frame: Weeks 0, 24, 40 and 64
Face Pain Scale-Revised (FPS-R) scores to examine health-related Quality of Life
Time frame: Weeks 0, 24, 40 and 64
Patient-Reported Outcomes Measurement Information System (PROMIS) scores to examine health-related Quality of Life
Time frame: Weeks 0, 24, 40 and 64
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.
KRN23 Study Director study director
Kyowa Kirin Co., Ltd.
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 12 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 2, 4, 8, 12, 16, 24, 32, 40, 52, and 64). 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.