X-linked Hypophosphatemic Rickets/OsteomalaciaPhase 3NCT03233126
A Study of KRN23 in Pediatric Patients With X-linked Hypophosphatemic Rickets/Osteomalacia
A Phase 3 study testing KRN23 in people with X-linked Hypophosphatemic Rickets/Osteomalacia, run by Kyowa Kirin Co., Ltd. at 4 sites in Japan.
Trial summary
Before switching to the post-marketing study: To evaluate the efficacy and safety of KRN23 administered subcutaneously once every 2 weeks in children with X-linked hypophosphatemic rickets/osteomalacia(XLH). Read more about this study
- Who is it for?
- Ages 1 year to 12 years
- Conditions the study is for
- X-linked Hypophosphatemic Rickets/Osteomalacia
- What is being tested?
- KRN23
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 4 sitesJapan
- Study dates
- 6 Jul 2017to 17 Feb 2020
- Phase
- Phase 3
- 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
- 1）Personally submitted voluntary written informed consent by a legally authorized representative.If appropriate, written or verbal assent to participate in the study should be obtained from patients.
- 2) Aged ≥ 1 and ≤12 years 3）Patients who have open growth plate 4）Willing to perform a self-administration of KRN23 and available to perform a self-administration 5）Diagnosis of XLH, and meeting any of the followings;
- phosphate-regulating gene with homologies to endopeptidases on the X chromosome(PHEX) mutation in either the patient or in a directly related family member with appropriate X-linked inheritance
- Serum intact FGF23 level at screening ≥ 30 pg/mL 6） Finding evidence of rickets or clinical symptoms 7）Meeting all of following criteria for laboratory test related to XLH;
- a）Serum P: < 3.0 mg/dL b）Serum Cr: Within the age-adjusted normal limits c）Serum 25(OH)D: ≥ 16 ng/mL 8） For female patients who have reached menarche with child bearing potential; a negative urine pregnancy test at screening 9）For female patients with child baring potential, or male patients with reproductive capacity; willingness to use an acceptable method of contraception while participating in the study 10） Willingness to provide access to prior medical records to determine eligibility including data on imaging tests, blood chemistry, diagnosis, medication, and surgical history 11） Willingness and ability to cooperatively complete all study procedures, adhere to the visit schedule and follow the investigator's instructions, as considered by the investigator or subinvestigator
Who cannot join
- 1）Height percentile > 50% based on age-adjusted Japanese norms at screening 2）Use of aluminum hydroxide antacids, systemic corticosteroids, acetazolamide, and thiazides within 7 days prior to screening 3）Current or prior use of leuprorelin, triptorelin, goserelin, or other drugs known to delay puberty 4）Use of growth hormone therapy within 12 months before screening 5）Use of medication to suppress parathyroid hormone within 60 days prior to screening 6）Serum calcium levels outside the age-adjusted normal limits 7）Intact parathyroid hormone(iPTH) levels ≥ 163 pg/mL 8）Presence of nephrocalcinosis on renal ultrasound grade 4 based on the following scale: 0 = Normal
- = Faint hyperechogenic rim around the medullary pyramids
- = More intense echogenic rim with echoes faintly filling the entire pyramid
- = Uniformly intense echoes throughout the pyramid
- = Stone formation: solitary focus of echoes at the tip of the pyramid 9）Planned or recommended orthopedic surgery 10）Blood or blood product transfusion within 60 days prior to screening 11）History of malignancy within 5 years prior to registration 12）History of being positive for human immunodeficiency virus antibody, hepatitis B antigen and/or hepatitis C virus antibody 13）Predisposition to infection, or history of recurrent infection or known immunodeficiency 14）Use of any investigational product or investigational medical device within 4 months prior to screening, or requirement for any investigational agent prior to completion of all scheduled study assessments 15）Receiving investigational agent in the UX023-CL301 study 16）Use of a therapeutic monoclonal antibody other than KRN23 within 90 days prior to screening 17）History of allergic or anaphylactic reactions to KRN23, any of the KRN23 ingredients, or any other monoclonal antibodies 18）Anyone otherwise considered unsuitable participation in the study by the investigator or subinvestigator
- Subjects eligible for enrollment in the post-marketing clinical study must meet both of the following criteria:
- 1) Personally submitted voluntary written informed consent to participate in the postmarketing clinical study by a legally authorized representative. If appropriate, written or verbal assent to participate in the post-marketing clinical study should be obtained from subjects.
Trial locations and contacts
4 sites in 1 country.
Japan4 sites
Okayama Saiseikai General Hospital Outpatient Center
Okayama
Osaka Hospital, Japan Community Healthcare Organization (JCHO)
Osaka, Osaka
National University Corporation Osaka University Hospital
Suita, Osaka
Kanagawa Prefectural Hospital Organization Kanagawa Children's Medical Center
Yokohama, Kanagwa
About this study
Official title: A Phase 3 Open-Label Trial to Assess the Efficacy and Safety of KRN23 in Pediatric Patients With X-linked Hypophosphatemic Rickets/Osteomalacia and a Postmarketing Study of KRN23 Switched From the Phase 3 Trial
Before switching to the post-marketing study:
To evaluate the efficacy and safety of KRN23 administered subcutaneously once every 2 weeks in children with X-linked hypophosphatemic rickets/osteomalacia(XLH).
After switching to the post-marketing study:
To evaluate the safety and efficacy of KRN23, which is switched from the investigational product to the post-marketing study drug, at the approved dose and dosing regimen in subjects who continue treatment
- Being tested
- KRN23
- Medical subject headings
- Familial Hypophosphatemic Rickets, Osteomalacia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KRN23Drug
Subjects will receive subcutaneous injections of KRN23 every 2 weeks from Week 0 through Week 86
| Study group | Role | What they receive |
|---|---|---|
| KRN23 | Experimental | Subjects will receive subcutaneous injections of KRN23 every 2 weeks from Week 0 through Week 128 Receives: Drug: KRN23 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of subjects for each adverse events
Measured: up to week 128
Percentage of subjects for each adverse events
Measured: up to week 128
Secondary outcomes (25)
Effect to body temperature
Measured: up to week 128
Effect to pulse rate
Measured: up to week 128
Effect to respiratory rate
Measured: up to week 128
Effect to blood pressure
Measured: up to week 128
Effect to 12-Lead Electrocardiogram
Measured: up to week 128
Effect to Renal Ultrasound
Measured: up to week 128
Effect to Echocardiogram
Measured: up to week 128
Serum phosphorus concentration at each test time point
Measured: up to week 128
1,25(OH)2D at each test time point
Measured: up to week 128
Alkaline phosphatase at each test time point
Measured: up to week 128
Urine phosphorus at each test time point
Measured: up to week 128
Tubular reabsorption of phosphate at each test time point
Measured: up to week 128
TmP/GFR at each test time point
Measured: up to week 128
Change from baseline in serum phosphorus
Measured: up to week 128
Change from baseline in 1,25(OH)2D
Measured: up to week 128
Change from baseline in alkaline phosphatase
Measured: up to week 128
Change from baseline in urine phosphorus
Measured: up to week 128
Change from baseline in tubular reabsorption of phosphate
Measured: up to week 128
Change from baseline in TmP/GFR
Measured: up to week 128
Improvement in Radiographic Global Impression of Change(RGI-C) global score
Measured: up to week 128
Change from baseline on Rickets Severity Score (RSS) total score
Measured: up to week 128
Change from baseline in the Six Minute Walk Test
Measured: up to week 128
Change in height-for-age z-scores from baseline
Measured: up to week 128
Serum KRN23 concentration
Measured: up to week 128
Anti-KRN23 antibody
Measured: up to week 128
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jul 2017
- Study start6 Jul 2017
- Primary completion17 Feb 2020
- Study completion17 Feb 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for X-linked Hypophosphatemic Rickets/OsteomalaciaStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 16 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
- NCT03233126
- Sponsor's protocol ID
- KRN23-003
- Status last verified
- Aug 2022
- First submitted
- 11 Jul 2017
- Last updated
- 6 Sep 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Kubota T, Namba N, Tanaka H, Muroya K, Imanishi Y, Takeuchi Y, Kanematsu M, Sun W, Seino Y, Ozono K. Self-Administration of Burosumab in Children and Adults with X-Linked Hypophosphataemia in Two Open-Label, Single-Arm Clinical Studies. Adv Ther. 2023 Apr;40(4):1530-1545. doi: 10.1007/s12325-022-02412-x. Epub 2023 Jan 31.
PubMed 36719566
Study at a glance
From the registry record, last updated by the sponsor on 6 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3 Open-Label Trial to Assess the Efficacy and Safety of KRN23 in Pediatric Patients With X-linked Hypophosphatemic Rickets/Osteomalacia and a Postmarketing Study of KRN23 Switched From the Phase 3 Trial
- ClinicalTrials.gov ID
- NCT03233126
- Acronym / sponsor ID
- KRN23-003
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Kyowa Kirin Co., Ltd.Industry (pharma, biotech, devices)
- Study start
- 6 Jul 2017 (actual)
- Primary completion
- 17 Feb 2020 (actual)
- Study completion
- 17 Feb 2020 (actual)
- First posted
- 28 Jul 2017 (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.
Before switching to the post-marketing study:
To evaluate the efficacy and safety of KRN23 administered subcutaneously once every 2 weeks in children with X-linked hypophosphatemic rickets/osteomalacia(XLH).
After switching to the post-marketing study:
To evaluate the safety and efficacy of KRN23, which is switched from the investigational product to the post-marketing study drug, at the approved dose and dosing regimen in subjects who continue treatment
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: KRN23Subjects will receive subcutaneous injections of KRN23 every 2 weeks from Week 0 through Week 128 |
Who may qualify
- Ages
- 1 year to 12 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- 1）Personally submitted voluntary written informed consent by a legally authorized representative.If appropriate, written or verbal assent to participate in the study should be obtained from patients.
- 2) Aged ≥ 1 and ≤12 years 3）Patients who have open growth plate 4）Willing to perform a self-administration of KRN23 and available to perform a self-administration 5）Diagnosis of XLH, and meeting any of the followings;
- phosphate-regulating gene with homologies to endopeptidases on the X chromosome(PHEX) mutation in either the patient or in a directly related family member with appropriate X-linked inheritance
- Serum intact FGF23 level at screening ≥ 30 pg/mL 6） Finding evidence of rickets or clinical symptoms 7）Meeting all of following criteria for laboratory test related to XLH;
- a）Serum P: < 3.0 mg/dL b）Serum Cr: Within the age-adjusted normal limits c）Serum 25(OH)D: ≥ 16 ng/mL 8） For female patients who have reached menarche with child bearing potential; a negative urine pregnancy test at screening 9）For female patients with child baring potential, or male patients with reproductive capacity; willingness to use an acceptable method of contraception while participating in the study 10） Willingness to provide access to prior medical records to determine eligibility including data on imaging tests, blood chemistry, diagnosis, medication, and surgical history 11） Willingness and ability to cooperatively complete all study procedures, adhere to the visit schedule and follow the investigator's instructions, as considered by the investigator or subinvestigator
Key exclusion criteria (7 listed)
- 1）Height percentile > 50% based on age-adjusted Japanese norms at screening 2）Use of aluminum hydroxide antacids, systemic corticosteroids, acetazolamide, and thiazides within 7 days prior to screening 3）Current or prior use of leuprorelin, triptorelin, goserelin, or other drugs known to delay puberty 4）Use of growth hormone therapy within 12 months before screening 5）Use of medication to suppress parathyroid hormone within 60 days prior to screening 6）Serum calcium levels outside the age-adjusted normal limits 7）Intact parathyroid hormone(iPTH) levels ≥ 163 pg/mL 8）Presence of nephrocalcinosis on renal ultrasound grade 4 based on the following scale: 0 = Normal
- = Faint hyperechogenic rim around the medullary pyramids
- = More intense echogenic rim with echoes faintly filling the entire pyramid
- = Uniformly intense echoes throughout the pyramid
- = Stone formation: solitary focus of echoes at the tip of the pyramid 9）Planned or recommended orthopedic surgery 10）Blood or blood product transfusion within 60 days prior to screening 11）History of malignancy within 5 years prior to registration 12）History of being positive for human immunodeficiency virus antibody, hepatitis B antigen and/or hepatitis C virus antibody 13）Predisposition to infection, or history of recurrent infection or known immunodeficiency 14）Use of any investigational product or investigational medical device within 4 months prior to screening, or requirement for any investigational agent prior to completion of all scheduled study assessments 15）Receiving investigational agent in the UX023-CL301 study 16）Use of a therapeutic monoclonal antibody other than KRN23 within 90 days prior to screening 17）History of allergic or anaphylactic reactions to KRN23, any of the KRN23 ingredients, or any other monoclonal antibodies 18）Anyone otherwise considered unsuitable participation in the study by the investigator or subinvestigator
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 |
|---|---|---|
| KRN23Subjects will receive subcutaneous injections of KRN23 every 2 weeks from Week 0 through Week 86 | Drug | KRN23 |
Primary outcome
Number of subjects for each adverse events
Time frame: up to week 128
Percentage of subjects for each adverse events
Time frame: up to week 128
25 secondary outcomes
Effect to body temperature
Time frame: up to week 128
Effect to pulse rate
Time frame: up to week 128
Effect to respiratory rate
Time frame: up to week 128
Effect to blood pressure
Time frame: up to week 128
Effect to 12-Lead Electrocardiogram
Time frame: up to week 128
Effect to Renal Ultrasound
Time frame: up to week 128
Effect to Echocardiogram
Time frame: up to week 128
Serum phosphorus concentration at each test time point
Time frame: up to week 128
1,25(OH)2D at each test time point
Time frame: up to week 128
Alkaline phosphatase at each test time point
Time frame: up to week 128
Urine phosphorus at each test time point
Time frame: up to week 128
Tubular reabsorption of phosphate at each test time point
Time frame: up to week 128
TmP/GFR at each test time point
Time frame: up to week 128
Change from baseline in serum phosphorus
Time frame: up to week 128
Change from baseline in 1,25(OH)2D
Time frame: up to week 128
Change from baseline in alkaline phosphatase
Time frame: up to week 128
Change from baseline in urine phosphorus
Time frame: up to week 128
Change from baseline in tubular reabsorption of phosphate
Time frame: up to week 128
Change from baseline in TmP/GFR
Time frame: up to week 128
Improvement in Radiographic Global Impression of Change(RGI-C) global score
Time frame: up to week 128
Change from baseline on Rickets Severity Score (RSS) total score
Time frame: up to week 128
Change from baseline in the Six Minute Walk Test
Time frame: up to week 128
Change in height-for-age z-scores from baseline
Time frame: up to week 128
Serum KRN23 concentration
Time frame: up to week 128
Anti-KRN23 antibody
Time frame: up to week 128
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 6 Sep 2022.
- Derived from this study: PubMed 36719566Kubota T, Namba N, Tanaka H, Muroya K, Imanishi Y, Takeuchi Y, Kanematsu M, Sun W, Seino Y, Ozono K. Self-Administration of Burosumab in Children and Adults with X-Linked Hypophosphataemia in Two Open-Label, Single-Arm Clinical Studies. Adv Ther. 2023 Apr;40(4):1530-1545. doi: 10.1007/s12325-022-02412-x. Epub 2023 Jan 31.
- Individual participant dataSharing planned: No
Related trials for X-linked Hypophosphatemic Rickets/Osteomalacia
Active, not recruitingObservational study
Study of Longitudinal Observation for Patient With X-linked Hypophosphatemic Rickets/Osteomalacia in Collaboration With Asian Partners
X-Linked Hypophosphatemia
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.
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing KRN23 in people with X-linked Hypophosphatemic Rickets/Osteomalacia, run by Kyowa Kirin Co., Ltd. at 4 sites in Japan.
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 5 inclusion and 7 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 6 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Japan. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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?
Number of subjects for each adverse events (time frame: up to week 128). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03233126, which also lists 1 linked publication.
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 6 Sep 2022.