Tumor-Induced Osteomalacia (TIO)Phase 4NCT05357573
Study to Assess the Safety, Pharmacokinetics and Efficacy of KRN23 in Adult Chinese Patients With TIO
A Phase 4 study testing KRN23 in people with Tumor-Induced Osteomalacia (TIO), run by Kyowa Kirin Co., Ltd. at 3 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 TIO Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Tumor-Induced Osteomalacia (TIO)
- 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
- 9 participants
- Where
- 3 sitesChina
- Study dates
- 7 Sep 2022to 22 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Have a clinical diagnosis of TIO based on evidence of excessive FGF23 that is not amenable to cure by surgical excision of the offending tumor (documented by Investigator)
- Male or female Chinese patients aged ≥18 years at the time of signing the informed consent form
- Have a fasting serum phosphorus level < 2.5 mg/dL (0.81 mmol/L) at Screening
- Have a serum iFGF23 level ≥ 100 pg/mL by Kainos assay at Screening
- Have a TmP/GFR < 2.5 mg/dL at Screening
- Have an estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73m2(using CKD-EPI formula) at Screening. Subjects with an eGFR ≥ 30 but < 60 mL/min at screening will be considered eligible so long as in the opinion of the Investigator the decline in renal function is not related to nephrocalcinosis
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- Have a corrected serum calcium level < 10.8 mg/dL (2.69 mmol/L) at Screening (Corrected serum calcium = serum calcium in mg/dL + 0.8 × [4 - serum albumin in g/dL])
- 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 to provide access to prior medical records to determine eligibility including imaging, biochemical, and diagnostic, medical, and surgical history data
- Provide written informed consent 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 (in the opinion of the Investigator)
Who cannot join
- Use of the following drugs within 14 days prior to screening: pharmacologic vitamin D metabolites or analogs, or drugs for treating TIO including oral phosphate, aluminum hydroxide antacids, acetazolamide, or thiazide diuretics
- Medication to suppress parathyroid hormone (PTH) (e.g., cinacalcet hydrochloride) within 60 days prior to screening
- Blood or blood product transfusion within 60 days prior to screening
- History of malignancy within 5 years of study entry with the exception of PMT-MCT (phosphaturic mesenchymal tumors of the mixed connective tissue type)
- 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
- Predisposition to infection, or history of recurrent infection or known immunodeficiency
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- Pregnant or breastfeeding at screening or intention to become pregnant during the study; for male subjects, the partner's intention to become pregnant during the study
- Use of an investigational product (IP) or device within 4 months prior to screening, or planning to receive other IP before completing all assessments in this study.
- Use of KRN23, or any other therapeutic mAb within 90 days before signing the informed consent form.
- History of allergic or anaphylactic reactions to KRN23, any of the KRN23 ingredients, or any other monoclonal antibodies
- Anyone otherwise considered unsuitable participation in the study by the investigator or subinvestigator
Trial locations and contacts
3 sites in 1 country.
China3 sites
Peking Union Medical College Hospital
Beijing
West China Hospital, Sichuan University
Chengdu
Shanghai Jiaotong University Affiliated Sixth People's 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 Tumor-Induced Osteomalacia (TIO)
The purpose of this study is to assess the safety, pharmacokinetics and efficacy of KRN23 in adult Chinese patients with TIO
- Conditions
- Tumor-Induced Osteomalacia (TIO)
- Being tested
- KRN23
- Medical subject headings
- Oncogenic osteomalacia
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 administered subcutaneously (SC) every 4 weeks for 48 weeks. The dose varies according to serum phosphorus level which include 0.3,0.6,1.0,1.4 and 2.0 mg/kg. Receives: Drug: KRN23 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from Baseline in mean serum phosphorus level at the end of the dosing cycle.
Measured: Week 20, 24, 28, 32, 36, 40, 44 and 48
Secondary outcomes (17)
Change from Baseline in mean serum phosphorus level.
Measured: Week 22
Proportion of patients achieving serum phosphorus level above the lower limit of normal (LLN; 2.5 mg/dL [0.81 mmol/L])
Measured: Week 22
Proportion of patients achieving mean serum phosphorus level above the LLN (2.5 mg/dL [0.81 mmol/L]) at the end of the dose cycle as averaged across dose period
Measured: Weeks 20, 24, 28, 32, 36, 40, 44 and 48
Change from Baseline in mean level of serum 1,25(OH)2D over time
Measured: Week 0, 1, 2, 12, 16, 24, 36 and 48
Change from Baseline in mean level of serum creatinine over time
Measured: Week 0, 4, 8, 12, 16, 24, 36 and 48
Change from Baseline in mean level of urinary phosphorus over time
Measured: Week 0, 4, 8, 12, 16, 24, 36 and 48
Change from Baseline in level of tubular reabsorption of phosphate(TRP) over time
Measured: Week 0, 4, 8, 12, 16, 24, 36 and 48
Change from Baseline in ratio of renal tubular maximum reabsorption rate of phosphate to glomerular filtration rate (TmP/GFR) over time
Measured: Week 0, 4, 8, 12, 16, 24, 36 and 48
Change in concentration of alkaline phosphatase (ALP) over time
Measured: Week 0, 8, 16, 24 and 48
Change in concentration of bone-specific alkaline phosphatase (BALP) over time
Measured: Week 0, 8, 16, 24 and 48
Change in concentration of carboxy-terminal cross-linked telopeptide of type 1 collagen (CTx) over time
Measured: Week 0, 8, 16, 24 and 48
Change in concentration of procollagen type 1 N propeptide(P1NP) over time
Measured: Week 0, 8, 16, 24 and 48
Change in concentration of osteocalcin (OC) over time
Measured: Week 0, 8, 16, 24 and 48
Change from Baseline in six-minute walking test (6MWT) over time
This test will measure the distance that the subject can walk a previously measured course in a period of 6 minutes.
Measured: Week 0, 12, 24 and 48
Change from Baseline in Brief Pain Inventory (BPI) score over time
Evaluate the degree of pain and its impact on daily functioning over previous 24 hours, the subject will fill out a 15-item self-administered questionnaire. 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: Week 0, 12, 24 and 48
Change from Baseline in Brief Fatigue Inventory (BFI) score over time
Evaluate the degree of fatigue and its impact on daily functioning over previous 24 hours, the subject will fill out a 9-item self-administered questionnaire.
Two dimensions are measured: fatigue severity (now, usual and worst) and the impact of fatigue on functioning (fatigue interference with general activity, mood, walking ability, normal work, relations with other people, enjoyment of life). The severity of fatigue in the last 24 hours is rated on a scale of 0 (no fatigue or does not interfere) to 10 (fatigue as bad as you can imagine or completely interferes). Scores are normalized to a 0-10 metric where 0 was the best health state and 90 was the worst.
Measured: Week 0, 12, 24 and 48
36-item short-form health survey (SF-36) scores to examine health-related Quality of Life
Evaluate physical and mental health status, the subject will fill out a 36-item self-administered questionnaire.
The SF-36 questionnaire consists of eight scales yielding two summary measures: physical and mental health. The physical health measure includes four scales of physical functioning (10 items), role-physical (4 items), bodily pain (2 items), and general health (5 items). The mental health measure is composed of vitality (4 items), social functioning (2 items), role-emotional (3 items), and mental health (5 items). The score will be calculated based on scoring system, and the Higher scores are associated with better functioning/quality of life; a positive change from Baseline score indicates an improvement.
Measured: Week 0, 12, 24 and 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 May 2022
- Study start7 Sep 2022
- Primary completion22 Nov 2023
- Study completion22 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Tumor-Induced Osteomalacia (TIO)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
- 9 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
- NCT05357573
- Sponsor's protocol ID
- KRN23-CN007
- Status last verified
- Jul 2024
- First submitted
- 27 Apr 2022
- 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 Tumor-Induced Osteomalacia (TIO)
- ClinicalTrials.gov ID
- NCT05357573
- Acronym / sponsor ID
- KRN23-CN007
- Conditions
- Tumor-Induced Osteomalacia (TIO)
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Kyowa Kirin Co., Ltd.Industry (pharma, biotech, devices)
- Study start
- 7 Sep 2022 (actual)
- Primary completion
- 22 Nov 2023 (actual)
- Study completion
- 22 Dec 2023 (actual)
- First posted
- 3 May 2022 (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 TIO
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 administered subcutaneously (SC) every 4 weeks for 48 weeks. The dose varies according to serum phosphorus level which include 0.3,0.6,1.0,1.4 and 2.0 mg/kg. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Have a clinical diagnosis of TIO based on evidence of excessive FGF23 that is not amenable to cure by surgical excision of the offending tumor (documented by Investigator)
- Male or female Chinese patients aged ≥18 years at the time of signing the informed consent form
- Have a fasting serum phosphorus level < 2.5 mg/dL (0.81 mmol/L) at Screening
- Have a serum iFGF23 level ≥ 100 pg/mL by Kainos assay at Screening
- Have a TmP/GFR < 2.5 mg/dL at Screening
Key exclusion criteria (11 listed)
- Use of the following drugs within 14 days prior to screening: pharmacologic vitamin D metabolites or analogs, or drugs for treating TIO including oral phosphate, aluminum hydroxide antacids, acetazolamide, or thiazide diuretics
- Medication to suppress parathyroid hormone (PTH) (e.g., cinacalcet hydrochloride) within 60 days prior to screening
- Blood or blood product transfusion within 60 days prior to screening
- History of malignancy within 5 years of study entry with the exception of PMT-MCT (phosphaturic mesenchymal tumors of the mixed connective tissue type)
- 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
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 in mean serum phosphorus level at the end of the dosing cycle.
Time frame: Week 20, 24, 28, 32, 36, 40, 44 and 48
17 secondary outcomes
Change from Baseline in mean serum phosphorus level.
Time frame: Week 22
Proportion of patients achieving serum phosphorus level above the lower limit of normal (LLN; 2.5 mg/dL [0.81 mmol/L])
Time frame: Week 22
Proportion of patients achieving mean serum phosphorus level above the LLN (2.5 mg/dL [0.81 mmol/L]) at the end of the dose cycle as averaged across dose period
Time frame: Weeks 20, 24, 28, 32, 36, 40, 44 and 48
Change from Baseline in mean level of serum 1,25(OH)2D over time
Time frame: Week 0, 1, 2, 12, 16, 24, 36 and 48
Change from Baseline in mean level of serum creatinine over time
Time frame: Week 0, 4, 8, 12, 16, 24, 36 and 48
Change from Baseline in mean level of urinary phosphorus over time
Time frame: Week 0, 4, 8, 12, 16, 24, 36 and 48
Change from Baseline in level of tubular reabsorption of phosphate(TRP) over time
Time frame: Week 0, 4, 8, 12, 16, 24, 36 and 48
Change from Baseline in ratio of renal tubular maximum reabsorption rate of phosphate to glomerular filtration rate (TmP/GFR) over time
Time frame: Week 0, 4, 8, 12, 16, 24, 36 and 48
Change in concentration of alkaline phosphatase (ALP) over time
Time frame: Week 0, 8, 16, 24 and 48
Change in concentration of bone-specific alkaline phosphatase (BALP) over time
Time frame: Week 0, 8, 16, 24 and 48
Change in concentration of carboxy-terminal cross-linked telopeptide of type 1 collagen (CTx) over time
Time frame: Week 0, 8, 16, 24 and 48
Change in concentration of procollagen type 1 N propeptide(P1NP) over time
Time frame: Week 0, 8, 16, 24 and 48
Change in concentration of osteocalcin (OC) over time
Time frame: Week 0, 8, 16, 24 and 48
Change from Baseline in six-minute walking test (6MWT) over time
Time frame: Week 0, 12, 24 and 48
Change from Baseline in Brief Pain Inventory (BPI) score over time
Time frame: Week 0, 12, 24 and 48
Change from Baseline in Brief Fatigue Inventory (BFI) score over time
Time frame: Week 0, 12, 24 and 48
36-item short-form health survey (SF-36) scores to examine health-related Quality of Life
Time frame: Week 0, 12, 24 and 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.
3 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 Tumor-Induced Osteomalacia (TIO), run by Kyowa Kirin Co., Ltd. at 3 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 11 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 3 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 in mean serum phosphorus level at the end of the dosing cycle. (time frame: Week 20, 24, 28, 32, 36, 40, 44 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.