Tumor-Induced Osteomalacia or Epidermal Nevus SyndromePhase 2NCT02722798
A Study of KRN23 in Subjects With Tumor-Induced Osteomalacia or Epidermal Nevus Syndrome
A Phase 2 study testing KRN23 in people with Tumor-Induced Osteomalacia or Epidermal Nevus Syndrome, run by Kyowa Kirin Co., Ltd. at 3 sites in 2 countries.
Trial summary
Before switching to the post-marketing study: To evaluate the efficacy and safety of KRN23 after its 144-week once every 4 weeks (Q4W) repeated SC administration to Japanese and Korean patients with TIO or ENS by a multicenter, open-label, intraindividual dose adjustment study. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Tumor-Induced Osteomalacia or Epidermal Nevus Syndrome
- 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
- 14 participants
- Where
- 3 sitesin 2 countries
- Study dates
- Apr 2016to Oct 2020
- Phase
- Phase 2
- 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
- Aged ≥ 18 years
- Diagnosis of Tumor-Induced Osteomalacia(TIO) or Epidermal Nevus Syndrome(ENS) and not amenable to receive surgical excision of the offending tumor/lesion
- Serum phosphorus level < 2.5 mg/dL
- Serum FGF23 level ≥ 100 pg/mL
- Ratio of renal tubular maximum phosphate reabsorption rate to glomerular filtration rate< 2.5 mg/dL
- Estimated glomerular filtration rate (eGFR) at screening ≥ 60 mL/min/1.73 m2, or eGFR ≥ 30 and < 60 mL/min/1.73 m2 with an evidence of no renal failure related to nephrocalcinosis
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- Corrected serum calcium level < 10.8 mg/dL
- For female subjects of childbearing potential; negative urine pregnancy test and willingness to undergo additional pregnancy tests during the study
- Willingness to use an acceptable method of contraception while participating in the study
- Willingness to provide access to prior medical records to determine eligibility including data on imaging tests, blood chemistry, diagnosis, medication, and surgical history
- 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
- Use of the following drugs within 14 days prior to screening: pharmacologic vitamin D metabolites or analogs, or drugs for treating TIO/ENS including oral phosphate, aluminum hydroxide antacids, acetazolamide, or thiazide diuretics
- Medication to suppress parathyroid hormone (PTH) within 60 days prior to screening
- Blood or blood product transfusion within 60 days prior to screening
- Chemotherapy for TIO or other malignant tumors within 4 months prior to screening
- History of being positive for human immunodeficiency virus antibody, hepatitis B antigen and/or hepatitis C virus antibody
- 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 or device within 4 months prior to screening, or planning to receive other investigational product before completing all assessments in this study
- Use of therapeutic monoclonal antibodies including KRN23 within 90 days prior to screening
- 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
- At the time of switching to the post-marketing study:
- Voluntary written informed consent to participate in the post-marketing study (if aged < 20 years at the time of consent, written informed consent must be obtained from his or her legally acceptable representative as well)
- Switching to the post-marketing study is necessary and appropriate for the subject from the viewpoint of efficacy and safety, as judged by the investigator or subinvestigator.
Trial locations and contacts
3 sites in 2 countries.
3 sites in 2 countries
About this study
Official title: A Phase 2 Open-Label Trial to Assess the Efficacy and Safety of KRN23 in Patients With Tumor-Induced Osteomalacia or Epidermal Nevus Syndrome and a Post-marketing Study of KRN23 Switched From the Phase 2 Trial
Before switching to the post-marketing study:
To evaluate the efficacy and safety of KRN23 after its 144-week once every 4 weeks (Q4W) repeated SC administration to Japanese and Korean patients with TIO or ENS by a multicenter, open-label, intraindividual dose adjustment study.
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 investigational product, at the approved dose and dosing regimen in subjects who continue treatment after the marketing approval of KRN23 in Japan.
- Being tested
- KRN23
- Medical subject headings
- Oncogenic osteomalacia, Nevus, Sebaceous of Jadassohn
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KRN23Drug
Doses may be titrated to achieve the target peak serum phosphorus range
| Study group | Role | What they receive |
|---|---|---|
| KRN23 | Experimental | Subjects will receive subcutaneous injections of KRN23 every 4 weeks from Week 0 through Week 224 Receives: Drug: KRN23 |
What is being measured
The primary outcome is the main question the study is designed to answer.
serum phosphorus concentration at each test time point
Measured: up to week 224
Secondary outcomes (22)
Change from Baseline in Serum Phosphorus Level
Measured: up to week 224
Achievement Proportion of Mid-Cycle-Mean Serum Phosphorus Value (mg/dL) Exceeding the Lower Limit (2.5 mg/dL [0.81 mmol/L])
Measured: at week 24
Achievement Proportion of End-Cycle-Mean Serum Phosphorus Value (mg/dL) Exceeding the Lower Limit (2.5 mg/dL [0.81 mmol/L])
Measured: at week 48
Changes from baseline over time in serum Type I Collagen C-Telopeptides (CTx)
Measured: up to week 224
Changes from baseline over time in serum Procollagen 1 N-Terminal Propeptide (P1NP)
Measured: up to week 224
Changes from baseline over time in serum Bone Specific Alkaline Phosphatase (BALP)
Measured: up to week 224
Changes from baseline over time in serum Osteocalcin (OC)
Measured: up to week 224
change from baseline in FGF23
Measured: up to week 224
change from baseline in alkaline phosphatase
Measured: up to week 224
change from baseline in 1,25(OH)2D
Measured: up to week 224
change from baseline in urine P
Measured: up to week 224
change from baseline in tubular reabsorption of phosphate
Measured: up to week 224
change from baseline in ratio of renal tubular maximum phosphate reabsorption rate to glomerular filtration rate
Measured: up to week 224
change from baseline in skeletal disease/osteomalacia through trans-iliac crest bone biopsy
Measured: up to week 224
Effect to Sit to Stand (STS) test
Measured: up to week 224
Effect to Hand Held Dynamometry (HHD)
Measured: up to week 224
Effect to Weighted Arm Lift (WAL) test
Measured: up to week 224
Effect to 6 minute walking test (6MWT)
Measured: up to week 224
Effect to patient reported outcomes
Measured: up to week 224
maximum concentration (Cmax) of KRN23
Measured: up to week 224
area under the curve (AUC) of KRN23
Measured: up to week 224
time to peak (tmax) of KRN23
Measured: up to week 224
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Mar 2016 (estimated)
- Study startApr 2016
- Primary completionJul 2017
- Study completionOct 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Tumor-Induced Osteomalacia or Epidermal Nevus SyndromeStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 14 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
- NCT02722798
- Sponsor's protocol ID
- KRN23-002
- Status last verified
- Aug 2022
- First submitted
- 7 Mar 2016
- Last updated
- 6 Sep 2022
- Results posted
- No
- Data monitoring committee
- Yes
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 2 Open-Label Trial to Assess the Efficacy and Safety of KRN23 in Patients With Tumor-Induced Osteomalacia or Epidermal Nevus Syndrome and a Post-marketing Study of KRN23 Switched From the Phase 2 Trial
- ClinicalTrials.gov ID
- NCT02722798
- Acronym / sponsor ID
- KRN23-002
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Kyowa Kirin Co., Ltd.Industry (pharma, biotech, devices)
- Study start
- Apr 2016
- Primary completion
- Jul 2017 (actual)
- Study completion
- Oct 2020 (actual)
- First posted
- 30 Mar 2016 (estimated)
- 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 after its 144-week once every 4 weeks (Q4W) repeated SC administration to Japanese and Korean patients with TIO or ENS by a multicenter, open-label, intraindividual dose adjustment study.
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 investigational product, at the approved dose and dosing regimen in subjects who continue treatment after the marketing approval of KRN23 in Japan.
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 4 weeks from Week 0 through Week 224 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Aged ≥ 18 years
- Diagnosis of Tumor-Induced Osteomalacia(TIO) or Epidermal Nevus Syndrome(ENS) and not amenable to receive surgical excision of the offending tumor/lesion
- Serum phosphorus level < 2.5 mg/dL
- Serum FGF23 level ≥ 100 pg/mL
- Ratio of renal tubular maximum phosphate reabsorption rate to glomerular filtration rate< 2.5 mg/dL
Key exclusion criteria (14 listed)
- Use of the following drugs within 14 days prior to screening: pharmacologic vitamin D metabolites or analogs, or drugs for treating TIO/ENS including oral phosphate, aluminum hydroxide antacids, acetazolamide, or thiazide diuretics
- Medication to suppress parathyroid hormone (PTH) within 60 days prior to screening
- Blood or blood product transfusion within 60 days prior to screening
- Chemotherapy for TIO or other malignant tumors within 4 months prior to screening
- History of being positive for human immunodeficiency virus antibody, hepatitis B antigen and/or hepatitis C virus antibody
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 |
|---|---|---|
| KRN23Doses may be titrated to achieve the target peak serum phosphorus range | Drug | KRN23 |
Primary outcome
serum phosphorus concentration at each test time point
Time frame: up to week 224
22 secondary outcomes
Change from Baseline in Serum Phosphorus Level
Time frame: up to week 224
Achievement Proportion of Mid-Cycle-Mean Serum Phosphorus Value (mg/dL) Exceeding the Lower Limit (2.5 mg/dL [0.81 mmol/L])
Time frame: at week 24
Achievement Proportion of End-Cycle-Mean Serum Phosphorus Value (mg/dL) Exceeding the Lower Limit (2.5 mg/dL [0.81 mmol/L])
Time frame: at week 48
Changes from baseline over time in serum Type I Collagen C-Telopeptides (CTx)
Time frame: up to week 224
Changes from baseline over time in serum Procollagen 1 N-Terminal Propeptide (P1NP)
Time frame: up to week 224
Changes from baseline over time in serum Bone Specific Alkaline Phosphatase (BALP)
Time frame: up to week 224
Changes from baseline over time in serum Osteocalcin (OC)
Time frame: up to week 224
change from baseline in FGF23
Time frame: up to week 224
change from baseline in alkaline phosphatase
Time frame: up to week 224
change from baseline in 1,25(OH)2D
Time frame: up to week 224
change from baseline in urine P
Time frame: up to week 224
change from baseline in tubular reabsorption of phosphate
Time frame: up to week 224
change from baseline in ratio of renal tubular maximum phosphate reabsorption rate to glomerular filtration rate
Time frame: up to week 224
change from baseline in skeletal disease/osteomalacia through trans-iliac crest bone biopsy
Time frame: up to week 224
Effect to Sit to Stand (STS) test
Time frame: up to week 224
Effect to Hand Held Dynamometry (HHD)
Time frame: up to week 224
Effect to Weighted Arm Lift (WAL) test
Time frame: up to week 224
Effect to 6 minute walking test (6MWT)
Time frame: up to week 224
Effect to patient reported outcomes
Time frame: up to week 224
maximum concentration (Cmax) of KRN23
Time frame: up to week 224
area under the curve (AUC) of KRN23
Time frame: up to week 224
time to peak (tmax) of KRN23
Time frame: up to week 224
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.
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 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing KRN23 in people with Tumor-Induced Osteomalacia or Epidermal Nevus Syndrome, run by Kyowa Kirin Co., Ltd. at 3 sites in 2 countries.
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 11 inclusion and 14 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 3 sites in Japan, South Korea. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
serum phosphorus concentration at each test time point (time frame: up to week 224). 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 6 Sep 2022.