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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT02722798
Other study ID # KRN23-002
Secondary ID
Status Completed
Phase Phase 2
First received
Last updated
Start date April 2016
Est. completion date October 2020

Study information

Verified date August 2022
Source Kyowa Kirin Co., Ltd.
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical 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. 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.


Recruitment information / eligibility

Status Completed
Enrollment 14
Est. completion date October 2020
Est. primary completion date July 2017
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: 1. Aged = 18 years 2. Diagnosis of Tumor-Induced Osteomalacia(TIO) or Epidermal Nevus Syndrome(ENS) and not amenable to receive surgical excision of the offending tumor/lesion 3. Serum phosphorus level < 2.5 mg/dL 4. Serum FGF23 level = 100 pg/mL 5. Ratio of renal tubular maximum phosphate reabsorption rate to glomerular filtration rate< 2.5 mg/dL 6. 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 7. Corrected serum calcium level < 10.8 mg/dL 8. For female subjects of childbearing potential; negative urine pregnancy test and willingness to undergo additional pregnancy tests during the study 9. 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 Exclusion Criteria: 1. 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 2. Medication to suppress parathyroid hormone (PTH) within 60 days prior to screening 3. Blood or blood product transfusion within 60 days prior to screening 4. Chemotherapy for TIO or other malignant tumors within 4 months prior to screening 5. History of being positive for human immunodeficiency virus antibody, hepatitis B antigen and/or hepatitis C virus antibody 6. Predisposition to infection, or history of recurrent infection or known immunodeficiency 7. 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 8. 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 9. Use of therapeutic monoclonal antibodies including KRN23 within 90 days prior to screening 10. History of allergic or anaphylactic reactions to KRN23, any of the KRN23 ingredients, or any other monoclonal antibodies 11. Anyone otherwise considered unsuitable participation in the study by the investigator or subinvestigator At the time of switching to the post-marketing study: 1. 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) 2. 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.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
KRN23
Doses may be titrated to achieve the target peak serum phosphorus range

Locations

Country Name City State
n/a

Sponsors (1)

Lead Sponsor Collaborator
Kyowa Kirin Co., Ltd.

Countries where clinical trial is conducted

Japan,  Korea, Republic of, 

Outcome

Type Measure Description Time frame Safety issue
Other Number and types of adverse events up to week 224
Primary serum phosphorus concentration at each test time point up to week 224
Secondary Change from Baseline in Serum Phosphorus Level up to week 224
Secondary Achievement Proportion of Mid-Cycle-Mean Serum Phosphorus Value (mg/dL) Exceeding the Lower Limit (2.5 mg/dL [0.81 mmol/L]) at week 24
Secondary Achievement Proportion of End-Cycle-Mean Serum Phosphorus Value (mg/dL) Exceeding the Lower Limit (2.5 mg/dL [0.81 mmol/L]) at week 48
Secondary Changes from baseline over time in serum Type I Collagen C-Telopeptides (CTx) up to week 224
Secondary Changes from baseline over time in serum Procollagen 1 N-Terminal Propeptide (P1NP) up to week 224
Secondary Changes from baseline over time in serum Bone Specific Alkaline Phosphatase (BALP) up to week 224
Secondary Changes from baseline over time in serum Osteocalcin (OC) up to week 224
Secondary change from baseline in FGF23 up to week 224
Secondary change from baseline in alkaline phosphatase up to week 224
Secondary change from baseline in 1,25(OH)2D up to week 224
Secondary change from baseline in urine P up to week 224
Secondary change from baseline in tubular reabsorption of phosphate up to week 224
Secondary change from baseline in ratio of renal tubular maximum phosphate reabsorption rate to glomerular filtration rate up to week 224
Secondary change from baseline in skeletal disease/osteomalacia through trans-iliac crest bone biopsy up to week 224
Secondary Effect to Sit to Stand (STS) test up to week 224
Secondary Effect to Hand Held Dynamometry (HHD) up to week 224
Secondary Effect to Weighted Arm Lift (WAL) test up to week 224
Secondary Effect to 6 minute walking test (6MWT) up to week 224
Secondary Effect to patient reported outcomes up to week 224
Secondary maximum concentration (Cmax) of KRN23 up to week 224
Secondary area under the curve (AUC) of KRN23 up to week 224
Secondary time to peak (tmax) of KRN23 up to week 224