NCT04308096CompletedPhase 3
A Phase 3 Long-term Extension Study of KRN23 in Patients With X-linked Hypophosphatemic Rickets/Osteomalacia and a Post-marketing Study of KRN23 Switched From the Phase 3 Long-term Extension Study
Kyowa Kirin Co., Ltd.10 sites in 2 countries27 target enrollmentStarted: January 9, 2018Last updated:
Conditions
Interventions
Drugs
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Kyowa Kirin Co., Ltd.
- Enrollment
- 27
- Locations
- 10
- Primary Endpoint
- Effect to Pulse rate
Study Overview
Brief Summary
Before switching to the post-marketing study:
Assess the efficacy and safety of KRN23 administered subcutaneously once every 4 or 2 weeks in adult or children with XLH
After switching to the post-marketing study:
To evaluate the safety and efficacy of KRN23, which was switched from the investigational product to the post-marketing investigational product, at the approved dose and dosing regimen in subjects who continued treatment
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Personally submitted voluntary written informed consent to participate in the study; For pediatric patients, 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.
- •Patients meeting any of the followings;
- •For adult XLH patients, completion the final observation at Week 96 in UX023-CL303 or UX023-CL304
- •For pediatric patients, completion the final observation at Week 64 in UX023-CL301
- •For female patients; women of childbearing potential (except for females who have not reached menarche, permanently sterilized, postmenopausal [12 months with no menses without an alternative medical cause] or anatomically not of childbearing potential) with negative pregnancy test at pre-treatment assessment of Week 0
- •For female patient with childbearing potential, or male patients with reproductive capacity; willingness to use acceptable methods of contraception while participating in the study
- •Willingness and ability to cooperatively complete all study procedures, adhere to the visit schedule and follow the investigator's instructions, as considered by investigator or subinvestigator
Exclusion Criteria
- •Use of oral phosphate for treating XLH, pharmacologic vitamin D metabolites or analogs, aluminum hydroxide antacids, systemic corticosteroids, acetazolamide, and thiazides within 7 days prior to scheduled initial administration of investigational drug
- •Planned or recommended orthopedic surgery (implantation or removal), including staples, 8 plates or osteotomy, during the study period
- •Blood or blood product transfusion within 60 days prior to scheduled initial administration of investigational drug
- •Use of growth hormone therapy within 12 months prior to scheduled initial administration of investigational drug
- •Use of medication to suppress the secretion of parathyroid hormone (e.g., cinacalcet) within 60 days prior to scheduled initial administration of investigational drug
- •Use of any investigational product (except for investigational product of the preceding study) or investigational medical device within 4 months prior to scheduled initial administration of investigational drug, or requirement for any investigational agent prior to completion of all scheduled study assessments
- •Use of a therapeutic monoclonal antibody other than KRN23 within 90 days prior to scheduled initial administration of investigational drug
- •History of being positive for HIV antibody, HBs antigen and/or HCV antibody
- •Anyone otherwise considered unsuitable for the study by the investigator or subinvestigator
- •At the time of switching to the post-marketing clinical study:
- •Subjects eligible for enrollment in the post-marketing clinical study must have met both of the following criteria:
- •Personally submitted voluntary written informed consent to participate in the postmarketing clinical study. For pediatric patients, personally submitted voluntary written informed consent by a legally authorized representative. If appropriate, written or verbal assent to participate in the post-marketing clinical study was to be obtained from subjects.
- •Switching to the post-marketing clinical study was necessary and appropriate for the subject from the viewpoint of efficacy and safety, as judged by the investigator or subinvestigator
Arms & Interventions
KRN23
Experimental
Subjects will receive subcutaneous injections of KRN23 every 4 weeks (adult) or 2 weeks (pediatric) from Week 0 through Week 140.
Intervention: KRN23 (Drug)
Outcomes
Primary Outcomes
Effect to Pulse rate
Time Frame: up to week 140
Effect to Respiratory rate
Time Frame: up to week 140
Effect to Systolic blood pressure in sitting position
Time Frame: up to week 140
Effect to Diastolic blood pressure in sitting position
Time Frame: up to week 140
Effect to 12-lead electrocardiogram (ECG)
Time Frame: up to week 140
The presence of abnormality in the electrocardiogram
Effect to renal ultrasound
Time Frame: up to week 140
The evaluation to nephrocalcinosis in five grades by renal ultrasound
Effect to Echocardiogram
Time Frame: up to week 140
The presence of ectopic calcification in the heart by Echocardiogram
Number of subjects for each adverse events
Time Frame: up to week 140
Effect to Body temperature
Time Frame: up to week 140
Secondary Outcomes
- Concentration of serum phosphorus(up to week 140)
- Concentration of serum 1,25(OH)2D(up to week 140)
- Concentration of urinary phosphorus(up to week 140)
- Concentration of tubular resorption of phosphorus（TRP）(up to week 140)
- Concentration of maximum tubular reabsorption of phosphate/glomerular filtration rate (TmP/GFR)(up to week 140)
- concentration of Carboxy terminal cross-linked telopeptide of type 1 collagen (CTx) (Adult patients with XLH)(up to week 140)
- concentration of Procollagen type 1 N-propeptide (P1NP) (Adult patients with XLH)(up to week 140)
- concentration of Bone-specific alkaline phosphatase (BALP)(Adult patients with XLH)(up to week 140)
- Concentration of serum alkaline phosphatase (ALP) (Pediatric patients with XLH)(up to week 140)
- Motor functions (6 minutes walk test (6MWT))(up to week 140)
- Radiographic findings of fracture and enthesopathy (Adult patients with XLH)(up to week 140)
- Rickets Severity Score (RSS) (Pediatric patients with XLH)(up to week 140)
- Radiographic Global Impression of Change (RGI-C)(Pediatric patients with XLH)(up to week 140)
- Z score of height (LMS method) (Pediatric patients with XLH)(up to week 140)
Investigators
Study Sites (10)
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