X-linked Hypophosphatemia
Conditions
Keywords
XLH
Brief summary
The primary purpose of this study is to assess the safety and efficacy of repeated subcutaneous (SC) injections of KRN23 in adult subjects with X-Linked Hypophosphatemia (XLH). A Bone Substudy will evaluate the effects of single-blind KRN23 versus Placebo on bone mineral density and bone quality.
Interventions
DRUGKRN23
Subjects will receive escalating doses of KRN23 administered by SC injections every 28-days (up to 4 doses) based on a dosing algorithm and discretion of the investigator and sponsor.
Sponsors
Kyowa Kirin Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Main Inclusion Criteria: 1. 18 years or older 2. Clinical diagnosis of XLH 3. TmP/GFR \< 2.0 mg/dL 4. GFR ≥60 mL/min 5. Corrected Ca \<10.8 mg/dL 6. A willingness to utilize adequate contraception and not become pregnant\[or to have their partner(s) become pregnant\] during the study 7. Additional inclusion criteria apply Main
Exclusion criteria
1. Have any sign of active infectious disease or have had an infection requiring treatment with antibiotics within 3-weeks of Screening 2. History of known immunodeficiency 3. Pregnant or lactating females subjects or female planning to be become pregnant during the study 4. Receipt of a live (attenuated) vaccine (except for influenza vaccines) within 3-months of Screening, and/or during the study 5. Use of pharmacologic vitamin D metabolite or its analog, phosphate, calcimimetics, and ingestion of aluminum hydroxide antacids within 10-days prior to Screening and/or dosing 6. Use of any supplement containing phosphate, calcium and/or vitamin D within 10-days prior to Screening and/or dosing 7. Condition which could present a concern for either the subject's safety or difficulty with data interpretation 8. Additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Efficacy of Repeated SC Injections of KRN23 | On-Treatment: 6.5 months, 27 total visits | Safety and efficacy of repeated SC injections of KRN23 from baseline as assessed by serum phosphorus levels,immunogenicity, adverse events and clinically significant changes in vital signs and laboratory testing. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of Effect of Repeated SC Injections of KRN23 | On-Treatment: 6.5 months, 27 total visits | Effect of repeated SC injections of KRN23, from baseline, on pharmacodynamic parameters including serum phosphorus, sex hormone, bone biomarkers, quality of life assessments and population pharmacokinetics of KRN23 dose levels from cumulative dosing. Summary of serum phosphorus by visit/day is captured below. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of Effect of Repeated SC Injections of KRN23 in Bone Substudy | On-Treatment: 6.5 months, 27 total visits | Evaluation of effect of repeated SC injections of KRN23, compared to Placebo on bone mineral density and bone quality. |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| KRN23 Escalating doses of KRN23 (0.05, 0.10, 0.30 and 0.60 mg/kg) will be administered SC every 28 days (up to 4 doses)
KRN23: Subjects will receive escalating doses of KRN23 administered by SC injections every 28-days (up to 4 doses) based on a dosing algorithm and discretion of the investigator and sponsor. | 27 |
| Bone Substudy KRN23 | 1 |
| Bone Substudy Placebo | 1 |
| Total | 29 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 | 0 |
Baseline characteristics
| Characteristic | KRN23 | Bone Substudy KRN23 | Bone Substudy Placebo | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 26 Participants | 1 Participants | 1 Participants | 28 Participants |
| Age, Continuous | 42 years | 21 years | 28 years | 41 years |
| Race/Ethnicity, Customized Black/African American/African Caribbean | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White/Caucasian | 26 Participants | 1 Participants | 1 Participants | 28 Participants |
| Region of Enrollment Canada | 0 participants | 1 participants | 1 participants | 2 participants |
| Region of Enrollment United States | 27 participants | 0 participants | 0 participants | 27 participants |
| Sex: Female, Male Female | 18 Participants | 1 Participants | 1 Participants | 20 Participants |
| Sex: Female, Male Male | 9 Participants | 0 Participants | 0 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 27 | 0 / 1 | 0 / 1 |
| other Total, other adverse events | 24 / 27 | 1 / 1 | 1 / 1 |
| serious Total, serious adverse events | 0 / 27 | 0 / 1 | 0 / 1 |
Outcome results
Primary
Safety and Efficacy of Repeated SC Injections of KRN23
Safety and efficacy of repeated SC injections of KRN23 from baseline as assessed by serum phosphorus levels,immunogenicity, adverse events and clinically significant changes in vital signs and laboratory testing.
Time frame: On-Treatment: 6.5 months, 27 total visits
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| KRN23 | Safety and Efficacy of Repeated SC Injections of KRN23 | Subjects reporting at least one DLT | 0 Participants |
| KRN23 | Safety and Efficacy of Repeated SC Injections of KRN23 | Subjects reporting SAE other than death | 0 Participants |
| KRN23 | Safety and Efficacy of Repeated SC Injections of KRN23 | Subjects reporting at least one TEAE | 24 Participants |
| KRN23 | Safety and Efficacy of Repeated SC Injections of KRN23 | Subjects who died | 0 Participants |
| KRN23 | Safety and Efficacy of Repeated SC Injections of KRN23 | Subjects reporting AE leading to discontinuation | 1 Participants |
| Bone Substudy KRN23 | Safety and Efficacy of Repeated SC Injections of KRN23 | Subjects reporting SAE other than death | 0 Participants |
| Bone Substudy KRN23 | Safety and Efficacy of Repeated SC Injections of KRN23 | Subjects reporting at least one TEAE | 1 Participants |
| Bone Substudy KRN23 | Safety and Efficacy of Repeated SC Injections of KRN23 | Subjects who died | 0 Participants |
| Bone Substudy KRN23 | Safety and Efficacy of Repeated SC Injections of KRN23 | Subjects reporting at least one DLT | 0 Participants |
| Bone Substudy KRN23 | Safety and Efficacy of Repeated SC Injections of KRN23 | Subjects reporting AE leading to discontinuation | 0 Participants |
| Bone Substudy Placebo | Safety and Efficacy of Repeated SC Injections of KRN23 | Subjects reporting AE leading to discontinuation | 0 Participants |
| Bone Substudy Placebo | Safety and Efficacy of Repeated SC Injections of KRN23 | Subjects reporting at least one DLT | 0 Participants |
| Bone Substudy Placebo | Safety and Efficacy of Repeated SC Injections of KRN23 | Subjects reporting at least one TEAE | 1 Participants |
| Bone Substudy Placebo | Safety and Efficacy of Repeated SC Injections of KRN23 | Subjects reporting SAE other than death | 0 Participants |
| Bone Substudy Placebo | Safety and Efficacy of Repeated SC Injections of KRN23 | Subjects who died | 0 Participants |
Secondary
Evaluation of Effect of Repeated SC Injections of KRN23
Effect of repeated SC injections of KRN23, from baseline, on pharmacodynamic parameters including serum phosphorus, sex hormone, bone biomarkers, quality of life assessments and population pharmacokinetics of KRN23 dose levels from cumulative dosing. Summary of serum phosphorus by visit/day is captured below.
Time frame: On-Treatment: 6.5 months, 27 total visits
Population: Efficacy analysis set: All subjects who received at least 1 dose of KRN23 and completed at least one 28-day post-dose evaluation.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 | Visit 2 (D0)/0 | 1.89 mg/dL |
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 | Visit 3 (D3)/3 | 2.18 mg/dL |
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 | Visit 4 (D7)/7 | 2.20 mg/dL |
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 | Visit 5 (D12)/12 | 2.14 mg/dL |
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 | Visit 6 (D18)/18 | 2.15 mg/dL |
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 | Visit 7 (D26)/26 | 1.96 mg/dL |
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 | Visit 8 (D28)/0 | 1.93 mg/dL |
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 | Visit 9 (D31)/3 | 2.35 mg/dL |
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 | Visit 10 (D35)/7 | 2.45 mg/dL |
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 | Visit 11 (D40)/12 | 2.31 mg/dL |
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 | Visit 12 (D46)/18 | 2.28 mg/dL |
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 | Visit 13 (D54)/26 | 2.15 mg/dL |
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 | Visit 14 (D56)/0 | 2.12 mg/dL |
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 | Visit 15 (D59)/3 | 2.57 mg/dL |
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 | Visit 16 (D63)/7 | 2.85 mg/dL |
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 | Visit 17 (D68)/12 | 2.83 mg/dL |
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 | Visit 18 (D74)/18 | 2.60 mg/dL |
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 | Visit 19 (D82)/26 | 2.33 mg/dL |
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 | Visit 20 (D84)/0 | 2.26 mg/dL |
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 | Visit 21 (D87)/3 | 2.64 mg/dL |
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 | Visit 22 (D91)/7 | 3.03 mg/dL |
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 | Visit 23 (D96)/12 | 2.94 mg/dL |
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 | Visit 24 (D102)/18 | 2.82 mg/dL |
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 | Visit 25 (D110)/26 | 2.54 mg/dL |
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 | End of Study - Visit 26 (D120) | 2.22 mg/dL |
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 | Early Withdrawal | 1.30 mg/dL |
Other Pre-specified
Evaluation of Effect of Repeated SC Injections of KRN23 in Bone Substudy
Evaluation of effect of repeated SC injections of KRN23, compared to Placebo on bone mineral density and bone quality.
Time frame: On-Treatment: 6.5 months, 27 total visits
Population: Subjects randomized to the bone density substudy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 in Bone Substudy | NA units on a scale |
| Bone Substudy KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 in Bone Substudy | NA units on a scale |