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).
Interventions
DRUGKRN23
Subjects will receive escalating doses of KRN23 administered by SC injection every 28-days (up to 12 doses) based on a dosing algorithm and discretion of Investigator and Sponsor.
Sponsors
Kyowa Hakko Kirin Pharma, Inc.
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
1. Satisfactory completion of KKP's sponsored KRN23-INT-001 clinical trial 2. eGFR ≥ 60 mL/min 3. Corrected Ca \< 10.8 mg/dL 4. For female of child-bearing potential, a negative serum pregnancy test 5. A willingness to utilize adequate contraception and not become pregnant \[or to have their partner(s) become pregnant\] during the study 6. Additional inclusion criteria apply
Exclusion criteria
1. Subject experienced a safety-related event in the KRN23-INT-001 study 2. Pregnant or lactating female subject or pregnant or female planning to become pregnant during the study 3. Receipt of a live (attenuated) vaccine (except for influenza vaccines) during the course of the KRN23-INT-001 study and/or of this study 4. Condition which could present a concern for either the subject's safety or difficulty with data interpretation 5. Additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Efficacy of Repeated SC Injections of KRN23. | 13.5 months,(50 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 | 13.5 months, (50 visits) | Effect of repeated SC injections of KRN23, from baseline, on pharmacodynamic parameters (serum phosphorus) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of Effect of Repeated SC Injections of KRN23 in Bone Substudy | 13.5 months,(50 visits) | Evaluation of effect of repeated SC injections of KRN23, compared to Placebo on bone mineral density, bone quality and histomorphometric parameters. |
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 12 doses)
KRN23: Subjects will receive escalating doses of KRN23 administered by SC injection every 28-days (up to 12 doses) based on a dosing algorithm and discretion of Investigator and Sponsor. | 21 |
| Bone Substudy KRN23 | 1 |
| Bone Substudy Placebo | 1 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 | 0 |
| Overall Study | Study Terminated by the Sponsor | 0 | 1 | 1 |
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 | 20 Participants | 1 Participants | 1 Participants | 22 Participants |
| Age, Continuous | 43.0 years | 22 years | 28 years | 41.1 years |
| Race/Ethnicity, Customized Black/African American/African Caribbean | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White/Caucasian | 20 Participants | 1 Participants | 1 Participants | 22 Participants |
| Region of Enrollment Canada | 0 participants | 1 participants | 1 participants | 2 participants |
| Region of Enrollment United States | 21 participants | 0 participants | 0 participants | 21 participants |
| Sex: Female, Male Female | 12 Participants | 1 Participants | 1 Participants | 14 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 / 21 | 0 / 1 | 0 / 1 |
| other Total, other adverse events | 21 / 21 | 1 / 1 | 1 / 1 |
| serious Total, serious adverse events | 3 / 21 | 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: 13.5 months,(50 visits)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| KRN23 | Safety and Efficacy of Repeated SC Injections of KRN23. | With Any TEAE | 21 Participants |
| KRN23 | Safety and Efficacy of Repeated SC Injections of KRN23. | With Any Drug-related TEAE | 13 Participants |
| KRN23 | Safety and Efficacy of Repeated SC Injections of KRN23. | With Any TEAE with an Outcome of Death | 0 Participants |
| KRN23 | Safety and Efficacy of Repeated SC Injections of KRN23. | With Any Serious TEAE | 3 Participants |
| KRN23 | Safety and Efficacy of Repeated SC Injections of KRN23. | With Any Drug-related Serious TEAE | 0 Participants |
| KRN23 | Safety and Efficacy of Repeated SC Injections of KRN23. | With Any Serious TEAE with an Outcome of Death | 0 Participants |
| Bone Substudy KRN23 | Safety and Efficacy of Repeated SC Injections of KRN23. | With Any Serious TEAE with an Outcome of Death | 0 Participants |
| Bone Substudy KRN23 | Safety and Efficacy of Repeated SC Injections of KRN23. | With Any TEAE | 1 Participants |
| Bone Substudy KRN23 | Safety and Efficacy of Repeated SC Injections of KRN23. | With Any Serious TEAE | 0 Participants |
| Bone Substudy KRN23 | Safety and Efficacy of Repeated SC Injections of KRN23. | With Any Drug-related Serious TEAE | 0 Participants |
| Bone Substudy KRN23 | Safety and Efficacy of Repeated SC Injections of KRN23. | With Any Drug-related TEAE | 1 Participants |
| Bone Substudy KRN23 | Safety and Efficacy of Repeated SC Injections of KRN23. | With Any TEAE with an Outcome of Death | 0 Participants |
| Bone Substudy Placebo | Safety and Efficacy of Repeated SC Injections of KRN23. | With Any Drug-related TEAE | 0 Participants |
| Bone Substudy Placebo | Safety and Efficacy of Repeated SC Injections of KRN23. | With Any TEAE with an Outcome of Death | 0 Participants |
| Bone Substudy Placebo | Safety and Efficacy of Repeated SC Injections of KRN23. | With Any Serious TEAE with an Outcome of Death | 0 Participants |
| Bone Substudy Placebo | Safety and Efficacy of Repeated SC Injections of KRN23. | With Any Serious TEAE | 0 Participants |
| Bone Substudy Placebo | Safety and Efficacy of Repeated SC Injections of KRN23. | With Any TEAE | 1 Participants |
| Bone Substudy Placebo | Safety and Efficacy of Repeated SC Injections of KRN23. | With Any Drug-related Serious TEAE | 0 Participants |
Secondary
Evaluation of Effect of Repeated SC Injections of KRN23
Effect of repeated SC injections of KRN23, from baseline, on pharmacodynamic parameters (serum phosphorus)
Time frame: 13.5 months, (50 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 | Ext Visit 44 /25 | 2.43 mg/dL |
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 | Ext Visit 45 /0 | 2.25 mg/dL |
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 | Ext Visit 46 /7 | 2.73 mg/dL |
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 | Baseline | 1.85 mg/dL |
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 | Ext Visit 1 /0 | 1.88 mg/dL |
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 | Ext Visit 2 /7 | 2.86 mg/dL |
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 | Ext Visit 3 /14 | 2.87 mg/dL |
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 | Ext Visit 4 /25 | 2.48 mg/dL |
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 | Ext Visit 5 /0 | 2.25 mg/dL |
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 | Ext Visit 6 /7 | 2.91 mg/dL |
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 | Ext Visit 7 /14 | 2.95 mg/dL |
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 | Ext Visit 8 /25 | 2.67 mg/dL |
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 | Ext Visit 9 /0 | 2.43 mg/dL |
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 | Ext Visit 10 /7 | 2.96 mg/dL |
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 | Ext Visit 11 /14 | 2.84 mg/dL |
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 | Ext Visit 12 /25 | 2.59 mg/dL |
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 | Ext Visit 13 /0 | 2.42 mg/dL |
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 | Ext Visit 14 /7 | 2.92 mg/dL |
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 | Ext Visit 15 /14 | 2.90 mg/dL |
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 | Ext Visit 16 /25 | 2.57 mg/dL |
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 | Ext Visit 17 /0 | 2.35 mg/dL |
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 | Ext Visit 18 /7 | 2.82 mg/dL |
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 | Ext Visit 19 /14 | 2.74 mg/dL |
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 | Ext Visit 20 /25 | 2.60 mg/dL |
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 | Ext Visit 21 /0 | 2.35 mg/dL |
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 | Ext Visit 22 /7 | 2.94 mg/dL |
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 | Ext Visit 23 /14 | 2.93 mg/dL |
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 | Ext Visit 24 /25 | 2.60 mg/dL |
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 | Ext Visit 25 /0 | 2.37 mg/dL |
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 | Ext Visit 26 /7 | 2.83 mg/dL |
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 | Ext Visit 27 /14 | 2.79 mg/dL |
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 | Ext Visit 28 /25 | 2.59 mg/dL |
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 | Ext Visit 29 /0 | 2.41 mg/dL |
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 | Ext Visit 30 /7 | 2.87 mg/dL |
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 | Ext Visit 31 /14 | 2.81 mg/dL |
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 | Ext Visit 32 /25 | 2.55 mg/dL |
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 | Ext Visit 33 /0 | 2.42 mg/dL |
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 | Ext Visit 34 /7 | 2.79 mg/dL |
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 | Ext Visit 35 /14 | 2.75 mg/dL |
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 | Ext Visit 36 /25 | 2.53 mg/dL |
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 | Ext Visit 37 /0 | 2.52 mg/dL |
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 | Ext Visit 38 /7 | 2.85 mg/dL |
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 | Ext Visit 39 /14 | 2.69 mg/dL |
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 | Ext Visit 40 /25 | 2.48 mg/dL |
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 | Ext Visit 41 /0 | 2.29 mg/dL |
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 | Ext Visit 42 /7 | 2.71 mg/dL |
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 | Ext Visit 43 /14 | 2.70 mg/dL |
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 | Ext Visit 47 /14 | 2.61 mg/dL |
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 | Ext Visit 48 /25 | 2.43 mg/dL |
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 | Ext Visit 49 /38 | 2.07 mg/dL |
| KRN23 | Evaluation of Effect of Repeated SC Injections of KRN23 | Ext Visit 50 /81 | 1.78 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, bone quality and histomorphometric parameters.
Time frame: 13.5 months,(50 visits)
| 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 |