X-linked Hypophosphatemia
Conditions
Keywords
Gene Mutation, Bone Disease, Metabolic Disease, Musculoskeletal Disease,, Rare Disease, Hypophosphatemia, Familial Renal Tubular Transport, Inborn Errors, Kidney Diseases
Brief summary
A first-in-human study of KK8123 in adults with X-linked hypophosphatemia.
Detailed description
Study 8123-001 is a Phase 1/2, multicenter, open-label, dose-escalation study to assess the safety, tolerability, PK and PD of KK8123, with an optional safety extension period. This study is comprised of a Screening Period followed by Part 1 and Part 2. The Screening Period will last up to 28 days (including obtaining informed consent). Part 1 is a Dose Escalation Period consisting of a nominal (planned) Treatment Period (all cohorts) and Observation Period of 32 to 44 weeks, and Part 2 is an optional Extension Period.
Interventions
DRUGKK8123
Subcutaneous administration
Sponsors
Kyowa Kirin, Inc.
Kyowa Kirin Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Part 1: Inclusion Criteria: 1. Male or female patients aged 18 to 65 years inclusive at the time of signing the ICF. 2. Body weight is at least 40 kg. 3. Diagnosed with XLH (as documented by the investigator). 4. Have a value of fasting serum phosphorus \< 2.5 mg/dL (0.81 mmol/L) at Screening. 5. Have a value of renal TmP/GFR \< 2.5 mg/dL (0.81 mmol/L) at Screening. 6. eGFR ≥ 60 mL/min (using the Chronic Kidney Disease Epidemiology Collaboration equation \[Inker, 2021\]) at Screening. 7. Have a corrected serum calcium level \< 10.8 mg/dL (2.7 mmol/L) at Screening. 8. Provide a signed ICF. 9. Agree not to change diet and exercise regimen from one week prior to dosing to end of study. 10. Have a negative pregnancy test at Screening and be willing to have additional pregnancy tests during the study (female participants only). 11. If taking chronic pain medications (including narcotic pain medications/opioids), must be on a stable regimen for at least 21 days prior to the Screening visit, and be willing to maintain medications at the same stable dose(s) and schedule throughout the clinical trial. The dose must not exceed 60 mg oral morphine equivalents/day. 12. Be willing to use a method of contraception following local country guidelines while participating in the study and for 5 months after the last dose (all sexually active participants of childbearing potential). Women of non-childbearing potential are defined as permanently sterile (i.e., due to tubal ligation at least one year before Screening, hysterectomy or bilateral oophorectomy) or postmenopausal (defined as at least 12 months post cessation of menses without an alternative medical cause). Postmenopausal status of female participants will be confirmed with a Screening serum follicle-stimulating hormone level \>40 mIU/mL. 13. Must, in the opinion of the investigator, be willing and able to complete all aspects of the study, adhere to the study visit schedule and comply with the assessments.
Exclusion criteria
* Part 1:
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part 2: To evaluate the effect of multiple SC administrations of KK8123 on serum phosphorus levels | For up to 52 weeks. |
| Part 2: KK8123 concentrations by time to steady state | For up to 52 weeks. |
| Part 1: KK8123 concentrations by accumulation ratio | For up to 44 weeks. |
| Part 2: KK8123 concentrations by accumulation ratio | For up to 52 weeks. |
| Part 1: To evaluate the effect of single and multiple SC administrations of KK8123 on serum phosphorus levels | For up to 44 weeks. |
| Part 1: Change from baseline in continuous variables for pulse rate | For up to 44 weeks. |
| Part 2: Change from baseline in continuous variables for pulse rate | For up to 52 weeks. |
| Part 1: Change from baseline in continuous variables for temperature | For up to 44 weeks. |
| Part 1: Number of participants with TEAEs | For up to 44 weeks. |
| Part 1: Percentage of participants with TEAEs | For up to 44 weeks. |
| Part 2: Number of participants with TEAEs | For up to 52 weeks. |
| Part 2: Change from baseline in continuous variables for temperature | For up to 52 weeks. |
| Part 2: Percentage of participants with TEAEs | For up to 52 weeks. |
| Part 1: Change from baseline for haematology laboratories values | For up to 44 weeks. |
| Part 2: Change from baseline for haematology laboratories values | For up to 52 weeks. |
| Part 1: Change from baseline for clinical chemistry laboratories values | For up to 44 weeks. |
| Part 2: Change from baseline for clinical chemistry laboratories values | For up to 52 weeks. |
| Part 1: Change from baseline in continuous variables for FSH | For up to 44 weeks. |
| Part 2: Change from baseline in continuous variables for FSH | For up to 52 weeks. |
| Part 1: Change from baseline in continuous variables for estradiol | For up to 44 weeks. |
| Part 2: Change from baseline in continuous variables for estradiol | For up to 52 weeks. |
| Part 1: Change from baseline in continuous variables for respiratory rate | For up to 44 weeks. |
| Part 2: Change from baseline in continuous variables for respiratory rate | For up to 52 weeks. |
| Part 1: Change from baseline in continuous variables for systolic and diastolic blood pressure | For up to 44 weeks. |
| Part 2: Change from baseline in continuous variables for systolic and diastolic blood pressure | For up to 52 weeks. |
| Part 1: Change from baseline in continuous variables for QT | For up to 44 weeks. |
| Part 2: Change from baseline in continuous variables for QT | For up to 52 weeks. |
| Part 1: Change from baseline in continuous variables for QTc | For up to 44 weeks. |
| Part 2: Change from baseline in continuous variables for QTc | For up to 52 weeks. |
| Part 1: Change from baseline in continuous variables for QTCF | For up to 44 weeks. |
| Part 2: Change from baseline in continuous variables for QTCF | For up to 52 weeks. |
| Part 1: Change from baseline in continuous variables for QRS | For up to 44 weeks. |
| Part 2: Change from baseline in continuous variables for QRS | For up to 52 weeks. |
| Part 1: Change from baseline in continuous variables for heart rate | For up to 44 weeks. |
| Part 2: Change from baseline in continuous variables for heart rate | For up to 52 weeks. |
| Part 1: The presence or absence of abnormality on ectopic mineralization, any sign of left ventricular hypertrophy or heart failures before and after administration of KK8123 on Echocardiogram | For up to 44 weeks. |
| Part 2: The presence or absence of abnormality on ectopic mineralization, any sign of left ventricular hypertrophy or heart failures before and after administration of KK8123 on Echocardiogram | For up to 52 weeks. |
| Part 1: Before and after administration presented at each time point in categorical variables for renal ultrasound | For up to 44 weeks. |
| Part 2: Before and after administration presented at each time point in categorical variables for renal ultrasound | For up to 52 weeks. |
| Part 1: KK8123 concentrations by maximum plasma concentration (Cmax) | For up to 44 weeks. |
| Part 2: KK8123 concentrations by maximum plasma concentration (Cmax) | For up to 52 weeks. |
| Part 1: KK8123 concentrations by maximum serum concentration (tmax) | For up to 44 weeks. |
| Part 2: KK8123 concentrations by maximum serum concentration (tmax) | For up to 52 weeks. |
| Part 1: KK8123 concentrations by area under the serum concentration time curve from zero to last detectable time point (AUClast) | For up to 44 weeks. |
| Part 2: KK8123 concentrations by area under the serum concentration time curve from zero to last detectable time point (AUClast) | For up to 52 weeks. |
| Part 1: KK8123 concentrations by the area under the serum concentration time curve from zero to infinity (AUC00-inf) | For up to 44 weeks. |
| Part 2: KK8123 concentrations by the area under the serum concentration time curve from zero to infinity (AUC00-inf) | For up to 52 weeks. |
| Part 1: KK8123 concentrations by apparent volume of distribution (V/F) | For up to 44 weeks.. |
| Part 2: KK8123 concentrations by apparent volume of distribution (V/F) | For up to 52 weeks. |
| Part 1: KK8123 concentrations by terminal half-life (t1/2) | For up to 44 weeks. |
| Part 2: KK8123 concentrations by terminal half-life (t1/2) | For up to 52 weeks. |
| Part 1: KK8123 concentrations by apparent clearance (CL/F) | For up to 44 weeks. |
| Part 2: KK8123 concentrations by apparent clearance (CL/F) | For up to 52 weeks. |
| Part 1: KK8123 concentrations by maximum plasma concentration steady state (Cmax,ss) | For up to 44 weeks. |
| Part 2: KK8123 concentrations by maximum plasma concentration steady state (Cmax,ss) | For up to 52 weeks. |
| Part 1: KK8123 concentrations by time to maximum serum concentration steady state (tmax,ss) | For up to 44 weeks. |
| Part 2: KK8123 concentrations by time to maximum serum concentration steady state (tmax,ss) | For up to 52 weeks. |
| Part 1: KK8123 concentrations over time by area under the serum concentration curve within a dosing interval at steady state (AUCtau,ss) | For up to 44 weeks. |
| Part 2: KK8123 concentrations over time by area under the serum concentration curve within a dosing interval at steady state (AUCtau,ss) | For up to 52 weeks. |
| Part 1: KK8123 concentrations by time to steady state | For up to 44 weeks. |
Secondary
| Measure | Time frame |
|---|---|
| Part 1: ADA positivity titers to be assessed by percentage | For up to 44 weeks. |
| Part 2: ADA positivity titers to be assessed by absolute number | For up to 52 weeks. |
| Part 2: ADA positivity titers to be assessed by percentage | For up to 52 weeks. |
| Part 1: ADA positivity titers to be assessed by absolute number | For up to 44 weeks. |
Countries
France, Germany, Spain, United States
Contacts
Primary ContactKyowa Kirin
Outcome results
None listed