KK8123 for X-linked hypophosphatemia

Inclusion criteria

• {"criterion_text":"- Male or female patients aged 18 to 65 years inclusive at the time of signing the ICF.\n- 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.\n- Be willing to use an effective (US participants only) or highly effective method of contraception while participating in the study and for 5 months after the last dose (all sexually active participants of childbearing potential).\n- 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.\n- Diagnosed with XLH (as documented by the investigator).\n- Have a value of fasting serum phosphorus < 2.5 mg/dL (0.81 mmol/L) at Screening.\n- Have a value of renal TmP/GFR < 2.5 mg/dL at Screening.\n- eGFR ≥ 60 mL/min (using the Chronic Kidney Disease Epidemiology Collaboration equation) at Screening.\n- Have a corrected serum calcium level < 10.8 mg/dL (2.7 mmol/L) at Screening.\n- Body weight at least 40 kg.\n- Part 2: Body weight at least 40 kg\n- Provide a signed ICF after the nature of the study has been explained, and prior to any research-related procedures initiation.\n- Part 2: Be willing to use an effective (US participants only) or highly effective method of contraception while participating in the study and for 5 months after the last dose (all sexually active participants of childbearing potential).\n- Agree not to change diet and exercise regimen from one week prior to dosing to end of study.\n- Have a negative pregnancy test at Screening and be willing to have additional pregnancy tests during the study (female participants only).\n- Part 2: Completion of relevant cohort in Part 1 of the study.\n- Part 2: Provide a signed informed consent after the nature of Part 2 of the study has been explained.\n- Part 2: Negative pregnancy test at Week 0 of Part 2 and willing to have additional pregnancy tests until the end of the study.\n- Part 2: If taking chronic pain medications, must be on a stable regimen and be willing to maintain medications at the same stable dose(s) and schedule throughout the study.\n- Part 2: 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 all the assessments."}

Exclusion criteria

• {"criterion_text":"- For XLH patients previously treated with other drugs, use of them within 7 months prior to ICF signature.\n- Part 2: Planned or recommended orthopedic surgery during the study.\n- Part 2: History of traumatic fracture or orthopedic surgery within 6 months prior to Week 0 of Part 2.\n- Grade 3 or greater nephrocalcinosis as confirmed by renal ultrasound.\n- Part 2: Current active and symptomatic COVID-19 infection, or a history of suffering any long-term sequalae from COVID-19 infection.\n- Part 2: Presence or history of any condition that, in the view of the investigator, places the participant at high risk of poor treatment compliance or of not completing the study.\n- Use of any therapeutic mAb within 90 days prior to Screening.\n- Planned or recommended orthopedic surgery during the study.\n- Use of pharmacologically active vitamin D, its metabolites or analogs, oral phosphate for treatment of XLH, aluminum hydroxide antacids, acetazolamide, thiazide diuretics, and/or systemic corticosteroids within 14 days prior to Screening.\n- Use of medication to suppress PTH (e.g., calcimimetics) within 2 months prior to Screening and for the duration of the study.\n- Use of denosumab within 6 months prior to Screening.\n- Part 2: Use of any investigational product other than KK8123, or investigational medical device, within 30 days prior to Week 0 of Part 2, or requirement for any investigational agent prior to completion of all scheduled study assessments.\n- Use of oral bisphosphonates in the 2 years prior to Screening.\n- Use of teriparatide or abaloparatide in the 2 months prior to Screening.\n- Prior history of positive test for human immunodeficiency virus antibody, positive test for hepatitis B surface antigen, and/or hepatitis C virus antibody at Screening.\n- History of traumatic fracture or orthopedic surgery within 6 months prior to Screening.\n- Current active and symptomatic COVID-19 infection.\n- Presence or history of any condition that, in the view of the investigator, places the participant at high risk of poor treatment compliance or of not completing the study, or that would confound safety or interpretation of results.\n- History of hypersensitivity to any ingredient of any therapeutic monoclonal antibody.\n- Have an active infection.\n- Part 2: Use of burosumab following completion of Part 1 of the study.\n- History of donation of blood within 60 days prior to Screening.\n- Part 2: Use of any therapeutic mAb other than KK8123 within 90 days prior to Week 0 of Part 2.\n- Uncontrolled diabetes mellitus at Screening.\n- History of known immunodeficiency.\n- History of alcoholism or drug abuse.\n- Part 2: have an active infection.\n- Part 2: Donation of blood within 60 days prior to Week 0 of Part 2.\n- Participants who are lactating.\n- Part 2: Participants who are lactating.\n- Serum iPTH ≥ 2.5 × ULN at Screening.\n- Part 2: Use of pharmacologically active vitamin D, its metabolites or analogs, oral phosphate for treatment of XLH, aluminum hydroxide antacids, acetazolamide, thiazide diuretics, and/or systemic corticosteroids within 14 days prior to Week 0 of Part 2.\n- Part 2: Use of medication to suppress PTH (e.g., calcimimetics) within 2 months prior to Week 0 of Part 2.\n- Part 2: Use of oral bisphosphonates following completion of Part 1 of the study.\n- Use of any IP or investigational medical device within 30 days prior to Screening, or requirement for any investigational agent prior to completion of all scheduled study assessments.\n- Part 2: Use of teriparatide or abaloparatide in the 2 months prior to Week 0 of Part 2."}

Primary endpoints

• {"endpoint_text":"- TEAEs.","definition_or_measurement_approach":"Treatment-emergent adverse events (TEAEs) reported throughout the study period; safety monitoring by investigator assessments and AE reporting."}
• {"endpoint_text":"- Laboratory values","definition_or_measurement_approach":"Clinical laboratory tests (hematology, biochemistry, etc.) measured at scheduled visits."}
• {"endpoint_text":"- Vital signs.","definition_or_measurement_approach":"Standard vital sign measurements (e.g., blood pressure, heart rate) at scheduled visits."}
• {"endpoint_text":"- 12-lead electrocardiogram.","definition_or_measurement_approach":"12-lead ECG recordings performed at scheduled timepoints."}
• {"endpoint_text":"- Echocardiogram.","definition_or_measurement_approach":"Cardiac echocardiography performed per schedule to assess cardiac structure/function."}
• {"endpoint_text":"- Renal ultrasound.","definition_or_measurement_approach":"Renal ultrasound imaging to assess nephrocalcinosis and renal structure per schedule."}
• {"endpoint_text":"- Serum KK8123 concentrations over time and PK parameters.","definition_or_measurement_approach":"Measurement of serum KK8123 concentrations at specified PK timepoints and derivation of PK parameters (e.g., Cmax, AUC, t1/2)."}

Secondary endpoints

• {"endpoint_text":"- Change in serum phosphorus levels over time.","definition_or_measurement_approach":"Serial measurement of serum phosphorus at scheduled visits to evaluate temporal change."}
• {"endpoint_text":"- Change from baseline in serum phosphorus levels.","definition_or_measurement_approach":"Comparison of serum phosphorus at timepoints versus baseline values."}
• {"endpoint_text":"- Achieving serum phosphorus levels within the normal range through the last dosing interval.","definition_or_measurement_approach":"Proportion of participants whose serum phosphorus is within normal range at last dosing interval."}
• {"endpoint_text":"- Achieving average serum phosphorus levels within the normal range across all dosing intervals.","definition_or_measurement_approach":"Assessment of average serum phosphorus across dosing intervals compared to normal range."}
• {"endpoint_text":"- Incidence of anti-drug antibodies over time.","definition_or_measurement_approach":"Assessment of anti-drug antibody presence/levels in blood samples collected over time."}

Methods

• Pre-ICF telephone contact (Scout Phone Pre-ICF Data Consent) for initial contact/consent screening
• Site-based recruitment via participating hospitals/clinics (listed trial sites in France, Germany, Spain)
• Patient Study Participation Card and travel reimbursement arrangements (site materials)

France

Earliest CTIS Part Ii Submission Date

14-10-2024

Latest Decision Or Authorization Date

15-11-2024

Processing Time Days

32

Number Of Sites

1

Number Of Participants

4

Germany

Earliest CTIS Part Ii Submission Date

28-10-2024

Latest Decision Or Authorization Date

12-11-2024

Processing Time Days

15

Number Of Sites

2

Number Of Participants

5

Spain

Earliest CTIS Part Ii Submission Date

20-09-2024

Latest Decision Or Authorization Date

11-11-2024

Processing Time Days

52

Number Of Sites

1

Number Of Participants

3

Primary sponsor

Full Name

Kyowa Kirin Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Premier Research Group S.L.

Responsibilities

Study management duties (codes: 1,10,11,12,15(eTMF),5,6)

Name

Icon (Lr) Limited

Responsibilities

Laboratory/site support (code: 4)

Name

Icon Development Solutions LLC

Responsibilities

Laboratory/site support (code: 4)

Name

Medidata Solutions Inc.

Responsibilities

Electronic data capture / data platform (code: 7)

Name

Suvoda LLC

Responsibilities

Interactive response/other support (code: 3)

Third parties

• {"country":"Spain","full_name":"Premier Research Group S.L.","duties_or_roles":"codes: 1,10,11,12,15(eTMF),5,6","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Icon (Lr) Limited","duties_or_roles":"codes: 4","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Icon Development Solutions LLC","duties_or_roles":"codes: 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"codes: 7","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Scout Clinical","duties_or_roles":"codes: 15 (Patient travel reimbursement)","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"codes: 15 (Imaging)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Azenta US Inc.","duties_or_roles":"codes: 15 (Long-term storage of biological samples)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Suvoda LLC","duties_or_roles":"codes: 3","organisation_type":"Non-Pharmaceutical company"}