A Multicenter, Open-label, Phase 1/2, Dose-escalation and Subsequent Safety Extension Study of Subcutaneous KK8123 in Adult Patients with X-linked Hypophosphatemia

Study on Investigational Medication for X-linked Hypophosphatemia (XLH)

E
Erik Imel, MD

Primary Investigator

Enrolling By Invitation
18 years - 65 years
All
Phase 1/2
1 participants needed
2 Locations

Brief description of study

The purpose of this study is to test the safety and effectiveness of an investigational drug called KK8123 in adults with X-linked hypophosphatemia.
 
THIS STUDY IS ENROLLING BY INVITATION ONLY - Potential subjects may come from our practice. If they are from our practice, the chart may be reviewed for additional issues that would cause the patient to screen fail. If something is found that would be recorded. Once identified by a physician, the coordinator will call to follow up and assess if patient meets screening criteria. Potential subjects may also come from an outside physician. If a potential subject is referred from an physician outside of IU, the patient will be given our information and asked to contact us. 

Detailed description of study

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.

Eligibility of study

You may be eligible for this study if you meet the following criteria:

  • Conditions: X-linked Hypophosphatemia
  • Age: 18 years - 65 years
  • Gender: All

Description

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. Diagnosed with XLH (as documented by the investigator).
    3. Have a value of fasting serum phosphorus < 2.5 mg/dL (0.81 mmol/L) at Screening.
    4. Have a value of renal TmP/GFR < 2.5 mg/dL at Screening.
    5. eGFR ≥ 60 mL/min (using the Chronic Kidney Disease Epidemiology Collaboration equation [Inker, 2021]) at Screening.
    6. Have a corrected serum calcium level < 10.8 mg/dL (2.7 mmol/L) at Screening.
    7. Provide a signed ICF.
    8. Agree not to change diet and exercise regimen from one week prior to dosing to end of study.
    9. Have a negative pregnancy test at Screening and be willing to have additional pregnancy tests during the study (female participants only).
    10. 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.

    11. Be willing to use an effective method of contraception while participating in the study and for 5 months after the last dose (all sexually active participants of childbearing potential).

      Postmenopausal status of female participants will be confirmed with a Screening serum follicle-stimulating hormone level >40 mIU/mL.

    12. 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: Exclusion Criteria:
    1. For XLH patients previously treated with burosumab, use of burosumab within 7 months prior to ICF signature.
    2. 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.
    3. History of hypersensitivity to any ingredient of any therapeutic monoclonal antibody.
    4. Have an active infection.
    5. Grade 3 or greater nephrocalcinosis as confirmed by renal ultrasound.
    6. Uncontrolled hypertension, defined as systolic blood pressure >160 mmHg or diastolic blood pressure >100 mmHg at Screening.
    7. Uncontrolled diabetes mellitus at Screening.
    8. History of known immunodeficiency.
    9. History of alcoholism or drug abuse.
    10. History of donation of blood within 16 weeks prior to Screening.
    11. 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.
    12. Use of any therapeutic mAb within 90 days prior to Screening.
    13. 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 (if taken by the participant, such therapy should be discontinued after ICF signature and other Screening assessments indicate eligibility).
    14. Use of medication to suppress PTH (e.g., calcimimetics) within 2 months prior to Screening and for the duration of the study.
    15. Use of denosumab within 6 months prior to Screening.
    16. Use of oral bisphosphonates in the 2 years prior to Screening.
    17. Use of teriparatide or abaloparatide in the 2 months prior to Screening.
    18. Plasma iPTH ≥ 2.5 × ULN at Screening.
    19. Planned or recommended orthopedic surgery during the study.
    20. History of traumatic fracture or orthopedic surgery within 6 months prior to Screening.
    21. Current active and symptomatic COVID-19 infection at Day -1.
    22. 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.

Part 2: Inclusion Criteria:

  1. Completion of relevant cohort in Part 1 of the study.
  2. Provide a signed informed consent after the nature of Part 2 of the study has been explained.
  3. Negative pregnancy test at Week 0 of Part 2 and willing to have additional pregnancy tests until the end of the study (female participants only).
  4. If taking chronic pain medications (including narcotic pain medications/opioids), must be on a stable regimen for at least 21 days prior to Week 0 of Part 2, and be willing to maintain medications at the same stable dose(s) and schedule throughout the study. The dose must not exceed 60 mg oral morphine equivalents/day.
  5. Be willing to use an effective method of contraception 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 Week 0 serum follicle-stimulating hormone level >40 mIU/mL.
  6. 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.

Part 2: Exclusion Criteria:

  1. Use of burosumab following completion of Part 1 of the study.
  2. Have an active infection.
  3. Donation of blood within 16 weeks prior to Week 0 of Part 2.
  4. 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.
  5. Use of any therapeutic mAb other than KK8123 within 90 days prior to Week 0 of Part 2.
  6. 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.
  7. Use of medication to suppress PTH (e.g., calcimimetics) within 2 months prior to Week 0 of Part 2.
  8. Use of oral bisphosphonates following completion of Part 1 of the study.
  9. Use of teriparatide or abaloparatide in the 2 months prior to Week 0 of Part 2.
  10. Planned or recommended orthopedic surgery during the study.
  11. History of traumatic fracture or orthopedic surgery within 6 months prior to Week 0 of Part 2.
  12. Current active and symptomatic COVID-19 infection, or a history of suffering any long-term sequalae from COVID-19 infection.
  13. 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.

This study investigates the safety and effectiveness of an investigational medication for adults with X-linked hypophosphatemia (XLH). XLH is a rare genetic disorder that affects the bones and teeth, leading to low levels of phosphate in the blood, which can cause bone pain and deformities. The study is open-label, meaning both the researchers and participants know what treatment is being administered, and it involves dose escalation to determine the best dosage for safety and efficacy.

Participants will undergo a Screening Period that lasts up to 28 days, followed by two main parts of the study. Part 1 includes a Dose Escalation Period where participants receive different doses of the investigational medication to find the safest and most effective dose. Part 2 is an optional Extension Period where participants may continue receiving the medication. The study involves regular monitoring and assessments to ensure participant safety and to gather data on the medication's effects.

  • Who can participate: Adults aged 18 to 65 years with X-linked hypophosphatemia and specific blood test results, such as low phosphate levels, are eligible. Women must have a negative pregnancy test and use effective contraception.
  • Study details: Participants will receive the investigational medication through subcutaneous injections without a placebo. A stable medication regimen is required if on chronic pain medication.
Updated on 04 Nov 2025. Study ID: ENDO-KYOWA-HYPOPHOSPHATEMIA, 23898
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Interested in the study?

This study is accepting only persons who receive care at a certain clinic or doctor or who are part of an invited group. Questions about this study can be directed to the study team listed in the description or contact your doctor to see if you are eligible.

Accepting Referrals by Invitation Only