A First-in-human Study of KK8123 in Adults With X-linked Hypophosphatemia

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

A first-in-human study of KK8123 in adults with X-linked hypophosphatemia.

Study Overview

• Status: Recruiting
• Conditions: X-linked Hypophosphatemia
• Intervention / Treatment: Drug: KK8123

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.

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Kyowa Kirin; Phone Number: 609-919-1100; Email: KKD.Clintrial.82@kyowakirin.com

Study Locations

• France
  • Paris
    • Le Kremlin-Bicêtre, Paris, France, 94275
      • Recruiting
      • Hoptial Bictre
      • Contact: Guilaine Guiose; Phone Number: 33 1 45 21 74 53 Dect : 24119; Email: guilaine.guiose@aphp.fr
      • Principal Investigator: Peter Kamenicky, MD
• Germany
  • Hamburg, Germany, 22529
    • Recruiting
    • Institute of Osteology and Biomechanics (IOBM)
    • Principal Investigator: Ralf Oheim, MD
    • Contact: Alison Schoen; Phone Number: 0152 2281 6702; Email: Ali.Schoen@uke.de
  • Würzburg, Germany, 97074
    • Recruiting
    • Universitaetsklinikum Würzburg
    • Principal Investigator: Lothar Seefried, MD
    • Contact: Jasmin Baumann; Phone Number: 0049 931/803-3590; Email: jasmin.baumann@klh.de
• Spain
  • Madrid, Spain, 28046
    • Recruiting
    • Hospital Universitario La Paz
    • Contact: Darío Aguilar Rico; Phone Number: +34 917277193; Email: darioaguilarrico.hulp@gmail.com
    • Principal Investigator: Pilar Aguado Acin, MD
• United States
  • California
    • San Francisco, California, United States, 94158
      • Recruiting
      • University of California - San Francisco
      • Principal Investigator: Farzana Perwad, MD
      • Contact: Farzana Perwad; Phone Number: 415-476-2423; Email: farzana.perwad@ucsf.edu
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Recruiting
      • Yale Center for XLH/ Yale University School of Medicine
      • Contact: Elizabeth Olear, MS, MA; Phone Number: 203-785-6779; Email: ycxlhinfo@yale.edu
      • Principal Investigator: Clemens Bergwitz, MD
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Recruiting
      • Indiana University School of Medicine University Hospital
      • Contact: Fridah Mbatia; Phone Number: 317-278-6123; Email: fwmbatia@iu.edu
      • Principal Investigator: Erik Imel, MD
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Not yet recruiting
      • Mayo Clinic
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Recruiting
      • Vanderbilt University Medical Center
      • Contact: Margo Black, MSN RN CCRP; Phone Number: 615-343-5846; Email: margo.black@vumc.org
      • Principal Investigator: Kathryn Dahir, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

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. 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: 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 diabetes mellitus at Screening.
  7. History of known immunodeficiency.
  8. History of alcoholism or drug abuse.
  9. History of donation of blood within 60 days prior to Screening.
  10. 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.
  11. Use of any therapeutic mAb within 90 days prior to Screening.
  12. 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 the participant takes any of these medications, a washout period of 14 days will be required after signing the ICF and before any other screeening assessments begin.
  13. Use of medication to suppress PTH (e.g., calcimimetics) within 2 months prior to Screening and for the duration of the study.
  14. Use of denosumab within 6 months prior to Screening.
  15. Use of oral bisphosphonates in the 2 years prior to Screening.
  16. Use of teriparatide or abaloparatide in the 2 months prior to Screening.
  17. Plasma iPTH ≥ 2.5 × ULN at Screening.
  18. Planned or recommended orthopedic surgery during the study.
  19. History of traumatic fracture or orthopedic surgery within 6 months prior to Screening.
  20. Participants who are lactating.
  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. Body weight is at least 40 kg.
4. 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).
5. 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.
6. 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 Week 0 serum follicle-stimulating hormone level >40 mIU/mL.
7. 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 60 days 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. Participants who are lactating.
13. Current active and symptomatic COVID-19 infection, or a history of suffering any long-term sequalae from COVID-19 infection.
14. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part I: Cohort 1; Low Dose, single dose of KK8123	Drug: KK8123; Subcutaneous administration
Experimental: Part I: Cohort 2; Mild dose, multiple doses of KK8123	Drug: KK8123; Subcutaneous administration
Experimental: Part I: Cohort 3; High dose, multiple doses of KK8123	Drug: KK8123; Subcutaneous administration
Experimental: Part I: Cohort 4; Optional, multiple doses of KK8123	Drug: KK8123; Subcutaneous administration
Experimental: Part 2: Extension Period; High dose, multiple doses as confirmed for Cohort 3 of KK8123.	Drug: KK8123; Subcutaneous administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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: 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 temperature	For up to 44 weeks.
Part 2: Change from baseline in continuous variables for temperature	For up to 52 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 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.
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 2: To evaluate the effect of multiple SC administrations of KK8123 on serum phosphorus levels	For up to 52 weeks.

Secondary Outcome Measures

Outcome Measure	Time Frame
Part 1: ADA positivity titers to be assessed by absolute number	For up to 44 weeks.
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.

Collaborators and Investigators

• Sponsor: Kyowa Kirin Co., Ltd.
• Collaborators: Kyowa Kirin, Inc.
• Investigators: Study Chair: Kyowa Kirin, Kyowa Kirin, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): October 9, 2024
• Primary Completion (Estimated): February 11, 2028
• Study Completion (Estimated): May 10, 2028

Study Registration Dates

• First Submitted: May 10, 2024
• First Submitted That Met QC Criteria: July 24, 2024
• First Posted (Actual): July 29, 2024

Study Record Updates

• Last Update Posted (Estimated): November 14, 2025
• Last Update Submitted That Met QC Criteria: November 12, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Kidney Diseases; Metabolic Disease; Hypophosphatemia; Bone Disease; Inborn Errors; Rare Disease; Gene Mutation; Musculoskeletal Disease,; Familial Renal Tubular Transport
• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Nutrition Disorders; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Disease Attributes; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Bone Diseases, Metabolic; Phosphorus Metabolism Disorders; Avitaminosis; Deficiency Diseases; Malnutrition; Metal Metabolism, Inborn Errors; Rickets, Hypophosphatemic; Rickets; Hypophosphatemia, Familial; Renal Tubular Transport, Inborn Errors; Calcium Metabolism Disorders; Vitamin D Deficiency; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Hypophosphatemia; Rare Diseases; Musculoskeletal Diseases; Kidney Diseases; Metabolic Diseases; Familial Hypophosphatemic Rickets; Bone Diseases
• Other Study ID Numbers: 8123-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No