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

NCT ID: NCT06525636

Last Updated: 2025-11-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

24 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-10-09

Study Completion Date

2028-05-10

Brief Summary

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

Detailed Description

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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.

Conditions

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X-linked Hypophosphatemia

Keywords

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Gene Mutation Bone Disease Metabolic Disease Musculoskeletal Disease, Rare Disease Hypophosphatemia Familial Renal Tubular Transport Inborn Errors Kidney Diseases

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Part I: Cohort 1

Low Dose, single dose of KK8123

Group Type EXPERIMENTAL

KK8123

Intervention Type DRUG

Subcutaneous administration

Part I: Cohort 2

Mild dose, multiple doses of KK8123

Group Type EXPERIMENTAL

KK8123

Intervention Type DRUG

Subcutaneous administration

Part I: Cohort 3

High dose, multiple doses of KK8123

Group Type EXPERIMENTAL

KK8123

Intervention Type DRUG

Subcutaneous administration

Part I: Cohort 4

Optional, multiple doses of KK8123

Group Type EXPERIMENTAL

KK8123

Intervention Type DRUG

Subcutaneous administration

Part 2: Extension Period

High dose, multiple doses as confirmed for Cohort 3 of KK8123.

Group Type EXPERIMENTAL

KK8123

Intervention Type DRUG

Subcutaneous administration

Interventions

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KK8123

Subcutaneous administration

Intervention Type DRUG

Eligibility Criteria

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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.


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.

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.


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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Kyowa Kirin, Inc.

INDUSTRY

Sponsor Role collaborator

Kyowa Kirin Co., Ltd.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Kyowa Kirin

Role: STUDY_CHAIR

Kyowa Kirin, Inc.

Locations

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University of California - San Francisco

San Francisco, California, United States

Site Status RECRUITING

Yale Center for XLH/ Yale University School of Medicine

New Haven, Connecticut, United States

Site Status RECRUITING

Indiana University School of Medicine University Hospital

Indianapolis, Indiana, United States

Site Status RECRUITING

Mayo Clinic

Rochester, Minnesota, United States

Site Status NOT_YET_RECRUITING

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status RECRUITING

Hoptial Bictre

Le Kremlin-Bicêtre, Paris, France

Site Status RECRUITING

Institute of Osteology and Biomechanics (IOBM)

Hamburg, , Germany

Site Status RECRUITING

Universitaetsklinikum Wurzburg

Würzburg, , Germany

Site Status RECRUITING

Hospital Universitario La Paz

Madrid, , Spain

Site Status RECRUITING

Countries

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United Kingdom United States France Germany Spain

Central Contacts

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Kyowa Kirin

Role: CONTACT

Phone: 609-919-1100

Email: [email protected]

Facility Contacts

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Farzana Perwad

Role: primary

Elizabeth Olear, MS, MA

Role: primary

Fridah Mbatia

Role: primary

Margo Black, MSN RN CCRP

Role: primary

Guilaine Guiose

Role: primary

Alison Schoen

Role: primary

Jasmin Baumann

Role: primary

Darío Aguilar Rico

Role: primary

Other Identifiers

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8123-001

Identifier Type: -

Identifier Source: org_study_id