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

NCT06525636 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 8123-001
• Study Type: interventional
• Target: 24
• Locations: 4 countries
• Sites: 9

Brief Summary

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

Conditions

X-linked Hypophosphatemia

Keywords

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

Outcome Measures

Primary Outcomes (60)

• 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 Outcomes (4)

• 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.

Study Arms (5)

Part I: Cohort 1

EXPERIMENTAL

Low Dose, single dose of KK8123

Drug: KK8123

Part I: Cohort 2

EXPERIMENTAL

Mild dose, multiple doses of KK8123

Drug: KK8123

Part I: Cohort 3

EXPERIMENTAL

High dose, multiple doses of KK8123

Drug: KK8123

Part I: Cohort 4

EXPERIMENTAL

Optional, multiple doses of KK8123

Drug: KK8123

Part 2: Extension Period

EXPERIMENTAL

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

Drug: KK8123

Interventions

KK8123 DRUG

Subcutaneous administration

Part 2: Extension Period; Part I: Cohort 1; Part I: Cohort 2; Part I: Cohort 3; Part I: Cohort 4

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients aged 18 to 65 years inclusive at the time of signing the ICF.
• Body weight is at least 40 kg.
• Diagnosed with XLH (as documented by the investigator).
• Have a value of fasting serum phosphorus \< 2.5 mg/dL (0.81 mmol/L) at Screening.
• Have a value of renal TmP/GFR \< 2.5 mg/dL (0.81 mmol/L) at Screening.
• eGFR ≥ 60 mL/min (using the Chronic Kidney Disease Epidemiology Collaboration equation \[Inker, 2021\]) at Screening.
• Have a corrected serum calcium level \< 10.8 mg/dL (2.7 mmol/L) at Screening.
• Provide a signed ICF.
• Agree not to change diet and exercise regimen from one week prior to dosing to end of study.
• Have a negative pregnancy test at Screening and be willing to have additional pregnancy tests during the study (female participants only).
• 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.
• 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.
• 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.

You may not qualify if:

• For XLH patients previously treated with burosumab, use of burosumab within 7 months prior to ICF signature.
• 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.
• History of hypersensitivity to any ingredient of any therapeutic monoclonal antibody.
• Have an active infection.
• Grade 3 or greater nephrocalcinosis as confirmed by renal ultrasound.
• Uncontrolled diabetes mellitus at Screening.
• History of known immunodeficiency.
• History of alcoholism or drug abuse.
• History of donation of blood within 60 days prior to Screening.
• 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.
• Use of any therapeutic mAb within 90 days prior to Screening.
• 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.
• Use of medication to suppress PTH (e.g., calcimimetics) within 2 months prior to Screening and for the duration of the study.
• Use of denosumab within 6 months prior to Screening.
• Use of oral bisphosphonates in the 2 years prior to Screening.

Sponsors & Collaborators

• Kyowa Kirin Co., Ltd.: lead
• Kyowa Kirin, Inc.: collaborator

Study Sites (9)

University of California - San Francisco

San Francisco, California, 94158, United States

RECRUITING

Yale Center for XLH/ Yale University School of Medicine

New Haven, Connecticut, 06510, United States

RECRUITING

Indiana University School of Medicine University Hospital

Indianapolis, Indiana, 46202, United States

RECRUITING

Mayo Clinic

Rochester, Minnesota, 55905, United States

NOT YET RECRUITING

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

RECRUITING

Hoptial Bictre

Le Kremlin-Bicêtre, Paris, 94275, France

RECRUITING

Institute of Osteology and Biomechanics (IOBM)

Hamburg, 22529, Germany

RECRUITING

Universitaetsklinikum Wurzburg

Würzburg, 97074, Germany

RECRUITING

Hospital Universitario La Paz

Madrid, 28046, Spain

RECRUITING

MeSH Terms

Conditions

Familial Hypophosphatemic Rickets; Bone Diseases; Metabolic Diseases; Musculoskeletal Diseases; Rare Diseases; Hypophosphatemia; Kidney Diseases

Condition Hierarchy (Ancestors)

Rickets, Hypophosphatemic; Rickets; Bone Diseases, Metabolic; Hypophosphatemia, Familial; Renal Tubular Transport, Inborn Errors; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Metal Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Calcium Metabolism Disorders; Phosphorus Metabolism Disorders; Vitamin D Deficiency; Avitaminosis; Deficiency Diseases; Malnutrition; Nutrition Disorders; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Kyowa Kirin

  Kyowa Kirin, Inc.

  STUDY CHAIR

Central Study Contacts

Kyowa Kirin

CONTACT

609-919-1100; KKD.Clintrial.82@kyowakirin.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 10, 2024
• First Posted: July 29, 2024
• Study Start: October 9, 2024
• Primary Completion (Estimated): February 11, 2028
• Study Completion (Estimated): May 10, 2028
• Last Updated: November 14, 2025

Record last verified: 2025-11

Locations

ES (1); FR (1); US (5); DE (2)