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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Kyowa Kirin Inc.

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

Trial duration

29 Aug 2025 → ongoing

Decision date (initial)

2024-11-15

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Kyowa Kyrin, Inc.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Dose response, Safety, Pharmacokinetic

Part 1: to assess the safety and tolerability of KK8123 and to characterize the PK profile of KK8123.
Part 2: to evaluate the safety and tolerability of KK8123 after multiple SC dosing.

Secondary objectives 5

1. For Part 1: To evaluate the effect of single and multiple SC administrations of KK8123 on serum phosphorus levels.
2. For Part 1: To assess the immunogenicity of single and multiple SC administrations of KK8123.
3. For Part 2: To characterize the PK profile of multiple SC administrations of KK8123.
4. For Part 2: To evaluate the effect of multiple SC administrations of KK8123 on serum phosphorus levels
5. For Part 2: To assess the immunogenicity of multiple SC administrations of KK8123

Conditions and MedDRA coding

X-linked hypophosphatemia.

Study design 2 periods

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

Plan to share IPD

Yes

IPD plan description

The datasets generated and/or analyzed during the study sponsored by Kyowa Kirin, Inc. will be available in the Vivli repository: https://vivli.org/ourmember/kyowa-kirin/ as long as conditions of data disclosure specified in the policy section of the Vivli website are satisfied.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 20

1. Male or female patients aged 18 to 65 years inclusive at the time of signing the ICF.
2. Provide a signed ICF after the nature of the study has been explained, and prior to any research-related procedures initiation.
3. Agree not to change diet and exercise regimen from one week prior to dosing to end of study.
4. Have a negative pregnancy test at Screening and be willing to have additional pregnancy tests during the study (female participants only).
5. Part 2: Completion of relevant cohort in Part 1 of the study.
6. Part 2: Provide a signed informed consent after the nature of Part 2 of the study has been explained.
7. Part 2: Negative pregnancy test at Week 0 of Part 2 and willing to have additional pregnancy tests until the end of the study.
8. 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.
9. 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.
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.
11. 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).
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.
13. Diagnosed with XLH (as documented by the investigator).
14. Have a value of fasting serum phosphorus < 2.5 mg/dL (0.81 mmol/L) at Screening.
15. Have a value of renal TmP/GFR < 2.5 mg/dL at Screening.
16. eGFR ≥ 60 mL/min (using the Chronic Kidney Disease Epidemiology Collaboration equation) at Screening.
17. Have a corrected serum calcium level < 10.8 mg/dL (2.7 mmol/L) at Screening.
18. Body weight at least 40 kg.
19. Part 2: Body weight at least 40 kg
20. 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).

Exclusion criteria 36

1. For XLH patients previously treated with other drugs, use of them within 7 months prior to ICF signature.
2. 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.
3. Part 2: Use of any therapeutic mAb other than KK8123 within 90 days prior to Week 0 of Part 2.
4. Serum iPTH ≥ 2.5 × ULN at Screening.
5. 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.
6. Part 2: Use of medication to suppress PTH (e.g., calcimimetics) within 2 months prior to Week 0 of Part 2.
7. Part 2: Use of oral bisphosphonates following completion of Part 1 of the study.
8. 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.
9. Part 2: Use of teriparatide or abaloparatide in the 2 months prior to Week 0 of Part 2.
10. Part 2: Planned or recommended orthopedic surgery during the study.
11. Part 2: History of traumatic fracture or orthopedic surgery within 6 months prior to Week 0 of Part 2.
12. Grade 3 or greater nephrocalcinosis as confirmed by renal ultrasound.
13. Part 2: Current active and symptomatic COVID-19 infection, or a history of suffering any long-term sequalae from COVID-19 infection.
14. 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.
15. Use of any therapeutic mAb within 90 days prior to Screening.
16. Planned or recommended orthopedic surgery during the study.
17. 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.
18. Use of medication to suppress PTH (e.g., calcimimetics) within 2 months prior to Screening and for the duration of the study.
19. Use of denosumab within 6 months prior to Screening.
20. Use of oral bisphosphonates in the 2 years prior to Screening.
21. Use of teriparatide or abaloparatide in the 2 months prior to Screening.
22. 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.
23. History of traumatic fracture or orthopedic surgery within 6 months prior to Screening.
24. Current active and symptomatic COVID-19 infection.
25. 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.
26. History of hypersensitivity to any ingredient of any therapeutic monoclonal antibody.
27. Have an active infection.
28. Part 2: Use of burosumab following completion of Part 1 of the study.
29. History of donation of blood within 60 days prior to Screening.
30. Uncontrolled diabetes mellitus at Screening.
31. History of known immunodeficiency.
32. History of alcoholism or drug abuse.
33. Part 2: have an active infection.
34. Part 2: Donation of blood within 60 days prior to Week 0 of Part 2.
35. Participants who are lactating.
36. Part 2: Participants who are lactating.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 7

1. TEAEs.
2. Laboratory values
3. Vital signs.
4. 12-lead electrocardiogram.
5. Echocardiogram.
6. Renal ultrasound.
7. Serum KK8123 concentrations over time and PK parameters.

Secondary endpoints 5

1. Change in serum phosphorus levels over time.
2. Change from baseline in serum phosphorus levels.
3. Achieving serum phosphorus levels within the normal range through the last dosing interval.
4. Achieving average serum phosphorus levels within the normal range across all dosing intervals.
5. Incidence of anti-drug antibodies over time.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Kyowa Kirin Inc.

Sponsor organisation

Kyowa Kirin Inc.

Address

510 Carnegie Center Suite 600

City

Princeton

Postcode

08540-6241

Country

United States

Scientific contact point

Organisation

Kyowa Kirin Inc.

Contact name

Regulatory Group

Public contact point

Organisation

Kyowa Kirin Inc.

Contact name

Regulatory Group

Third parties 8

Locations

3 EU/EEA countries · 4 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 49 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications