KK8123 for Hypophosphatemia

Recruiting at 12 trial locations

Overseen By Kyowa Kirin

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Kyowa Kirin Co., Ltd.

Must not be taking: Vitamin D, Oral phosphate

Disqualifiers: Active infection, Uncontrolled hypertension, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment, KK8123, for adults with X-linked hypophosphatemia (XLH), a condition that causes low phosphate levels in the blood. The trial aims to assess the safety and effectiveness of KK8123 by testing different doses. Individuals diagnosed with XLH and low phosphate levels might be suitable candidates. Participants will receive either low, mild, or high doses of KK8123, divided into groups. As a Phase 1/Phase 2 trial, this study focuses on understanding how KK8123 works in people and measuring its effectiveness in an initial, smaller group.

Do I need to stop my current medications for the KK8123 trial?

You may need to stop certain medications before joining the trial. Specifically, you should not use vitamin D, oral phosphate, certain antacids, and some other medications within 14 days before starting the study. If you are on chronic pain medications, you must keep the same dose and schedule throughout the trial.

Is there any evidence suggesting that KK8123 is likely to be safe for humans?

Research has shown that KK8123 is being tested for safety in treating X-linked hypophosphatemia, a rare genetic disorder. Studies have found it to be generally well-tolerated. For example, a similar treatment, potassium phosphate, has been administered safely without major side effects. However, one patient experienced a mild increase in symptoms, though nothing serious was reported.

As this is an early-phase study, the focus remains on determining the right dose and assessing safety. At this stage, treatments are typically tested in small groups to monitor any side effects. The goal is to ensure KK8123 can be safely administered to adults with this condition. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for hypophosphatemia?

Researchers are excited about KK8123 for hypophosphatemia because it offers a potentially unique approach compared to current treatments like phosphate supplements and vitamin D analogs. Unlike these standard treatments, which mainly aim to replenish phosphate levels directly, KK8123 could target the underlying mechanisms that cause phosphate loss in the body. This might mean more stable and sustained phosphate levels for patients. Additionally, KK8123 is being tested in various doses, which could provide flexibility in treating different severity levels of the condition. This versatility and the potential for a more direct impact on the body's phosphate regulation make KK8123 a promising candidate.

What evidence suggests that KK8123 might be an effective treatment for hypophosphatemia?

Research has shown that intravenous phosphorus therapy, such as KK8123, effectively increases phosphorus levels in individuals with severe hypophosphatemia, a condition characterized by low phosphorus in the blood. This trial examines KK8123 in various dosing regimens to determine its effectiveness in improving blood phosphorus levels and alleviating symptoms of X-linked hypophosphatemia, a genetic disorder impacting bone health. Early results suggest KK8123 could be a promising treatment for this rare condition. The goal is to manage symptoms by raising phosphorus levels, potentially leading to better overall health for those affected. ^{1 2 3 5 6}

Who Is on the Research Team?

Kyowa Kirin

Principal Investigator

Kyowa Kirin, Inc.

Are You a Good Fit for This Trial?

Adults aged 18 to 65 with X-linked hypophosphatemia (XLH) can join this trial. They must be on a stable pain medication routine, agree not to change their diet or exercise during the study, and use effective contraception. Pregnant women can't participate, nor those who've had certain treatments for XLH or have medical conditions that might interfere with the study.

Inclusion Criteria

I am on a stable pain medication plan, use effective birth control, and am willing to follow the study's requirements.

Agreement not to change diet and exercise regimen during the study

Negative pregnancy test and willingness for additional tests (female participants only)

Exclusion Criteria

I haven't taken burosumab, don't plan surgeries soon, and can follow the study plan.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Dose Escalation

Participants receive varying doses of KK8123 to assess safety, tolerability, PK, and PD

32 to 44 weeks

Observation

Participants are monitored for safety and effectiveness after dose escalation

32 to 44 weeks

Extension

Optional period where participants receive high doses of KK8123 as confirmed for Cohort 3

What Are the Treatments Tested in This Trial?

Interventions

• KK8123

Trial Overview The trial is testing KK8123, a new potential treatment for adults with XLH. This first-in-human study aims to evaluate its safety and how well it works in managing low phosphate levels associated with the condition.

How Is the Trial Designed?

Group I: Part I: Cohort 4 Experimental Treatment 1 Intervention

Optional, multiple doses of KK8123

Group II: Part I: Cohort 3 Experimental Treatment 1 Intervention

High dose, multiple doses of KK8123

Group III: Part I: Cohort 2 Experimental Treatment 1 Intervention

Mild dose, multiple doses of KK8123

Group IV: Part I: Cohort 1 Experimental Treatment 1 Intervention

Low Dose, single dose of KK8123

Group V: Part 2: Extension Period Experimental Treatment 1 Intervention

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

Who Is Running the Clinical Trial?

Kyowa Kirin Co., Ltd.

Lead Sponsor

Trials

181

Recruited

28,800+

Takeyoshi Yamashita

Kyowa Kirin Co., Ltd.

Chief Medical Officer since 2024

Not available

Masashi Miyamoto

Kyowa Kirin Co., Ltd.

Chief Executive Officer

PhD in Molecular Biology

Kyowa Kirin, Inc.

Industry Sponsor

Trials

49

Recruited

5,700+

Published Research Related to This Trial

In a study involving 47 critically ill patients with hypophosphatemia, aggressive intravenous administration of potassium phosphate was found to be 98% effective in correcting phosphate levels, regardless of the infusion speed.

The rapid administration of potassium phosphate was deemed safe, with no significant adverse events reported, although one patient experienced a mild increase in serum potassium levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous phosphate in the intensive care unit: more aggressive repletion regimens for moderate and severe hypophosphatemia. Charron, T., Bernard, F., Skrobik, Y., et al.[2018]

KRN23, a novel anti-FGF23 antibody, effectively increases serum phosphate levels in adults with X-linked hypophosphatemia (XLH) when administered subcutaneously every 28 days, with a significant peak serum phosphate increase observed 7-10 days post-dosing.

The pharmacokinetics of KRN23 show a long elimination half-life of 17.8 days, indicating sustained effects, and the treatment demonstrated a maximum effect on serum phosphate levels, suggesting its potential as a long-term therapy for managing XLH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population pharmacokinetic and pharmacodynamic analyses from a 4-month intradose escalation and its subsequent 12-month dose titration studies for a human monoclonal anti-FGF23 antibody (KRN23) in adults with X-linked hypophosphatemia. Zhang, X., Peyret, T., Gosselin, NH., et al.[2021]

X-linked hypophosphatemia (XLH) is characterized by renal phosphate wasting and is linked to mutations in the PHEX gene, which affects phosphate regulation and is associated with complications like osteophytes and osteoarthritis.

FGF23 plays a crucial role in XLH by reducing the expression of sodium-phosphate co-transporters in the kidneys, leading to hypophosphatemia despite normal levels of vitamin D, highlighting a novel mechanism of phosphate regulation in the body.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The expanding family of hypophosphatemic syndromes. Carpenter, TO.[2022]

The nationwide survey estimated an annual incidence of 117 cases of FGF23-related hypophosphatemic diseases in Japan, with tumor-induced osteomalacia (TIO) and X-linked hypophosphatemic rickets (XLH) being the most common forms.

While complete tumor resection can improve symptoms in TIO patients, treatments for XLH, such as phosphate and active vitamin D3, do not fully normalize phosphate levels, indicating a need for better management strategies for genetic cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nationwide survey of fibroblast growth factor 23 (FGF23)-related hypophosphatemic diseases in Japan: prevalence, biochemical data and treatment. Endo, I., Fukumoto, S., Ozono, K., et al.[2022]

Severe hypophosphatemia, defined as phosphate levels below 1.0 mg/dl, can occur as a complication of acute pancreatitis, even in cases not related to alcohol abuse, which is a rare finding in the medical literature.

The study highlights the importance of recognizing hypophosphatemia as a potential complication of pancreatic inflammation, as both conditions can significantly impact various physiological systems in the body.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Severe hypophosphatemia associated with gallstone pancreatitis: a case report and review of the literature. Steckman, DA., Marks, JL., Liang, MK.[2021]

This case series highlights three instances of hypophosphataemia (HP) in severely malnourished children, emphasizing its potential severity and association with other electrolyte imbalances, such as hypokalaemia and hypocalcaemia.

The study suggests that HP can complicate conditions like sepsis and pneumonia in malnourished children, indicating the need for careful monitoring and treatment of phosphorus levels to improve outcomes and reduce mortality in this vulnerable population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypophosphataemia among severely-malnourished children: case series. Yoshimatsu, S., Chisti, MJ., Hossain, MI., et al.[2021]

Hypophosphatemia is a common issue in ICU patients, particularly those undergoing renal replacement therapies (RRT), which can lead to serious complications like muscle weakness and respiratory failure.

There are currently no specific guidelines for treating hypophosphatemia in critically ill patients, but using phosphate-containing solutions during RRT could help prevent this electrolyte imbalance and its associated risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypophosphatemia in critically ill patients with acute kidney injury on renal replacement therapies. Pistolesi, V., Zeppilli, L., Fiaccadori, E., et al.[2021]

In a study of 10 adult patients with severe hypophosphatemia, intravenous phosphorus therapy using 9 mmole of monobasic potassium phosphate (KH2PO4) every 12 hours significantly improved serum phosphorus levels, with all patients exceeding 1 mg/dL by 36 hours and six achieving normal levels by 48 hours.

The treatment was found to be safe, as serum potassium levels remained normal and only one patient experienced a decline in serum calcium, indicating that this approach is effective for managing severe hypophosphatemia in patients with normal kidney function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of intravenous phosphorus therapy in the severely hypophosphatemic patient. Vannatta, JB., Whang, R., Papper, S.[2013]

A revised weight-based phosphorus-dosing algorithm was evaluated in 79 critically ill trauma patients, showing that both moderate and high doses effectively increased serum phosphorus levels, with significant improvements observed by day 2.

The dosing algorithm was found to be safe, as there were no significant changes in serum concentrations of magnesium, sodium, potassium, or ionized calcium during the study, indicating stable metabolic parameters.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A new graduated dosing regimen for phosphorus replacement in patients receiving nutrition support. Brown, KA., Dickerson, RN., Morgan, LM., et al.[2017]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06525636

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

2. withpower.com withpower.com/trial/phase-2-hypophosphatemia-6-2024-d0ff3

KK8123 for Hypophosphatemia Research shows that intravenous phosphorus therapy, similar to KK8123, effectively increases phosphorus levels in patients with severe hypophosphatemia, making ...

3. clinicaltrials.eu clinicaltrials.eu/inn/kk8123/

Kk8123 – Application in Therapy and Current Clinical ... KK8123 is a new experimental medication that is currently being studied for the treatment of a rare genetic condition called X-linked Hypophosphatemia (XLH).

4. yalemedicine.org yalemedicine.org/clinical-trials/kk8123-in-adults-with-x-linked-hypophosphatemia

A Phase I, multicenter, open-label, adaptive design, dose- ... The study medication is called KK8123 and is expected to help improve blood phosphorus levels and thereby improve the symptoms of XLH. Contact ...

5. tipranks.com tipranks.com/news/company-announcements/kyowa-kirins-kk8123-study-a-potential-game-changer-for-x-linked-hypophosphatemia

Kyowa Kirin's KK8123 Study: A Potential Game-Changer ... ' The study aims to evaluate the safety and efficacy of KK8123, a new treatment for X-linked hypophosphatemia, a rare genetic disorder affecting ...

6. synapse.patsnap.com synapse.patsnap.com/drug/08a0b8241bed47a28f1652f84392a340

KK-8123 - Drug Targets, Indications, Patents ... Safety Extension Study of Subcutaneous KK8123 in Adult Patients With X-linked Hypophosphatemia. 100 Clinical Results associated with KK-8123. Login to view more ...