A Study to Evaluate Safety, Tolerability and Efficacy of AP306 at Fixed Doses in Dialysis Participants With Hyperphosphatemia

A Phase 2b, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Safety, Tolerability, and Serum Phosphate Lowering Effect of Fixed Dose AP306 in Participants With Hyperphosphatemia Receiving Maintenance Hemodialysis

This study is being conducted to characterize the safety, tolerability, and efficacy of AP306 at fixed doses in adults with hyperphosphatemia receiving maintenance hemodialysis.

Study Overview

• Status: Recruiting
• Conditions: Hyperphosphatemia; End Stage Renal Disease on Dialysis; Chronic Kidney Disease Requiring Chronic Dialysis
• Intervention / Treatment: Drug: AP306 75 mg BID; Drug: AP306 125 mg BID; Drug: AP306 150 mg BID; Drug: AP306 75 mg TID; Drug: AP306 100 mg TID; Drug: AP306 125 mg TID; Drug: Placebo

Detailed Description

Hyperphosphatemia, one of the most common complications of advanced chronic kidney disease, becomes increasingly prevalent as kidney function declines and is found almost universally in patients with end-stage kidney disease requiring dialysis. Hyperphosphatemia is an independent risk factor for cardiovascular outcomes, fractures, and mortality in patients with chronic kidney disease, especially in patients receiving dialysis.

AP306 is a pan-phosphate transporter inhibitor that may stop phosphate absorption in the gut, controlling hyperphosphatemia.

This is a randomized, double-blind, placebo-controlled, study to characterize the safety, tolerability, and efficacy of AP306 given daily for 8 weeks at fixed doses in adults with hyperphosphatemia receiving maintenance hemodialysis.

• Study Type: Interventional
• Enrollment (Estimated): 168
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Clinical Trials Information; Phone Number: (844) 697-3339; Email: ClinicalTrials@r1therapeutics.com

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100044
      • Not yet recruiting
      • Peking University People's Hospital
    • Beijing, Beijing Municipality, China, 100035
      • Not yet recruiting
      • Peking University First Hospital
  • Henan
    • Zhengzhou, Henan, China, 450003
      • Not yet recruiting
      • Zhengzhou University-First Affiliated Hospital
  • Jiangsu
    • Nanjing, Jiangsu, China, 210009
      • Not yet recruiting
      • Zhongda Hospital Southeast University
    • Nanjing, Jiangsu, China, 210003
      • Not yet recruiting
      • The Second Affiliated Hospital of Nanjing Medical University
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 201112
      • Not yet recruiting
      • Shanghai Jiao Tong University School of Medicine, Renji Hospital
  • Sichuan
    • Chengdu, Sichuan, China, 610072
      • Not yet recruiting
      • Sichuan Provincial People'S Hospital
• United States
  • Alabama
    • Huntsville, Alabama, United States, 35801
      • Not yet recruiting
      • Apogee Clinical Research, LLC
  • California
    • Chula Vista, California, United States, 91910
      • Not yet recruiting
      • California Institute of Renal Research
    • Los Angeles, California, United States, 90022
      • Recruiting
      • Academic Medical Research Institute
  • Colorado
    • Denver, Colorado, United States, 80220
      • Recruiting
      • Colorado Kidney Care
  • Connecticut
    • Middlebury, Connecticut, United States, 06762
      • Recruiting
      • DaVita Clinical Research
    • Orange, Connecticut, United States, 06477
      • Not yet recruiting
      • US Renal Care
  • Florida
    • Fort Myers, Florida, United States, 33912
      • Not yet recruiting
      • US Renal Care
  • Georgia
    • Dalton, Georgia, United States, 30720
      • Not yet recruiting
      • US Renal Care
  • Michigan
    • Shelby, Michigan, United States, 48315
      • Recruiting
      • St. Clair Nephrology Research
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Recruiting
      • Johnson County Clinical Trials
  • Nevada
    • Las Vegas, Nevada, United States, 89107
      • Recruiting
      • DaVita Clinical Research
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • Not yet recruiting
      • Renal Medicines Associates
  • Ohio
    • Toledo, Ohio, United States, 43613
      • Not yet recruiting
      • US Renal Care
  • Texas
    • Greenville, Texas, United States, 75402
      • Recruiting
      • Sunbeam Research
    • Houston, Texas, United States, 77054
      • Recruiting
      • DaVita Clinical Research
    • McAllen, Texas, United States, 78503
      • Not yet recruiting
      • Gamma Medical Research
    • San Antonio, Texas, United States, 78251
      • Not yet recruiting
      • US Renal Care
    • San Antonio, Texas, United States, 78258
      • Not yet recruiting
      • DaVita Clinical Research
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Not yet recruiting
      • DaVita Clinical Research

Participation Criteria

Eligibility Criteria

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

Description

Important Inclusion Criteria:

• Signs a written informed consent form (ICF) and is willing to comply with all study requirements in the study
• Receiving a stable hemodialysis (including hemodialysis, hemodiafiltration, and hemoadsorption) regimen, which is defined as a frequency of three times per week for at least 12 weeks before signing the ICF, and does not plan to change in the study
• Who has a blood phosphate level within the study-required range
• Who has a dialysis adequacy, assessed by single pooled Kt/V (SpKt/V, estimated with blood urea) ≥1.20, at screening or any documented value ≥1.20 within 12 weeks prior to signing the ICF
• If the participant is receiving etelcalcetide, their doses must be unchanged for at least 4 weeks prior to signing the ICF
• If the participant is receiving any of the following therapies, their doses are stable for at least 14 days prior to signing the ICF: phosphate-lowering products other than tenapanor or phosphate binders, active vitamin D and analogs, cinacalcet, calcitonin, and P-glycoprotein inhibitors
• Agreement to use highly effective contraception for women of childbearing potentially and non-sterile sexually active males throughout the study and for 90 days after the final dose of study drug

Important Exclusion Criteria:

• Pregnant or breastfeeding
• Scheduled for a living donor kidney transplant in the next 6 months, planned change to peritoneal dialysis or home hemodialysis in the study; planned relocation to another dialysis center in the study
• Any history of a non-pharmacological parathyroid intervention within 6 months prior to the ICF sign off, or planned parathyroid intervention in the study
• Blood calcium or blood intact parathyroid hormone abnormality
• Adequate organ and bone marrow function
• Acute hepatitis or significant chronic liver disease
• Any clinically significant GI disorders within 4 weeks prior to signing the ICF; or any history of gastrectomy; or any GI tract surgery (excluding appendectomy and polypectomy), within 12 weeks of signing the ICF
• Uncontrolled hypertension
• Hospitalization for cardiac or cardiocerebrovascular disease within 24 weeks prior to signing the ICF
• Significant abnormalities of QT interval and heart rhythm on an electrocardiograph (ECG) test
• Any clinically significant active infection or infestation or any treatment with systemic antimicrobial treatment within 2 weeks prior to signing the ICF
• History or presence of malignancy within 3 years prior to signing the ICF, except basal cell skin cancer, in-situ carcinoma of the cervix, and in-situ prostate cancer
• Taking moderate or strong cytochrome P450 (CYP) 3A inhibitors within 2 weeks or 5 half-lives, whichever is longer, prior to signing the ICF (topical use is allowed)
• Treatment with any investigational medication or medical device within 30 days prior to signing the ICF
• Life expectancy less than 12 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1	Drug: AP306 75 mg BID; AP306 75 mg by mouth, twice daily (150 mg/day). Placebo given once daily. Treatment given daily for 8 weeks.
Experimental: Cohort 2	Drug: AP306 125 mg BID; AP306 125 mg by mouth, twice daily (250 mg/day). Placebo given once daily. Treatment given daily for 8 weeks.
Experimental: Cohort 3	Drug: AP306 150 mg BID; AP306 150 mg by mouth, twice daily (300 mg/day). Placebo given once daily. Treatment given daily for 8 weeks.
Experimental: Cohort 4	Drug: AP306 75 mg TID; AP306 75 mg by mouth, three times daily (225 mg/day). Treatment given daily for 8 weeks.
Experimental: Cohort 5	Drug: AP306 100 mg TID; AP306 100 mg by mouth, three times daily (300 mg/day). Treatment given daily for 8 weeks.
Experimental: Cohort 6	Drug: AP306 125 mg TID; AP306 125 mg by mouth, three times daily (375 mg/day). Treatment given daily for 8 weeks.
Placebo Comparator: Cohort 7	Drug: Placebo; Placebo given by mouth, three times daily. Treatment given daily for 8 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To investigate the ability of AP306 at different fixed doses to lower serum phosphate in participants with hyperphosphatemia receiving maintenance hemodialysis	The change in serum phosphate from baseline to the end of treatment or before the initiation of rescue therapy, or before the interruption of study drug due to serum phosphate <2.5 mg/dL (0.81 mmol/L)	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the proportion of participants with serum phosphate in the target range	Achievement of serum phosphate concentrations within the target range (between 3.5 and 5.5 mg/dL [1.13 and 1.78 mmol/L], inclusive) at any time during the Treatment Period	8 weeks
To assess the change in serum phosphate from baseline to the end of the Treatment Period	The change in serum phosphate from baseline to the end of Treatment Week 8.	8 weeks
To assess the time to response on serum phosphate reduction	The change in serum phosphate over time; The time to the first occurrence of serum phosphate ≤5.5 mg/dL (1.78 mmol/L) and ≤4.5 mg/dL (1.45 mmol/L)	8 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the pharmacokinetic (PK) characteristics of AP306	The plasma concentration of AP306 at the following time points: baseline, after 4 weeks of treatment, and after 8 weeks of treatment; The constituent and proportion of metabolites at PK sampling time points	8 weeks
To evaluate the overall safety and tolerability of AP306	The nature, frequency, and severity of all treatment emergent and serious adverse events (AEs); The effects on laboratory values, vital signs, electrocardiogram (ECG) parameters, and Bristol Stool Form Scale	12 weeks
To assess the effects of AP306 on intact parathyroid hormone (iPTH) and fibroblast growth factor (FGF23) concentration	The change in iPTH and FGF23 from the baseline to the end of Treatment Week 8 (or early termination (ET) visit for those who terminate study drug), and the end of the study	12 weeks

Collaborators and Investigators

• Sponsor: R1 Therapeutics
• Collaborators: Alebund Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2026
• Primary Completion (Estimated): February 28, 2027
• Study Completion (Estimated): March 31, 2027

Study Registration Dates

• First Submitted: November 27, 2024
• First Submitted That Met QC Criteria: November 27, 2024
• First Posted (Actual): December 2, 2024

Study Record Updates

• Last Update Posted (Actual): June 9, 2026
• Last Update Submitted That Met QC Criteria: June 8, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: AP306; AP-306; EOS789; pan-phosphate transporter inhibitor
• Additional Relevant MeSH Terms: Metabolic Diseases; Phosphorus Metabolism Disorders; Nutritional and Metabolic Diseases; Hyperphosphatemia; BID protein, human
• Other Study ID Numbers: AP306-HP-202

Plan for Individual participant data (IPD)

• IPD Plan Description: The study will enroll part of participants from China. Sharing of individual participant data from them is not possible due to the Personal Information Protection Law of the People's Republic of China (Presidential Decree No. 91, August 2021). The IPD sharing will be decided later.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No