A Phase 3, Open-label, Uncontrolled Study to Evaluate the Activity, Safety, Pharmacokinetics and Pharmacodynamics of Roxadustat for the Treatment of Anemia in Pediatric Participants with Chronic Kidney Disease
- Trial ID
- 2022-501980-42-00
- Protocol
- 1517-CL-1003
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the **activity** of roxadustat for the treatment of anemia in adolescents and children with chronic kidney disease (CKD). This is clinically relevant as anemia is a common complication in pediatric patients with CKD, and effective management is crucial for improving patient outcomes and quality of life.
Secondary objectives include:
- Evaluating the pharmacokinetics (PK) and pharmacodynamics (PD) of roxadustat in this population, which is essential for understanding the drug's absorption, distribution, metabolism, and excretion, as well as its biological effects.
- Assessing the safety of roxadustat, including cardiovascular and thrombotic risks, to ensure the treatment does not pose significant health risks to the patients.
- Further evaluating other activity parameters of roxadustat to gain a comprehensive understanding of its therapeutic potential.
- Evaluating the palatability, taste, and ability to swallow oral roxadustat, which is important for adherence to treatment in pediatric patients.
- Assessing the quality of life (QoL) in adolescents and children taking roxadustat, as improved QoL is a key goal in managing chronic conditions like CKD.
Participants
The clinical trial involves a total of **63 participants** diagnosed with **anemia associated with Chronic Kidney Disease** (CKD). The study population comprises both male and female subjects, aged between 2 to less than 18 years. Participants include those with CKD stages 3, 4, or 5, encompassing individuals not on dialysis as well as those undergoing hemodialysis, peritoneal dialysis, or hemodiafiltration. The trial population was selected based on specific health criteria, including hemoglobin levels and iron status, with participants either being treated with erythropoiesis-stimulating agents (ESA) or being ESA-naïve. The study considers lifestyle factors such as the requirement for contraception use among participants of childbearing potential and restrictions on breastfeeding and ova or sperm donation during and after the trial period. The trial includes a vulnerable population, emphasizing the need for informed consent from participants or their legal guardians.
Plans and Procedures
The clinical trial is designed to evaluate the activity, safety, pharmacokinetics, and pharmacodynamics of **roxadustat** for the treatment of **anemia** in pediatric participants with chronic kidney disease. This is a Phase 3, open-label, uncontrolled study. The trial is expected to commence recruitment on December 1, 2023, and is estimated to conclude by June 30, 2026. The study involves a 52-week treatment period, with participants receiving **roxadustat** in the form of film-coated tablets. The trial will include multiple study visits, starting with an inclusion (screening) visit to assess eligibility based on specific criteria, such as age, diagnosis, and laboratory values. Participants will be required to have a diagnosis of anemia associated with chronic kidney disease and meet other inclusion criteria, such as specific hemoglobin and ferritin levels.
Following the screening visit, participants will undergo a series of follow-up visits throughout the treatment period. These visits will be scheduled to monitor the primary endpoint, which is the change in hemoglobin level between baseline and the average level over treatment weeks 20 to 24. Secondary endpoints include pharmacokinetic parameters, safety assessments, and quality of life evaluations. The study will also assess the percentage of participants achieving target hemoglobin levels and the use of intravenous and oral iron supplementation. The end-of-study visit will occur at the conclusion of the 52-week treatment period, where final assessments will be conducted.
Participant involvement is expected to last for the entire 52-week treatment period unless conditions arise that necessitate early termination. Such conditions may include adverse events, non-compliance with study procedures, or withdrawal of consent. The trial will adhere to ethical guidelines, ensuring informed consent is obtained from participants or their legal guardians. The study aims to provide comprehensive data on the efficacy and safety of **roxadustat** in treating anemia in this specific patient population.
Treatment
The clinical trial involves the administration of several treatments, including both experimental and non-experimental medications. The primary experimental medication is **roxadustat**, which is provided in three different dosages: 5 mg, 20 mg, and 50 mg. These are formulated as film-coated tablets and are administered orally. The maximum daily dose is 200 mg, with a total maximum dose of 31,200 mg over a treatment period of up to 52 weeks. Roxadustat is a chemical-origin medication specifically designed for pediatric use, as indicated by its paediatric formulation status.
In addition to roxadustat, the trial includes the use of **erythropoietin** as a comparator treatment. Erythropoietin is administered either subcutaneously or intravenously, with the pharmaceutical form designated as PHF00231MIG. The treatment period for erythropoietin is up to 4 weeks. The medication is not formulated for pediatric use and is classified under the ATC code B03XA01, indicating its role in erythropoiesis.
Another comparator treatment in the trial is **methoxy polyethylene glycol-epoetin beta**, which is also administered subcutaneously or intravenously. This medication is a chemically modified erythropoiesis-stimulating agent, with a pharmaceutical form of PHF00231MIG. The treatment period is similarly limited to 4 weeks, and it is not specifically formulated for pediatric use. The ATC classification for this medication is B03XA03.
**Darbepoetin alfa** is also included as a comparator treatment, administered via subcutaneous and intravenous routes. It shares the same pharmaceutical form, PHF00231MIG, and treatment duration of 4 weeks as the other comparator treatments. Darbepoetin alfa is not a pediatric formulation and is classified under the ATC code B03XA02.
Additionally, **packed red blood cells** are used as a non-experimental treatment in the study. This treatment is administered through intravenous infusion and serves as a standard-of-care therapy. The pharmaceutical form is designated as PHF00230MIG, and the treatment period is up to 4 weeks. This treatment is not specifically formulated for pediatric use.
Participant compliance with the dosing schedules is monitored throughout the trial to ensure adherence to the prescribed treatment regimens. The trial aims to evaluate the activity, safety, pharmacokinetics, and pharmacodynamics of roxadustat in treating anemia in pediatric participants with chronic kidney disease.
Efficacy
Efficacy in this clinical trial will be assessed primarily through the change in **hemoglobin (Hb)** levels. The primary endpoint is defined as the change in Hb level between baseline (before the start of dosing) and the average Hb level over treatment weeks 20 to 24. This 24-week treatment period includes 4 weeks of fixed-dose treatment followed by 20 weeks of dose titration. Secondary endpoints include pharmacokinetic (PK) parameters such as Cmax, AUC, CL/F, and Tmax, as well as pharmacodynamic (PD) assessments of Hb levels and dose titration history at all timepoints. Additionally, the trial will evaluate the number and percentage of treatment-emergent adverse events (TEAEs), cardiovascular and thrombotic adverse events, and safety assessments including clinical laboratory tests, vital signs, growth parameters, and physical examinations.
Further secondary endpoints involve the percentage of participants achieving two consecutive Hb values within 1 g/dL of baseline or the target range of 10.0 to 12.0 g/dL at the end of the 24-week treatment period. The study will also summarize monthly intravenous (IV) iron usage, the percentage of participants using IV and oral iron by study period, and the percentage of participants using rescue therapy. Additionally, responses on the 5-point Likert Scale regarding the palatability, taste, and ability to swallow oral roxadustat will be summarized overall and by age group at weeks 4, 24, and 52/end-of-treatment (EOT). Quality of life (QoL) assessments will be conducted using the Pediatric Quality of Life Inventory version 4.0 and the Pediatric Quality of Life Multidimensional Fatigue Scale standard version, with summaries provided overall, by age group, and by visit from day 1 to weeks 8 to 52/EOT.
Inclusion and Exclusion Criteria
Inclusion Criteria
- IRB/IEC approved written informed consent and privacy language as per national regulations (e.g., Health Insurance Portability and Accountability Act authorization for US study sites) must be obtained from the participant or participant’s parent or legal guardian, and if required, child assent, prior to any study-related procedures (including withdrawal of prohibited medication, if applicable)
- Participant is aged 2 to < 18 years old at the screening/first study visit.
- Participant has a diagnosis of anemia in CKD Kidney Disease Outcomes Quality Initiative stages 3 or 4 or 5. This can include participants not on dialysis or DD participants (including hemodialysis, peritoneal dialysis and hemodiafiltration participants)
- Participants not on dialysis must have an estimated glomerular filtration rate (Schwartz formula) of < 60 mL/min per 1.73 m2.
- ESA-treated participants should have a screening Hb level, assessed via HemoCue, between 10.0 and 12.0 g/dL; ESA-naïve participants can have a Hb level ≤ 11 g/dL.
- Participant has a ferritin level > 100 ng/mL or a TSAT value > 20%
- Participant has an ALT and AST ≤ 2 x ULN and TBL ≤ 1.5 x ULN at enrollment visit.
- Participant is treated with an ESA or is ESA-naïve, where ESA status is defined as: a. ESA-treated: Participant is taking a stable dose of an ESA for at least 4 weeks prior to screening. b. ESA-naïve: Participant has no prior ESA exposure OR participant’s total prior ESA exposure ≤ 3 weeks within the preceding 4 weeks from screening OR participant was previously treated with and discontinued an ESA ≥ 8 weeks prior to screening.
- Female participant is not pregnant and at least 1 of the following conditions apply: Not a WOCBP, WOCBP who agrees to follow the contraceptive guidance from the time of informed consent through at least 4 weeks after final study intervention administration.
- Female participant must agree not to breastfeed starting at screening and throughout the study and for 4 weeks post-last roxadustat dose.
- Female participant must not donate ova starting at first administration of roxadustat and throughout the study period and for 4 weeks post-last roxadustat dose.
- Male participants with female partner(s) of childbearing potential (including breastfeeding partner) must agree to use contraception throughout the treatment period and for 4 weeks post-last roxadustat dose.
- Male participants must not donate sperm during the treatment period and for 4 weeks post-last roxadustat dose.
- Male participants with pregnant partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy throughout the study period and for 4 weeks post-last roxadustat dose.
- Participant and/or participant’s parent or legal guardian agrees for the participant not to participate in another interventional study while participating in the present study
Exclusion Criteria
- Participant has received any investigational therapy within 28 days or 5 half-lives, whichever is longer, prior to screening.
- Participant has a known active malignancy or malignancy within 18 months before the screening visit. Radiation or chemotherapy must be completed at least 12 months before the screening visit.
- Participant has a scheduled living donor organ transplantation date within 12 weeks of screening. If participant becomes eligible for a kidney transplant during study conduct, the participant should be discontinued.
- Participant has uncontrolled hypertension (defined as ≥ 95th percentile + 12 mm Hg or ≥ 140/90 mm Hg [whichever is lower] for participants < 13 years of age and ≥ 140/90 mm Hg for participants ≥ 13 years of age measured 3 times at the same visit) and as judged by the principal investigator in the 2 weeks prior to screening.
- Participant has any current condition leading to active significant blood loss in the past 4 weeks.
- Participant has a diagnosis of hemolytic uremic syndrome within 12 weeks prior to screening. a. Participant who has a previous diagnosis of atypical hemolytic syndrome must be relapse-free (stable Hb, normal platelet count, normal serum lactate dehydrogenase, and normal haptoglobin level) for more than 12 weeks prior to screening.
- Participant has a history of chronic liver disease, including comorbidity with autosomal recessive polycystic kidney disease, cystinosis, and primary hyperoxaluria
- Participant had an episode of peritonitis within 30 days of screening.
- Participant has active inflammation such as glomerulonephritis flare (i.e., lupus nephritis, IgA nephritis, rapidly progressive glomerulonephritis, membranoproliferative glomerulonephritis, antineutrophil cytoplasmic antibodies vasculitis) requiring pulse corticosteroid treatment or induction treatment with an immunosuppressive agent (i.e., cyclophosphamide, rituximab, or another monoclonal antibody) within 6 weeks of screening visit. Receipt of monoclonal antibody or biologic for maintenance treatment of underlying condition is acceptable.
- Participant has a known history of human immunodeficiency virus infection.
- Participant has a scheduled living donor organ transplantation date within 12 weeks of screening. If participant becomes eligible for a kidney transplant during study conduct, the participant should be discontinued.
- Participant has a known or suspected hypersensitivity to roxadustat, related HIF-PHI, or any components of the formulation used.
- Participant has uncontrolled hypertension (defined as ≥ 95th percentile + 12 mm Hg or ≥ 140/90 mm Hg [whichever is lower] for participants < 13 years of age and ≥ 140/90 mm Hg for participants ≥ 13 years of age measured 3 times at the same visit) and as judged by the principal investigator in the 2 weeks prior to screening.
- Participant has a known hematologic disease other than anemia secondary to renal disease, (e.g., history of sickle cell disease, sickle cell anemia, hemoglobin sickle cell disease, or hemoglobin sickle cell beta thalassemia).
- Participant has untreated hypothyroidism.
- Participant has severe hyperparathyroidism defined as serum PTH levels above 1000 pg/mL intact PTH within 4 weeks of screening.
- Participant has a functioning kidney allograft.
- Participant has a folate or B12 or carnitine deficiency. Acceptable if treated to normal values within 4 weeks of screening.
- Participant has rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption or is allergic to peanut or soya.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Belgium | Recruiting | 01 Dec 2023 | 5 |
 Bulgaria | Not Recruiting | 01 Dec 2023 | 2 |
 Croatia | Recruiting | 01 Dec 2023 | 2 |
 Czechia | Recruiting | 01 Dec 2023 | 3 |
 Denmark | Recruiting | 01 Dec 2023 | 2 |
 Finland | Recruiting | 01 Dec 2023 | 1 |
 France | Not Yet Recruiting | 01 Dec 2023 | 5 |
 Germany | Recruiting | 01 Dec 2023 | 1 |
 Greece | Recruiting | 01 Dec 2023 | 1 |
 Ireland | Recruiting | 01 Dec 2023 | 1 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
roxadustat 5 mg azo-dye free tablets | Test | FILM-COATED TABLET | ORAL USE | 200 | 52 | PRD10010466 |
- | Other | PHF00230MIG | INTRAVENOUS INFUSION | 00 | 4 | B05AA |
ERYTHROPOIETIN | Other | PHF00231MIG | SUBCUTANEOUS OR INTRAVENOUS | 00 | 4 | SCP1779966 |
roxadustat 50 mg azo-dye free tablets | Test | FILM-COATED TABLET | ORAL | 200 | 52 | PRD10070298 |
METHOXY POLYETHYLENE GLYCOL-EPOETIN BETA | Other | PHF00231MIG | SUBCUTANEOUS AND INTRAVENOUS USE | 00 | 4 | SCP47391743 |
roxadustat 20 mg azo-dye free tablets | Test | FILM-COATED TABLET | ORAL USE | 200 | 52 | PRD10070297 |
DARBEPOETIN ALFA | Other | PHF00231MIG | SUBCUTANEOUS AND INTRAVENOUS USE | 00 | 4 | SCP32526793 |