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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Astellas Pharma Global Development Inc.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

21 Dec 2023 → ongoing

Decision date (initial)

2023-11-10

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Astellas Pharma Global Development, Inc

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacodynamic, Others, Pharmacokinetic

Evaluate the activity of roxadustat for the treatment of anemia in adolescents and children with CKD

Secondary objectives 5

1. Evaluate the PK and PD of roxadustat for the treatment of anemia in adolescents and children with CKD
2. Evaluate the safety of roxadustat for the treatment of anemia in adolescents and children with CKD, including cardiovascular and thrombotic risks
3. Evaluate the palatability, taste, and ability to swallow oral roxadustat in adolescents and children with CKD
4. Evaluate the QoL in adolescents and children taking roxadustat for anemia in CKD
5. Further evaluate other activity parameters of roxadustat for the treatment of anemia in adolescents and children with CKD

Conditions and MedDRA coding

Anemia associated with Chronic Kidney Disease

Study design 3 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-001557-PIP01-13

Plan to share IPD

No

IPD plan description

none

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 15

1. 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)
2. Participant is aged 2 to < 18 years old at the screening/first study visit.
3. 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)
4. Participants not on dialysis must have an estimated glomerular filtration rate (Schwartz formula) of < 60 mL/min per 1.73 m2.
5. 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.
6. Participant has a ferritin level > 100 ng/mL or a TSAT value > 20%
7. Participant has an ALT and AST ≤ 2 x ULN and TBL ≤ 1.5 x ULN at enrollment visit.
8. 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.
9. 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.
10. Female participant must agree not to breastfeed starting at screening and throughout the study and for 4 weeks post-last roxadustat dose.
11. 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.
12. 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.
13. Male participants must not donate sperm during the treatment period and for 4 weeks post-last roxadustat dose.
14. 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.
15. 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 19

1. Participant has received any investigational therapy within 28 days or 5 half-lives, whichever is longer, prior to screening.
2. 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.
3. 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.
4. 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.
5. Participant has any current condition leading to active significant blood loss in the past 4 weeks.
6. 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.
7. Participant has a history of chronic liver disease, including comorbidity with autosomal recessive polycystic kidney disease, cystinosis, and primary hyperoxaluria
8. Participant had an episode of peritonitis within 30 days of screening.
9. 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.
10. Participant has a known history of human immunodeficiency virus infection.
11. 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.
12. Participant has a known or suspected hypersensitivity to roxadustat, related HIF-PHI, or any components of the formulation used.
13. 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.
14. 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).
15. Participant has untreated hypothyroidism.
16. Participant has severe hyperparathyroidism defined as serum PTH levels above 1000 pg/mL intact PTH within 4 weeks of screening.
17. Participant has a functioning kidney allograft.
18. Participant has a folate or B12 or carnitine deficiency. Acceptable if treated to normal values within 4 weeks of screening.
19. Participant has rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption or is allergic to peanut or soya.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change in Hb level between baseline (before start of dosing) and average Hb level over treatment weeks 20 to 24. The 24-week treatment period is defined as 4 weeks of fixed dose treatment followed by 20 weeks of dose titration(s)

Secondary endpoints 6

1. 1●PK parameters: Cmax, AUC, CL/F, Tmax; ●PD assessments: Hb level and dose titration history at all timepoints
2. 2● Number and percent of TEAEs ● Number and percent of treatment-emergent cardiovascular and thrombotic AEs ● Tabulations of safety assessments (clinical laboratory tests, vital signs, growth parameters and physical examinations)
3. 3a●Percentage of participants achieving 2 consecutive Hb values within 1 g/dL of baseline (ESA-treated participants only) or achieving the target range of 10.0 to 12.0 g/dL at the end of the 24-week treatment period ● Summaries of monthly IV iron usage (number of IV iron administrations and total IV iron dosage)
4. 3b●Percentage of participants using IV iron by study period (day 1 to week 24 and week 25 to week 52/EOT) ●Percentage of participants using oral iron by study period (day 1 to week 24 and week 25 to week 52/EOT) ● Percentage of participants using rescue therapy by study period (day 1 to week 24, week 25 to week 52/EOT, and overall)
5. 4● Summaries overall and by age group (adolescents and children) for responses on the 5-point Likert Scale on palatability, taste and ability to swallow oral roxadustat at weeks 4, 24 and 52/EOT
6. 5●Summaries overall, by age group (adolescents and children), and by visit (day 1, weeks 8 to 52/EOT), for QoL ePRO assessments scores and changes from baseline ● Pediatric Quality of Life Inventory version 4.0 ● Pediatric Quality of Life Multidimensional Fatigue Scale standard version

Investigational products

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

Test 3

Auxiliary 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Astellas Pharma Global Development Inc.

Sponsor organisation

Astellas Pharma Global Development Inc.

Address

1 Astellas Way

City

Northbrook

Postcode

60062-6111

Country

United States

Scientific contact point

Organisation

Astellas Pharma Global Development Inc.

Contact name

Head of Clinical Trial Unit Regulatory Affairs

Public contact point

Organisation

Astellas Pharma Global Development Inc.

Contact name

Head of Clinical Trial Unit Regulatory Affairs

Third parties 10

Locations

20 EU/EEA countries · 40 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Corrective measures 1 · Art. 77 CTR

Results and documents

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

Documents 464 files

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

Application history

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