A Single-arm, Multicenter, Phase III Study to Assess Efficacy, Pharmacokinetics, Safety and Tolerability of Atrasentan in Pediatric Patients of 2 to <18 Years of Age With Primary Immunoglobulin A Nephropathy (IgAN)

A Phase III, single-arm, multicenter pediatric clinical study evaluating atrasentan in children and adolescents aged 2 to <18 years with primary immunoglobulin A nephropathy (IgAN).

CT.gov Identifier

NCT07498335

EudraCT Identifier

N/A

CTIS:

2025-522824-29-00

Collaborator

AbbVie/AbbVie Ireland

Study Contact Information

+41 61 324 0000

Recruiting

Study Details

Diseases

IgA nephropathy

Study Drug

Atrasentan hydrochloride

Undisclosed - FDA approved drug

Undisclosed - ACE inhibitor

Undisclosed - angiotensin II receptor antagonist

Undisclosed-diuretics

Genes

N/A

Study Dates

Jul 2026 - Sep 2031

Sex

Female & Male

Age

2 - 18 Years

Inclusion and Exclusion Criteria

Inclusion Criteria:

Before conducting any study-specific assessments, signed informed consent must be obtained from the parents/legal guardians of pediatric patients. Some participants may also require consent or permission, depending on their Age and local requirements.
Participants Age 2 to < 18 years on Day 1.
At screening, eGFR ≥ 30 mL/min/1.73m2 (calculated using the modified Schwartz formula (Schwartz et al 2009)) was used, and confirmed during the induction period.
Primary IgAN* confirmed by renal biopsy, with the biopsy completed within 3 years prior to screening, accompanied by renal tubulointerstitial fibrosis < 50% and crescent proportion < 25%. If renal biopsy results within 3 years prior to screening are not available, renal biopsy may be performed provided that it is part of the participant's planned diagnostic approach and clinical management.
Even if the patient received at least 120 days of treatment with the maximum tolerated dose of an ACE inhibitor/ARB prior to day 1, proteinuria due to primary diagnosis of IgAN was defined as a UPCR ≥ 1 g/g (113 mg/mmol) collected and assessed from FMV (in exceptional cases, random urine samples may be collected from participants in cohorts 2, 3, or 4) at screening on day -90 and day -60 and during the introductory period.
Prior to the first administration of the study drug, all participants must have received supportive care, including a stable dose of an ACE inhibitor or ARB regimen at the locally approved maximum daily dose based on body weight or the maximum tolerated dose (as determined by the investigator for pediatric use) for at least 120 days. Additionally, if participants are using diuretics, other antihypertensive treatments, other IgAN background therapies (e.g., SGLT2 inhibitors), or other medications that may affect UPCR levels (e.g., GLP-1 agonists), the relevant doses should also be stable for at least 120 days prior to the first administration of the study treatment.
The minimum weight for enrolled pediatric participants at screening was 10 kg, and this was confirmed on day 1.
Parents/guardians must be able to communicate smoothly with researchers and understand and comply with the research requirements for participants.

Exclusion Criteria:

At the time of enrollment, within 5 elimination half-lives prior to enrollment, within 30 days prior to enrollment (whichever is longer), or for a longer period as required by local regulations, participate in any other investigational drug trial or use other investigational drugs.
History of hypersensitivity to any investigational drug or its excipients or drugs of similar chemical class.
Researchers believe that any secondary IgAN exists prior to treatment; secondary IgAN may be associated with cirrhosis, celiac disease, human immunodeficiency virus (HIV) infection, herpes simplex virus infection, herpetic dermatitis, seronegative arthritis, small cell carcinoma, lymphoma, disseminated tuberculosis, bronchiolitis obliterans, inflammatory bowel disease, and familial Mediterranean fever.
Based on typical palpable purpura with or without joint pain and abdominal pain, the clinical diagnosis is IgA vasculitis (IgAV or allergic purpura).
Evidence of severe urinary tract obstruction or difficulty urinating at the time of screening, or any urinary tract disease that causes significant urinary tract obstruction or difficulty urinating, confirmed at baseline/day 1.
In addition to IgAN, CKD was diagnosed at the time of screening and before the first administration of the study drug.
Acute kidney injury (AKI) was identified within 4 weeks prior to screening according to the Acute Kidney Injury Network Expert Group (AKIN) criteria (Mehta et al 2007 and Section 10.6).
Rapidly progressive glomerulonephritis (RPGN) is defined as a decrease in eGFR of 50% within 3 months prior to screening or during the screening and induction periods.
According to the researchers' assessment, nephrotic syndrome was present during the screening period.
During screening, the BNP value should be > 200 pg/mL.
At the time of screening, hemoglobin levels were below 9 g/dL or individuals had a history of blood transfusions for anemia within the three months prior to screening.
Platelet count < 80,000/μL at screening.
Participants weighed less than the lower limit of their initial screening cohort on day 1, and the corresponding cohort with lower weight had not yet opened for enrollment.
Prior to treatment, patients should have a known history of congenital heart disease, heart failure, or clinically significant fluid retention (such as pulmonary edema, uncontrolled peripheral edema, pleural effusion, or ascites).
Prior to treatment, any homeopathic remedies and/or herbs currently used to treat IgAN disease, such as, but not limited to, tripterygium wilfordii , Sedum sarmentosum, and Sedum sarmentosum.
During the screening process, candidates were required to have a history of alcohol abuse or illicit drug use within the past three years.
Based on the average of three measurements taken at screening, the following conditions were confirmed: systolic blood pressure > 150 mmHg or diastolic blood pressure > 95 mmHg in the Age group of 12 to < 18 years; systolic blood pressure > 140 mmHg or diastolic blood pressure > 90 mmHg in the Age group of 6 to < 12 years; systolic blood pressure > 120 mmHg or diastolic blood pressure > 80 mmHg in the Age group of 2 to < 6 years; or clinically significant hypotension was present at screening.
Participants who received immunosuppressants or other immunomodulatory agents within 120 days prior to the first dose of the study drug (or 180 days rituximab administration), such as, but not limited to: cyclophosphamide, rituximab, infliximab, cananumab, mycophenolate mofetil(MMF) or mycophenolate sodium(MPS), calcineurin inhibitors, complement inhibitors, any dose of oral budesonide, systemic Glucocorticoid exposure ≥ 0.5 mg/kg/day, or total daily prednisone/ prednisone equivalent exposure > 7.5 mg. Participants who received endothelin (receptor) antagonists (including sparsentan) within 120 days prior to the first dose of the study drug.
Subjects with a history of organ transplantation prior to treatment (excluding subjects with a history of corneal transplantation).
Major comorbidities prior to treatment include, but are not limited to, advanced heart disease (e.g., NYHA Class III (6 to < 18 years), Ross Class III (2 to < 6 years), severe lung disease (e.g., WHO Class III (17 years), Pulmonary Vascular Research Institute (PVRI) Class III (2 to < 17 years)) or liver disease that the investigators believe would prevent the subject from participating in the study (e.g., active hepatitis).
20
:
twenty one Prior to treatment, any medical conditions that might interfere with a subject's participation in the study should be identified.
21
:
twenty two The study investigated active systemic bacterial, viral (including COVID-19), or fungal infections within 14 days prior to drug administration.
22
:
twenty three Fever ≥ 38°C (100.4°F) within 7 days prior to administration of the study drug.
23
:
twenty four Human immunodeficiency virus (HIV) infection (known history of HIV or positive HIV antibody test at screening).
Liver disease, such as active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection (defined as positive hepatitis B surface antigen (HBsAg) or positive hepatitis C virus ribonucleic acid (HCV-RNA) at screening), or liver damage shown by abnormal liver function tests as follows at screening and baseline: ? None of the parameters ALT, AST, GGT, or Phosphate must exceed 3 times the upper limit of normal (ULN)? ? Serum bilirubin must not exceed 2 × ULN
For children aged 2 to < 5 years, a history of any organ system malignancy (excluding localized basal cell carcinoma of the skin or cervical cancer in situ that has been treated radically), including malignancies diagnosed at birth and during neonatal and childhood years, regardless of treatment or evidence of local recurrence or metastasis; for children aged 2 to < 5 years, a history of any organ system malignancy (excluding localized basal cell carcinoma of the skin or cervical cancer in situ), including malignancies diagnosed at birth and during neonatal and childhood years, regardless of treatment or evidence of local recurrence or metastasis.
Pregnant or lactating female patients (of fertility), pregnancy is defined as the state from the time of a woman's conception until the termination of pregnancy, confirmed by a positive laboratory test for human chorionic gonadotropin (hCG) at the time of screening.
Subjects who received the contraindicated treatments listed in Tables 10-4 and 10-5.
Women of reproductive potential are defined as all women who are physiologically likely to become pregnant from menarche to premenopause, unless they use highly effective contraception (annual failure rate < 1%) during the administration of study treatment and for one month after discontinuation of study treatment.
For fertile male participants, participants must not plan to conceive or donate sperm during the study treatment and for at least one month afterward. All fertile male participants who have sexual relations with WOCBP must agree to use condoms during the trial and for up to one month after the last administration of the study drug. Male participants who have completed puberty are considered fertile unless permanently infertile due to bilateral orchiectomy/orchiectomy.

Protocol Summary

A Phase III, single-arm, multicenter pediatric clinical study evaluating atrasentan in children and adolescents aged 2 to <18 years with primary immunoglobulin A nephropathy (IgAN).

Study Locations

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