A Study to Evaluate Setanaxib in Patients With Alport Syndrome

NCT06274489 | Completed Phase 1 Results DMC

• 1 other identifier: GSN000500
• Study Type: interventional
• Target: 20
• Locations: 5 countries
• Sites: 17

Brief Summary

The purpose of the study is to learn about the safety and tolerability of setanaxib in subjects with Alport syndrome, when added to their standard of care treatment. The study will assess how safe setanaxib is when compared to placebo. Study participants will be asked if they are experiencing any side effects at each study visit. In addition, tests in blood, urine and other examinations will be used to look at the safety of setanaxib. The study will also measure how well setanaxib works in comparison to a placebo, by measuring urine protein and certain markers in the blood and urine. The concentration of setanaxib in the blood will also be measured throughout the course of the study. Setanaxib is planned for use together with the current standard of care to hopefully provide additional therapeutic benefits by preserving kidney function. The study will be conducted at multiple research sites in the UK, Spain, and Czech Republic. Eligible participants will be randomly assigned to receive either setanaxib or placebo. Setanaxib dose level will depend on age and all participants will receive their standard of care in addition to setanaxib or placebo. The study consists of a Screening period of up to 4 weeks, a 24-week Treatment period and a 4- week Follow-up period.

Conditions

Alport Syndrome

Outcome Measures

Primary Outcomes (2)

• Percentage of Patients With Serious Adverse Events (SAEs)

  Count and percentage of patients experiencing SAEs

  From informed consent up to 30 days post-final dose, up to 32 weeks

• Percentage of Patients With Treatment-emergent Adverse Events of Special Interest (AESIs)

  Count and percentage of patients experiencing treatment-emergent AEISIs. CTCAE Grade ≥2 anemia will be considered an AESI. During the course of the study, additional AESIs may be identified by the Sponsor

  From informed consent up to 30 days post-final dose

Secondary Outcomes (6)

• The Ratio of Urine Protein to Creatinine Ratio (UPCR) Analysed in 24-hour Urine Sample

  At baseline and week 24

• Percentage of Patients With a 25% Reduction in UPCR Analysed in 24-hour Urine Sample

  At baseline and week 24

• The Ratio of Estimated Glomerular Filtration Rate (eGFR) at 24 Weeks Compared to Baseline.

  At baseline and Week 24.

• Pre-dose and Post-dose Plasma Concentrations of Setanaxib and GKT138184 Measured as the Area Under the Concentration-time Curve Over 24 Hours at Steady State (AUC0-24-ss)

  within 90 minutes prior to dose and 0-, 1-, 2-, 3-, 4- and 6-hours post-dose at week 2; and prior to dose at weeks 12 and 24

• Pre-dose and Post-dose Plasma Concentrations of Setanaxib and GKT138184 Measured as the Minimum Plasma Concentration at Steady State (Cmin-ss)

  within 90 minutes prior to dose and 0-, 1-, 2-, 3-, 4- and 6-hours post-dose at week 2; and prior to dose at weeks 12 and 24

Other Outcomes (7)

• Percentage of Patients With Clinically Significant Changes in Heart Rate

  From baseline by visit up to week 28 (study visit 9, Follow-Up)

• Percentage of Patients With Clinically Significant Changes Blood Pressure

  From baseline by visit up to week 28 (study visit 9, Follow-Up)

• Percentage of Patients With Clinically Significant Changes in 12-lead Electrocardiogram (ECG)

  From baseline by visit up to week 28 (study visit 9, Follow-Up)

Study Arms (2)

Setanaxib

EXPERIMENTAL

Patients will receive the following setanaxib doses according to age at the time of consent/assent: * For patients aged 12 to 17 years 1200 mg/day: 2 tablets in the morning (800 mg) and 1 tablet in the evening (400 mg) * For patients aged ≥18 years 1600 mg/day: 2 tablets in the morning (800 mg) and 2 tablets in the evening (800 mg)

Drug: Setanaxib

Setanaxib placebo

PLACEBO COMPARATOR

Matching placebo will be provided.

Drug: Placebo

Interventions

Placebo DRUG

Matching film-coated placebo tablets, containing only excipients

Setanaxib placebo

Setanaxib DRUG

Setanaxib (formerly GKT137831) is a first-in-class inhibitor of the human protein NADPH NOX1/4. It is a low molecular weight organic molecule and a member of the pyrazolopyridine dione chemical class.

Setanaxib

Eligibility Criteria

• Age: 12 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Male or female patients aged 12 to 50 years inclusive, at the time of informed consent/assent. For sites in the European Union: Male or female patients aged 18 to 50 years, inclusive, at the time of informed consent;
• Diagnosis of Alport syndrome by genetic testing (documented mutation in a gene associated with Alport syndrome \[ie, COL4A3, COL4A4, or COL4A5\]); Patients with a variant of uncertain significance should not be included in the study;

You may not qualify if:

• Weight ≥40 kg;
• Willing and able to give informed consent (and assent, where applicable), in accordance with local age requirements, and to comply with the requirements of the study;
• Female patients of childbearing potential must use a highly effective method of contraception to prevent pregnancy for ≥4 weeks before randomization and must agree to continue strict contraception (as specified in 5c) up to 90 days after the last dose of investigational medicinal product (IMP);
• For the purposes of this study, women of childbearing potential (WOCBP) are defined as "fertile, following menarche and until becoming postmenopausal unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy";
• Postmenopausal state is defined as no menses for 12 months without an alternative medical cause. In female patients who are not using hormonal contraception or hormonal replacement therapy but with suspected menopause and less than 12 months of amenorrhea, a high follicle-stimulating hormone level in the postmenopausal range will be required at Screening to confirm a postmenopausal state; and
• Highly effective contraception is defined as methods that can achieve a failure rate of less than 1% per year when used consistently and correctly. These methods include the following:
• Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, or transdermal);
• Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, or implantable);
• Intrauterine device;
• Intrauterine hormone-releasing system;
• Bilateral tubal occlusion;
• Vasectomized partner; and
• Sexual abstinence (refraining from heterosexual intercourse during the entire period of risk associated with the study treatments, ie, up to 90 days after the last dose of IMP). The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the patient. Periodic abstinence (calendar, symptothermal, or post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhea method are not acceptable methods of contraception.
• Female patients of childbearing potential must have a negative serum pregnancy test at Screening and a negative urine pregnancy test at Visit 3 (after randomization and before dosing);
• Male patients must be willing not to donate sperm and female study patients must be willing not to donate eggs from baseline until 90 days after the last dose of IMP;

Sponsors & Collaborators

• Calliditas Therapeutics AB: lead

Study Sites (17)

Medizinische Universitaet Wien

Vienna, State of Vienna, 1090, Austria

Location

Fakultni Nemocnice Hradec Kralove

Hradec Králové, Czechia

Location

Fakultni Nemocnice Olomouc

Olomouc, Czechia

Location

Institut Klinicke a Experimentalni Mediciny

Prague, Czechia

Location

Vseobecna Fakultni Nemocnice v Praze

Prague, Czechia

Location

AP-HP Hopital Necker-Enfants Malades

Paris, 75015, France

Location

Hospital Universitario 12 de Octubre

Madrid, Usera, 28041, Spain

Location

Fundacio Puigvert

Barcelona, 08025, Spain

Location

Hospital Clinic Barcelona

Barcelona, 08036, Spain

Location

Hospital Universitario Vall d'Hebron

Barcelona, Spain

Location

Hospital Universitario Reina Sofia

Córdoba, 14004, Spain

Location

Hospital Universitario Virgen de las Nieves

Granada, 18014, Spain

Location

Hospital Fundacion Jimenez Diaz

Madrid, 28040, Spain

Location

Royal Free London NHS Foundation Trust

London, NW3 2QG, United Kingdom

Location

Great Ormond Street Hospital for Children

London, WC1N 3JH, United Kingdom

Location

Royal Manchester Children's Hospital

Manchester, M13 9WL, United Kingdom

Location

Nottingham City Hospital

Nottingham, United Kingdom

Location

Related Publications (1)

• Rheault MN. Treatment Approaches for Alport Syndrome. J Am Soc Nephrol. 2026 Jan 1;37(1):172-179. doi: 10.1681/ASN.0000000897. Epub 2025 Sep 12.

  PMID: 40938675 DERIVED

MeSH Terms

Conditions

Nephritis, Hereditary

Interventions

setanaxib

Condition Hierarchy (Ancestors)

Urogenital Abnormalities; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Nephritis; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Collagen Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Head of Clinical Operations
• Organization: Calliditas Therapeutics AB

info@calliditas.com

+4684113005

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 15, 2024
• First Posted: February 23, 2024
• Study Start: November 27, 2023
• Primary Completion: June 24, 2025
• Study Completion: June 25, 2025
• Last Updated: April 13, 2026
• Results First Posted: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

ES (7); AU (1); CZ (4); FR (1); GB (4)