Efficacy and safety of DMX-200 in patients with focal segmental glomerulosclerosis

• Register: EUCTR
• Last refreshed on: 26 February 2024
• Main ID: EUCTR2021-004174-64-DK
• Date of registration: 16/12/2021
• Prospective Registration: Yes
• Primary sponsor: Dimerix Bioscience Pty Ltd
• Public title: Efficacy and safety of DMX-200 in patients with focal segmental glomerulosclerosis
• Scientific title: A pivotal Phase 3, multicenter, randomized, double-blind, placebo-controlled study of the efficacy and safety of DMX-200 in patients with focal segmental glomerulosclerosis (FSGS) who are receiving an angiotensin II receptor blocker (ARB) - ACTION3
• Date of first enrolment: 08/03/2022
• Target sample size: 286
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2021-004174-64
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Brazil, Denmark, France, Hong Kong, New Zealand, Spain, Taiwan, United Kingdom, United States

Contacts

• Name: Clinical Trials Information
• Affiliation: Dimerix Bioscience Pty Ltd

• Name: Clinical Trials Information
• Affiliation: Dimerix Bioscience Pty Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
Key Inclusion Criteria:
- A diagnosis of FSGS confirmed by kidney biopsy or documentation of a genetic mutation in a podocyte protein associated with FSGS. NOTE: The biopsy can have been obtained at any time. Diagnosis of FSGS should be based on light microscopy with supportive findings on either electron microscopy or immunofluorescence analysis and the clinical history and disease course consistent with primary FSGS, genetic FSGS, or FSGS of undetermined cause.
- Must be either receiving an ARB at the maximal tolerated dose and =50% of the maximum recommended dose per the product label prior to Screening, or willing to transition to this treatment.
- If taking corticosteroids, the dosage must be stable for =4 weeks prior to Screening and during Stabilization, and patients must have no plan to change their treatment regimen during study.
- If taking aldosterone inhibitors, mineralocorticoid receptor antagonists, direct renin inhibitors, or sodium-glucose co-transporter-2 inhibitors, the dose and regimen must be stable for =26 weeks prior to Screening and during Stabilization and patients must have no plan to change their treatment regimen during the study.
- Urine protein/creatinine ratio (PCR) >1.5 g/g (>169.5 mg/mmol) or 24-hour total protein >1.5 g/day based on 24-hour urine collection during Screening.
- Estimated glomerular filtration rate (eGFR) =25 mL/min/1.73 m2 at Screening using the CKD Epidemiology Collaboration (CKD-EPI) Creatinine Equation (2009) (see Appendix 3 for calculation details).
- Seated blood pressure =160/100 mm Hg (mean of 3 values) at Screening.
- Body mass index =40 kg/m2 at Screening.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 263
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 23

Exclusion criteria:
Key Exclusion Criteria:
- Has FSGS secondary to another condition.
- History of type 1 diabetes mellitus, or uncontrolled type 2 diabetes mellitus (defined as glycated hemoglobin >8%).
- History of lymphoma, leukemia, or any active malignancy within the past 2 years (except for basal cell or squamous cell carcinomas of the skin or cervical carcinoma in situ that have been resected and with no evidence of metastatic disease).
- Active clinically significant hepatobiliary disease.
- Documented history of heart failure (New York Heart Association Class III/IV) or a major adverse cardiac event within 12 weeks prior to Screening.
- Serum potassium levels >5.5 mmol/L at Screening.
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) >2 × upper limit of normal at Screening.
- Treatment with immunosuppressant biological drugs, calcineurin inhibitors, cyclophosphamide, azathioprine, or mycophenolate mofetil within 26 weeks prior to Screening.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Focal segmental glomerulosclerosis
MedDRA version: 21.1 Level: PT Classification code 10067757 Term: Focal segmental glomerulosclerosis System Organ Class: 10038359 - Renal and urinary disorders
MedDRA version: 21.1 Level: LLT Classification code 10016832 Term: Focal & segmental glomerulosclerosis System Organ Class: 10038359 - Renal and urinary disorders

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Intervention(s)

Product Name: Repagermanium
Product Code: DMX-200
Pharmaceutical Form: Capsule
INN or Proposed INN: Repagermanium
Current Sponsor code: DMX-200
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 120-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): 1.Percent change in urine PCR (based on 24-hour urine collection) following treatment with DMX-200 compared with placebo
2.Slope of eGFR following treatment with DMX-200 compared with placebo

Secondary Objective: - To evaluate the safety and tolerability of treatment with DMX-200 in patients with FSGS who are receiving an ARB
- To evaluate the effect of DMX-200 on kidney function parameters including proteinuria in patients with FSGS who are receiving an ARB

Main Objective: To evaluate the efficacy of DMX-200 in terms of urine PCR and eGFR slope in patients with FSGS who are receiving an ARB

Timepoint(s) of evaluation of this end point: 1. from Baseline to Week 35
2. from Baseline to Week 104

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 1 to 4. Throughout study duration

Secondary end point(s): 1. Incidence and severity of AEs following treatment with DMX-200 compared with placebo
2. Incidence of clinically significant changes in the safety profile of patients treated with DMX-200 compared with placebo, as measured by changes from baseline in clinical laboratory evaluations (hematology, coagulation, clinical chemistry, and urinalysis), ECGs, vital signs, and physical examinations
3. Proportion of responders and non-responders following treatment with DMX-200 compared with placebo, defined as:
- Complete response: 24-hour urine PCR reduction to <0.3 g/g [<33.9 mg/mmol]
- Modified partial remission (FPRE): 24-hour urine PCR reduction =40% from Baseline and <1.5 g/g [<169.5 mg/mmol]
- No response (failure to meet any response criteria)
4. Proportion of patients on treatment with DMX 200 compared with placebo that meet a composite endpoint of worsening in kidney function, as defined by the onset of kidney failure (initiation of chronic dialysis, kidney transplantation, or a sustained eGFR of <15 mL/min/1.73 m2), a 30% decline in eGFR from Baseline, or death from kidney or cardiovascular causes

Secondary ID(s)

146154

DMX-200-301

NCT05183646

Source(s) of Monetary Support

Dimerix Bioscience Pty Ltd

Ethics review

Status: Approved
Approval date: 08/03/2022
Contact: