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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Dimerix Bioscience Pty Limited

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

25 Mar 2022 → ongoing

Decision date (initial)

2025-03-24

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Dimerix Bioscience Pty Ltd · Dimerix Bioscience Pty Ltd

External identifiers

EU CT number

2023-504597-37-00

EudraCT number

2021-004174-64

ClinicalTrials.gov

NCT05183646

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacokinetic, Safety

To evaluate the efficacy of DMX-200 in terms of urine PCR and eGFR slope in adult patients with FSGS who are receiving an ARB.
OLE: To assess the long-term safety and tolerability of open-label treatment with DMX-200 in patients with FSGS who are receiving an ARB.

Secondary objectives 4

1. To evaluate the safety and tolerability of treatment with DMX-200 in adult and adolescent patients with FSGS who are receiving an ARB
2. To evaluate the effect of DMX-200 on kidney function parameters including proteinuria in adult patients with FSGS who are receiving an ARB
3. OLE: To assess the long-term efficacy of open-label treatment with DMX-200 in patients with FSGS who are receiving an ARB
4. OLE: To evaluate the long-term effect of open-label treatment with DMX-200 on kidney function parameters in patients with FSGS who are receiving an ARB

Conditions and MedDRA coding

Focal segmental glomerulosclerosis

Study design 4 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-003154-PIP01-21

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Primary FSGS, genetic FSGS, or FSGS of undetermined cause (FSGS-UC) with timing of initial diagnosis within 7 years prior to screening. NOTE: i) Primary FSGS and FSGS-UC, the initial diagnosis must be biopsy-proven within 7 years prior to Screening. The kidney biopsy could have been obtained at any time within the previous 7 years and should be based on light microscopy with supportive findings on either electron microscopy or immunofluorescence. ii) For Genetic FSGS, no biopsy is required where there is a documented genetic mutation of a podocyte protein associated with FSGS. The genetic testing should have been obtained within 7 years prior to screening. iii) All patients should demonstrate a clinical history and disease course consistent with FSGS.
2. 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 (including transition from an ACE inhibitor) prior to stabilization
3. If taking corticosteroids, the dosage must be ≤ 10mg / day prednisone (or equivalent) and stable for ≥4 weeks prior to and during both Screening and Stabilization, and there must be no plan to change their corticosteroid treatment regimen during study. Use of inhaled corticosteroids for respiratory diseases is allowed.
4. If taking aldosterone inhibitors, mineralocorticoid receptor antagonists, direct renin inhibitors, sodium-glucose co-transporter-2 inhibitors, or endothelin receptor antagonists (including dual antagonists), the dose and regimen must be stable for ≥12 weeks prior to Screening and maintained during Stabilization and patients must have no plan to change their treatment regimen during the study
5. 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 and Qualification
6. Estimated glomerular filtration rate (eGFR) at screening: For adults (≥ 18 years): eGFR ≥25 and ≤120 mL/min/1.73 m2 using the CKD Epidemiology Collaboration (CKD-EPI) Creatinine Equation (2009) For adolescent patients (<18): eGFR ≥25mL/min/1.73 m2using the Modified Schwartz formula
7. Seated blood pressure ≤160/100 mm Hg (mean of 3 values) (patients ≥18 years of age) or between the 5th and 95th percentile for age, sex, and height (patients <18 years of age) at Screening
8. Body weight ≥35 kg (all patients) AND a body mass index (BMI) ≤40 kg/m2 (patients ≥18 years of age) or between the 5th and 98th percentile for age and sex (patients <18 years of age) at Screening. For patients with moderate or severe edema, BMI will be calculated based on remission or premorbid weight measured within 3 months prior to Screening, if available. If not available, BMI will be calculated based on the estimated dry weight, based on the Investigator’s clinical judgment
9. OLE: Patients who have completed participation in the double-blind period, including the Week 104 visit (including non-responders, those with disease worsening, and those receiving additional FSGS-directed therapies)
10. OLE: The patient received blinded IP throughout the duration of the double-blind period up to the Week 104 (EOT – DB) visit (ie, did not prematurely and permanently discontinue the IP).

Exclusion criteria 11

1. Has FSGS secondary to another condition
2. OLE: Any safety concerns identified during the double-blind period which, in the Investigator’s opinion, may interfere with the patient’s continued participation during the OLE period.
3. History of type 1 diabetes mellitus, or uncontrolled type 2 diabetes mellitus (defined as glycated hemoglobin >8%)
4. 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)
5. Active clinically significant hepatobiliary disease
6. Documented history of heart failure (New York Heart Association Class III/IV) or a major adverse cardiac event within 12 weeks prior to Screening
7. Serum potassium levels >5.5 mmol/L at Screening
8. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) >2 × upper limit of normal at Screening
9. Received any of the following with the specified timeframe prior to Screening - Treatment with non-steroid immunosuppressant agents including biological drugs (eg. rituximab), calcineurin inhibitors, cyclophosphamide, azathioprine, or mycophenolate mofetil within 12 weeks prior to Screening
10. OLE: The patient has met the criteria for premature and permanent IP discontinuation as defined in Section 7.1 or study discontinuation as defined in Section 7.2 at Week 104, or prior to the first open-label dose of DMX 200 at Week 108.
11. Patients with nephrotic syndrome (>3.5 g/day proteinuria and serum albumin <30 g/L) who have not previously been treated with standard of care FSGS- directed therapies (including steroids).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

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
3. OLE: Incidence and severity of treatment-related AEs and any AESIs and SAEs following long-term treatment with DMX-200

Secondary endpoints 8

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 patients achieving proteinuria response following treatment with DMX-200 compared with placebo at any time during the double-blind period, 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 40% decline in eGFR from Baseline, or death from kidney or cardiovascular causes
5. OLE: Slope of eGFR from Week 108 (Baseline)
6. OLE: Percent change in urine PCR (based on first morning void urine samples) from Week 108 (Baseline) at each visit
7. OLE: Proportion of patients on treatment with DMX 200 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 40% decline in eGFR from Baseline, or death from kidney or cardiovascular causes
8. OLE: Change in eGFR from Week 108 (Baseline) at each visit

Investigational products

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

Test 1

Placebo 1

Auxiliary 7

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Dimerix Bioscience Pty Limited

Sponsor organisation

Dimerix Bioscience Pty Limited

Address

425 Smith Street

City

Fitzroy

Postcode

3065

Country

Australia

Scientific contact point

Organisation

Dimerix Bioscience Pty Limited

Contact name

Clinical Trials Information

Public contact point

Organisation

Dimerix Bioscience Pty Limited

Contact name

Clinical Trials Information

Third parties 5

Locations

7 EU/EEA countries · 48 investigational sites

By country

Investigational sites

Country notifications

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

Results and documents

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

Documents 172 files

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

Application history

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