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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05183646
Other study ID # DMX-200-301
Secondary ID
Status Recruiting
Phase Phase 3
First received
Last updated
Start date May 30, 2022
Est. completion date June 2026

Study information

Verified date October 2023
Source Dimerix Bioscience Pty Ltd
Contact David Fuller
Phone +61 1300 813 321
Email ACTION3@dimerix.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

DMX-200 (repagermanium) is a C-C chemokine receptor type 2 (CCR2) inhibitor that, when administered concurrently with an ARB, is designed to inhibit recruitment of monocytes implicated in the inflammatory chemokine environment of chronic disease. The purpose of this pivotal randomized double-blind study is to investigate the efficacy and safety of DMX-200 120 mg twice daily (BID) compared with placebo over a treatment period of 104 weeks in adult patients with FSGS who are being treated with an ARB. Given the rarity of the disease and the similarities between adults and pediatric patients with FSGS, Dimerix will also investigate the efficacy and safety of DMX 200 in adolescents aged 12 to 17 years. The double-blind period will be followed by an open-label extension (OLE) which aims to assess the long-term efficacy and safety of DMX 200 for up to 2 additional years.


Description:

This is a pivotal Phase 3, multicenter, randomized, double-blind, placebo-controlled study of the efficacy and safety of DMX-200 in patients with FSGS. The duration of the double-blind period per patient is estimated to be maximum of 122 weeks, a Screening and Qualification period of between 6 and 14 weeks (including a 4 week period to complete the assessments required for Screening, Titration (if required, up to 4 weeks) and, 6-weeks of Stabilization, a 104-week Treatment period, and up to a 4-week off-treatment Follow-up period. The treatment duration of the OLE period per patient is estimated to be a minimum of 104 weeks (2 years) with a 4-week off-treatment Follow-up period. The total study duration (double-blind period and OLE combined) is currently estimated to be a minimum of 230 weeks.


Recruitment information / eligibility

Status Recruiting
Enrollment 286
Est. completion date June 2026
Est. primary completion date June 2024
Accepts healthy volunteers No
Gender All
Age group 12 Years to 80 Years
Eligibility DOUBLE BLIND PERIOD Inclusion Criteria: 1. Patients must be 12 to 80 years old 2. A diagnosis of primary FSGS, genetic FSGS, or FSGS of undetermined cause. Confirmed by kidney biopsy or documentation of a genetic mutation in a podocyte protein associated with FSGS 3. Must be either receiving an ARB at the maximal tolerated dose or willing to transition 4. If taking corticosteroids, the dosage must be stable for =4 weeks prior to Screening and during Stablization 5. If taking aldosterone inhibitors, mineralocorticoid receptor antagonists, direct renin inhibitors, sodium-glucose co-transporter-2 (SGLT2) inhibitors, or endothelin receptor antagonists (ERAs, including dual antagonists), the dose and regimen must be stable for =12 weeks prior to Screening and during Stablization 6. Urine 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. 7. Estimated GFR =25 mL/min/1.73 m2 at Screening 8. 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 29 (patients <18 years of age) at Screening. 9. Body weight =35 kg (all patients) AND a 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. 10. A female patient is eligible to participate if she is not pregnant or planning to become pregnant during the study, not breastfeeding, and at least one of the following conditions applies: 1. Is not of childbearing potential 2. If of childbearing potential and beginning at menarche, agrees to use a highly effective method of contraception consistently during the treatment period. 11. A male patient with a female partner of childbearing potential is eligible to participate if he agrees to use acceptable contraception 12. A patient or parent/legal guardian (as appropriate) who is capable of giving signed informed consent, and where required, the patient is capable of providing assent. Exclusion Criteria: 1. Has FSGS secondary to another condition. 2. History of type 1 diabetes mellitus, or uncontrolled type 2 diabetes mellitus (defined as glycated hemoglobin [HbA1c] >8%) 3. History of lymphoma, leukemia, or any active malignancy within the past 2 years 4. Active clinically significant hepatobiliary disease. 5. Documented history of heart failure (New York Heart Association Class III/IV) or a major adverse cardiac event within 12 weeks prior to Screening. 6. Has a physical, medical, or psychological condition, that in the opinion of the Investigator, may interfere with the evaluation the study. 7. The patient has a history of alcohol or illicit drug use disorder within 1 year prior to Screening. 8. Had a prior organ transplant or stem cell transplant, with the exception of corneal transplant. 9. Positive screening assessment for viral hepatitis B surface antigen, or anti-hepatitis C virus antibody AND positive HCV RNA, or human immunodeficiency virus 1 and 2. 10. Serum potassium levels >5.5 mmol/L at Screening. 11. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) >2 × upper limit of normal (ULN) at Screening 12. Treatment with immunosuppressant biological drugs, calcineurin inhibitors, cyclophosphamide, azathioprine, or mycophenolate mofetil within 12 weeks prior to Screening. 13. History of serious side effects or allergic response to an angiotensin II antagonist or has a known sensitivity to any components in the Investigational Product. 14. Unable to swallow oral medication. 15. Prior participation in any Dimerix-sponsored DMX-200 clinical study. 16. Participation in a clinical study with an Investigational Product within 28 days or 5 half-lives (whichever is longer) prior to Screening or plans to participate in another study during the course of this study. 17. Are study site personnel directly affiliated with this study and their immediate families. OLE PERIOD Inclusion Criteria: 1. A patient or parent/legal guardian (as appropriate) who is capable of giving signed informed consent, and where required, the patient is capable of providing assent. 2. Patients who have completed participation in the double-blind period, including the Week 104 visit, and who may derive benefit from (continued) treatment with DMX-200, and/or continued follow-up 3. The patient received blinded Investigational Product throughout the duration of the double-blind period up to the Week 104 visit 4. The patient continues to meet the contraceptive requirements Exclusion Criteria: 1. The patient has met the criteria for permanent IP discontinuation or study discontinuation 2. 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.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
DMX-200
DMX-200 (repagermanium) is a C-C chemokine receptor type 2 (CCR2) inhibitor.
Placebo
Patients will receive 120 mg capsules of Placebo twice daily

Locations

Country Name City State
Argentina ACTION3 Investigational Site 5 Buenos Aires
Argentina ACTION3 Investigational Site 1 Ciudad Autonoma Buenos Aires
Argentina ACTION3 Investigational Site 4 Ciudad Autonoma Buenos Aires
Argentina ACTION3 Investigational Site 2 Córdoba
Argentina ACTION3 Investigational Site 3 Santa Fe
Australia ACTION3 Investigational Site 1 Brisbane
Australia ACTION3 Investigational Site 2 Melbourne
Australia Action3 Investigator Site 6 Melbourne
Australia ACTION3 Investigational Site 4 Sydney
Australia ACTION3 Investigational Site 5 Sydney
Australia ACTION3 Investigational Site 7 Sydney
Australia Action3 Investigator Site 3 Sydney
Brazil ACTION3 Investigational Site 5 Botucatu
Brazil ACTION3 Investigational Site 4 Recife
Brazil ACTION3 Investigational Site 1 Rio De Janeiro
Brazil ACTION3 Investigational Site 2 São Paulo
Brazil ACTION3 Investigational Site 3 São Paulo
Denmark ACTION3 Investigational Site 2 Copenhagen
Denmark ACTION3 Investigational Site 1 Kolding
Denmark ACTION3 Investigational Site 3 Odense
France ACTION3 Investigational Site 4 Bordeaux Gironde
France ACTION3 Investigational Site 5 Créteil
France ACTION3 Investigational Site 1 Grenoble
France ACTION3 Investigational Site 2 Marseille
France ACTION3 Investigational Site 3 Montpellier
France ACTION3 Investigational Site 7 Paris
France ACTION3 Investigational Site 6 Saint-Priest-en-Jarez
Hong Kong ACTION3 Investigational Site 1 Hong Kong
Hong Kong ACTION3 Investigational Site 2 Hong Kong
Hong Kong ACTION3 Investigational Site 3 Hong Kong
New Zealand ACTION3 Investigational Site 1 Auckland
New Zealand ACTION3 Investigational Site 2 Hamilton
Spain ACTION3 Investigational Site 3 Barcelona
Spain ACTION3 Investigational Site 5 Barcelona
Spain ACTION3 Investigational Site 7 Córdoba
Spain ACTION3 Investigational Site 2 Madrid
Spain ACTION3 Investigational Site 8 Madrid
Spain ACTION3 Investigational Site 9 Madrid
Spain ACTION3 Investigational Site 1 Sevilla
Spain ACTION3 Investigational Site 4 Sevilla
Taiwan ACTION3 Investigational Site 5 Kaohsiung
Taiwan ACTION3 Investigational Site 2 New Taipei City
Taiwan ACTION3 Investigational Site 4 New Taipei City
Taiwan ACTION3 Investigational Site 6 Taichung
Taiwan ACTION3 Investigational Site 3 Taipei
Taiwan ACTION3 Investigational Site 1 Taipei CITY
United Kingdom ACTION3 Investigational Site 3 Carshalton
United Kingdom ACTION3 Investigational Site 6 Glasgow
United Kingdom ACTION3 Investigational Site 5 Leicester
United Kingdom ACTION3 Investigational Site 2 London
United Kingdom ACTION3 Investigational Site 1 Salford
United States ACTION3 Investigational Site 8 Baltimore Maryland
United States ACTION3 Investigational Site 20 Coral Gables Florida
United States ACTION3 Investigational Site 1 Coral Springs Florida
United States ACTION3 Investigational Site 14 Dallas Texas
United States ACTION3 Investigational Site 2 Dallas Texas
United States ACTION3 Investigational Site 18 Edina Minnesota
United States ACTION3 Investigational Site 15 Evanston Illinois
United States ACTION3 Investigational Site 3 Houston Texas
United States ACTION3 Investigational Site 5 Kansas City Missouri
United States ACTION3 Investigational Site 17 Lincoln Nebraska
United States ACTION3 Investigational Site 10 Northridge California
United States ACTION3 Investigational Site 13 Northridge California
United States ACTION 3 Investigator Site 19 Oak Brook Illinois
United States ACTION3 Investigational Site 4 Phoenix Arizona
United States ACTION3 Investigational Site 12 Roseburg Oregon
United States ACTION3 Investigational Site 7 Salt Lake City Utah
United States ACTION3 Investigational Site 9 Spartanburg South Carolina
United States ACTION3 Investigational Site 21 Springfield Massachusetts
United States ACTION3 Investigational Site 16 Webster Texas

Sponsors (1)

Lead Sponsor Collaborator
Dimerix Bioscience Pty Ltd

Countries where clinical trial is conducted

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

Outcome

Type Measure Description Time frame Safety issue
Primary Evaluate the efficacy of DMX-200 in terms of urine PCR in patients with FSGS who are receiving an ARB. Percent change in urine PCR (based on 24-hour urine collection) Baseline to Week 35
Primary Evaluate the efficacy of DMX-200 in terms of eGFR slope in patients with FSGS who are receiving an ARB (Analysis at week 35 and Week 104). Slope of eGFR Baseline to Week 104
Primary OLE - Assess the long-term safety and tolerability of open-label treatment with DMX-200 in patients with FSGS who are receiving an ARB. Incidence and severity of treatment-related AEs and any AESIs and SAEs following long-term treatment with DMX-200. Double-blind baseline to Week 216
Secondary Evaluate the incidence and severity of AEs with treatment of DMX-200 in patients with FSGS who are receiving an ARB. Incidence and severity of AEs and clinically significant changes following treatment with DMX-200 compared with placebo. Baseline to Week 104
Secondary To evaluate the effect of DMX-200 on kidney function parameters including proteinuria in patients with FSGS who are receiving an ARB. Proportion of responders and non-responders following treatment with DMX-200 compared with placebo.
Proportion of patients on treatment with DMX-200 compared with placebo that meet a composite endpoint of worsening in kidney function.
Baseline to Week 104
Secondary OLE - Assess the long-term efficacy of open-label treatment with DMX-200 in patients with FSGS who are receiving an ARB. Slope of eGFR and percent change in urine PCR From Week 108 (Baseline) at each visit
Secondary OLE - 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. Proportion of patients on treatment with DMX-200 that meet a composite endpoint of worsening in kidney function. Double blind baseline to Week 216
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