Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622000066785
Ethics application status
Approved
Date submitted
8/12/2021
Date registered
20/01/2022
Date last updated
22/04/2024
Date data sharing statement initially provided
20/01/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
A Pivotal Phase 3 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)
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)
Secondary ID [1] 305985 0
Nil
Universal Trial Number (UTN)
Trial acronym
ACTION3
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Focal segmental glomerulosclerosis (FSGS) 324607 0
Condition category
Condition code
Renal and Urogenital 322060 322060 0 0
Kidney disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The intervention, 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 tablet twice daily (BID) orally compared with placebo over a treatment period of 104 weeks in adult patients with FSGS who are being treated with an ARB.
During the treatment period, patients will have periodic on-site/remote visits up to Week 104 and will undergo assessments of safety, tolerability, treatment efficacy, including blood and urine-based assessments of kidney function, and pharmacokinetics. 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. The OLE period schedule involves participant visits to the site approximately every 6 months.
Intervention code [1] 322381 0
Treatment: Drugs
Comparator / control treatment
Placebo. Hypromellose capsule.
Patients will receive placebo capsules 120 mg twice daily (BID)
Control group
Placebo

Outcomes
Primary outcome [1] 329824 0
Evaluate the efficacy of DMX-200 in terms of urine PCR in patients with FSGS who are receiving an ARB (based on 24-hour urine collection)
Timepoint [1] 329824 0
Baseline to Week 35
Primary outcome [2] 329996 0
Evaluate the efficacy of DMX-200 in terms of eGFR slope in patients with FSGS who are receiving an ARB (based on collected blood samples)
Timepoint [2] 329996 0
Baseline to Week 104
Primary outcome [3] 338058 0
OLE - Assess the long-term safety and tolerability of open-label treatment with DMX-200 in patients with FSGS who are receiving an ARB. Measured via incidence and severity of treatment-related AEs and any AESIs and SAEs following long-term treatment with DMX-200. AEs include for example: abnormal lab results; exacerbation of a chronic or intermittent pre-existing condition; new conditions after IP administration; signs, symptoms, clinical sequelae resulting from a drug-drug interaction, an overdose, and/or a lack of efficacy. AEs will be assessed by clinical examination.
Timepoint [3] 338058 0
Primary outcome [4] 338059 0
OLE - Assess the long-term safety and tolerability of open-label treatment with DMX-200 in patients with FSGS who are receiving an ARB. Measured via incidence and severity of treatment-related AEs and any AESIs and SAEs following long-term treatment with DMX-200. AEs include for example: abnormal lab results; exacerbation of a chronic or intermittent pre-existing condition; new conditions after IP administration; signs, symptoms, clinical sequelae resulting from a drug-drug interaction, an overdose, and/or a lack of efficacy. AEs will be assessed by clinical examination.
Timepoint [4] 338059 0
Double-blind baseline to Week 216. The OLE period schedule involves participant visits to the site approximately every 6 months.
Secondary outcome [1] 403972 0
Evaluate the safety and tolerability of treatment with DMX-200 in patients with FSGS who are receiving an ARB. The Incidence and severity of AEs and clinically significant changes following treatment with DMX-200 compared with placebo will be monitored.
Timepoint [1] 403972 0
Baseline to Week 104
Secondary outcome [2] 403973 0
Evaluate the effect of DMX-200 on kidney function parameters as defined by the onset of kidney failure, a 30% decline in eGFR from Baseline, or death from kidney or cardiovascular causes in patients with FSGS who are receiving an ARB
Timepoint [2] 403973 0
Baseline to Week 104
Secondary outcome [3] 434332 0
OLE - Assess the long-term efficacy of open-label treatment with DMX-200 in patients with FSGS who are receiving an ARB via slope of eGFR and percent change in urine PCR.
Timepoint [3] 434332 0
Secondary outcome [4] 434333 0
OLE - Assess the long-term efficacy of open-label treatment with DMX-200 in patients with FSGS who are receiving an ARB via slope of eGFR and percent change in urine PCR.
Timepoint [4] 434333 0
From Week 108 (Baseline) at each visit until week 216. The OLE period schedule involves participant visits to the site approximately every 6 months.

Eligibility
Key inclusion criteria
DOUBLE BLIND PERIOD
1. Patients must be 12 to 80 years old (adolescents will only be recruited in Argentina, Mexico, UK, US).
2. A diagnosis of primary FSGS, genetic FSGS, or FSGS of undetermined cause.
4. If taking corticosteroids, the dosage must be stable for greater than or equal to 4 weeks prior to Screening and during Stabilization.
5. If taking aldosterone inhibitors, mineralocorticoid receptor antagonists, direct renin inhibitors, or sodium-glucose co-transporter-2 (SGLT2) inhibitors, or endothelin receptor antagonists (ERAs, including dual antagonists), the dose and regimen must be stable for greater than or equal to 12 weeks prior to Screening and during Stabilization.
7. Estimated GFR
8. Seated blood pressure less than or equal to 160/100 mm Hg (mean of 3 values) (patients greater than or equal to 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 greater than or equal to 35 kg (all patients) AND a BMI less than or equal to 40 kg/m2 (patients greater than or equal to 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:
b. Is of childbearing potential and beginning at menarche, agrees to use a highly effective method of contraception consistently during the treatment period.
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

OLE PERIOD
1. 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
2. The patient received blinded Investigational Product throughout the duration of the double-blind period up to the Week 104 visit
3. The patient continues to meet the contraceptive requirements
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
DOUBLE-BLIND PERIOD
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
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
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Central randomisation by phone/fax/computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
The study will be assessed using industry-standard statistical methods including statistical testing of the accelerated approval endpoint and final study endpoint using a repeat measures mixed model analysis with shared alpha between these endpoints

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
24/01/2022
Actual
30/05/2022
Date of last participant enrolment
Anticipated
28/06/2024
Actual
Date of last data collection
Anticipated
30/06/2026
Actual
Sample size
Target
286
Accrual to date
167
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment outside Australia
Country [1] 24378 0
Brazil
State/province [1] 24378 0
Country [2] 24379 0
Denmark
State/province [2] 24379 0
Country [3] 24380 0
France
State/province [3] 24380 0
Country [4] 24381 0
Hong Kong
State/province [4] 24381 0
Country [5] 24382 0
New Zealand
State/province [5] 24382 0
Country [6] 24384 0
Spain
State/province [6] 24384 0
Country [7] 24385 0
Taiwan, Province Of China
State/province [7] 24385 0
Country [8] 24386 0
United Kingdom
State/province [8] 24386 0
Country [9] 24387 0
United States of America
State/province [9] 24387 0
Country [10] 24388 0
Argentina
State/province [10] 24388 0

Funding & Sponsors
Funding source category [1] 310326 0
Commercial sector/Industry
Name [1] 310326 0
Dimerix Bioscience Pty Ltd
Country [1] 310326 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Dimerix Bioscience Pty Ltd
Address
425 Smith Street
Fitzroy
VIC 3065
AUSTRALIA
Country
Australia
Secondary sponsor category [1] 311606 0
None
Name [1] 311606 0
Address [1] 311606 0
Country [1] 311606 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309986 0
St Vincent’s Hospital Melbourne HREC
Ethics committee address [1] 309986 0
Ethics committee country [1] 309986 0
Australia
Date submitted for ethics approval [1] 309986 0
Approval date [1] 309986 0
16/10/2021
Ethics approval number [1] 309986 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 116086 0
A/Prof Ross Francis
Address 116086 0
Princess Alexandra Hospital
199 Ipswich Rd, Woolloongabba QLD 4102
Country 116086 0
Australia
Phone 116086 0
+61 731765080
Fax 116086 0
Email 116086 0
[email protected]
Contact person for public queries
Name 116087 0
David Fuller
Address 116087 0
Dimerix
425 Smith Street
Fitzroy
VIC 3065
AUSTRALIA
Country 116087 0
Australia
Phone 116087 0
+61 1300 813 321
Fax 116087 0
Email 116087 0
[email protected]
Contact person for scientific queries
Name 116088 0
David Fuller
Address 116088 0
Dimerix
425 Smith Street
Fitzroy
VIC 3065
AUSTRALIA
Country 116088 0
Australia
Phone 116088 0
+61 1300 813 321
Fax 116088 0
Email 116088 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.