DMX-200 for Focal Segmental Glomerulosclerosis
(ACTION3 Trial)
Recruiting in Palo Alto (17 mi)
+85 other locations
Age: Any Age
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: Dimerix Bioscience Pty Ltd
Must be taking: ARBs
Must not be taking: Immunosuppressants, Calcineurin inhibitors
Disqualifiers: Diabetes, Malignancy, Heart failure, others
Pivotal Trial (Near Approval)
Prior Safety Data
Trial Summary
What is the purpose of this trial?
This trial is testing DMX-200, a drug designed to reduce inflammation by blocking signals that attract immune cells. It targets adult patients with a specific kidney disease called FSGS. The drug works by preventing immune cells from gathering in the kidneys, which may help slow down the disease.
Will I have to stop taking my current medications?
The trial does not specify that you must stop taking your current medications. However, if you are taking corticosteroids, aldosterone inhibitors, or certain other medications, your dosage must be stable for a specific period before joining the trial.
What data supports the effectiveness of the drug DMX-200 for Focal Segmental Glomerulosclerosis?
Is DMX-200 (Repagermanium/Irbesartan) safe for human use?
Irbesartan, a component of DMX-200, has been shown to be safe in humans, with studies indicating it is well tolerated and has a safety profile similar to a placebo in treating high blood pressure. No significant adverse effects were observed, and it did not cause unexpected changes in lab tests.678910
How is the drug DMX-200 different from other treatments for Focal Segmental Glomerulosclerosis?
DMX-200 is unique because it combines irbesartan, an angiotensin receptor blocker, with propagermanium, which may offer additional benefits in reducing proteinuria and improving kidney function. This combination could provide a novel approach compared to standard treatments that typically involve angiotensin receptor blockers alone.111121314
Research Team
DF
David Fuller
Principal Investigator
Dimerix Bioscience Pty Ltd
Eligibility Criteria
Adults with FSGS (a kidney disease) confirmed by biopsy or genetic testing, who are not breastfeeding, have a BMI ≤40 kg/m2, and are on stable doses of certain medications can join. They must be taking or agree to take an ARB at the highest dose they can handle. Those with serious side effects to angiotensin II antagonists, recent drug abuse, organ transplants (except corneal), heart failure, or conditions that could affect study results cannot participate.Inclusion Criteria
My medication doses for certain heart or diabetes drugs have been stable for the last 12 weeks.
Body mass index ≤40 kg/m2 at Screening
I am taking the highest dose of ARB I can tolerate or am willing to start.
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Exclusion Criteria
You have a health condition or mental health issue that could affect your ability to participate in the study.
You have experienced severe side effects or allergic reactions in the past to an angiotensin II antagonist or any of the investigational product's components.
You have had problems with alcohol or illegal drugs within the past year.
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Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
6-14 weeks
Includes Screening, Titration, and Stabilization visits
Treatment
Participants receive DMX-200 or placebo for 104 weeks
104 weeks
Regular visits for monitoring and assessment
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Off-treatment follow-up visits
Open-label extension
Participants receive DMX-200 in an open-label setting for long-term assessment
104 weeks
Regular visits for long-term monitoring
Treatment Details
Interventions
- DMX-200 (CCR2 Inhibitor)
Trial OverviewThe trial is testing DMX-200's effectiveness and safety in treating FSGS when taken alongside an ARB medication. Participants will either receive DMX-200 or a placebo twice daily for 104 weeks in this randomized double-blind study where neither the participants nor the researchers know who gets which treatment until after the study ends.
Participant Groups
2Treatment groups
Experimental Treatment
Placebo Group
Group I: DMX-200 (repagermanium)Experimental Treatment1 Intervention
Patients will receive 120 mg immediate release capsules of DMX-200 twice daily during the treatment period (104 weeks)
OLE: Patients will receive 120 mg immediate release capsules of DMX-200 twice daily during the OLE period (108-212 weeks)
Group II: PlaceboPlacebo Group1 Intervention
Patients will receive 120 mg immediate release capsules of Placebo twice daily
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
ACTION3 Investigational Site 21Springfield, MA
ACTION3 Investigational Site 8Baltimore, MD
ACTION3 Investigational Site 11Tampa, FL
ACTION3 Investigational Site 18Edina, MN
More Trial Locations
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Who Is Running the Clinical Trial?
Dimerix Bioscience Pty Ltd
Lead Sponsor
Trials
3
Patients Recruited
340+
Findings from Research
High-dose telmisartan significantly improved kidney function and reduced proteinuria in rats with mesangioproliferative glomerulonephritis, showing benefits beyond just lowering blood pressure.
The treatment also down-regulated specific receptors and chemokines associated with kidney damage, suggesting that telmisartan may protect the kidneys through multiple mechanisms, including reducing inflammation and fibrosis.
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Late angiotensin II receptor blockade in progressive rat mesangioproliferative glomerulonephritis: new insights into mechanisms.Villa, L., Boor, P., Konieczny, A., et al.[2018]
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Cost-effectiveness of irbesartan 300 mg given early versus late in patients with hypertension and a history of type 2 diabetes and renal disease: a Canadian perspective.Coyle, D., Rodby, R., Soroka, S., et al.[2018]
In a study involving rats with chronic interstitial renal disease, both enalapril (an ACE inhibitor) and irbesartan (an angiotensin receptor blocker) effectively reduced proteinuria, but enalapril was more effective in preserving renal function as indicated by creatinine clearance.
The results suggest that while both medications can protect against kidney damage, the mechanisms may differ, with enalapril providing additional benefits possibly through effects on angiotensin II and bradykinin pathways.
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Differential effects of enalapril and irbesartan in experimental papillary necrosis.Garber, SL., Mirochnik, Y., Arruda, JA., et al.[2018]
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Therapeutic Efficacy of Piperazine Ferulate Combined With Irbesartan in Diabetic Nephropathy: A Systematic Review and Meta-analysis.Li, D., Li, B., Peng, LX., et al.[2021]
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
[The efficacy and safety of high-dose irbesartan in treatment of clinical proteinuria in patients with chronic kidney disease].Li, X., Chen, XD., Li, ZX.[2018]
In a study involving 479 patients with primary chronic glomerulonephritis, the combination of Rehmannia glutinosa acteosides and irbesartan led to a significant 36.42% reduction in 24-hour proteinuria after 8 weeks, compared to a 27.97% reduction with irbesartan alone.
The safety profile was similar for both treatment groups, with low rates of adverse drug reactions (0.4% in the treatment group vs. 1.2% in the control group), indicating that the combination therapy is both effective and safe.
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Treatment of primary chronic glomerulonephritis with Rehmannia glutinosa acteosides in combination with the angiotensin receptor blocker irbesartan: a randomized controlled trial.Qiu, H., Fu, P., Fan, W., et al.[2018]
In a study of 118 high-risk hypertensive patients, switching to irbesartan for 12 weeks led to significant improvements in lipid profiles and reductions in inflammatory markers, indicating its potential benefits beyond blood pressure control.
Irbesartan was associated with decreased oxidative stress, as shown by lower levels of reactive oxygen metabolites, and improved metabolic parameters, suggesting it may be a valuable treatment option for patients with hypertension and metabolic syndrome.
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Irbesartan, an angiotensin receptor blocker, exhibits metabolic, anti-inflammatory and antioxidative effects in patients with high-risk hypertension.Taguchi, I., Toyoda, S., Takano, K., et al.[2022]
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
High doses of irbesartan offer long-term kidney protection in cases of established diabetic nephropathy.Ros-Ruiz, S., Aranda-Lara, P., Fernández, JC., et al.[2018]
Irbesartan (Irbe) specifically activates renal peroxisome proliferator-activated receptor α (PPARα) in healthy mice, which is not seen with losartan, indicating a unique mechanism of action for Irbe in protecting the kidneys.
In a model of protein-overload nephropathy, Irbe treatment led to significant reductions in kidney damage markers, oxidative stress, and inflammation, demonstrating its renoprotective effects through PPARα activation.
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Peroxisome proliferator-activated receptor α-dependent renoprotection of murine kidney by irbesartan.Harada, M., Kamijo, Y., Nakajima, T., et al.[2020]
Irbesartan, an angiotensin II receptor blocker, was found to be well tolerated in a study involving 1,965 patients over 4 to 12 weeks, with no evidence of dose-related adverse effects.
Compared to placebo, irbesartan showed a lower incidence of adverse events and serious adverse events, indicating a safety profile similar to that of a placebo, with no significant changes in laboratory results or rebound hypertension upon withdrawal.
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Safety of irbesartan in the treatment of mild to moderate systemic hypertension.Simon, TA., Gelarden, RT., Freitag, SA., et al.[2019]
In a study using a 5/6 nephrectomized rat model, telmisartan significantly improved renal function and reduced kidney injury markers, indicating its potential efficacy in treating chronic kidney disease (CKD).
Telmisartan's protective effects are linked to its ability to enhance nitric oxide (NO) generation in the kidneys through PPARγ signaling, suggesting a specific mechanism of action that could be targeted in CKD therapies.
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Telmisartan protects 5/6 Nx rats against renal injury by enhancing nNOS-derived NO generation via regulation of PPARγ signaling.Zou, R., He, Y., Li, YQ., et al.[2021]
In three cases of focal glomerular sclerosis (FGS), treatment with angiotensin type 1 receptor blockers (ARBs) like losartan and valsartan led to significant improvements in proteinuria and renal function.
Combining ARB treatment with steroids and immunosuppressants resulted in even greater reductions in proteinuria and glomerular injury, suggesting a potentially effective therapeutic strategy for FGS patients.
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
[Angiotensin type 1 receptor blocker reduced proteinuria in patients of focal glomerular sclerosis].Chihara, Y., Ono, H., Ono, Y., et al.[2017]
In a case of recurrent focal segmental glomerulosclerosis (FSGS) after kidney transplantation, complete remission was achieved using angiotensin receptor blocker therapy, suggesting a potential alternative treatment approach.
While plasmapheresis is typically the standard treatment for recurrent FSGS, this case highlights the variability in treatment outcomes and the possibility of effective management with different medications.
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Remission of post-transplant focal segmental glomerulosclerosis with angiotensin receptor blockers.Bansal, SB., Sethi, SK., Jha, P., et al.[2020]
Telmisartan, an angiotensin II type 1 receptor blocker, effectively up-regulates PPARgamma levels and inhibits TGF-beta-induced glomerulosclerosis in rat mesangial cells, suggesting its potential as a treatment for kidney diseases.
The study demonstrated that telmisartan reduces harmful effects like collagen IV secretion and alpha-smooth muscle actin expression in mesangial cells, indicating its mechanism of action may involve PPARgamma activation, which could be beneficial for conditions like diabetic nephropathy.
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Telmisartan but not valsartan inhibits TGF-beta-mediated accumulation of extracellular matrix via activation of PPARgamma.Yao, Y., Zou, R., Liu, X., et al.[2018]
References
Late angiotensin II receptor blockade in progressive rat mesangioproliferative glomerulonephritis: new insights into mechanisms. [2018]
Cost-effectiveness of irbesartan 300 mg given early versus late in patients with hypertension and a history of type 2 diabetes and renal disease: a Canadian perspective. [2018]
Differential effects of enalapril and irbesartan in experimental papillary necrosis. [2018]
Therapeutic Efficacy of Piperazine Ferulate Combined With Irbesartan in Diabetic Nephropathy: A Systematic Review and Meta-analysis. [2021]
[The efficacy and safety of high-dose irbesartan in treatment of clinical proteinuria in patients with chronic kidney disease]. [2018]
Treatment of primary chronic glomerulonephritis with Rehmannia glutinosa acteosides in combination with the angiotensin receptor blocker irbesartan: a randomized controlled trial. [2018]
Irbesartan, an angiotensin receptor blocker, exhibits metabolic, anti-inflammatory and antioxidative effects in patients with high-risk hypertension. [2022]
High doses of irbesartan offer long-term kidney protection in cases of established diabetic nephropathy. [2018]
Peroxisome proliferator-activated receptor α-dependent renoprotection of murine kidney by irbesartan. [2020]
Safety of irbesartan in the treatment of mild to moderate systemic hypertension. [2019]
Telmisartan protects 5/6 Nx rats against renal injury by enhancing nNOS-derived NO generation via regulation of PPARγ signaling. [2021]
[Angiotensin type 1 receptor blocker reduced proteinuria in patients of focal glomerular sclerosis]. [2017]
Remission of post-transplant focal segmental glomerulosclerosis with angiotensin receptor blockers. [2020]
Telmisartan but not valsartan inhibits TGF-beta-mediated accumulation of extracellular matrix via activation of PPARgamma. [2018]