DMX-200 for Focal Segmental Glomerulosclerosis

(ACTION3 Trial)

Recruiting at 85 trial locations

Overseen By David Fuller

Age: Any Age

Sex: Any

Travel: May Be Covered

Trial Phase: Phase 3

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) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 104 weeks

286 Participants Needed

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?

Research shows that irbesartan, a component of DMX-200, is effective in reducing proteinuria (excess protein in urine) in patients with chronic kidney disease and diabetic nephropathy, which suggests it may help in managing kidney-related conditions like Focal Segmental Glomerulosclerosis. ^{1 2 3 4 5}

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. ^{6 7 8 9 10}

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. ^{1 11 12 13 14}

Research Team

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.

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.

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

Trial Overview The 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

Group I: DMX-200 (repagermanium) Experimental Treatment 1 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: Placebo Placebo Group 1 Intervention

Patients will receive 120 mg immediate release capsules of Placebo twice daily

Who Is Running the Clinical Trial?

Dimerix Bioscience Pty Ltd

Lead Sponsor

Trials

3

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]

The early addition of irbesartan to conventional treatment for hypertension in patients with type 2 diabetes and early renal disease is both more effective and cost-saving compared to delaying treatment or using conventional antihypertensives alone.

Using a Markov model over a 25-year period, the study found that early treatment with irbesartan resulted in significant savings and improved health outcomes, delaying the progression to end-stage renal disease (ESRD) and saving the Canadian health system money.

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]

A meta-analysis of 12 trials involving 1300 patients showed that combining piperazine ferulate (PF) with irbesartan significantly improved treatment outcomes for diabetic nephropathy, with a total effective rate nearly five times higher than irbesartan alone.

The combination therapy also led to significant reductions in key health markers, including fasting plasma glucose, serum creatinine, and urinary protein levels, indicating enhanced renal function and better blood sugar control.

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]

In a study of 96 chronic kidney disease patients, high-dose irbesartan (300-600 mg/d) significantly reduced proteinuria by 63.4%, demonstrating its efficacy in treating mild to moderate proteinuria over 48 weeks.

The treatment was found to be safe, with no significant increase in serum creatinine levels, and while serum potassium levels did rise, they remained within normal limits, indicating good tolerance among patients.

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]

In a 3-year study involving 40 diabetic patients, ultra-high doses of irbesartan (600 mg daily) significantly reduced proteinuria by 59.2% and improved blood pressure, indicating its efficacy in managing overt diabetic nephropathy.

The treatment was found to be safe, with no patients experiencing side effects leading to withdrawal, and serum potassium levels remaining stable throughout the study.

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

1. England pubmed.ncbi.nlm.nih.gov

Late angiotensin II receptor blockade in progressive rat mesangioproliferative glomerulonephritis: new insights into mechanisms. [2018]

2. United States 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. [2018]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Differential effects of enalapril and irbesartan in experimental papillary necrosis. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

Therapeutic Efficacy of Piperazine Ferulate Combined With Irbesartan in Diabetic Nephropathy: A Systematic Review and Meta-analysis. [2021]

5. China pubmed.ncbi.nlm.nih.gov

[The efficacy and safety of high-dose irbesartan in treatment of clinical proteinuria in patients with chronic kidney disease]. [2018]

6. England 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. [2018]

7. England pubmed.ncbi.nlm.nih.gov

Irbesartan, an angiotensin receptor blocker, exhibits metabolic, anti-inflammatory and antioxidative effects in patients with high-risk hypertension. [2022]

8. Spain pubmed.ncbi.nlm.nih.gov

High doses of irbesartan offer long-term kidney protection in cases of established diabetic nephropathy. [2018]

9. England pubmed.ncbi.nlm.nih.gov

Peroxisome proliferator-activated receptor α-dependent renoprotection of murine kidney by irbesartan. [2020]

10. United States pubmed.ncbi.nlm.nih.gov

Safety of irbesartan in the treatment of mild to moderate systemic hypertension. [2019]

11. United States 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. [2021]

12. Japan pubmed.ncbi.nlm.nih.gov

[Angiotensin type 1 receptor blocker reduced proteinuria in patients of focal glomerular sclerosis]. [2017]

13. India pubmed.ncbi.nlm.nih.gov

Remission of post-transplant focal segmental glomerulosclerosis with angiotensin receptor blockers. [2020]

14. China pubmed.ncbi.nlm.nih.gov

Telmisartan but not valsartan inhibits TGF-beta-mediated accumulation of extracellular matrix via activation of PPARgamma. [2018]