DMX-200 for Focal Segmental Glomerulosclerosis

(ACTION3 Trial)

Recruiting at 488 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, DMX-200 (also known as Repagermanium or Irbesartan/propagermanium), for focal segmental glomerulosclerosis (FSGS), a kidney condition that causes scarring and damage. The trial aims to determine if DMX-200, when combined with a common medication called an ARB, can safely and effectively reduce this damage. Individuals diagnosed with FSGS and currently taking an ARB might be suitable candidates for this trial. Participants will receive either the experimental treatment or a placebo (inactive pill) for about two years, with an option to continue treatment for an additional two years. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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.

Is there any evidence suggesting that DMX-200 is likely to be safe for humans?

Research has shown that DMX-200, also known as repagermanium, is generally safe and well-tolerated by patients. In earlier studies, patients who took DMX-200 with an ARB (a type of blood pressure medicine) experienced no major safety issues. The common side effects were mild and similar to those in patients taking a placebo (a pill with no active ingredients). This suggests that DMX-200 is unlikely to cause serious problems when used to treat focal segmental glomerulosclerosis (FSGS), a kidney disease. So far, all safety checks in studies have been passed, making DMX-200 a promising option for those considering participation in clinical trials. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for FSGS?

Most treatments for focal segmental glomerulosclerosis (FSGS) aim to manage symptoms and slow kidney damage, often using medications like corticosteroids or immunosuppressants. However, DMX-200 is unique because it utilizes repagermanium, which targets the chemokine receptor CCR2. This novel mechanism is designed to reduce inflammation and fibrosis in the kidneys, offering a potentially more effective approach to treating FSGS at its core. Researchers are excited about DMX-200 because it could provide a new pathway to alleviate the condition's progression, promising better outcomes for patients.

What evidence suggests that DMX-200 might be an effective treatment for FSGS?

Research has shown that DMX-200, which participants in this trial may receive, might help treat Focal Segmental Glomerulosclerosis (FSGS), a kidney condition. In earlier studies, DMX-200 combined with a type of blood pressure medicine called an ARB appeared to reduce the inflammation linked to FSGS. This treatment works by blocking a specific part of the body that aids disease progression. Reports indicate that DMX-200 has been safe and well-tolerated by patients. These findings offer hope that DMX-200 may effectively manage FSGS symptoms. ^{1 2 4 5 6}

Who Is on the Research Team?

David Fuller

Principal Investigator

Dimerix Bioscience Pty Ltd

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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]

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]

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]

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]

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 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 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]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S2468024925006199

DMX-200 in Patients with Primary Focal Segmental ... DMX-200 in Patients with Primary Focal Segmental Glomerulosclerosis: Results of the Phase 2 ACTION2 Trial. Author links open overlay panel

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05183646

A Study of the Efficacy and Safety of DMX-200 in Patients ... 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 ...

3. academic.oup.com academic.oup.com/ndt/article/doi/10.1093/ndt/gfaf116.0253/8294851

#296 A mid-study update on the ACTION3 pivotal Phase 3 trial ... DMX-200 (repagermanium) has shown encouraging signs of safety and efficacy in combination with an ARB for the treatment of FSGS. The ...

4. kireports.org kireports.org/article/S2468-0249(24)01247-6/fulltext

WCN24-1132 ACTION3 – Phase 3 study of DMX-200 for ... DMX-200 (repagermanium) has shown encouraging signs of safety and efficacy in combination with an ARB for the treatment of FSGS.

5. dimerix.com dimerix.com/wp-content/uploads/2024/11/ACTION3-poster-ASN2024_Final.pdf

ACTION3 pivotal Phase 3 study assessing the CCR2 ... DMX-200 has a half-life of 3.6 hours in renal impairment and shows large fluctuations in plasma concentrations following BID administration. Using data from ...

6. dimerix.com dimerix.com/products/dmx-200-for-focal-segmental-glomerulosclerosis/

DMX-200 for Focal Segmental Glomerulosclerosis (FSGS) All trial endpoints were achieved, and DMX-200 was determined to be safe and tolerable. The common clinical marker for progression of kidney disease is an ...