RDX-002 for Triglycerides

Overseen By Trisha Stamp, PhD, PA-C

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Response Pharmaceuticals

Must not be taking: Diabetes drugs, Weight loss drugs

Disqualifiers: Diabetes, Cardiovascular events, Hypertension, others

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

Compensation: Varies

Number of Visits: 3

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called RDX-002 to determine if it can lower high triglyceride levels in the blood after consuming a fatty meal. Researchers aim to discover if RDX-002 is effective for individuals who have recently stopped using semaglutide or tirzepatide for weight loss. The trial will also assess whether RDX-002 affects cholesterol levels and body weight. Participants should have lost at least 10% of their weight with semaglutide or tirzepatide and recently discontinued these medications. As a Phase 2 trial, this research measures RDX-002's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant medical advancements.

Do I have to stop taking my current medications for the trial?

The trial requires you to stop taking semaglutide or tirzepatide before starting. You can continue other medications, but recent changes in lipid-lowering drugs are not allowed. The protocol does not specify a washout period for other medications.

Is there any evidence suggesting that RDX-002 is likely to be safe for humans?

Research shows that RDX-002 may help manage weight and lower triglyceride levels, which are fats in the blood, in patients. In earlier studies, RDX-002 significantly reduced triglycerides after meals and helped control weight gain in people who had stopped using other weight-loss drugs like semaglutide or tirzepatide.

Researchers have tested the treatment in over 400 people. So far, it appears well-tolerated, with patients experiencing less weight regain compared to those not taking the drug. While more research is needed, these findings suggest RDX-002 is relatively safe for use at this stage. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

RDX-002 is unique because it targets triglyceride levels in patients who have recently stopped using GLP-1 agonists, like semaglutide or tirzepatide, typically used for obesity management. Unlike standard treatments that primarily focus on ongoing medication adherence, RDX-002 is being explored for its potential to manage triglycerides and cholesterol levels in a relatively short 12-week period. Researchers are excited about RDX-002 because it could offer a new approach to controlling lipid levels, especially for those transitioning off GLP-1 agonists, potentially leading to better long-term cardiovascular health outcomes.

What evidence suggests that RDX-002 might be an effective treatment for triglycerides?

Research has shown that RDX-002, which participants in this trial may receive, may help control blood fat levels, particularly triglycerides. In earlier studies, individuals taking RDX-002 gained less weight and had lower triglyceride levels after stopping treatments like semaglutide or tirzepatide, compared to those who took a placebo. Specifically, those on RDX-002 regained 34% less weight. RDX-002 also helped lower LDL cholesterol, known as "bad" cholesterol. These findings suggest that RDX-002 could be effective in managing triglycerides and weight for people discontinuing other obesity treatments. ^{1 2 5 6 7}

Who Is on the Research Team?

Trisha Stamp, PhD, PA-C

Principal Investigator

Nucleus Network

Are You a Good Fit for This Trial?

This trial is for adults with high blood fat levels who recently stopped taking semaglutide or tirzepatide for obesity. Participants will take RDX-002 or a placebo daily for 12 weeks and visit the clinic every 4 weeks.

Inclusion Criteria

12-lead ECG at Screening with no abnormalities that compromise safety

Willing and able to provide written informed consent prior to the conduct of any study specific procedures

I have lost 10% or more of my original weight with semaglutide or tirzepatide.

Exclusion Criteria

I have diabetes.

Total fasting TGs ≥400 mg/dL at Screening

Uncontrolled hypertension (SBP >160 mmHg and DBP >100 mmHg)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive RDX-002 or placebo daily for 12 weeks to assess its effect on postprandial triglycerides, body weight, and fasting cholesterol levels

12 weeks

3 visits (in-person, every 4 weeks)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• RDX-002

Trial Overview The study tests if RDX-002 can lower triglycerides after a high-fat meal in patients no longer on GLP-1 agonists. It compares RDX-002's effects on post-meal triglycerides, body weight, and fasting cholesterol to a placebo.

How Is the Trial Designed?

Group I: Investigational drug Experimental Treatment 1 Intervention

The effect of 12 weeks of treatment with RDX-002 on postprandial TGs, fasting levels of cholesterol, and body weight among patients who have recently discontinued treatment with the GLP-1 agonists, semaglutide or tirzepatide, for obesity.

Group II: Placebo Placebo Group 1 Intervention

Matching placebo

Who Is Running the Clinical Trial?

Response Pharmaceuticals

Lead Sponsor

Trials

9

Recruited

530+

Published Research Related to This Trial

A new high-performance liquid chromatography method was developed to analyze triacylglycerols in menhaden oil, successfully identifying 137 different triacylglycerols with varying fatty acid compositions.

This study is the first to provide a detailed characterization of the triacylglycerol fraction in menhaden oil, which could have implications for understanding its nutritional and health benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mass spectrometric elucidation of triacylglycerol content of Brevoortia tyrannus (menhaden) oil using non-aqueous reversed-phase liquid chromatography under ultra high pressure conditions. Dugo, P., Beccaria, M., Fawzy, N., et al.[2016]

A new fully enzymatic assay for measuring triglycerides was developed, utilizing triacylglycerol acylhydrolase and glycerol kinase to produce glycerol-3-phosphate, which is then converted to hydrogen peroxide for detection.

The method was rigorously evaluated for accuracy and precision, ensuring that each enzymatic reaction step is complete, and additional HPTLC and HPLC techniques were created to monitor the assay's performance effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reagent for the enzymatic determination of serum total triglycerides with improved lipolytic efficiency. Nägele, U., Hägele, EO., Sauer, G., et al.[2022]

A 52-year-old woman experienced clinical inefficacy with Olevia(®) omega-3 treatment for high triglycerides, but showed improvement after switching to Esapent(®), indicating that not all omega-3 formulations are equally effective.

In vitro tests revealed significant differences in dissolution times among various omega-3 formulations, suggesting that formulation characteristics may impact their clinical efficacy and absorption.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Different Omega-3 Formulations Yield to Diverse Clinical Response: A Case-Report. Gallelli, L., Michniewicz, A., Stefanelli, R., et al.[2019]

UAB30, a novel RXR ligand, shows greater efficacy than bexarotene in inhibiting the growth of cutaneous T-cell lymphomas (CTCLs) by effectively targeting the G1 cell cycle checkpoint and increasing the stability of the cell cycle inhibitor p27kip1.

Unlike bexarotene, UAB30 does not elevate serum triglycerides or induce hypothyroidism, making it a potentially safer alternative for CTCL treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The retinoid X receptor agonist, 9-cis UAB30, inhibits cutaneous T-cell lymphoma proliferation through the SKP2-p27kip1 axis. Chou, CF., Hsieh, YH., Grubbs, CJ., et al.[2020]

In a study of 116 patients with cutaneous T-cell lymphoma (CTCL) undergoing bexarotene therapy, 82.7% experienced hypertriglyceridemia, highlighting this as a common side effect of the treatment.

Genetic screening for polymorphisms in the APOA5 and APOC3 genes may help predict triglyceride levels during treatment, allowing for better patient selection and management of bexarotene therapy based on individual risk profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of APOA5 and APOC3 Genetic Polymorphisms With Severity of Hypertriglyceridemia in Patients With Cutaneous T-Cell Lymphoma Treated With Bexarotene. Cabello, I., Alia, P., Pintó, X., et al.[2020]

A new fluorometric assay can accurately measure triglycerides in very small amounts (nanomoles) by using a series of enzymatic reactions to produce a detectable fluorescent signal.

The assay is effective over a linear range of 0.05 to 35 nanomoles of triglycerides, making it a precise tool for triglyceride quantification in research and clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A fluorometric method for the determination of triglycerides in nanomolar quantities. Mendez, AJ., Cabeza, C., Hsia, SL.[2019]

Bexarotene treatment inhibits the growth and migration of non-small cell lung cancer (NSCLC) cells while promoting their apoptosis, with a significant role played by the slc10a2 gene.

Overexpression of slc10a2 enhances the anti-cancer effects of bexarotene by activating the PPARγ signaling pathway, which leads to increased PTEN expression and decreased mTOR activity, further supporting its potential as a therapeutic target in NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bexarotene inhibits the viability of non-small cell lung cancer cells via slc10a2/PPARγ/PTEN/mTOR signaling pathway. Ai, X., Mao, F., Shen, S., et al.[2022]

SC401, a new ω-3 fatty acid formulation, demonstrated significantly higher bioavailability of EPA and DHA compared to Lovaza, achieving this with a lower dose of 1530 mg versus Lovaza's 3600 mg.

The study found that SC401 had a faster absorption rate, with a shorter time to peak concentration (Tmax) compared to Lovaza, indicating it may be more effective in delivering these essential fatty acids under low-fat feeding conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Novel ω-3 Acid Ethyl Ester Formulation Incorporating Advanced Lipid TechnologiesTM (ALT®) Improves Docosahexaenoic Acid and Eicosapentaenoic Acid Bioavailability Compared with Lovaza®. Lopez-Toledano, MA., Thorsteinsson, T., Daak, A., et al.[2019]

A new assay for measuring triacylglycerol (TG) in cells and animal tissues allows for rapid and economical quantification of TG from multiple samples, making it efficient for research purposes.

The assay uses an organic extraction method that avoids expensive reagents and harmful solvents, ensuring a cost-effective and environmentally friendly approach to TG detection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A simple and rapid method to assay triacylglycerol in cells and tissues. Schwartz, DM., Wolins, NE.[2021]

DX-9065a is a selective inhibitor of activated factor X (FXa) that shows protective effects against tumor-induced disseminated intravascular coagulation (DIC) in a rat model, indicating its potential as a therapeutic agent in cancer-related coagulopathy.

In doses of 0.03 and 0.1 mg/kg/hour, DX-9065a significantly prevented the decrease in plasma fibrinogen and platelet counts, suggesting it effectively counteracts the hypercoagulable state associated with solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A specific inhibitor of factor Xa, DX-9065a, exerts effective protection against experimental tumor induced disseminated intravascular coagulation in rats. Tanabe, K., Terada, Y., Shibutani, T., et al.[2019]

Subgroup analyses from the ROCKET AF study indicate that rivaroxaban is effective and safe for patients with moderate renal failure, heart failure, and diabetes, providing insights into its use in these specific clinical conditions.

The X-VeRT trial, which focused on patients undergoing electrical cardioversion while on new oral anticoagulants, adds valuable data to the understanding of rivaroxaban's efficacy and safety in managing atrial fibrillation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Rivaroxaban in non valvular atrial fibrillation: subgroups analysis]. Greco, C.[2016]

In a study involving 1,472 patients with deep-vein thrombosis (DVT), those treated with rivaroxaban reported significantly higher treatment satisfaction compared to those receiving enoxaparin/vitamin K antagonist therapy, as measured by the Anti-Clot Treatment Scale (ACTS).

Rivaroxaban not only reduced the perceived burden of anticoagulation treatment (mean ACTS Burdens score of 55.2 vs 52.6) but also showed a consistent improvement in patient-reported benefits over 12 months, indicating it may enhance overall patient experience in managing DVT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported treatment satisfaction with oral rivaroxaban versus standard therapy in the treatment of acute symptomatic deep-vein thrombosis. Bamber, L., Wang, MY., Prins, MH., et al.[2022]

CX3002, a new factor Xa inhibitor, was found to be safe and well-tolerated in a study involving 84 healthy participants, with no serious adverse effects reported.

The study demonstrated that CX3002 produced dose-related increases in anti-Xa activity, indicating its potential efficacy, and the pharmacokinetics were predictable, supporting further clinical investigations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, pharmacokinetics and exploratory exposure-response analysis of CX3002, a novel inhibitor of Xa, in Chinese healthy subjects. Chen, W., Ruan, Z., Lou, H., et al.[2023]

In a phase-I study involving 12 healthy subjects, the oral factor Xa inhibitor DU-176b significantly reduced thrombus formation by 28% and 21% at 1.5 and 5 hours post-dose, respectively, indicating its potential efficacy in preventing blood clots.

The study also found that DU-176b decreased thrombin generation by 28% at 1.5 hours, suggesting that its mechanism of action effectively inhibits clotting processes, which could be useful for monitoring in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antithrombotic effects of factor Xa inhibition with DU-176b: Phase-I study of an oral, direct factor Xa inhibitor using an ex-vivo flow chamber. Zafar, MU., Vorchheimer, DA., Gaztanaga, J., et al.[2019]

A new method was developed to quantitatively analyze diacylglycerol and alkylacylglycerol in cultured cells, identifying 36 different molecular species in Madin-Darby canine kidney cells.

The analysis revealed that these cells contain specific amounts of diacylglycerol and alkylacylglycerol, predominantly consisting of monoenoic and saturated species, which could enhance our understanding of their roles as intracellular mediators.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A method for the quantitative analysis of molecular species of alkylacylglycerol and diacylglycerol. Warne, TR., Robinson, M.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06640972

Study Details | NCT06640972 | Effects of RDX-002 on ... Difference in the proportion of patients treated with RDX-002 exhibiting at least a 5% increase from baseline in body weight as compared with placebo at Week ...

2. appliedclinicaltrialsonline.com appliedclinicaltrialsonline.com/view/response-investigational-small-molecule-inhibitor-promising-post-glp-1-weight-management-cardiometabolic-benefits

Response's Investigational Small Molecule Inhibitor Shows ... Less weight regain: Patients on RDX-002 experienced 34% less weight regain and smaller increases in total body fat compared with placebo.

3. biospace.com biospace.com/press-releases/response-pharmaceuticals-announces-positive-top-line-results-from-phase-2-study-of-rdx-002-in-post-glp-1-management

Response Pharmaceuticals Announces Positive Top-Line ... Individuals receiving RDX-002 gained less weight after GLP-1 discontinuation: -2.92% (-34% relative difference) versus placebo (p=0.019); ...

4. hcplive.com hcplive.com/view/rdx-002-achieves-primary-endpoint-in-trial-for-post-glp-1-weight-management

RDX-002 Achieves Primary Endpoint in Trial for Post-GLP- ... During the trial, RDX-002 demonstrated statistically significant reductions in blood fat levels after eating and reduction in weight regain ...

5. clinicaltrialsarena.com clinicaltrialsarena.com/news/response-rdx-002-weight-management/

Response begins enrolment for trial of RDX-002 for weight The trials have shown promising results, with RDX-002 lowering post-prandial triglyceride and LDL cholesterol levels, as well as contributing ...

6. firstwordpharma.com firstwordpharma.com/story/5989006

Response Pharma says RDX-002 limits weight regain post ... Additionally, patients taking RDX-002 regained an average 2.9% of their body weight, although that was still about a third less (34%) than ...

7. trial.medpath.com trial.medpath.com/news/44f8380f6e30ae8f/phase-2-trial-for-post-glp-1-weight-management-drug-rdx-002-completes-enrollment-early

Phase 2 Trial for Post-GLP-1 Weight Management Drug RDX-002 ... The drug candidate, RDX-002, previously showed promising results in managing antipsychotic-induced weight gain and has been tested in over 400 subjects across ...