Sirogen for Arteriovenous Fistula Outcomes

(ACCESS2 Trial)

Recruiting at 26 trial locations

Overseen By Rakesh Raghubanshi

Age: 65+

Sex: Any

Trial Phase: Phase 3

Sponsor: Vascular Therapies, Inc.

Disqualifiers: Prior AV access, Peritoneal dialysis, Hypersensitivity, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Intraoperative (single dose)

136 Participants Needed

Trial Summary

What is the purpose of this trial?

The primary study objective is to evaluate the benefit of the Sirolimus eluting Collagen implant (SeCI; Sirogen), a single dose prophylactic treatment delivered intraoperatively at the time of surgical creation of an arteriovenous fistula for hemodialysis vascular access.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the drug Sirolimus (Rapamune) for improving arteriovenous fistula outcomes?

Research shows that rapamycin, which is similar to sirolimus, can improve the long-term function of arteriovenous fistulas by reducing inflammation and thickening of the vessel walls. This suggests that sirolimus might also help in improving fistula outcomes. ^{1 2 3 4 5}

Is sirolimus generally safe for humans?

Sirolimus, also known as Rapamune, is generally considered safe for humans and has been used since 1999 to prevent organ rejection in kidney transplants. It has a lower risk of kidney, nerve, and certain blood-related complications compared to other similar drugs, but it can increase lipid levels (fats in the blood) in some patients. ^{3 4 5 6 7}

Research Team

Sriram Iyer, MD

Principal Investigator

Vascular Therapies, Inc.

Eligibility Criteria

This trial is for people aged 65 or older who have been on hemodialysis for less than a year and are getting a new arteriovenous fistula. It's not for those with previous AV access in the same limb, planned peritoneal dialysis soon, sirolimus or bovine collagen allergies, HIV positive individuals, prisoners, or substance abusers.

Inclusion Criteria

I have had a successful single stage radiocephalic fistula surgery.

I am 65 years old or older.

I have been on hemodialysis for 12 months or less.

Exclusion Criteria

I am scheduled to start peritoneal dialysis within the next 6 months.

I have had a previous surgery for vein access in the same arm where my fistula surgery is planned.

Prisoner, mentally incompetent, and/or current alcohol or drug abuser

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo AV fistula surgery, with the treatment arm receiving the Sirolimus eluting Collagen Implant (SeCI)

Intraoperative (single dose)

Follow-up

Participants are monitored for fistula maturation and safety for one year after surgery

12 months

Treatment Details

Interventions

• Sirolimus

Trial Overview The study tests Sirogen—a Sirolimus eluting Collagen implant—given once during surgery to create an arteriovenous fistula used in hemodialysis. The goal is to see if this treatment can prevent complications related to vascular access.

Participant Groups

Group I: Treatment Arm Experimental Treatment 1 Intervention

Subjects randomized to the treatment arm will undergo AV fistula surgery and will receive the Sirolimus eluting Collagen Implant (SeCI).

Group II: Control Arm Active Control 1 Intervention

Subjects randomized to the control arm will undergo AV fistula surgery alone and will not receive an implant.

Sirolimus is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Rapamune for:

• Prevention of organ rejection in kidney transplant patients
• Treatment of lymphangioleiomyomatosis (LAM)

Approved in European Union as Rapamune for:

• Prevention of organ rejection in kidney transplant patients
• Treatment of lymphangioleiomyomatosis (LAM)

Approved in Canada as Rapamune for:

• Prevention of organ rejection in kidney transplant patients
• Treatment of lymphangioleiomyomatosis (LAM)

Approved in Japan as Rapamune for:

• Prevention of organ rejection in kidney transplant patients

Who Is Running the Clinical Trial?

Vascular Therapies, Inc.

Lead Sponsor

Trials

2

Recruited

410+

Findings from Research

Sirolimus (rapamycin) is an effective immunosuppressant approved for preventing graft rejection in kidney transplants, with a lower risk of complications compared to other immunosuppressants.

Recent findings suggest that sirolimus may also have potential in treating skin disorders and extending lifespan, making it a promising candidate for addressing age-related diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sirolimus: a therapeutic advance for dermatologic disease. Peters, T., Traboulsi, D., Tibbles, LA., et al.[2014]

Sirolimus (RAPA) treatment in renal transplant patients significantly increases plasma triglyceride levels and VLDL-apoB100 concentrations due to a reduced catabolic rate of these lipoproteins, rather than increased production.

The study found that RAPA-induced hyperlipidemia is linked to decreased clearance of apoB100-containing lipoproteins, highlighting a metabolic pathway that could be targeted to manage lipid levels in patients undergoing immunosuppression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of sirolimus on the metabolism of apoB100- containing lipoproteins in renal transplant patients. Hoogeveen, RC., Ballantyne, CM., Pownall, HJ., et al.[2019]

In a study involving 209 kidney transplant recipients in Korea, Rapamune (Sirolimus) demonstrated an acceptable safety profile, with 54.07% of subjects reporting adverse events, most of which were mild and resolved by the end of the study.

The efficacy of Rapamune was notable, with a low incidence of biopsy-proven acute rejection at 2.87% and a high graft survival rate of 99.51%, indicating its effectiveness in preventing kidney allograft rejection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of Rapamune® (Sirolimus) in kidney transplant recipients: results of a prospective post-marketing surveillance study in Korea. Jeon, HJ., Lee, HE., Yang, J.[2019]

The Selution Sustained Limus Release (SLR) sirolimus-coated balloon shows promise for improving the patency of failing arterio-venous fistulas in hemodialysis patients, with a focus on safety and efficacy in a pilot study involving 40 patients.

Pre-clinical studies indicate that the sirolimus coating has prolonged retention in arterial tissue and demonstrates safety with no significant adverse effects, suggesting it may be a viable alternative to existing treatments for conduit stenosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intervention with selution SLR™ Agent Balloon for Endovascular Latent Limus therapy for failing AV Fistulas (ISABELLA) Trial: Protocol for a pilot clinical study and pre-clinical results. Tang, TY., Chong, TT., Yap, CJQ., et al.[2023]

References

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

Inhibition of the Akt1-mTORC1 Axis Alters Venous Remodeling to Improve Arteriovenous Fistula Patency. [2021]

2. China pubmed.ncbi.nlm.nih.gov

[Local applied slow-releasing rapamycin inhibits neointima hyperplasia in vein graft]. [2013]

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

Treatment of childhood kaposiform hemangioendothelioma with sirolimus. [2022]

4. Canada pubmed.ncbi.nlm.nih.gov

Sirolimus: a therapeutic advance for dermatologic disease. [2014]

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

Effect of sirolimus on the metabolism of apoB100- containing lipoproteins in renal transplant patients. [2019]

6. England pubmed.ncbi.nlm.nih.gov

Safety and efficacy of Rapamune® (Sirolimus) in kidney transplant recipients: results of a prospective post-marketing surveillance study in Korea. [2019]

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

Intervention with selution SLR™ Agent Balloon for Endovascular Latent Limus therapy for failing AV Fistulas (ISABELLA) Trial: Protocol for a pilot clinical study and pre-clinical results. [2023]