eRapa for Adenomatous Polyposis

Not currently recruiting at 9 trial locations

Overseen By Nancy Gady

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Rapamycin Holdings Inc.

Must not be taking: NSAIDs, Immunosuppressants

Disqualifiers: Recent colectomy, High grade dysplasia, Cancer, Pregnancy, Immunosuppressed, others

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

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 8

Duration: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, Encapsulated Rapamycin (eRapa), to determine if it can reduce the number of polyps in individuals with Familial Adenomatous Polyposis (FAP), a condition causing numerous polyps in the large intestine. Participants will receive varying doses and schedules of eRapa over a year to identify the most effective approach. The trial seeks individuals with FAP who have at least 10 polyps and can undergo regular endoscopy procedures and take oral medication. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group.

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

The trial requires a 4-week washout period for any FAP-directed drug therapy, including NSAIDs, except for aspirin. You can continue taking up to 81 mg of aspirin a day or 650 mg per week. Other medications that significantly alter rapamycin metabolism are not allowed.

Will I have to stop taking my current medications?

The trial requires participants to stop taking non-steroidal anti-inflammatory drugs (NSAIDs) other than aspirin during the study. If you are on other FAP-directed drug therapy, you must complete a 4-week period without these medications before enrolling.

Is there any evidence suggesting that Encapsulated Rapamycin (eRapa) is likely to be safe for humans?

Research has shown that encapsulated rapamycin (eRapa) is generally safe and well-tolerated in people. In a study involving patients with Familial Adenomatous Polyposis (FAP), eRapa proved safe and resulted in a 17% average reduction in the total number of polyps over 12 months. This indicates that the treatment can reduce polyps without causing significant harm. Previous studies have primarily focused on safety and patient tolerance, yielding positive results. ^{1 2 3 4 5}

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

Unlike the standard treatments for adenomatous polyposis, which often involve surgical interventions or NSAIDs like sulindac, Encapsulated Rapamycin (eRapa) introduces a novel approach by using a unique encapsulation method that potentially enhances drug stability and absorption. Researchers are excited about eRapa because it targets the mTOR pathway, a crucial player in cell growth and proliferation, which is different from the way current NSAID treatments work. This new mechanism of action offers hope for a more effective and potentially less invasive treatment option for patients with adenomatous polyposis.

What evidence suggests that Encapsulated Rapamycin might be an effective treatment for adenomatous polyposis?

Research has shown that a treatment called encapsulated rapamycin (eRapa) may benefit people with Familial Adenomatous Polyposis (FAP). In earlier studies with mice that had FAP, eRapa helped them live a normal lifespan without harming their immune system, suggesting it might lower cancer risk in humans. The U.S. FDA has given eRapa a Fast Track designation, indicating its potential to address a significant medical need. While studies with humans are ongoing, these early results suggest eRapa could help reduce polyp growth in people with FAP. Participants in this trial will receive eRapa in different dosing schedules to evaluate its effectiveness and safety. ^{1 2 3 4 5}

Who Is on the Research Team?

George E Peoples, MD

Principal Investigator

Sponsor CMO

Are You a Good Fit for This Trial?

This trial is for adults over 18 with Familial Adenomatous Polyposis (FAP), who have at least 10 polyps and can undergo endoscopy. They must be able to take oral medication, follow the study plan, and not breastfeed or donate eggs. Women should use effective birth control during the study and for 12 weeks after.

Inclusion Criteria

A woman must agree not to breast feed or donate eggs (ova, oocytes) during the study and for a period of 12 weeks after the last administration of study drug.

For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation and for an additional 12 weeks after the end of eRapa administration.

I have FAP with more than 10 polyps or a family history of it.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Encapsulated Rapamycin (eRapa) at one of three escalating doses/schedules for 12 months to reduce polyp burden

12 months

Endoscopy at baseline, 6 months, and 12 months

Food Effect Evaluation

Subjects undergo evaluation under fed and fasted states to determine the food effect on eRapa absorption

2 months

Randomized into fed and fasted states with a 2-week washout period

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Encapsulated Rapamycin (eRapa)

Trial Overview The trial tests Encapsulated Rapamycin (eRapa) in three different doses/schedules over a year on patients with FAP under surveillance to see if it reduces the number of polyps in their large intestine.

How Is the Trial Designed?

Group I: Food Effect Experimental Treatment 1 Intervention

Upon identification of the RP2D, after a 2 week washout (14 days), subjects will be randomized into a fed and fasted (2 weeks - 14 days) two period cross over, with an intervening 2 week washout (14 days) for a total of 2 months (8 weeks).

Group II: Cohort 3 Experimental Treatment 1 Intervention

Cohort 3 will receive 0.5 mg of eRapa daily.

Group III: Cohort 2 Experimental Treatment 1 Intervention

Cohort 2 will receive 0.5mg of eRapa daily with 7 days on therapy, followed by 7 days off therapy.

Group IV: Cohort 1 Experimental Treatment 1 Intervention

Cohort 1 will receive 0.5mg of eRapa every other day.

Encapsulated Rapamycin (eRapa) is already approved in United States, European Union for the following indications:

Approved in United States as Rapamune for:

• Organ rejection in renal transplantation

Approved in European Union as Rapamune for:

• Organ rejection in renal transplantation

Who Is Running the Clinical Trial?

Rapamycin Holdings Inc.

Lead Sponsor

Trials

1

Recruited

30+

Rapamycin Holdings, Inc. dba Emtora Biosciences

Lead Sponsor

Trials

3

Recruited

210+

Biodexa Pharmaceuticals

Industry Sponsor

Trials

2

Recruited

30+

Cancer Insight, LLC dba Lumabridge

Collaborator

Trials

1

Recruited

30+

LumaBridge

Collaborator

Trials

6

Recruited

410+

Cancer Insight, LLC

Industry Sponsor

Trials

10

Recruited

520+

Published Research Related to This Trial

Rapamycin (sirolimus) is an effective drug that inhibits the mTOR protein, which plays a crucial role in cell growth and proliferation, making it useful in treating various cancers and as an immunosuppressant.

Recent studies have shown that rapamycin can effectively manage symptoms of tuberous sclerosis, such as renal angiomyolipoma and giant cell astrocytoma, and it also improves cosmetic outcomes when applied topically for facial angiofibromas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical rapamycin (sirolimus) for facial angiofibromas. Madke, B.[2021]

Chronic treatment with an enteric formulation of rapamycin (eRapa) in genetically diverse mice extended their maximum lifespan and showed potential for reducing cancer, suggesting it could be a viable pharmacological approach for humans.

The study highlights the importance of understanding the role of the mTOR pathway in both cancer and aging, and addresses misconceptions about rapamycin's immunosuppressive effects, indicating a need for safer cancer prevention strategies for the aging population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic mechanistic target of rapamycin inhibition: preventing cancer to delay aging, or vice versa?. Sharp, ZD., Curiel, TJ., Livi, CB.[2021]

mTOR inhibitors, such as everolimus and sirolimus, are effective immunosuppressive agents for organ transplant recipients and cancer treatments, but they are associated with a range of adverse events (AEs) including stomatitis, wound-healing complications, and diabetes.

Most AEs related to mTOR inhibitors can be effectively managed or reversed through careful monitoring and appropriate interventions, highlighting the importance of patient selection and management strategies in optimizing treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Strategies for the management of adverse events associated with mTOR inhibitors. Kaplan, B., Qazi, Y., Wellen, JR.[2022]

The phase I trial of encapsulated rapamycin (eRapa) in 14 patients with low-grade prostate cancer showed that the treatment was safe and well-tolerated, with only mild adverse events reported, particularly in the daily dosing cohort.

No disease progression was observed during the study, suggesting that eRapa may have potential as a treatment to delay the progression of low-grade prostate cancer, which is a significant unmet medical need.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Trial of Encapsulated Rapamycin in Patients with Prostate Cancer Under Active Surveillance to Prevent Progression. Kemp Bohan, PM., Chick, RC., O'Shea, AE., et al.[2022]

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]

Enterically targeted rapamycin (eRapa) significantly improved the survival of Apc(Min/+) mice, with most living beyond the median lifespan of wild-type mice, indicating its potential as a cancer preventative in familial adenomatous polyposis (FAP).

Chronic treatment with eRapa did not negatively impact the immune system in mouse models, suggesting that it could be a safe long-term option for preventing cancer in FAP patients, potentially reducing the need for surgical interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

eRapa restores a normal life span in a FAP mouse model. Hasty, P., Livi, CB., Dodds, SG., et al.[2021]

Rapamycin and its analogs, like everolimus, have shown strong potential in preventing cancer by targeting pre-cancerous cells and slowing down aging processes, as demonstrated in numerous mouse studies.

These drugs not only delay cancer onset in various mouse models but also show promise in organ-transplant patients, suggesting their cancer-preventive effects could be further explored in clinical trials for high-risk groups, such as smokers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cancer prevention with rapamycin. Blagosklonny, MV.[2023]

Rapamycin effectively suppressed the growth of colorectal tumors in both syngenic and xenograft mouse models, demonstrating its potential as a treatment for advanced colorectal cancer.

Combining rapamycin with standard chemotherapy drugs like 5-fluorouracil and oxaliplatin enhanced its antitumor effects without causing acute toxicity, and serum levels of TIMP-1 may serve as a useful marker for treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effective treatment of advanced colorectal cancer by rapamycin and 5-FU/oxaliplatin monitored by TIMP-1. Wagner, M., Roh, V., Strehlen, M., et al.[2023]

Familial adenomatous polyposis (FAP) is a hereditary condition that leads to a very high risk of colorectal cancer, and while prophylactic colectomy is the standard treatment, it does not prevent other disease manifestations and carries risks of complications.

Current chemoprevention agents have not met the necessary safety and efficacy criteria, highlighting the need for new treatments; the mTOR inhibitor rapamycin shows promise based on preclinical studies, and a clinical trial is proposed to formally test its effectiveness in preventing disease progression in FAP patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemoprevention in familial adenomatous polyposis: past, present and future. Kemp Bohan, PM., Mankaney, G., Vreeland, TJ., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4058993/

eRapa Restores A Normal Life Span in a FAP Mouse Model eRapa or other mTORC1 inhibitors could serve as effective cancer preventatives for people with FAP without suppressing the immune system, thus reducing the ...

2. biodexapharma.com biodexapharma.com/biodexa-receives-us-fda-fast-track-designation-for-erapa-in-familial-adenomatous-polyposis/

Biodexa Receives US FDA Fast Track Designation for ... The US Food and Drug Administration (FDA) has granted Fast Track designation for eRapa, a proprietary encapsulated form of rapamycin being developed for the ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06950385

Study Details | NCT06950385 | Phase 3 Trial of eRapa in ... The main goal of this clinical trial is to learn if the drug eRapa works to slow down the progression of disease in patients diagnosed with Familial Adenomatous ...

4. adisinsight.springer.com adisinsight.springer.com/trials/700306849

Phase IIA Trial of Encapsulated Rapamycin (eRapa) to ... This trial will evaluate Encapsulated sirolimus (eRapaTM) for the treatment of patients with Familial Adenomatous Polyposis.

5. gastroenterologyadvisor.com gastroenterologyadvisor.com/news/encapsulated-rapamycin-fast-tracked-for-familial-adenomatous-polyposis/

Encapsulated Rapamycin Fast Tracked for Familial ... The primary endpoints of the trial were safety and tolerability, as well as the change from baseline in polyp burden at 6 months. Patients ...