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Familial Adenomatous PolyposisPhase 2NCT04230499

Trial of eRapa to Prevent Progression in Familial Adenomatous Polyposis Patients Under Active Surveillance

A Phase 2 study testing Encapsulated Rapamycin (eRapa) in people with Familial Adenomatous Polyposis, run by Rapamycin Holdings Inc. at 4 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Patients with Familial Adenomatous Polyposis (FAP) who are undergoing endoscopic surveillance will be given Encapsulated Rapamycin (eRapa) at one of three escalating doses/schedules for 12 months with the aim of reducing polyp burden. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Familial Adenomatous Polyposis
What is being tested?
Encapsulated Rapamycin (eRapa)
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
4 sitesUnited States
Study dates
18 Jan 2021to 22 May 2025
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Sign and date an informed consent form.
  • Stated willingness to comply with all study procedures and availability for the duration of the study.
  • Male or female, age at least 18 years at the time of consent.
  • Phenotypic familial adenomatous polyposis (FAP) with disease involvement of the colorectum by either genetic or clinical diagnosis: Adenomatous polyposis coli (APC) germline mutation with or without family history, or with greater than a cumulative lifetime history of (>) 100 adenomas in large intestine and a family history of FAP, or FAP phenotype post colectomy for polyposis with a family history of FAP. Minimum number of polyps required for enrollment is 10.
  • Abilitiy to safely undergo endoscopy.
  • Ability to take oral medication and be willing to adhere to the eRapa regimen.
  • 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.
  • 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.

Who cannot join

  • Risk-reduction surgery (colectomy or partial colectomy) within the 12 months prior to screening.
  • Use of non-steroidal anti-inflammatory drugs other than aspirin during the study. The use of 81 milligrams (mg) of aspirin a day or 650 mg of aspirin per week is allowed.
  • Treatment with other FAP-directed drug therapy (including NSAID [Non-steroidal anti-inflammatory drug] drugs), unless completes a 4 week washout period prior to enrollment.
  • Duodenum or colon/ rectum with high grade dysplasia or cancer on biopsy at screening.
  • Duodenal or colorectal polyp > 1 centimeter (cm) not excised at the screening evaluation.
  • Pregnancy or breast feeding.
Show all 15Show fewer
  • Unable to provide consent or anticipated inability to attend appropriate follow-up visits.
  • Serum creatinine or measured/ calculated creatinine clearance (or glomerular filtration rate [GFR]) > 1.5 x ULN OR < 30mL/min for participants with creatine levels > 1.5 x institutional ULN. Bilirubin ≥ 1.5 x ULN unless conjugated bilirubin ≤ ULN; alkaline phosphatase > 5 x ULN; ALT/AST > 2 x ULN.
  • INR or PT or aPTT > 1.5 x institutional ULN unless the patient is receiving anticoagulant therapy as long as the PT or aPTT is within therapeutic range of intended use of anticoagulants.
  • Proteinuria > 1+ on urinalysis or > 1g/24h on 24h urine.
  • History of interstitial lung disease or non-infectious pneumonitis.
  • Immunosuppressed state (e.g., HIV, use of chronic steroids), active, uncontrolled infection.
  • On agents known to alter rapamycin metabolism significantly.
  • Concurrent involvement in other clinical trials specifically evaluating chemoprevention in FAP.
  • Patients with a colonic polyp burden too numerous to count.

Trial locations and contacts

4 sites in 1 country.

United States4 sites
  • Michigan Medicine

    Ann Arbor, Michigan, 48109

  • Cleveland Clinic

    Cleveland, Ohio, 44195

  • Ohio State University

    Columbus, Ohio, 43210

  • UT Health

    San Antonio, Texas, 78229

Other trials in United States

About this study

Official title: Phase IIa Trial of Encapsulated Rapamycin (eRapa) to Prevent Progression in Familial Adenomatous Polyposis Patients Under Active Surveillance

Patients with Familial Adenomatous Polyposis (FAP) who are undergoing endoscopic surveillance will be given Encapsulated Rapamycin (eRapa) at one of three escalating doses/schedules for 12 months with the aim of reducing polyp burden.

Read the detailed description

Patients with FAP who are undergoing endoscopic surveillance will be given eRapa at one of three escalating doses/ schedules (0.5mg every other day, 0.5mg daily every other week, or 0.5mg daily) for 12 months with the aim of reducing polyp burden. Patients will serve as their own controls. Patients will be assessed with surveillance endoscopy at baseline, 6 months, and 12 months for change in polyp burden. Correlation between immune markers and clinical outcomes will be explored.

This is a Phase IIa trial which will enroll at approximately 6-8 sites within the United States that have specialty expertise in FAP treatment and surveillance. The trial is anticipated to last approximately 24 months for treatment and follow up.

The trial will enroll 30 patients with the genetic or clinical diagnosis of FAP. The clinical diagnosis includes individuals with 100 or more cumulative tubular adenomas throughout the colorectum. Patients must be undergoing surveillance for known FAP and can include those with intact colons as well as those who have undergone surgical therapy. For those patients who have undergone partial or total colectomy, they must have documented residual polyps in their rectum for which they are receiving active surveillance.

Once the recommended phase 2 dose (RP2D) is identified, subjects will undergo evaluation under fed and fasted states to determine the food effect on eRapa absorption.

Being tested
Encapsulated Rapamycin (eRapa)
Medical subject headings
Adenomatous Polyposis Coli

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Encapsulated Rapamycin (eRapa)Drug

    Also called eRapa; Encapsulated sirolimus

    eRapa is encapsulated rapamycin. The rapamycin is encapsulated in order to deliver the rapamycin at a consistent and lower dosage. eRapa is a capsule, and is administered orally.

Study groups in NCT04230499
Study groupRoleWhat they receive
Cohort 1ExperimentalCohort 1 will receive 0.5mg of eRapa every other day.
Receives: Drug: Encapsulated Rapamycin (eRapa)
Cohort 2ExperimentalCohort 2 will receive 0.5mg of eRapa daily with 7 days on therapy, followed by 7 days off therapy.
Receives: Drug: Encapsulated Rapamycin (eRapa)
Cohort 3ExperimentalCohort 3 will receive 0.5 mg of eRapa daily.
Receives: Drug: Encapsulated Rapamycin (eRapa)
Food EffectExperimentalUpon 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).
Receives: Drug: Encapsulated Rapamycin (eRapa)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percent Change From Baseline in Colorectal Polyp Burden at Month 6

    Colorectal polyp burden was assessed by colonoscopy at baseline and Month 6 (180 days), performed by the same gastroenterologist whenever possible. Polyps measuring ≥3 mm were counted, and the diameter of each eligible polyp was measured. Colorectal polyp burden was defined as the sum of the diameters of all eligible colorectal polyps. Polyps removed at the baseline endoscopy were excluded from the baseline polyp burden calculation to avoid attributing reductions due to polypectomy to study treatment. Percent change from baseline was calculated as: (Month6polypburden-adjustedbaselinepolypburden)÷adjustedbaselinepolypburden × 100.

    Measured: 6 months

Secondary outcomes (8)
  1. Percent Change From Baseline in Colorectal Polyp Burden at Month 12

    Colorectal polyp burden was assessed by colonoscopy at baseline and Month 12 (360 days), performed by the same gastroenterologist whenever possible. Polyps measuring ≥3 mm were counted, and the diameter of each eligible polyp was measured. Colorectal polyp burden was defined as the sum of the diameters of all eligible colorectal polyps. Polyps removed at the baseline endoscopy were excluded from the baseline polyp burden calculation to avoid attributing reductions due to polypectomy to study treatment. Percent change from baseline was calculated as: [(Month 12 polyp burden - adjusted baseline polyp burden) ÷ adjusted baseline polyp burden] × 100.

    Measured: 12 months.

  2. Clinical Effect of eRapa on International Society for Gastrointestinal Hereditary Tumors (InSiGHT) Stage.

    The International Society for Gastrointestinal Hereditary Tumours (InSiGHT) Familial Adenomatous Polyposis (FAP) Staging System is a validated clinical scoring system used to assess the severity of polyposis in patients with FAP. Staging is based on polyp number, size, endoscopic resectability, and the presence of advanced pathology. The scale consists of a single overall stage (0-4) and does not include subscale scores: Stage 0 = 0-10 polyps, all <5 mm; Stage 1 = 10-25 polyps, predominantly <5 mm, none >1 cm; Stage 2 = 10-25 polyps with ≥1 polyp >1 cm, all amenable to complete removal; Stage 3 = >25 polyps amenable to complete removal, an incompletely removed sessile polyp, or high-grade dysplasia; Stage 4 = high-grade dysplasia in an incompletely removed lesion and/or invasive colorectal cancer. Change from baseline was calculated as the difference in stage between baseline and post-treatment assessment.

    Measured: Following patients out to 6 and 12 months.

  3. Clinical Effect of eRapa on Spigelman Stage Score.

    The Spigelman Staging System is a validated clinical scoring system used to assess the severity of duodenal polyposis in patients with Familial Adenomatous Polyposis (FAP). The score is based on four components evaluated during upper endoscopy: number of duodenal adenomas, size of the largest adenoma, histology, and degree of dysplasia. Points are assigned to each component and summed to generate a total score ranging from 0 to 12. The overall stage is classified as Stage 0 (0 points), Stage I (1-4 points), Stage II (5-6 points), Stage III (7-8 points), or Stage IV (9-12 points), with higher stages indicating more severe duodenal disease. The measure consists of a single overall stage and does not include subscale scores. Reported values represent absolute Spigelman stage at each assessment timepoint. Change from baseline was calculated as the difference in stage between baseline and post-treatment assessment.

    Measured: Following patients out to 6 and 12 months.

  4. Percent Change From Baseline in Duodenal Polyp Burden at Months 6 and 12

    Duodenal polyp burden was assessed by gastroduodenoscopy at baseline and at Months 6 (180 days) and 12 (360 days), performed by the same gastroenterologist whenever possible. Polyps measuring ≥3 mm were counted, and the diameter of each eligible duodenal polyp was measured. Duodenal polyp burden was defined as the sum of the diameters of all eligible duodenal polyps. Polyps removed at the baseline endoscopy were excluded from the baseline polyp burden calculation to avoid attributing reductions due to polypectomy to study treatment. Percent change from baseline was calculated separately for the Month 6 and Month 12 assessments as: [(follow-up polyp burden - adjusted baseline polyp burden) ÷ adjusted baseline polyp burden] × 100.

    Measured: Following patients out to 6 and 12 months.

  5. Determine the Effect of Food on eRapa Absorption cMax

    Cmax pharmacokinetic parameters to assess the effect of food on the bioavailability of the anticipated RP2D

    Measured: 2 months

  6. Determine the Effect of Food on eRapa Absorption AUC

    AUC₀-∞ Pharmakinetic parameters to assess the effect of food on eRapa absorption

    Measured: 2 months

  7. Sum of Diameters of Eligible Colorectal Polyps at Baseline

    Colorectal polyp burden was assessed by gastroduodenoscopy at baseline. Polyps measuring ≥3 mm were counted, and the diameter of each eligible colorectal polyp was measured. Baseline colorectal polyp burden was defined as the sum of the diameters of all eligible colorectal polyps. Polyps removed at the baseline endoscopy were excluded from the baseline polyp burden calculation.

    Measured: baseline

  8. Sum of Diameters of Eligible Duodenal Polyps at Baseline

    Duodenal polyp burden was assessed by gastroduodenoscopy at baseline. Polyps measuring ≥3 mm were counted, and the diameter of each eligible duodenal polyp was measured. Baseline duodenal polyp burden was defined as the sum of the diameters of all eligible duodenal polyps. Polyps removed at the baseline endoscopy were excluded from the baseline polyp burden calculation.

    Measured: baseline

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Jan 2020
  2. Study start18 Jan 2021
  3. Primary completion11 Dec 2024
  4. Study completion22 May 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Model description
Patients will receive one of three doses in a dose-escalating fashion. Cohort 1 will receive 0.5mg every other day, Cohort 2 will receive 0.5mg daily with 7 days on therapy followed by 7 days off therapy, and Cohort 3 will receive 0.5 mg daily. Patients will serve as their own control; no placebo will be given. Additionally, a subset of participants will be included in a randomized, balanced, single-schedule, two-treatment period (fed versus fasted) crossover study. Participants will receive eRapa under fed or fasted conditions in the first period, and then crossover to the other treatment (fed to fasted and vice versa) following a 2 week washout. Under this design, participants serve as their own control and will allow the assessment of the effect of food on the anticipated R2PD of eRapa
Masking
None (open label)
Enrolment
30 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04230499
Sponsor's protocol ID
EMT-FAP-001
Status last verified
Oct 2026
First submitted
12 Jan 2020
Last updated
22 Oct 2026
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Stone JK, Mehta NA, Singh H, El-Matary W, Bernstein CN. Endoscopic and chemopreventive management of familial adenomatous polyposis syndrome. Fam Cancer. 2023 Oct;22(4):413-422. doi: 10.1007/s10689-023-00334-3. Epub 2023 Apr 29.

    PubMed 37119510

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Encapsulated Rapamycin (eRapa) in people with Familial Adenomatous Polyposis, run by Rapamycin Holdings Inc. at 4 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 Oct 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percent Change From Baseline in Colorectal Polyp Burden at Month 6 (time frame: 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04230499, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Oct 2026.

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