SIROLIMUS for Familial adenomatous polyposis (FAP)

Inclusion criteria

• {"criterion_text":"- Participant must be ≥18 years of age inclusive, at the time of signing the informed consent.\n- Participant must have documented FAP, confirmed by APC genotype mutation testing or a clear family history of FAP\n- Participant must have at least 1 of the following high-risk features: >100 polyps but ≤500 polyps in the colon, or ≥10 polyps in the retained rectum/sigmoid or ileal pouch (≥3 mm in size), or Spigelman stage 3 or 4 with at least 1 polyp ≥10 mm to be removed at baseline or on endoscopy performed within 18 months of screening.\n- Male and/or female assigned at birth, inclusive of all gender identities. Contraceptive use by participants or participant partners should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. a.\tMale participants are eligible to participate if they agree to the following during the trial intervention period and for at least 12 weeks after the last dose of trial intervention: • Refrain from donating sperm • Be abstinent from intercourse where pregnancy can occur (abstinent on a long term and persistent basis) and agree to remain abstinent, OR • Must agree to use contraception/barrier as detailed below: o agree to use an external condom; with a CBP partner, agree to use of an additional highly effective contraceptive method with a failure rate of <1% per year as described in Appendix 4 when having sexual intercourse with a partner able to give birth who is not currently pregnant; agree to use an external condom when engaging in any activity that allows for passage of ejaculate to another person b. Female participants are eligible to participate if not pregnant or breastfeeding, and 1 of the following conditions applies: • Is of nonchildbearing potential as defined in Appendix 4, OR • Is of CBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), preferably with low user dependency, as described in Appendix 4 during the trial intervention period and for at least 12 weeks after thelast dose of trial intervention, and agrees not to donate eggs (ova, oocytes) for the purpose of reproduction during this period. The Investigator should evaluate the potential for contraceptive method failure (e.g., noncompliance, recently initiated) in relationship to the first dose of trial intervention. • A CBP participant must have a negative highly sensitive pregnancy test (serum at screening, urine or serum at baseline) as required by local regulations) within 24 hours before the first dose of trial intervention, see Section 8.3.4. o If a urine test cannot be confirmed as negative (e.g., an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive. • Additional requirements for pregnancy testing during and after trial intervention are located in Section 8.3.4. • The Investigator is responsible for review of medical history, menstrual history, and recent sexual activity where pregnancy can occur to decrease the risk for inclusion of a participant with an early undetected pregnancy. . All female partiicpants must agree to an effective method of contraception until one full menstrual cycle has been completed after last dose of trial treatment.\n- Signed informed consent as described in Appendix 1 which includes compliance with the requirements and restrictions listed in the informed consent form and in this protocol.\n- Participant must be willing and able to safely undergo routine endoscopic evaluation"}

Exclusion criteria

• {"criterion_text":"- Participant has unresected or incompletely resected high-grade dysplasia or cancer within the duodenum, colon, rectum, or ileal pouch at screening endoscopy\n- Participant has a history of, or currently has, an acquired or primary (congenital) immunodeficiency\n- Participant has active and clinically significant tuberculosis (positive Quantiferon Gold test), bacterial, fungal, or viral infection, including human immunodeficiency virus (HIV)\n- Presence of hepatitis B virus (HBV) or hepatitis C virus (HCV)\n- Participant has any medical or social condition that, in the opinion of the Investigator, might increase participant risk if enrolled, prevent participant compliance to trial procedures, or present an unacceptable confound to safety or clinical trial data.\n- Alanine transaminase or aspartate transaminase >2 x upper limit of normal (ULN)\n- Total bilirubin >1.5 x ULN (participants with Gilbert’s syndrome can be included with total bilirubin >1.5 x ULN as long as direct bilirubin is ≤1.5 x ULN)\n- .Patients with rare hereditary Galactose-Intolerance, total Lactase-Deficiency or Glucose-Galactose- Malabsorption disorders to be excluded\n- Participant has taken low-dose aspirin (doses between 75 and 100 mg QD) or non-steroidal anti-inflammatory drug (NSAID) therapy, other than occasional, intermittent treatment for analgesia, e.g., ibuprofen 400 mg 3 times daily (or equivalent) within 4 weeks prior to first dose of trial intervention\n- Participant has taken any FAP-directed drug therapy within 6 weeks of the first dose of trial intervention\n- Participant has had prior pelvic irradiation therapy\n- Absolute neutrophil count <1.0 × 109/L (without transfusion or administration of growth factors in the 2 weeks prior to screening).\n- Participant is taking medications that are considered strong inducers or inhibitors of cytochrome P450 (CYP) 3A4/5 (see Appendix 7) or strong inducers or inhibitors of P-glycoprotein 1 (P-gp1) that cannot be discontinued at least 1 week prior to first dose of trial intervention and for the duration of the trial\n- Participant, at the time of screening, is receiving systemic steroid therapy (≥10 mg/day of prednisone or equivalent) or is taking any immunosuppressive therapy. Note: Use of topical, inhaled, nasal, or ophthalmic steroids for no longer than 4 weeks is allowed. Note: Participants who were previously administered systemic steroid therapy or immunosuppressive therapy prior to screening, must have stopped treatment 30 days or 5 half lives (whichever is shorter) before the first dose of trial intervention.\n- Participant must not have received an experimental drug within 4 weeks or 5 half-lives (whichever is shorter) of screening or already be enrolled in a clinical trial\n- Hemoglobin <9 g/dL (without transfusion or administration of growth factors in the 2 weeks prior to screening).\n- Participant has >2 x ULN Serum Amylase level at screening.\n- Platelet count ≤75 × 109/L (without transfusion or administration of growth factors in the 2 weeks prior to screening).\n- Participant has any polyps ≥8 mm in the duodenum, colon, rectum, or ileal pouch remaining after screening endoscopy (polyps ≥8 mm are to be resected during screening endoscopy).\n- Serum creatinine or measured/calculated creatinine clearance (or glomerular filtration rate) >1.5 x ULN OR <30 mL/min for participants with creatine levels >1.5 x institutional ULN.\n- Prothrombin Time (PT)/ International Normalized Ratio (INR) or activated Partial Thromboplastin Time (PTT) >1.5 × the ULN. Note: Participants on stable doses of anticoagulation must have a PT/INR >3.0 to be eligible for the trial\n- Participant has >1+ proteinuria on urinalysis or >1 g of urine protein on 24-hour urine collection\n- Participant has had surgery within 6 weeks of the trial\n- Participant has active malignancy or history of malignancy diagnosed within 24 months of first dose of trial intervention"}

Primary endpoints

• {"endpoint_text":"- Progression-free survival (PFS) in high-risk patients with FAP treated with eRapa versus placebo. Disease progression is defined as a FAP-specific, clinically significant event. FAP-specific progression events will be defined as follows: Death from any cause • Cancer/high-grade dysplasia • Major FAP-related surgery (e.g., colectomy, proctectomy, total proctocolectomy with ileal pouch anal anastomosis [IPAA], pouch resection, ileostomy, duodenectomy, or surgical ampullectomy)","definition_or_measurement_approach":"PFS measured as time to a FAP-specific, clinically significant event; progression events defined as death from any cause, cancer/high-grade dysplasia, or major FAP-related surgery (examples listed)."}

Secondary endpoints

• {"endpoint_text":"- Frequency of all grades (as per the Common Terminology Criteria for Adverse Events [CTCAE] version [v] 5.0) treatment-emergent adverse events (TEAEs) in participants receiving eRapa","definition_or_measurement_approach":"All-grade TEAEs will be captured and graded per CTCAE v5.0; frequency reported for participants receiving eRapa."}
• {"endpoint_text":"- Frequency of Grade 3 and higher (as per the CTCAE v5.0) TEAEs in participants receiving eRapa","definition_or_measurement_approach":"Grade ≥3 TEAEs graded per CTCAE v5.0; frequency reported for participants on eRapa."}
• {"endpoint_text":"- Percentage of participants discontinuing eRapa treatment due to adverse drug reactions (ADRs)","definition_or_measurement_approach":"Proportion of participants who stop eRapa due to ADRs."}
• {"endpoint_text":"- Percent change from baseline in the PB (i.e., the sum of the diameters of all polyps >3 mm) at 6, 12, 18, 24, 30, and 36 months as observed by surveillance endoscopy Note: The total PB will be based on polyps observed in the upper GI tract (duodenum) and the lower GI tract (colon, retained rectum/sigmoid or pouch)","definition_or_measurement_approach":"Percent change from baseline in polyp burden (sum of diameters of all polyps >3 mm) assessed by surveillance endoscopy at specified time points; PB includes upper and lower GI tract polyps."}
• {"endpoint_text":"- Percent change from baseline in the PB in the upper GI tract (duodenum) at 6, 12, 18, 24, 30, and 36 months as observed by upper endoscopy","definition_or_measurement_approach":"Percent change from baseline in duodenal PB measured by upper endoscopy at specified time points."}
• {"endpoint_text":"- Percent change from baseline in the PB in the lower GI tract (colon, retained rectum/ sigmoid or pouch) at 6, 12, 18, 24, 30, and 36 months as observed by lower endoscopy","definition_or_measurement_approach":"Percent change from baseline in lower GI tract PB measured by lower endoscopy at specified time points."}
• {"endpoint_text":"- Change from baseline in Spigelman stage score at 6, 12, 18, 24, 30, and 36 months","definition_or_measurement_approach":"Change in Spigelman stage score measured at scheduled visits."}
• {"endpoint_text":"- Change from baseline in EQ-5D5L score at 6, 12, 18, 24, 30, and 36 months","definition_or_measurement_approach":"Change in EQ-5D-5L patient-reported health status at scheduled times."}
• {"endpoint_text":"- Change from baseline in EORTC QLQ-30 score at 6, 12, 18, 24, 30, and 36 months","definition_or_measurement_approach":"Change in EORTC QLQ-C30 quality-of-life scores at scheduled times."}

Italy

Earliest CTIS Part Ii Submission Date

05-02-2026

Latest Decision Or Authorization Date

16-02-2026

Processing Time Days

11

Number Of Sites

2

Number Of Participants

10

Spain

Earliest CTIS Part Ii Submission Date

26-09-2025

Latest Decision Or Authorization Date

30-10-2025

Processing Time Days

34

Number Of Sites

4

Number Of Participants

10

Netherlands

Earliest CTIS Part Ii Submission Date

17-10-2025

Latest Decision Or Authorization Date

31-10-2025

Processing Time Days

14

Number Of Sites

2

Number Of Participants

2

Germany

Earliest CTIS Part Ii Submission Date

02-10-2025

Latest Decision Or Authorization Date

28-10-2025

Processing Time Days

26

Number Of Sites

1

Number Of Participants

5

Denmark

Earliest CTIS Part Ii Submission Date

23-10-2025

Latest Decision Or Authorization Date

27-10-2025

Processing Time Days

4

Number Of Sites

1

Number Of Participants

5

Primary sponsor

Full Name

Biodexa Limited

Organisation Type

Pharmaceutical company

Country Of Registered Address

United Kingdom

Contract research organisations

Name

Labcorp Early Development Laboratories Limited

Responsibilities

Central Lab

Name

Advarra Inc.

Responsibilities

Data Safety Monitoring Board

Name

Perceptive Informatics Inc.

Responsibilities

Central Imaging

Name

Clinigen Healthcare Limited

Responsibilities

Pharmacovigilance, Safety Database

Name

Precision for Medicine (HU) Kft.

Responsibilities

Multiple operational roles (codes 1,10,11,12,2,6,7,8 as listed)

Name

Southwest Research Institute

Responsibilities

Investigational Product Manufacturing and Distribution

Name

Medrio Inc.

Responsibilities

EDC and ePRO Platform, Randomization and Trial Supply Management (RTSM)

Third parties

• {"country":"United Kingdom","full_name":"Labcorp Early Development Laboratories Limited","duties_or_roles":"Central Lab","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Advarra Inc.","duties_or_roles":"Data Safety Monitoring Board","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Perceptive Informatics Inc.","duties_or_roles":"Central Imaging","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Clinigen Healthcare Limited","duties_or_roles":"Pharmacovigilance, Safety Database","organisation_type":"Pharmaceutical company"}
• {"country":"Hungary","full_name":"Precision for Medicine (HU) Kft.","duties_or_roles":"Roles codes: 1,10,11,12,2,6,7,8","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Southwest Research Institute","duties_or_roles":"Investigational Product Manufacturing and Distribution","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medrio Inc.","duties_or_roles":"EDC and ePRO Platform, Randomization and Trial Supply Management (RTSM)","organisation_type":"Pharmaceutical company"}

Co-sponsors

• Rapamycin Holdings Inc.