EEN-RICH study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Klinikum Der Universitat Munchen AöR

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

21 Jan 2025 → ongoing

Decision date (initial)

2023-07-19

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Leona M. and Harry B. Helmsley Charitable Trust

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

The aim of the trial is to assess safety, feasibility and efficacy of multi-donor FMT via administration of INTESTIFIX 001 FMT capsules in children and adults with Crohn´s disease.
Primary objective: To evaluate the safety of multi-donor FMT for maintenance of remission after induction treatment with EEN in CD (week 0 to 32)

Secondary objectives 3

1. To evaluate the feasibility of multi-donor FMT for maintenance of remission after induction treatment with EEN in CD (week -8 to 32)
2. To evaluate overall clinical efficacy of multi-donor FMT (week 0 to 32)
3. To evaluate patient reported outcomes and quality of life (week -8 to 32)

Conditions and MedDRA coding

Crohn's disease

Study design 3 periods

Regulatory references

Scientific advice from competent authorities

Federal Institute For Drugs And Medical Devices

Plan to share IPD

No

IPD plan description

Dieser Eintrag ist eine rein administrative Formalität im Rahmen der IB-Verlängerung. Es ist keine Änderung des IPD-Sharing-Plans vorgesehen.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Provision of signed and dated, written informed consent form prior to any study specific procedures, sampling, and analyses. For Children: Written informed consent of both parents (legal guardians) and oral/written assent of patient due to age specific information.
2. Subjects / legan guardians (parents) with knowledge of language and the ability to understand and to follow the study protocol mentally, including following study instructions (e.g. willingness to provide fecal samples during the visits and follow-up period). Subjects are likely to attend and complete all required visits.
3. Males and females 8 to 45 years of age
4. Confirmation of Crohn’s disease active ileitis, colitis, or ileocolitis, confirmed at any time in the past by endoscopy and histology. Histology may be deferred for newly diagnosed patients until EEN2 (visit at week -4).
5. Ability to swallow IMP INTESTIFIX 001/placebo
6. Mild to moderate disease activity (wPCDAI 12.5-57.5 or CDAI 150-450) or milder disease activity with elevated fecal calprotectin > 250 mg/L prior to start of EEN.
7. Clinical response to EEN (EEN2, visit at week -4)
8. Receiving either no treatment or the listed treatment options with: a. Oral 5-aminosalicylic acid (5-ASA) compounds: stable or discontinued for ≥4 weeks prior to EEN3 (visit at week -1). The dose must be stable until OBS1. b. Methotrexate (MTX): ≥4 weeks from initiation and on a stable dose prior to EEN3 (visit at week -1). The dose must be stable until OBS1. c. 6-mercaptopurine (6-MP) or azathioprine (AZA): ≥12 weeks from initiation and on a stable dose for ≥4 weeks prior to EEN3 (visit at week -1). The dose must be stable until OBS1. d. Biologic: ≥16 weeks from initiation and on a stable dose prior to EEN3 (visit at week -1). The dose must be stable until OBS1. Combination treatment of biologic with immuno-modulator (6-MP, AZA or MTX) is allowed, as described in b or c; e. Oral or IV corticosteroids or budesonide or beclomethasone dipropionate or rectal corticosteroids: discontinued for ≥2 weeks prior to EEN3 (visit at week -1)
9. Steroid-free clinical remission (wPCDAI or CDAI) after at least 6 weeks of EEN (EEN3, visit at week -1)
10. Have negative stool results for enteric pathogens. Stool studies must include a stool culture and Clostridioides difficile toxin assay (C. difficile toxin/GDH with reflex to PCR testing). These must be performed during first four weeks of EEN run-in period or the current episode of disease exacerbation as long as the stool studies were performed within 2 months prior to study enrollment
11. Women of childbearing potential who are sexually active with opposite partners have to perform adequate contraception with a combination of a highly effective method of birth control and additional barrier contraception. [Highly effective method of birth control is defined as those, alone or in combination, that result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly for the entire study duration: combined (oestrogen and gestagen) oral contraceptives, hormone implants, hormone injectables, or hormone containing intrauterine device that needed to be in place for a period of at least 2 months prior to screening. Additional barrier contraception (at least the following methods are allowed: condom of the male, diaphragm with spermicide, portio cap with spermicide) has to be used for the duration of the trial, defined as from the time of screening to at least 90 days after Visit DB12 of the double-blind treatment phase. A single barrier method is not acceptable. Women of non-childbearing potential can be included if menstruation has not yet started, women are surgically sterile (documented complete hysterectomy or bi-tubal ligations) or post-menopausal >1 year.]
12. Men of reproductive potential must use condoms. In addition, the female partner should also be on a safe hormonal contraception (e.g. combined oral contraceptives, hormone implants, hormone injectables or hormone containing intrauterine device) or use a barrier contraception (e.g. intrauterine device, diaphragm or portio cap with spermicide), if she is of childbearing potential.

Exclusion criteria 15

1. Subject who is unable to understand the nature, scope, significance and consequences of this clinical trial
2. Simultaneously participation in another clinical trial involving an investigational medicinal product within 30 days prior to informed consent
3. Subjects with a physical (such as renal insufficiency, hepatitis, respiratory insufficiency, heart failure) or psychiatric condition which at the investigator’s discretion may put the subject at risk, may confound the trial results, or may interfere with the subject’s participation in this clinical trial
4. Patients with any malignancy or history of malignancy (excluding non-melanoma skin cancer)
5. Participants with clinically significant infections currently or within 3 months prior to baseline (eg, those requiring hospitalization or parenteral antimicrobial therapy or opportunistic infections)
6. Current (to be excluded by pregnancy test) or planned pregnancy or nursing women
7. The use of antibiotics or probiotics prescribed in the last 4 weeks prior to EEN3.
8. Previous EEN therapy without clinical efficacy or intolerance to Modulen IBD® (Nestlé Health Science).
9. Combination therapy with dual biologics or treatment with Tofacitinib, Rituximab, Alemtuzumab, Cyclosporine A, Tacrolimus, Sirolimus, Mycophenolat mofetil.
10. Known history of hypersensitivity or allergies to the investigational capsule coating substances or to any compound of the FMT product/excipients.
11. Anemia with hemglobin <8 g/dl, white blood cells <2500/µl, neutrophils <1500/µl, platelets <100.000/µl, elevated liver enzymes (>3-times ULN), elevate serum creatinine;
12. Fibrostenotic or penetrating CD phenotype
13. Fistulizing perianal disease, which is not in complete remission
14. Perianal or intraabdominal abcesses or other complications requiring surgical treatment
15. Prior intestinal resection, presence of stoma

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Incidence and severity of adverse events and serious adverse events in multi-donor-FMT-group compared to placebo
2. Summary of adjudicated safety events (e.g., opportunistic infection)

Secondary endpoints 18

1. 1. To evaluate the feasibility of multi-donor FMT for maintenance of remission after induction treatment with EEN in CD (week -8 to 32) a.) Rate of recruitment of patients
2. 1. To evaluate the feasibility of multi-donor FMT for maintenance of remission after induction treatment with EEN in CD (week -8 to 32) b.) Study withdrawal rates
3. 1. To evaluate the feasibility of multi-donor FMT for maintenance of remission after induction treatment with EEN in CD (week -8 to 32) c) Adherence rate to EEN as determined by the proportion of patients with undetectable fecal gluten immunogenic peptides (GIP)
4. 1. To evaluate the feasibility of multi-donor FMT for maintenance of remission after induction treatment with EEN in CD (week -8 to 32) d.) Proportion of patients having taken all capsules during the intervention period
5. 1. To evaluate the feasibility of multi-donor FMT for maintenance of remission after induction treatment with EEN in CD (week -8 to 32) e) Difference between the number of biosamples collected and the total number of biosamples scheduled per patient as a marker for completeness of sample collection
6. 2. To evaluate overall clinical efficacy of multi-donor FMT a. Difference in fecal calprotectin levels between week 0 and week 8 in multi-donor FMT compared to placebo
7. 2. To evaluate overall clinical efficacy of multi-donor FMT b) Difference in C-reactive protein (CRP) levels between baseline (week 0) and week 8 in multi-donor FMT compared to placebo
8. 2. To evaluate overall clinical efficacy of multi-donor FMT c) Change in CRP and fecal calprotectin levels over time (multi-donor FMT compared to placebo) (week -8 to 32)
9. 2. To evaluate overall clinical efficacy of multi-donor FMT d) Relapse-free survival time (multi-donor FMT compared to placebo) (week 0 to 32)
10. 2. To evaluate overall clinical efficacy of multi-donor FMT e) Clinical remission by physician global assessment at weeks 0, 4, 8, 12, 16, 24 and 32 (multi-donor FMT compared to placebo)
11. 2. To evaluate overall clinical efficacy of multi-donor FMT f) Clinical remission by PCDAI and wPCDAI (children) / CDAI (adults) score at weeks 0, 4, 8, 12, 16, 24 and 32 (multi-donor FMT compared to placebo)
12. 2. To evaluate overall clinical efficacy of multi-donor FMT g) Change from baseline (week -8) in PCDAI, shPCDAI and wPCDAI (children) / CDAI and HBI (adults) over time (multi-donor FMT compared to placebo)
13. 2. To evaluate overall clinical efficacy of multi-donor FMT h) Response by intestinal ultrasound (IUS) at weeks 0, 4, 8, 16 and 32 (multi-donor FMT compared to placebo) in patients with increased bowel wall thickness (BWT) before EEN (week -8).
14. 2. To evaluate overall clinical efficacy of multi-donor FMT i) Remission by IUS at weeks 0, 4, 8, 16 and 32 (multi-donor FMT compared to placebo).
15. 2. To evaluate overall clinical efficacy of multi-donor FMT j) Change from baseline (week -8) in IUS parameters over time (multi-donor FMT compared to placebo).
16. 2. To evaluate overall clinical efficacy of multi-donor FMT k) Prediction of clinical recurrence based on change of IUS parameters over time.
17. 3. To evaluate patient reported outcomes and quality of life (QoL) (week -8 to 32) a) Change from baseline (week -8) in QoL IMPACT-III scores at weeks 0, 4, 8, 16, 32 (multi-donor FMT compared to placebo)
18. 3. To evaluate patient reported outcomes and quality of life (QoL) (week -8 to 32) b) Change from baseline (week -8) in QoL SIBDQ scores at weeks 0, 4, 8, 16, 32 (multi-donor FMT compared to placebo)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Klinikum Der Universitat Munchen AöR

Sponsor organisation

Klinikum Der Universitat Munchen AöR

Address

Lindwurmstrasse 4, Ludwigsvorstadt-Isarvorstadt Ludwigsvorstadt-Isarvorstadt

City

Munich

Postcode

80337

Country

Germany

Scientific contact point

Organisation

Klinikum Der Universitat Munchen AöR

Contact name

Study Team

Public contact point

Organisation

Klinikum Der Universitat Munchen AöR

Contact name

Study Team

Locations

1 EU/EEA country · 6 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Application history

7 submissions — initial application plus substantial / non-substantial modifications