EEN-RICH study

Prior treatment

• Perianal or intraabdominal abcesses or other complications requiring surgical treatment
• Prior intestinal resection, presence of stoma
• Simultaneously participation in another clinical trial involving an investigational medicinal product within 30 days prior to informed consent
• Participants with clinically significant infections currently or within 3 months prior to baseline (eg, those requiring hospitalization or parenteral antimicrobial therapy or opportunistic infections)
• The use of antibiotics or probiotics prescribed in the last 4 weeks prior to EEN3.
• Previous EEN therapy without clinical efficacy or intolerance to Modulen IBD® (Nestlé Health Science).
• Combination therapy with dual biologics or treatment with Tofacitinib, Rituximab, Alemtuzumab, Cyclosporine A, Tacrolimus, Sirolimus, Mycophenolat mofetil.

Other illness

• Known history of hypersensitivity or allergies to the investigational capsule coating substances or to any compound of the FMT product/excipients.
• Fistulizing perianal disease, which is not in complete remission
• 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
• Patients with any malignancy or history of malignancy (excluding non-melanoma skin cancer)

Lab values

• 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;

Other

• Subject who is unable to understand the nature, scope, significance and consequences of this clinical trial
• Fibrostenotic or penetrating CD phenotype
• Current (to be excluded by pregnancy test) or planned pregnancy or nursing women

• 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.
• 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
• 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.]
• 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.
• 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.
• Males and females 8 to 45 years of age
• 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).
• Ability to swallow IMP INTESTIFIX 001/placebo
• 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.
• Clinical response to EEN (EEN2, visit at week -4)
• 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)
• Steroid-free clinical remission (wPCDAI or CDAI) after at least 6 weeks of EEN (EEN3, visit at week -1)