Inflammatory Bowel Disease (Crohn`s Disease and Ulcerative Colitis) MedDRA version: 19.0 Level: PT Classification code 10009900 Term: Colitis ulcerative System Organ Class: 10017947 - Gastrointestinal disorders MedDRA version: 19.0 Level: PT Classification code 10011401 Term: Crohn's disease System Organ Class: 10017947 - Gastrointestinal disorders
Conditions
Interventions
Product Code: FE 999301
Pharmaceutical Form: Concentrate for solution for infusion
Sponsors
University Hospital Schleswig-Holstein (UKSH)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. The patient is able and willing to give written informed consent before any trial-related procedures are performed and to comply with the requirements of this trial protocol. 2. =18 years of age. 3. Negative QuantiFERON-TB Gold In-Tube test within 3 months before screening (if this has not been performed, QuantiFERON-TB Gold In-Tube test must be obtained and confirmed as negative during the Screening Period). 4. Diagnosis of IBD >3 months prior to Visit 2. 5. Active IBD as confirmed by a CRP =5 mg/L. 6. Active moderate to severe mucosal inflammation despite use of mesalamine (5-ASAs), Budesonide (up to 9 mg/d), and/or the immunosuppressants AZA, 6-MP, and MTX evidenced by: a. UC patients: colonoscopy with a Mayo endoscopic appearance subscore =2 at baseline. b. CD patients: CDAI > 220 with active mucosal inflammation (Simple Endoscopic Score for Crohn’s disease [SES-CD] =7 if ileum can be intubated. SES-CD =5 if ileum is not intubatable). 7. Previous treatment for IBD using conventional, non-biologic therapy for at least 3 months which has been stable for at least 14 days prior to Visit 2. 8. Full colonoscopy with serial biopsies with no signs of malignancy during screening (which serves as baseline). This can be done anytime between Day -4 and Day 0 (i.e. immediately before Visit 2). Full colonoscopy is required in all CD patients. In UC patients, a full colonoscopy is required only if no prior, fully documented procedure with serial biopsies is available from the past 6 months. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 20 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Current diagnosis of fulminant disease foreseeably needing hospitalisation. 2. Discontinued use of AZA, 6-MP or MTX within 28 days of Visit 2. 3. Any need of parenteral therapies (except iron infusions). 4. Treatment with more than two different types of biologics drugs or any biologic which is not an anti-TNF molecule or vedolizumab. 5. Treatment with a biologic agent within 30 days or 5 half-lives prior to Visit 2 (whichever is longer). 6. Treatment with cyclosporine, tacrolimus, or mycophenolate mofetil within 30 days prior to Visit 2. 7. Treatment with IV corticosteroids within 14 days prior to Screening or during the Screening Period. 8. More than 20 mg (prednisolone equivalent) of oral corticosteroids within the last 28 days or not on a stable dose at least 14 days prior to Visit 2. 9. Any topical therapy of disease relevant lesions with corticosteroids in the last 10 days before Visit 2. 10. Treatment with aminosalicylates for less than 90 days prior to Visit 2, not on a stable dose for at least 28 days prior to Visit 2, or discontinued use within 28 days of Visit 2. 11. Treatment with any investigational medicinal product (IMP) within 30 days or 5 half-lives prior to Visit 2 (whichever is longer). 12. The patient received a live attenuated vaccine =28 days prior to Visit 2. 13. Infections (including diverticulitis) requiring treatment with i.v. antibiotics, i.v. antivirals, or i.v. antifungals within 60 days prior to Visit 2 or oral antibiotics, oral antivirals, or oral antifungals within 14 days prior to Visit 2. 14. Active infection including Clostridium difficile infection. The latter diagnosis should be based on a positive Clostridium difficile toxin assay. 15. History of listeria, psoriasis, histoplasmosis, chronic or active hepatitis B (as defined by presence of hepatitis B surface antigen [HBsAg]) or C infection (defined by presence of hepatitis C virus [HCV] RNA or positive hepatitis C antibody [anti-HCV]), human immunodeficiency virus, congenital immune deficiency, progressive multifocal leukoenchephalopathy, or central nervous system demyelinating disease. 16. Presence or history of active tuberculosis (TB) or latent TB infection where appropriate anti TB therapy cannot be documented. 17. If clinical suspicion of cytomegalovirus, cytomegalovirus testing should be undertaken. Patients with intestinal mucosa biopsy positive for cytomegalovirus at screening are to be excluded. 18. Immune deficiency demonstrated by neutropenia (absolute neutrophil count 2 mg/dL. 22. History of malignancy other than a successfully treated non-metastatic cutaneous squamous cell or basal cell carcinoma and/or localized carcinoma in situ of the cervix. If the Screening colonoscopy shows evidence of dysplasia or a malignancy, the patient is not eligible. 23. Impaired hepatic function in the absence of a diagnosis of primary sclerosing cholangitis (serum transaminases >2.5 x upper limit of normal [ULN], alkaline phosphatase >2.5 x ULN, or abnormalities in synthetic liver function tests judged by the investigator to be clinically significant), or a diagnosis of primary sclerosing cholangitis, serum transaminases >3 x ULN, alkaline phosphatase >3 x ULN, or abnormalities in synthetic liver function tests (total bilirubin >1.5 x ULN) judged by the investiga
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate changes from baseline to end of treatment in gene expression of TNFA, IL1A, REG1A, IL8, IL1B and ULRA as a composite score in mucosal biopsies induced by FE 999301 infusions in patients with active IBD (CD/UC) at one dose level (600 mg) for a total duration of 14 weeks. ;Secondary Objective: • To demonstrate changes in gene expression and methylation pattern of blood and biopsies from baseline during treatment. • To explore changes in the immunophenotyping in mononuclear cells from baseline during treatment. • To demonstrate changes from baseline to end of treatment in gene expression and methylation pattern of mucosal biopsies induced by FE 999301 infusions in patients with active IBD (CD/UC) at one dose level (600 mg) for a total duration of 14 weeks. • To explore changes of phylogenomic composition of the mucosal and stool microbiome from baseline during treatment. • To explore changes in metabolism/lipid parameters from baseline during treatment. • To explore the clinical effectiveness of treatment with FE 999301 at one dose level • To explore changes of inflammatory biomarkers (CRP, Calprotectin) during the treatment with FE 999301 at one dose level • To investigate the single dose and repeat dose PK during the treatment with FE 999301 at one dose level ;Primary end point(s): Change from baseline to Week 14 in gene expression of TNFA, IL1A, REG1A, IL8, IL1B and ULRA as a composite score in mucosal biopsies as assessed by RNA sequencing (RNAseq).;Timepoint(s) of evaluation of this end point: 14 weeks after Baseline. | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: -14 weeks after Baseline -10 weeks after Baseline -14 weeks after Baseline -14 weeks after Baseline -14 weeks after Baseline -14 weeks after Baseline -14 weeks after Baseline -14 weeks after Baseline -14 weeks after Baseline -14 weeks after Baseline -14 weeks after Baseline;Secondary end point(s): • Change from baseline to 4 and 24 hours after first i.v. infusion, Day 3, Weeks 2, 6, 10, and 14 in gene expression in blood and methylation pattern of blood and mucosal biopsies as assessed by RNAseq and reduced representation bisulfite sequencing (RRBS). • Change from baseline to 4 and 24 hours after first i.v. infusion, Day 3, Weeks 2, 6, and 10 in gene expression of muscosal biopsies as assessed by RNAseq. • Change from baseline to Week 14 in genome wide gene expression and methylation pattern of mucosal biopsies as assessed by RNA sequencing (RNAseq) and reduced representation bisulfite sequencing (RRBS). • Descriptive immunophenotyping by fluorescence-activated cell sorting (FACS) at baseline and 4 and 24 hours after first i.v. infusion, Day 3, Weeks 2, 6, 10, and 14. • Significant changes from baseline to Weeks 4 and 14 in phylogenomic composition of the mucosal and stool microbiome as assessed by 16s rDNA sequencing. • Descriptive targeted metabolomic profiling (adiponectine, leptin, insulin, wnt5a, fFRP5, Lp(a), glucose, total cholesterol, LDL, HDL, triglycerides, HbA1c, lipid electrophoresis) at baseline and Weeks 4 and 14. • Decrease in CRP from baseline to Week 14 (% of start); percent of patients with normal CRP in Week 14 • Improvement of the quality of life from baseline to week 14 measured by SF-36 • Change from baseline in IBD disease activity scores (Harvey-Bradshaw Index, Crohn's Disease Activity Index [CDAI], percentage of patients with CDAI 100 response, Mayo) over a 14-week time frame. • Decrease in calprotectin from baseline to Week 14 (% of start); percent of patients with normal calprotectin (only if | — |
Countries
Germany
Contacts
Public ContactProject Secretary
Department of Internal Medicine I
Outcome results
None listed