A phase 2 Dose-finding study of IMU-838 in patients with active Crohn’s disease
- Conditions
- Crohn’s disease (CD)MedDRA version: 20.0Level: PTClassification code 10011401Term: Crohn's diseaseSystem Organ Class: 10017947 - Gastrointestinal disordersTherapeutic area: Body processes [G] - Digestive System and Oral Physiological Phenomena [G10]
- Registration Number
- EUCTR2018-001895-39-CZ
- Lead Sponsor
- Immunic AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 258
INDUCTION TREATMENT PHASE
1 Male or female patient, aged 18-80 years
2 Confirmed diagnosis of active luminal CD, at least 3 months before Screening Visit S1
3 SES-CD score of at least 6, or of at least 4 in patients with isolated ileitis (screening ileocolonoscopy and SES-CD score assessed by an in-dependent central reader blinded to center and patient information)
4 At least one aphthous ulcerative lesion or more severe ulcer accessible by ileocolonoscopy (as confirmed by an independent central blinded reader from screening ileocolonoscopy)
5 Full CDAI score =220 and =450 at Screening Visit S1
6 Average daily very soft or liquid stool frequency score (based on the BSFS) =4.0 and/or AP-CDAI score =2.0 at Screening Visit S1 (according to retrospective data of the preceding 7 days)
7 Previous treatment failure defined as:
a Patient had an inadequate response with, lost response to, or was in-tolerant to approved or experimental immunomodulators or biologics. A maximum of 3 treatment failures with biologic drugs i.e. anti-tumor necrosis factor alpha antibodies, certolizumab pegol, vedolizumab, natalizumab, ustekinumab, or experimental antibodies, i.e. not approved for the use in CD or not approved but in development for CD, is allowed; or
b Patient had an inadequate response to corticosteroids (a corticosteroidrefractory patient is defined as having active disease despite prednisolone up to 1 mg/kg/day for a period of 4 weeks), was intolerant to corticosteroids, or is corticosteroid dependent (a corticosteroid-dependent patient is defined as i) unable to reduce steroids below the equivalent of prednisolone 10 mg/day [or budesonide be-low 3 mg/day] within 3 months of starting steroids, without recurrent active disease, or ii) who has a relapse within 3 months of stopping steroids.
8 Laboratory values: Neutrophil count >1500 cells/µL (>1.5 x 10^9 cells/L), platelet count
=100 000/mm3 (=100 x 10^9/L), serum creatinine <1.5 upper limit of normal (ULN), total bilirubin, alanine aminotransferase, and aspartate aminotransferase <1.5 ULN
9 Female patients
- must be of non-childbearing potential i.e. surgically sterilized (hysterectomy, bilateral salpingectomy, bilateral oophorectomy at least 6 weeks before Screening Visit S1) or postmenopausal (where postmenopausal is defined as no menses for 12 months without an alternative medical cause), or
- if of childbearing potential, must have a negative pregnancy test at Screening Visit S1 (blood test) and at Day 0 before IMP administration (urine test). They must agree not to attempt to become pregnant, not to donate ova and to use a highly effective contraceptive method at the start of the trial (trial consent), during treatment with IMU 838, and for at least 30 days after the last intake of the IMP.
10 Male patients must agree not to father a child or to donate sperm starting at Screening Visit S1, throughout the clinical trial and for 30 days after the last intake of the IMP. Male patients must also
- abstain from sexual intercourse with a female partner (acceptable only if it is the patient’s usual form of birth control/lifestyle choice), or use adequate barrier contraception during treatment with the IMP and for at least 30 days after the last intake of the IMP, and
- if they have a female partner of childbearing potential, ensure that the partner uses a highly effective contraceptive method as outlined in inclusion criterion 9
- if they have a pregnant partner, use condoms
GI CRITERIA
1 Diagnosis of ulcerative colitis, inflammatory bowel disease type unclassified, ischemic colitis, microscopic colitis, radiation colitis or diverticular disease-associated colitis
2 High likelihood of requiring bowel surgery during the 38 weeks of the BT period
3 Ileostomy, colostomy, or known fixed symptomatic stenosis of the intestine
4 Ileorectal anastomosis or ileal-pouch anal anastomosis
5 Celiac disease
6 Presence of intra-abdominal or perianal abscess that is undrained
7 History of subtotal colectomy or imminent need for colectomy (i.e. colectomy is being planned)
8 Malabsorption or short-bowel syndrome
9 History of small bowel or colorectal cancer or gastrointestinal dysplasia (with the exception of dysplasia in polyps that have been removed)
INFECTIOUS DISEASE
10 Clostridium difficile (C. difficile) infection
a Evidence of, or treatment for, C. difficile infection within 30 days before randomization
b Positive C. difficile toxin B stool assay at Screening Visit S1
11 Treatment for intestinal pathogens other than C. difficile within 30 days before randomization
12 Other chronic systemic infections
a History of chronic systemic infections including but not limited to tuberculosis, HIV, HBV, or HCV, within 6 months before Screening Visit S1
b Positive interferon-gamma release assay for Mycobacterium tuberculosis at Screening Visit S1
c Positive HBV surface antigen (HBsAg), hepatitis B core antibody (HBcAb), positive HCV and/or HIV-antigen-antibody (HIV-Ag/Ab) test at Screening Visit S1 (even without detectable virus load in blood)
13 Any live vaccinations within 30 days before randomization except for the influenza vaccine
OTHER MEDICAL HISTORY AND CONCOMITANT DISEASE EXCLUSION CRITERIA
14 Known history of nephrolithiasis or underlying condition with a strong association o nephrolithiasis, including hereditary hyperoxaluria or hereditary hyperuricemia
15 Diagnosis or suspected liver function impairment which may cause, as assessed by the investigator, a potential for fluctuating liver function tests during this trial
16 Renal impairment i.e. eGFR >60 mL/min/1.73 m²
17 Serum uric acid levels at Screening Visit S1 >1.2 x ULN (for women >6.8 mg/dL, for men >8.4 mg/dL)
18 History or clinical diagnosis of gout
19 Known or suspected Gilbert syndrome
20 Indirect (unconjugated) bilirubin =1.2 x ULN (i.e. =1.1 mg/dL) at Screening Visit S1
21 Concurrent malignancy or prior malignancy within the previous 10 years except for the following: adequately-treated non-melanoma skin cancer and adequately-treated cervical cancer
THERAPY EXCLUSION CRITERIA
22 Use of any IMP within 8 weeks or 5 x the respective half-life before randomization, whichever is longer
23 Use of the following medications within 2 weeks before randomization:
a Tofacitinib
b Methotrexate,
c Mycophenolate mofetil
d Any calcineurin inhibitors (e.g. tacrolimus, cyclosporine, or pimecrolimus)
e Oral systemic corticosteroids >20 mg/day prednisolone equivalent including beclomethasone dipropionate (at >5 mg/day) and budesonide (at >9 mg/day)
f Oral aminosalicylates (e.g. mesalazines) >4 g/day
24 Use of the following medications within 4 weeks before randomization:
a Use of intravenous corticosteroids
b Use of thiopurines including azathioprine, 6-mercaptopurine and 6-thioguanine
c Use of any rectal or topical aminosalicylates and/or budesonide
25 Use of oral systemic corticosteroids =20 mg/day prednisolone equiva
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method