A phase 2, multicenter, randomized, double-blind, placebo-controlled, dose-finding trial to evaluate the efficacy and safety of IMU-838 for treatment of patients with active Crohn*s disease with an option for open-label treatment extension (CALDOSE-2)
- Conditions
- Crohn's Disease10017969
- Registration Number
- NL-OMON48184
- Lead Sponsor
- Immunic AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 12
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 fem
BT-period
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 vaccineOTHER 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 cancerTHERAPY 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 includi
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p> Efficacy<br /><br>Induction treatment phase (BT period)<br /><br>• Proportion of patients with symptomatic remission at Week 14 i.e. fulfilling<br /><br>the following criteria:<br /><br>o Remission in AP-CDAI, defined as AP-CDAI score <=1 and not worse than at<br /><br>Baseline,<br /><br>and<br /><br>o Remission in SF-CDAI, defined as SF-CDAI score <=2.8 and not worse than at<br /><br>Baseline<br /><br>For the primary analysis, the 45 mg/day IMU-838 will be compared to placebo</p><br>
- Secondary Outcome Measures
Name Time Method <p>Efficacy<br />Induction treatment phase (BT period)<br />• Proportion of patients achieving endoscopic improvement at Week 14:<br />o Reduction of the SES-CD by >=50% versus Baseline, or SES-CD score <=4 (or in<br />patients with isolated ileitis an SES CD score <=2), a reduction of >=2 points<br />from Baseline, and no ulcer sub-score >1 in any of the 5 segments (ileum,<br />right/transverse/left colon, and rectum)<br />For the analysis of the key secondary endpoint, the 45 mg/day IMU-838<br />dose will be compared to placebo.<br /><br />The primary endpoint and the key secondary endpoint will be tested<br />hierarchically. If a statistically significant difference between the treatment<br />groups is found for the primary endpoint, the analysis of the key secondary<br />endpoint will be considered confirmative. Otherwise the analysis of the key<br />secondary endpoint is considered exploratory.</p>