A phase 2, multicenter, randomized, double-blind, placebo controlled, dose-finding study to evaluate the efficacy and safety of IMU 838 for induction and maintenance therapy in moderate-to-severe ulcerative colitis; CALDOSE-1
- Conditions
- ulcerative colitis10017969
- Registration Number
- NL-OMON55843
- Lead Sponsor
- Immunic AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 7
Induction phase
1. Male and female patients, aged 18 - 80 years
2. UC diagnosed more than 3 months before Screening (Day -30) as documented in
the medical chart
3. Previous treatment failure defined as:
a. Patient had an inadequate response with, lost response to, or was intolerant
to approved or experimental immunomodulators (azathioprine, 6-mercaptopurine,
6-thioguanine, methotrexate, or tofacitinib) or biologics (no more than 2
treatment failures with biologic drugs i.e. anti-tumor necrosis factor a
antibodies [infliximab, adalimumab, golimumab and their biosimilars],
vedolizumab, or certain experimental antibodies [ustekinumab]); or
b. Patient had an inadequate response to, was intolerant to, or is
corticosteroid dependent (corticosteroid-dependent patients are defined as i)
unable to reduce steroids below the equivalent of prednisolone 10 mg/day within
3 months of starting steroids, without recurrent active disease, or ii) who
have a relapse within 3 months of stopping steroids.
4. Active disease defined as
a. Mayo stool frequency score of >=2 at Screening Visit 1
b. Mayo rectal bleeding score of >=1 at Screening Visit 1
c. modified Mayo endoscopy subscore of >=2 at the screening flexible
sigmoidoscopy (endoscopy assessed by an independent central reader blinded to
screening center and patient information)
5. Endoscopic appearance typical for UC and extending >15 cm from the anal
verge as confirmed by an independent central reader (blinded to screening
center and patient information)
6. Laboratory values: Neutrophil count >1500 cells/µL (> 1.5 x 10^9/L),
platelet count >=100 000/mm3 (>= 100 10^9/L), serum creatinine <1.5 x upper
limit of normal (ULN), total bilirubin, alanine aminotransferase (ALT), and
gamma-glutamyl transferase (GGT) <1.5 x ULN
7. Female patients must
a. Be of non-child-bearing potential i.e. surgically sterilized (hysterectomy,
bilateral salpingectomy, bilateral oophorectomy at least 6 weeks before
Screening) or post-menopausal (where postmenopausal is defined as no menses for
12 months without an alternative medical cause), or
b. If of child-bearing potential, must have a negative pregnancy test at
Screening (blood test) and before the first study drug administration (Day 0
urine test). They must agree not to attempt to become pregnant, must not donate
ova, and must use a highly effective contraceptive method 2 months before
Screening, during treatment with IMU-838, and at least 3 months after the last
dose of study therapy
Highly effective forms of birth control are those with a failure rate less than
1% per year and include:
* oral, intravaginal, or transdermal combined (estrogen and progestogen
containing) hormonal contraceptives associated with inhibition of ovulation
* oral, injectable, or implantable progestogen-only hormonal contraceptives
associated with inhibition of ovulation
* intrauterine device or intrauterine hormone-releasing system
* bilateral tubal occlusion
* vasectomized partner (i.e. the patient*s male partner has undergone effective
surgical sterilization before the female patient entered the clinical trial and
he is the sole sexual partner of the female patient during the clinical trial)
* sexual abstinence (acceptable only if it is the patient*s usual form of birth
control/lifestyle ch
Gastrointestinal exclusion criteria:
1. Diagnosis of Crohn*s disease, inflammatory bowel disease type unclassified,
ischemic colitis, microscopic colitis, radiation colitis or diverticular
disease-associated colitis
2. Ileostomy, colostomy, or known fixed symptomatic stenosis of the intestine
3. History of colectomy with ileorectal anastomosis or ileal-pouch anal
anastomosis or imminent need for colectomy (i.e. colectomy is being planned)
4. Active therapeutically uncontrollable abscess or toxic megacolon
5. Malabsorption or short bowel syndrome
6. History of colorectal cancer or colorectal dysplasia (with the exception of
dysplasia in polyps which have been removed)
Infectious disease exclusion criteria
7. Clostridium difficile (C. difficile) infection
o Evidence of, or treatment for C. difficile infection within 30 days before
first randomization
o Positive C. difficile toxin B stool assay during the screening period
8. Treatment for intestinal pathogens other than C. difficile within 30 days
prior to first randomization
9. Other chronic systemic infections
o History of chronic systemic infections including but not limited to
tuberculosis, human immunodeficiency virus (HIV), hepatitis B or C, within 6
months before Screening
o Positive interferon-gamma release assay (IGRAs) for Mycobacterium
tuberculosis at Screening
o Positive HBsAg (hepatitis B virus surface antigen), HBcAb (hepatitis B core
antibody), positive hepatitis C virus and/or HIV-antigen-antibody (HIV-Ag/Ab)
test at Screening
10. Any live vaccinations within 30 days prior to study drug administration
except for the influenza vaccine
Other medical history and concomitant disease exclusion criteria
11. Known history of nephrolithiasis or underlying condition with a strong
association of nephrolithiasis, including hereditary hyperoxaluria or
hereditary hyperuricemia
12. Diagnosis or suspected liver function impairment which may cause, as
assessed by the investigator, a potential for fluctuating liver function tests
during this trial
13. Renal impairment i.e. estimated glomerular filtration rate <=60 mL/min/1.73m2
14. Serum uric acid levels at Screening >1.2 x ULN (for women >6.8 mg/dL, for
men >8.4 mg/dL)
15. History or clinical diagnosis of gout
16. Known or suspected Gilbert syndrome
17. Indirect (unconjucated) bilirubin >=1.2 x ULN at Screening (i.e. >= 1.1 mg/dL)
18. 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:
19. Use of any investigational product within 8 weeks or 5 x the respective
half-life before first randomization, whatever is longer
20. Use of the following medications within 2 weeks before first 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 diproprionate (at >5 mg/day) and budesonide (multi-matrix [MMX]
at >9 mg/day)
f. Oral aminosalicylates (e.g. mesalazines) >4 g/day
21. Use of the following medications within 4 weeks before first randomization:
a. Use of intravenous corticosteroids
b. Use of thiopurines inc
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary endpoint<br /><br>• Composite endpoint: Proportion of patients with both, symptomatic remission<br /><br>and endoscopic healing at Week 10</p><br>
- Secondary Outcome Measures
Name Time Method