Phase 2 Dose-finding IMU-838 for Ulcerative Colitis (CALDOSE-1)

Phase 1

• Conditions: lcerative Colitis; MedDRA version: 20.1Level: LLTClassification code 10045365Term: Ulcerative colitisSystem Organ Class: 100000004856; Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

• Registration Number: EUCTR2017-003703-22-PT
• Lead Sponsor: Immunic AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2019-12-18
• Study Completion: 2022-11-16
• Last Update Posted: 2 September 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 263

Inclusion Criteria

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. infliximab, adalimumab, golimumab and their biosimilars, vedolizumab, or 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
a. Mayo rectal bleeding score of =1 at Screening Visit 1
b. 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 choice)
8. Male patients must agree not to father a child or to donate sperm starting at Screening and throughout the clinical trial and for 3 months after the last dose of study medication. Male patients must also either
-abstain from sexual intercourse with a female partner (acceptab

Exclusion Criteria

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, 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 (women: >6.8 mg/dL, men: >8.4 mg/dL)
15. History or clinical diagnosis of gout
16. Known or suspected Gilbert syndrome
17. Indirect (unconjugated) 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 dipropionate (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. intravenous corticosteroids
b. thiopurines including azathioprine, mercaptopurine and 6-thioguanine
c. any rectal and topical aminosalicylates and/or budesonide
22. Use of oral systemic corticosteroids =20 mg/day prednisolone equivalent including beclomethasone dipropionate (at =5 mg/day) and budeson

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified