Phase 2 Dose-finding IMU-838 for Ulcerative Colitis

• Register: ClinicalTrials.gov
• Last refreshed on: 13 February 2023
• Main ID: NCT03341962
• Date of registration: 08/11/2017
• Prospective Registration: Yes
• Primary sponsor: Immunic AG
• Public title: Phase 2 Dose-finding IMU-838 for Ulcerative Colitis CALDOSE-1
• Scientific title: 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
• Date of first enrolment: March 15, 2018
• Target sample size: 263
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/show/NCT03341962
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Care Provider, Investigator).
• Phase: Phase 2

Countries of recruitment

Albania, Belarus, Bosnia and Herzegovina, Bulgaria, Croatia, Czechia, Georgia, Netherlands, North Macedonia, Poland, Portugal, Romania, Russian Federation, Serbia, Spain, Turkey, Ukraine, United Kingdom, United States

Contacts

• Name: Andreas Muehler
• Affiliation: Immunic Therapeutics

Key inclusion & exclusion criteria

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:

1. 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

2. 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, platelet count =100 000 /mm3,
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.

8. Male patients must also either

- 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 IMU-383 and for at least 3
months after the last dose of study medication

For Poland and the UK the following additional requirement apply:

- if male patients have a female partner of childbearing potential, the partner
should use a highly effective contraceptive method as outlined in inclusion
criterion 7

And additionally, for Poland only:

- if male patients have a pregnant partner, they must use condoms while taking
study medication to avoid exposure of the fetus to study medication

9. Ability to understand and comply with study procedures and restrictions

10. The patient is legally competent, has been informed of the nature, the scope and the
relevance of the study, voluntarily agrees to participation and the study's provisions
and has duly signed the informed consent form

Maintenance phase

1. Symptomatic remission achieved at Week 10 or Week 22 of the induction phase

Open-label treatment extension arm

1. Patient is in the induction phase, had received at least 6 weeks of blinded study
treatment and completed the sigmoidoscopy (incl. biopsy) regularly scheduled at Week 10/End
of Induction, and has neither reached symptomatic remission nor symptomatic response

OR

Patient is in the extended induction phase, had completed all Week 10 assessments, and has
not reached symptomatic remission during or at the end of the extended induction phase, Or
Patient is in the maintenance phase and discontinues from the maintenance phase due to
symptomatic UC relapse or other reasons with a flexible sigmoidoscopy performed at
discontinuation (if the previous sigmoidoscopy had been performed more than 4 weeks before
discontinuation)

OR

Patient has completed the maintenance phase as scheduled (including all Week 50
assessments)

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)




Age minimum: 18 Years
Age maximum: 80 Years
Gender: All

Health Condition(s) or Problem(s) studied

Ulcerative Colitis

Intervention(s)

Drug: IMU-838

Drug: Placebo

Primary Outcome(s)

Symptomatic remission and endoscopic healing [Time Frame: Week 10]

Secondary Outcome(s)

Fecal calprotectin (fCP) [Time Frame: Changes from Baseline over 10 or 22 weeks]

Maintenance Phase: fCP [Time Frame: up to Week 50]

Maintenance Phase: Proportion of patients with symptomatic response [Time Frame: up to Week 50]

Open-label Phase: symptom control [Time Frame: Up to 10 years]

Safety: 12-lead electrocardiogram (ECG) [Time Frame: up to Week 50]

Safety: Urinalysis [Time Frame: up to Week 50]

Partial Mayo Score [Time Frame: Up to Week 22]

PK: area under the drug concentration-time curve (AUC) from time zero to 24 hours (AUC0-24h) [Time Frame: pre-dose, 1, 2, 3, 4, 5, 6 hours post PK dose; 24 hours post PK dose; 48 hours post PK dose; 72 hours post PK dose]

Patient Reported Outcome (PRO)-2 Mayo Score [Time Frame: Up to Week 22]

PK: AUC time zero to infinity (AUC0-inf) [Time Frame: pre-dose, 1, 2, 3, 4, 5, 6 hours post PK dose; 24 hours post PK dose; 48 hours post PK dose; 72 hours post PK dose]

Proportion of patients with endoscopic healing [Time Frame: Week 10]

Symptomatic remission during induction [Time Frame: 22 weeks]

PK: AUC time zero to last measurable concentration (AUC0-t) [Time Frame: pre-dose, 1, 2, 3, 4, 5, 6 hours post PK dose; 24 hours post PK dose; 48 hours post PK dose; 72 hours post PK dose]

PK: IMU-838 trough level [Time Frame: up to Week 10]

PK: time to Cmax (Tmax) [Time Frame: pre-dose, 1, 2, 3, 4, 5, 6 hours post PK dose; 24 hours post PK dose; 48 hours post PK dose; 72 hours post PK dose]

Maintenance Phase: CRP [Time Frame: up to Week 50]

Maintenance Phase: Proportion of patients without relapse [Time Frame: Week 50]

Proportion of patients with clinical response [Time Frame: 10 weeks]

Safety: Adverse Events [Time Frame: up to Week 50]

Open-label Phase: CRP [Time Frame: Up to 10 years]

PK: IMU-838 plasma level [Time Frame: Week 2]

Safety: Blood Chemistry [Time Frame: up to Week 50]

Safety: Hematology [Time Frame: up to Week 50]

Maintenance Phase: corticosteroid-free remission [Time Frame: Week 50]

Safety: blood pressure [Time Frame: up to Week 50]

PK: maximum plasma concentration (Cmax) [Time Frame: pre-dose, 1, 2, 3, 4, 5, 6 hours post PK dose; 24 hours post PK dose; 48 hours post PK dose; 72 hours post PK dose]

C-reactive protein (CRP) [Time Frame: Changes from Baseline over 10 or 22 weeks]

Full Mayo Score [Time Frame: Week 10]

Maintenance Phase: Mayo PRO-2 score [Time Frame: Week 50]

Maintenance Phase: Proportion of patients with endoscopic healing [Time Frame: Week 50]

Maintenance Phase: Proportion of patients with microscopic healing [Time Frame: Week 50]

Open-label Phase: fCP [Time Frame: Up to 10 years]

Proportion of patients with symptomatic response [Time Frame: 22 weeks]

Time to achieving symptomatic remission [Time Frame: 22 weeks]

Safety: Coagulation [Time Frame: up to Week 50]

Safety: heart rate [Time Frame: up to Week 50]

Safety: Number of participants with clinically significant findings during physical examination [Time Frame: up to Week 50]

Symptomatic remission and endoscopic healing at different doses [Time Frame: Week 10]

Maintenance Phase: Time to relapse [Time Frame: up to Week 50]

Safety: body weight [Time Frame: up to Week 50]

Safety: Micro ribonucleic acid expression [Time Frame: pre-dose and 24 hours post-dose]

Secondary ID(s)

2017-003703-22

P2-IMU-838-UC

Source(s) of Monetary Support

Please refer to primary and secondary sponsors