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

• ClinicalTrials.gov Identifier: NCT03341962
• Recruitment Status: Active, not recruiting
• First Posted: November 14, 2017
• Last Update Posted: February 1, 2023
• Sponsor: Immunic AG
• Information provided by (Responsible Party): Immunic AG

Study Description

Brief Summary:

This is 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 with an option for open-label treatment extension in moderate-to-severe ulcerative colitis (CALDOSE-1).

Condition or disease	Intervention/treatment	Phase
Ulcerative Colitis	Drug: IMU-838; Drug: Placebo	Phase 2

Detailed Description:

The investigational medicinal product (IMP) IMU-838 (vidofludimus calcium) is a new compound that selectively inhibits the human enzyme dihydroorotate dehydrogenase (DHODH). Dihydroorotate dehydrogenase plays a major role in the de-novo pyrimidine synthesis and is specifically expressed at high levels in proliferating or activated lymphocytes. Resting lymphocytes satisfy their pyrimidine requirements through a DHODH-independent salvage pathway. Thus, IMU-838-mediated DHODH inhibition selectively affects activated, rapidly proliferating lymphocytes. The metabolic stress secondary to DHODH inhibition leads to a reduction of pro-inflammatory cytokine release including interleukin (IL)-17 (IL-17A and IL-17F) and interferon gamma (IFNγ), and to an increased apoptosis in activated lymphocytes.

This is a phase 2, multicenter, randomized, double-blind, and placebo-controlled trial in patients with moderate-to-severe UC with an option for open-label treatment extension. The study comprises a blinded induction phase to establish the optimal dose of IMU-838 to induce response and remission, a blinded maintenance phase to evaluate the potential of IMU-838 to maintain remission until Week 50, and an open-label treatment extension arm for all patients who discontinue the blinded phase as scheduled or prematurely, subject to certain restrictions. A subset of patients will undergo a pharmacokinetic (PK) period at the start of the open-label period to establish a full single-dose PK profile.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 263 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official 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
• Actual Study Start Date: March 15, 2018
• Actual Primary Completion Date: November 16, 2022
• Estimated Study Completion Date: June 30, 2029

Arms and Interventions

Arm	Intervention/treatment
Experimental: 10 mg IMU-838 (Induction); Two 5 mg tablets once daily of IMU-838 for 10 to 22 weeks depending on symptomatic remission at Weeks 10 or 22. Patients will receive only half of their assigned full dose during the first week of treatment.	Drug: IMU-838; IMU-838 tablet; Other Names: IM90838; vidofludimus calcium
Experimental: 30 mg IMU-838 (Induction); Two 15 mg tablets once daily of IMU-838 for 10 to 22 weeks depending on symptomatic remission at Weeks 10 or 22. Patients will receive only half of their assigned full dose during the first week of treatment.	Drug: IMU-838; IMU-838 tablet; Other Names: IM90838; vidofludimus calcium
Experimental: 45 mg IMU-838 (Induction); Two 22.5 mg tablets once daily of IMU-838 for 10 to 22 weeks depending on symptomatic remission at Weeks 10 or 22. Patients will receive only half of their assigned full dose during the first week of treatment.	Drug: IMU-838; IMU-838 tablet; Other Names: IM90838; vidofludimus calcium
Placebo Comparator: placebo (during induction); The placebo tablets will be identical to the IMU-838 tablets in terms of appearance, constitution of inactive ingredients, and packaging.	Drug: Placebo; Tablets manufactured to mimic IMU-838 tablets; Other Name: Placebo (for IMU-838)
Experimental: 10 mg IMU-838 (Maintenance); Two 5 mg tablets once daily of IMU-838 until Week 50 or ulcerative colitis relapse.	Drug: IMU-838; IMU-838 tablet; Other Names: IM90838; vidofludimus calcium
Experimental: 30 mg IMU-838 (Maintenance); Two 15 mg tablets once daily of IMU-838 until Week 50 or ulcerative colitis relapse.	Drug: IMU-838; IMU-838 tablet; Other Names: IM90838; vidofludimus calcium
Placebo Comparator: placebo (during maintenance); The placebo tablets will be identical to the IMU-838 tablets in terms of appearance, constitution of inactive ingredients, and packaging. Patients who have received placebo during the induction phase will be 're-randomized' to continue to receive placebo (in a blinded fashion).	Drug: Placebo; Tablets manufactured to mimic IMU-838 tablets; Other Name: Placebo (for IMU-838)
Experimental: 30 mg IMU-838 (Open-label); Two 15 mg tablets once daily of IMU-838 or one 30 mg tablet IMU-838 once daily for up to 10 years and up to 3 years in UK sites	Drug: IMU-838; IMU-838 tablet; Other Names: IM90838; vidofludimus calcium

Outcome Measures

Primary Outcome Measures :

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

   Composite endpoint: Proportion of patients with both, symptomatic remission and endoscopic healing at Week 10.

   All patients (both, Enrollment Period 1 and Enrollment Period 2 patients) who were randomized to 30 mg/day and 45 mg/day will be used for the assessment of the primary efficacy endpoint

Secondary Outcome Measures :

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

   Proportion of patients with both symptomatic remission and endoscopic healing at Week 10

   • (all individual IMU-838 doses will be compared with one another and to placebo)
2. Symptomatic remission during induction [ Time Frame: 22 weeks ]
   Proportion of patients achieving symptomatic remission during the induction phase (including extended induction phase)
3. Time to achieving symptomatic remission [ Time Frame: 22 weeks ]
   Time to achieving symptomatic remission within the induction/extended induction phase
4. Proportion of patients with clinical response [ Time Frame: 10 weeks ]
   Proportion of patients with clinical response at Week 10
5. Proportion of patients with endoscopic healing [ Time Frame: Week 10 ]
   Proportion of patients with endoscopic healing at Week 10
6. Proportion of patients with symptomatic response [ Time Frame: 22 weeks ]
   Proportion of patients with symptomatic response during the induction phase (including extended induction phase)
7. Full Mayo Score [ Time Frame: Week 10 ]
   Change in full Mayo Score compared to baseline at Week 10
8. Partial Mayo Score [ Time Frame: Up to Week 22 ]
   Change in partial mayo score over 10 or 22 weeks
9. Patient Reported Outcome (PRO)-2 Mayo Score [ Time Frame: Up to Week 22 ]
   Change in PRO-2 mayo score over 10 or 22 weeks
10. Fecal calprotectin (fCP) [ Time Frame: Changes from Baseline over 10 or 22 weeks ]
    Change in the presence of biomarker fCP in stool samples
11. C-reactive protein (CRP) [ Time Frame: Changes from Baseline over 10 or 22 weeks ]
    Change in the presence of biomarker CRP in blood samples
12. Safety: Adverse Events [ Time Frame: up to Week 50 ]
    Incidence and Severity of AEs
13. Safety: Number of participants with clinically significant findings during physical examination [ Time Frame: up to Week 50 ]
    The emergence of any clinically significant findings compared to screening will be captured during the induction and maintenance phases
14. Safety: body weight [ Time Frame: up to Week 50 ]
    Changes in body weight during the induction and maintenance phases
15. Safety: blood pressure [ Time Frame: up to Week 50 ]
    Changes in blood pressure (mm Hg) during the induction and maintenance phases
16. Safety: heart rate [ Time Frame: up to Week 50 ]
    Changes in heart rate (beats per minute) during the induction and maintenance phases
17. Safety: 12-lead electrocardiogram (ECG) [ Time Frame: up to Week 50 ]
    Number of patients with clinically significant changes in ECG
18. Safety: Hematology [ Time Frame: up to Week 50 ]
    Number of participants with abnormal hematology laboratory values
19. Safety: Blood Chemistry [ Time Frame: up to Week 50 ]
    Number of participants with abnormal blood chemistry laboratory values
20. Safety: Coagulation [ Time Frame: up to Week 50 ]
    Number of participants with abnormal coagulation laboratory values
21. Safety: Urinalysis [ Time Frame: up to Week 50 ]
    Number of participants with abnormal urinalysis laboratory values
22. Safety: Micro ribonucleic acid expression [ Time Frame: pre-dose and 24 hours post-dose ]
    Micro ribonucleic acid-122 (miR-122) expression (before first dose and 24 hours after first dose)
23. PK: IMU-838 trough level [ Time Frame: up to Week 10 ]
    Measurement of pre-dose (trough) blood plasma levels of IMU-838 throughout the induction period
24. PK: IMU-838 plasma level [ Time Frame: Week 2 ]
    Measurement of post-dose blood plasma levels of IMU-838 at Week 2
25. 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 ]
    Single-dose PK measurement of AUC0-24h in a subset of patients in the open-label phase
26. 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 ]
    Single-dose PK measurement of AUC0-t in a subset of patients in the open-label phase
27. 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 ]
    Single-dose PK measurement of AUC0-inf in a subset of patients in the open-label phase
28. 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 ]
    Single-dose PK measurement of Cmax in a subset of patients in the open-label phase
29. 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 ]
    Single-dose PK measurement of Tmax in a subset of patients in the open-label phase
30. Maintenance Phase: Proportion of patients with symptomatic response [ Time Frame: up to Week 50 ]
    Proportion of patients in symptomatic remission by visit up to Week 50
31. Maintenance Phase: Mayo PRO-2 score [ Time Frame: Week 50 ]
    Time course of Mayo PRO-2 score until Week 50
32. Maintenance Phase: Time to relapse [ Time Frame: up to Week 50 ]
    Time to symptomatic ulcerative colitis (UC) relapse
33. Maintenance Phase: Proportion of patients without relapse [ Time Frame: Week 50 ]
    Proportion of patients without symptomatic UC relapse until Week 50
34. Maintenance Phase: fCP [ Time Frame: up to Week 50 ]
    Change in the presence of biomarker fCP in stool samples
35. Maintenance Phase: CRP [ Time Frame: up to Week 50 ]
    Change in the presence of biomarker CRP in blood samples
36. Maintenance Phase: Proportion of patients with endoscopic healing [ Time Frame: Week 50 ]
    Proportion of patients with endoscopic healing at Week 50
37. Maintenance Phase: Proportion of patients with microscopic healing [ Time Frame: Week 50 ]
    Proportion of patients with microscopic healing at Week 50
38. Maintenance Phase: corticosteroid-free remission [ Time Frame: Week 50 ]
    Corticosteroid-free remission at Week 50 in patients receiving corticosteroids at Baseline
39. Open-label Phase: symptom control [ Time Frame: Up to 10 years ]
    Proportion of patients with symptom control
40. Open-label Phase: fCP [ Time Frame: Up to 10 years ]
    Change in the presence of biomarker fCP in stool samples
41. Open-label Phase: CRP [ Time Frame: Up to 10 years ]
    Change in the presence of biomarker fCP in blood samples

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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 α 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)

   Infectious disease exclusion criteria

7. Clostridium difficile (C. difficile) infection

   • Evidence of, or treatment for C. difficile infection within 30 days before first randomization
   • 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

   • History of chronic systemic infections including but not limited to tuberculosis, human immunodeficiency virus (HIV), hepatitis B or C, within 6 months before Screening
   • Positive interferon-gamma release assay (IGRAs) for Mycobacterium tuberculosis at Screening
   • 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 (eGFR) ≤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 (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:

    1. Tofacitinib
    2. Methotrexate
    3. Mycophenolate mofetil
    4. Any calcineurin inhibitors (e.g. tacrolimus, cyclosporine, or pimecrolimus)
    5. Oral systemic corticosteroids >20 mg/day prednisolone equivalent including beclomethasone dipropionate (at >5 mg/day) and budesonide (multi-matrix [MMX] at >9 mg/day)
    6. Oral aminosalicylates (e.g. mesalazines) >4 g/day

21. Use of the following medications within 4 weeks before first randomization:

    1. Use of intravenous corticosteroids
    2. Use of thiopurines including azathioprine, mercaptopurine and 6-thioguanine
    3. Use of 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 budesonide (MMX at ≤9 mg/day) unless they have been used for at least 4 weeks before first randomization and at a stable dose for at least 2 weeks before first randomization
23. Oral aminosalicylates (e.g. mesalazines) ≤4 g/day unless they have been used for at least 6 weeks and with a stable dose for at least 3 weeks before first randomization

24. Use of biologics as follows:

    1. anti-tumor necrosis factor α antibodies (infliximab, adalimumab, golimumab, including their biosimilars) within 4 weeks before first randomization
    2. vedolizumab and ustekinumab within 8 weeks before first randomization
25. Use of the DHODH inhibitors leflunomide or teriflunomide within 6 months before first randomization
26. Any use of natalizumab (Tysabri™) within 12 months before first randomization

27. Use of the following concomitant medications is prohibited at Screening and throughout the duration of the trial:

    • any medication known to significantly increase urinary elimination of uric acid, in particular lesinurad (Zurampic™) as well as uricosuric drugs such as probenecid
    • treatments for any malignancy, in particular irinotecan, paclitaxel, tretinoin, bosutinib, sorafenib, enasidenib, erlotinib, regorafenib, pazopanib and nilotinib
    • any drug significantly restricting water diuresis, in particular vasopressin and vasopressin analogs
    • Rosuvastatin at doses ˃10 mg/day

    General exclusion criteria

28. History of, or current serious, severe, or unstable (acute or progressive) physical or mental illness, or any medical condition, including laboratory anomalies or renal or hepatic impairment, that may require treatment or would put the patient in jeopardy if he/she was to participate in the study
29. Known hypersensitivity to DHODH inhibitors (teriflunomide, leflunomide) or any ingredient of the investigational product
30. Pregnancy or breastfeeding
31. History of drug or alcohol abuse during the past year
32. Concurrent participation in any other clinical trial using an investigational medicinal product or medical device
33. An employee of an investigator or sponsor or an immediate relative of an investigator

Exclusion criteria for open-label treatment extension arm

1. Any ongoing, clinically significant treatment-emergent (started during the IMU-838 treatment in the blinded treatment arms) adverse event (AE) or laboratory abnormality (including blood chemistry and urinalysis) as assessed by the investigator *
2. Significant treatment or study non-compliance during induction and/or maintenance phase (as assessed by the investigator), and/or inability or unwillingness to follow instructions by study personnel as assessed by the investigator

3. Significant protocol deviations during induction and/or maintenance phase that are assessed by the investigator to negatively affect further patient cooperation in this study

   • If treatment-emergent AEs are the reason for exclusion from the open-label extension arm, the eligibility can be re-assessed up to 30 days following the last treatment in the blinded treatment arms.

Contacts and Locations

Locations

United States, Arizona

Del Sol Research Management, LLC

Tucson, Arizona, United States, 85710

United States, California

Axis Clinical Trials

Los Angeles, California, United States, 90036

Ventura Clinical Trials

Ventura, California, United States, 93003

United States, Florida

Alliance Medical Research, LLC

Lighthouse Point, Florida, United States, 33071

Medley Research Associates

Medley, Florida, United States, 33166

Global Life Research LLC

Miami, Florida, United States, 33155-4630

Family Clinical Trials

Pembroke Pines, Florida, United States, 33026-3240

Clinical Research Trials of Florida, Inc.

Tampa, Florida, United States, 33607

United States, Georgia

Atlanta Gastroenterology Associates, LLC

Atlanta, Georgia, United States, 30308

United States, Iowa

McFarland Clinic, P.C.

Ames, Iowa, United States, 50010

United States, Massachusetts

Commonwealth Clinical Studies

Brockton, Massachusetts, United States, 02302

United States, North Carolina

PMG Research of Salisbury, LLC

Salisbury, North Carolina, United States, 28144

United States, South Carolina

Clinical Trials of South Carolina

Charleston, South Carolina, United States, 29406-7132

United States, Texas

First Street Surgical Hospital

Bellaire, Texas, United States, 77401

United States, Washington

Digestive Health Specialists

Tacoma, Washington, United States, 98405

Albania

Durres Regional Hospital

Durres, Albania, 2001

Regional Hospital of Shkoder

Shkoder, Albania, 4001

University Hospital Center Mother Teresa

Tirana, Albania, 1000

Belarus

Gomel Regional Clinical Hospital

Gomel, Belarus, 246029

Republican Scientific and Practical Center for Radiation Medicine and Human Ecology

Gomel, Belarus, 246040

Vitiebsk State Order of Peoples' Friendship Medical University

Vitebsk, Belarus, 210009

Bosnia and Herzegovina

University Clinical Centre of the Republic of Srpska, Internal Medicine Clinic, Department of Gastroenterology and Hepatology

Banja Luka, Bosnia and Herzegovina, 78000

University Clinical Hospital Mostar, Internal Medicine Clinic, Department of Gastroenterology

Mostar, Bosnia and Herzegovina, 88000

Bulgaria

Multiprofile Hospital for Active Treatment Blagoevgrad AD

Blagoevgrad, Bulgaria, 2700

Mhat Byala

Byala, Bulgaria, 187100

Multiprofile Hospital for Active Treatment "Dr. Hristo Stambolski" EOOD

Kazanlak, Bulgaria, 6100

Medical Center "Medconsult Pleven" OOD

Pleven, Bulgaria, 5800

Medical Center Exacta Medica

Pleven, Bulgaria, 5800

University Multiprofile Hospital for Active Treatment "Sveti Georgi" EAD, Plovdiv, Gastroenterology clinic

Plovdiv, Bulgaria, 4002

Medical Center "Hera" EOOD

Sofia, Bulgaria, 1510

Diagnostic-Consulting Center "Convex" EOOD

Sofia, Bulgaria, 1680

Croatia

General Hospital Bjelovar

Bjelovar, Croatia, 43000

Clinical Hospital Center Osijek

Osijek, Croatia, 31000

Clinical Hospital Center Rijeka

Rijeka, Croatia, 51000

Clinical Hospital Center Split

Split, Croatia, 21000

General Hospital Vukovar

Vukovar, Croatia, 32000

Clinical Hospital Center Zagreb

Zagreb, Croatia, 10000

Clinical Hospital Dubrava

Zagreb, Croatia, 10000

Polyclinic Solmed Zagreb

Zagreb, Croatia, 10000

Clinical Hospital Center Split

Zagreb, Croatia, 21000

Czechia

Asclepiades - Interna a gastroenterologie s.r.o. - Havířov

Havířov, Czechia, 73601

Hepato-Gastroenterologie HK, s.r.o. Poliklinika III

Hradec Králové, Czechia, 50012

Artroscan s.r.o.

Ostrava - Třebovice, Czechia, 72200

FaraCol s.r.o. - Prague

Praha, Czechia, 10100

MEDICON a.s. - Poliklinika Budějovická Gastroenterologie

Praha, Czechia, 14000

Klinika ResTrial

Praha, Czechia, 14300

Všeobecná fakultní nemocnice v Praze IV. interní klinika VFN a 1. LF UK

Praha, Czechia, 17004

Georgia

Academician Z.Tskhakaia West Georgia National Center of Interventional Medicine

Kutaisi, Georgia, 4600

LTD Unimedi Kakheti - Caraps Medline

Tbilisi, Georgia, 0159

Netherlands

Amsterdam UMC, locatie AMC

Amsterdam, Netherlands, 1105 AZ

Albert Schweitzer Hospital

Dordrecht, Netherlands, 3318 AT

Elisabeth-TweeSteden Hospital

Tilburg, Netherlands, 5022 GC

North Macedonia

City General Hospita 8th September

Skopje, North Macedonia, 1000

University Clinic for Hematology - Skopje - Macedonian Hematology Association

Skopje, North Macedonia, 1131

Poland

Centrum Usług Medycznych MaxMed

Bochnia, Poland, 32700

Centrum Medyczne Pratia Gdynia

Gdynia, Poland, 81338

Centrum Medyczne Endo-med Sp. z o.o.

Karczew, Poland, 05480

Vita Longa Sp. z o.o.

Katowice, Poland, 40748

GLOBE Badania Kliniczne Sp. z o.o.

Kłodzko, Poland, 57300

Samodzielny Publiczny Szpital Kliniczny Nr 4 w Lublinie Oddział Gastroenterologii

Lublin, Poland, 20954

Zakład leczniczy ALLMEDICA BADANIA KLINICZNE Sp. z o.o. Sp. K.

Nowy Targ, Poland, 34400

Etyka Ośrodek Badań Klinicznych

Olsztyn, Poland, 10117

Ars Medical - Szpital, Ars Medical - Ambulatorium

Piła, Poland, 64920

SOLUMED Centrum Medyczne

Poznań, Poland, 60529

Niepubliczny Zakład Opieki Zdrowotnej Centrum Medyczne HCP - Lecznictwo Stacjonarne

Poznań, Poland, 61485

Endoskopia Sp. z o.o.

Sopot, Poland, 81756

Klinika Medifem

Warszawa, Poland, 02-884

Centrum Badawcze Współczesnej Terapii, Prywatny Gabinet Lekarski dr Anna Bochenek-Mularczyk

Warszawa, Poland, 02679

Przychodnia Vistamed

Wroclaw, Poland, 53149

Centrum Medyczne OMNI Clinic Sp. z o.o. Spółka Komandytowa

Wrocław, Poland, 54204

Centrum Medyczne Med-Gastr Sp. z o.o. Spółka Komandytowa

Łódz, Poland, 91034

Salve Medica Sp. z o.o. Spółka Komandytowa

Łódź, Poland, 91211

Portugal

Centro Hospitalar e Universitário de Coimbra, EPE - Hospitais da Universidade de Coimbra

Coimbra, Portugal, 3000-075

Hospital da Senhora da Oliveira - Guimarães, EPE

Guimarães, Portugal, 4835-044

Centro Hospitalar de Entre o Douro e Vouga, EPE - Hospital São Sebastião

Santa Maria da Feira, Portugal, 4520-211

Romania

S.C. MEDLIFE S.A., Sectia Gastroenterologie

Bucharest, Romania, 10719

Spitalul Clinic Colentina, Sectia Gastroenterologie

Bucharest, Romania, 20125

Institutul Clinic Fundeni, Sectia Clinica Gastroenterologie III

Bucharest, Romania, 22328

S.C. Cabinet Particular Policlinic Algomed SRL, Specialitatea Gastroenterologie

Timisoara, Romania, 300002

Russian Federation

Kazan State Medical University

Kazan, Russian Federation, 420012

SEI HPE "Kuban State Medical University" of MoH and SD, CBHS Regional Clinical Hospital No.2

Krasnodar, Russian Federation, 350072

Central Clinical Hospital of the Russian Academy of Sciences

Moscow, Russian Federation, 119435

Federal Medical Biophysical Center n.a. Burnazyan

Moscow, Russian Federation, 123098

Clinical Research Institution of Moscow Region named after M. F. Vladimirsky

Moscow, Russian Federation, 129110

Novosibirskiy Gastrocenter, LLC

Novosibirsk, Russian Federation, 630007

FSBEI HE "Military Medical Academy n.a. S.M. Kirov" under the Ministry of Defence of Russian Federation

Saint Petersburg, Russian Federation, 191015

Hospital of Saint Martyr Elizaveta

Saint Petersburg, Russian Federation, 195257

Research Center Eco-Safety, LLC

Saint Petersburg, Russian Federation, 196143

Gastroenterological Center "Expert" LLC

Saint Petersburg, Russian Federation, 196620

Saint Petersburg State Medical University named after I.P. Pavlov

Saint Petersburg, Russian Federation, 197101

City Hospital No. 5 - Sochi

Sochi, Russian Federation, 354207

Siberian State Medical University

Tomsk, Russian Federation, 634050

Regional State Autonomous Healthcare Institution "Tomsk Regional Clinical Hospital"

Tomsk, Russian Federation, 634063

Serbia

Clinic for gastroenterohepatology

Belgrade, Serbia, 11000

Clinical Hospital Center Zemun

Belgrade, Serbia, 11070

University Hospital Center Bezaniska Kosa

Belgrade, Serbia, 11080

Clinical Center Kragujevac

Kragujevac, Serbia, 34000

General Hospital Leskovac

Leskovac, Serbia, 16000

Clinical Center Nis

Nis, Serbia, 18000

General Hospital Djordje Joanovic, Internal Deases Department, Gastroenterology

Zrenjanin, Serbia, 34000

Spain

Hospital Juan Ramón Jimenez

Huelva, Spain

Turkey

Bezmiâlem Vakıf Üniversitesi

Fatih, Turkey, 34093

Istanbul Universitesi Istanbul Tip Fakultesi Gastroenteroloji Bilim Dali

Fatih, Turkey, 34093

Karadeniz Teknik Üniversitesi Tip Fakultesi

Trabzon, Turkey, 61080

Ukraine

Public Enterprise "Dnipropetrovsk regional clinical hospital named after I.I. Mechnikova", Department of Gastroenterology (Hepatology)

Dnipro, Ukraine, 49005

MNPE "Regional Clinical Hospital of Ivano-Frankivsk Regional Council", Gastroenterology Department, SHEI "Ivano-Frankivsk National Medical University", Chair of Internal Medicine #1

Ivano-Frankivs'k, Ukraine, 76008

Ivano-Frankivsk City Clinical Hospital No. 1

Ivano-Frankivs'k, Ukraine, 76018

Municipal Non-profit Enterprise "City Clinical Hospital #2 named after prof. O.O. Shalimova", of Kharkiv City Council, Proctology Department

Kharkiv, Ukraine, 61037

Municipal Non-profit Enterprise of Kharkiv Regional Council "Regional Clinical Hospital", Gastroenterology Department

Kharkiv, Ukraine, 61201

Private Enterprise Private Manufacturing Firm "Acinus", Treatment and diagnostic Centre

Kropyvnytskyi, Ukraine, 25006

Medical Center Medical Clinic Blagomed LLC

Kyiv, Ukraine, 01001

Kyiv City Clinical Hospital #18, Proctology Department, National Medical University named after O.O.Bogomolets, Chair of Surgery #1

Kyiv, Ukraine, 01030

Kyiv City Clinical Hospital #1, Therapeutics Department #2

Kyiv, Ukraine, 02091

Medical Centre of Limited Liability Company "Medical Centre "Dopomoga plus""

Kyiv, Ukraine, 02132

Shalimov's National Institute of surgery and transplantation

Kyiv, Ukraine, 03680

Medical Centre of Limited Liability Company "Medical Centre "Consilium Medical", clinico-consultation department

Kyiv, Ukraine, 04050

Kyiv Regional Clinical Hospital No 2

Kyiv, Ukraine, 04073

Volyn Regional Clinical Hospital

Lutsk, Ukraine, 43000

Municipal Non-profit Enterprise of Lviv Regional Council "Lviv Regional Clinical Hospital", proctology department, Danylo Galytsky Lviv National Medical University, Chair of Surgery #1

Lviv, Ukraine, 79010

KARDIOKOM Ltd.

Mykolaiv, Ukraine, 08711

Transcarpathian Regional Clinical Hospital named after Andriy Novaka, gastroenterology department

Uzhhorod, Ukraine, 88018

Municipal Non-profit Enterprise "Vinnytsia Regional Clinical Hospital named after M.I. Pyrogova of Vinnytsia Regional Council, Regional Specialized Clinical Gastroenterological Center,

Vinnytsia, Ukraine, 20128

Municipal Non-profit Enterprise "Vinnytsia City Clinical Hospital #1, Gastroenterology Department, Vinnytsia National Medical University named after M.I.Pyrogova, Chair of Propaedeutics of Internal Medicine

Vinnytsia, Ukraine, 21029

Municipal Institution "Zaporizhzhska Regional Clinical Hospital" of Zaporizhzha Regional Council, gastroenterology department

Zaporizhzhya, Ukraine, 69600

United Kingdom

London North West University Healthcare NHS Trust (LNWH), St Mark's Hospital, R&D Department, Northwick Park Hospital

Harrow, United Kingdom, HA1 3UJ

Barts Health NHS Trust, of Royal London Hospital

London, United Kingdom, E1 1BB

University College London Hospitals NHS Foundation Trust

London, United Kingdom, NW1 2PG

St Helens & Knowsley Teaching Hospitals NHS Trust, Whiston Hospital

Prescot, United Kingdom, L35 5DR

University Hospitals Coventry and Warwickshire NHS Trust, University Hospital

Shrewsbury, United Kingdom, CV2 2DX

Shrewsbury and Telford Hospitals NHS Trust, Royal Shrewsbury Hospital

Shrewsbury, United Kingdom, SY3 8XQ

The Royal Wolverhampton NHS Trust, New Cross Hospital

Wolverhampton, United Kingdom, WV10 0QP

Sponsors and Collaborators

Immunic AG

Investigators

• Study Director: Andreas Muehler; Immunic Therapeutics

More Information

Additional Information:

European Medicines Agency (EMA). Guideline on the development of new medicinal products for the treatment of Ulcerative Colitis.[Online]. 2016. 

US Food and Drug Administration (FDA). Ulcerative Colitis: Clinical Trial Endpoints. Guidance for Industry.[Online]. 2016. 

European Union (EU). Directive 95/46/EC of the European Parliament and of the Council of 24 October 1995 on the protection of individuals with regard to the processing of personal data and on the free movement of such data. [Online]. 

EU. Regulation 2016/679 on the protection of natural persons with regard to the processing of personal data and on the free movement of such data, and repealing Directive 95/46/EC (General Data Protection Regulation). 2016; [Online]. 

• Responsible Party: Immunic AG
• ClinicalTrials.gov Identifier: NCT03341962
• Other Study ID Numbers: P2-IMU-838-UC; P2-IMU-838-UC ( Other Identifier: Sponsor protocol ID ); 2017-003703-22 ( EudraCT Number )
• First Posted: November 14, 2017
• Last Update Posted: February 1, 2023
• Last Verified: January 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Immunic AG:

Ulcerative Colitis; IMU-838; vidofludimus calcium

Additional relevant MeSH terms:

Colitis; Colitis, Ulcerative; Ulcer; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Colonic Diseases; Intestinal Diseases; Pathologic Processes; Inflammatory Bowel Diseases; Calcium; Calcium-Regulating Hormones and Agents; Physiological Effects of Drugs