Clinical trial NCT03341962: Phase 2 Dose-finding IMU-838 for Ulcerative Colitis
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Ulcerative Colitis
Keywords: Ulcerative Colitis
IMU-838
vidofludimus calcium
Lead sponsor: Immunic AG
Sponsor class: INDUSTRY
First posted: 2017-11-14
Enrollment: 263
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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.

Eligibility 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.

Primary outcomes:
measure: Induction Phase: Symptomatic Remission and Endoscopic Healing at Week 10
timeFrame: 10 weeks
Secondary outcomes:
measure: Induction Phase: Symptomatic Remission and Endoscopic Healing at Different Doses at Week 10
timeFrame: 10 weeks
measure: Induction Phase: Symptomatic Remission
timeFrame: 22 weeks
measure: Induction Phase: Time to Achieving Symptomatic Remission
timeFrame: 22 weeks
measure: Induction Phase: Proportion of Patients With Clinical Response
timeFrame: 10 weeks
measure: Induction Phase: Proportion of Patients With Endoscopic Healing
timeFrame: 10 weeks
measure: Induction Phase: Proportion of Patients With Symptomatic Response
timeFrame: 22 weeks
measure: Induction Phase: Full Mayo Score
timeFrame: 10 weeks
measure: Induction Phase: Partial Mayo Score
timeFrame: 22 weeks
measure: Induction Phase: Patient Reported Outcome (PRO)-2 Mayo Score
timeFrame: 22 weeks
measure: Induction Phase: Fecal Calprotectin (fCP)
timeFrame: 22 weeks
measure: Induction Phase: C-reactive Protein (CRP)
timeFrame: 22 weeks
measure: Safety: Adverse Events
timeFrame: 50 weeks
measure: Safety: Number of Participants With Clinically Significant Findings During Physical Examination
timeFrame: 50 weeks
measure: Safety: Body Weight
timeFrame: 50 weeks
measure: Safety: Blood Pressure
timeFrame: 50 weeks
measure: Safety: Heart Rate
timeFrame: 50 weeks
measure: Safety: 12-lead Electrocardiogram (ECG)
timeFrame: 50 weeks
measure: Safety: Hematology
timeFrame: up to Week 50
measure: Safety: Blood Chemistry
timeFrame: 50 weeks
measure: Safety: Coagulation
timeFrame: 10 weeks
measure: Safety: Urinalysis
timeFrame: 50 weeks
measure: Safety: Micro Ribonucleic Acid-122 Expression
timeFrame: 24 hours
measure: Pharmacodynamics (PK): IMU-838 Trough Level
timeFrame: Day 0, Day 1, Day 7, Week 2 and Week 10
measure: PK: IMU-838 Plasma Level
timeFrame: 2 weeks
measure: PK: Area Under the Drug Concentration-time Curve (AUC) From Time Zero to 24 Hours (AUC0-24h)
timeFrame: 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
measure: PK: AUC Time Zero to Last Measurable Concentration (AUC0-t)
timeFrame: 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
measure: PK: AUC Time Zero to Infinity (AUC0-inf)
timeFrame: 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
measure: PK: Maximum Plasma Concentration (Cmax)
timeFrame: 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
measure: PK: Time to Cmax (Tmax)
timeFrame: 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
measure: Maintenance Phase: Proportion of Patients in Symptomatic Remission
timeFrame: Week 14, Week 30, Week 50
measure: Maintenance Phase: Mayo PRO-2 Score
timeFrame: 50 weeks
measure: Maintenance Phase: Time to Relapse
timeFrame: 50 weeks
measure: Maintenance Phase: Proportion of Patients Without Relapse
timeFrame: 50 weeks
measure: Maintenance Phase: fCP
timeFrame: 50 weeks
measure: Maintenance Phase: CRP
timeFrame: 50 weeks
measure: Maintenance Phase: Proportion of Patients With Endoscopic Healing
timeFrame: 50 weeks
measure: Maintenance Phase: Proportion of Patients With Microscopic Healing
timeFrame: 50 weeks
measure: Maintenance Phase: Corticosteroid-free Remission
timeFrame: 50 weeks
measure: Open-label Phase: Symptom Control
timeFrame: up to 4 years
measure: Open-label Phase: fCP
timeFrame: Baseline, Week 4 OLE, Week 8 OLE, EoT up to 4 years (variable)
measure: Open-label Phase: CRP
timeFrame: Baseline, Week 4 OLE, Week 8 OLE, Week 10 OLE, Week 12 OLE, Week 16 OLE, Week 20 OLE, Week 24 OLE, Week 28 OLE, Week 32 or 38 OLE (depending if entry was after extended induction phase), EoT up to 4 years (variable)
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Del Sol Research Management, LLC
state: Arizona
city: Los Angeles
country: United States
facility: Axis Clinical Trials
state: California
city: Ventura
country: United States
facility: Ventura Clinical Trials
state: California
city: Lighthouse Point
country: United States
facility: Alliance Medical Research, LLC
state: Florida
city: Medley
country: United States
facility: Medley Research Associates
state: Florida
city: Miami
country: United States
facility: Global Life Research LLC
state: Florida
city: Pembroke Pines
country: United States
facility: Family Clinical Trials
state: Florida
city: Tampa
country: United States
facility: Clinical Research Trials of Florida, Inc.
state: Florida
city: Atlanta
country: United States
facility: Atlanta Gastroenterology Associates, LLC
state: Georgia
city: Ames
country: United States
facility: McFarland Clinic, P.C.
state: Iowa
city: Brockton
country: United States
facility: Commonwealth Clinical Studies
state: Massachusetts
city: Salisbury
country: United States
facility: PMG Research of Salisbury, LLC
state: North Carolina
city: Charleston
country: United States
facility: Clinical Trials of South Carolina
state: South Carolina
city: Bellaire
country: United States
facility: First Street Surgical Hospital
state: Texas
city: Tacoma
country: United States
facility: Digestive Health Specialists
state: Washington
city: Durres
country: Albania
facility: Durres Regional Hospital
city: Shkoder
country: Albania
facility: Regional Hospital of Shkoder
city: Tirana
country: Albania
facility: University Hospital Center Mother Teresa
city: Gomel
country: Belarus
facility: Gomel Regional Clinical Hospital
city: Gomel
country: Belarus
facility: Republican Scientific and Practical Center for Radiation Medicine and Human Ecology
city: Vitebsk
country: Belarus
facility: Vitiebsk State Order of Peoples' Friendship Medical University
city: Banja Luka
country: Bosnia and Herzegovina
facility: University Clinical Centre of the Republic of Srpska, Internal Medicine Clinic, Department of Gastroenterology and Hepatology
city: Mostar
country: Bosnia and Herzegovina
facility: University Clinical Hospital Mostar, Internal Medicine Clinic, Department of Gastroenterology
city: Blagoevgrad
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment Blagoevgrad AD
city: Byala
country: Bulgaria
facility: Mhat Byala
city: Kazanlak
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment "Dr. Hristo Stambolski" EOOD
city: Pleven
country: Bulgaria
facility: Medical Center "Medconsult Pleven" OOD
city: Pleven
country: Bulgaria
facility: Medical Center Exacta Medica
city: Plovdiv
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment "Sveti Georgi" EAD, Plovdiv, Gastroenterology clinic
city: Sofia
country: Bulgaria
facility: Medical Center "Hera" EOOD
city: Sofia
country: Bulgaria
facility: Diagnostic-Consulting Center "Convex" EOOD
city: Bjelovar
country: Croatia
facility: General Hospital Bjelovar
city: Osijek
country: Croatia
facility: Clinical Hospital Center Osijek
city: Rijeka
country: Croatia
facility: Clinical Hospital Center Rijeka
city: Split
country: Croatia
facility: Clinical Hospital Center Split
city: Vukovar
country: Croatia
facility: General Hospital Vukovar
city: Zagreb
country: Croatia
facility: Clinical Hospital Center Zagreb
city: Zagreb
country: Croatia
facility: Clinical Hospital Dubrava
city: Zagreb
country: Croatia
facility: Polyclinic Solmed Zagreb
city: Zagreb
country: Croatia
facility: Clinical Hospital Center Split
city: Havířov
country: Czechia
facility: Asclepiades - Interna a gastroenterologie s.r.o. - Havířov
city: Hradec Králové
country: Czechia
facility: Hepato-Gastroenterologie HK, s.r.o. Poliklinika III
city: Ostrava - Třebovice
country: Czechia
facility: Artroscan s.r.o.
city: Praha
country: Czechia
facility: FaraCol s.r.o. - Prague
city: Praha
country: Czechia
facility: MEDICON a.s. - Poliklinika Budějovická Gastroenterologie
city: Praha
country: Czechia
facility: Klinika ResTrial
city: Praha
country: Czechia
facility: Všeobecná fakultní nemocnice v Praze IV. interní klinika VFN a 1. LF UK
city: Kutaisi
country: Georgia
facility: Academician Z.Tskhakaia West Georgia National Center of Interventional Medicine
city: Tbilisi
country: Georgia
facility: LTD Unimedi Kakheti - Caraps Medline
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC, locatie AMC
city: Dordrecht
country: Netherlands
facility: Albert Schweitzer Hospital
city: Tilburg
country: Netherlands
facility: Elisabeth-TweeSteden Hospital
city: Skopje
country: North Macedonia
facility: City General Hospita 8th September
city: Skopje
country: North Macedonia
facility: University Clinic for Hematology - Skopje - Macedonian Hematology Association
city: Bochnia
country: Poland
facility: Centrum Usług Medycznych MaxMed
city: Gdynia
country: Poland
facility: Centrum Medyczne Pratia Gdynia
city: Karczew
country: Poland
facility: Centrum Medyczne Endo-med Sp. z o.o.
city: Katowice
country: Poland
facility: Vita Longa Sp. z o.o.
city: Kłodzko
country: Poland
facility: GLOBE Badania Kliniczne Sp. z o.o.
city: Lublin
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny Nr 4 w Lublinie Oddział Gastroenterologii
city: Nowy Targ
country: Poland
facility: Zakład leczniczy ALLMEDICA BADANIA KLINICZNE Sp. z o.o. Sp. K.
city: Olsztyn
country: Poland
facility: Etyka Ośrodek Badań Klinicznych
city: Piła
country: Poland
facility: Ars Medical - Szpital, Ars Medical - Ambulatorium
city: Poznań
country: Poland
facility: SOLUMED Centrum Medyczne
city: Poznań
country: Poland
facility: Niepubliczny Zakład Opieki Zdrowotnej Centrum Medyczne HCP - Lecznictwo Stacjonarne
city: Sopot
country: Poland
facility: Endoskopia Sp. z o.o.
city: Warszawa
country: Poland
facility: Klinika Medifem
city: Warszawa
country: Poland
facility: Centrum Badawcze Współczesnej Terapii, Prywatny Gabinet Lekarski dr Anna Bochenek-Mularczyk
city: Wroclaw
country: Poland
facility: Przychodnia Vistamed
city: Wrocław
country: Poland
facility: Centrum Medyczne OMNI Clinic Sp. z o.o. Spółka Komandytowa
city: Łódz
country: Poland
facility: Centrum Medyczne Med-Gastr Sp. z o.o. Spółka Komandytowa
city: Łódź
country: Poland
facility: Salve Medica Sp. z o.o. Spółka Komandytowa
city: Coimbra
country: Portugal
facility: Centro Hospitalar e Universitário de Coimbra, EPE - Hospitais da Universidade de Coimbra
city: Guimarães
country: Portugal
facility: Hospital da Senhora da Oliveira - Guimarães, EPE
city: Santa Maria da Feira
country: Portugal
facility: Centro Hospitalar de Entre o Douro e Vouga, EPE - Hospital São Sebastião
city: Bucharest
country: Romania
facility: S.C. MEDLIFE S.A., Sectia Gastroenterologie
city: Bucharest
country: Romania
facility: Spitalul Clinic Colentina, Sectia Gastroenterologie
city: Bucharest
country: Romania
facility: Institutul Clinic Fundeni, Sectia Clinica Gastroenterologie III
city: Timisoara
country: Romania
facility: S.C. Cabinet Particular Policlinic Algomed SRL, Specialitatea Gastroenterologie
city: Kazan
country: Russian Federation
facility: Kazan State Medical University
city: Krasnodar
country: Russian Federation
facility: SEI HPE "Kuban State Medical University" of MoH and SD, CBHS Regional Clinical Hospital No.2
city: Moscow
country: Russian Federation
facility: Central Clinical Hospital of the Russian Academy of Sciences
city: Moscow
country: Russian Federation
facility: Federal Medical Biophysical Center n.a. Burnazyan
city: Moscow
country: Russian Federation
facility: Clinical Research Institution of Moscow Region named after M. F. Vladimirsky
city: Novosibirsk
country: Russian Federation
facility: Novosibirskiy Gastrocenter, LLC
city: Saint Petersburg
country: Russian Federation
facility: FSBEI HE "Military Medical Academy n.a. S.M. Kirov" under the Ministry of Defence of Russian Federation
city: Saint Petersburg
country: Russian Federation
facility: Hospital of Saint Martyr Elizaveta
city: Saint Petersburg
country: Russian Federation
facility: Research Center Eco-Safety, LLC
city: Saint Petersburg
country: Russian Federation
facility: Gastroenterological Center "Expert" LLC
city: Saint Petersburg
country: Russian Federation
facility: Saint Petersburg State Medical University named after I.P. Pavlov
city: Sochi
country: Russian Federation
facility: City Hospital No. 5 - Sochi
city: Tomsk
country: Russian Federation
facility: Siberian State Medical University
city: Tomsk
country: Russian Federation
facility: Regional State Autonomous Healthcare Institution "Tomsk Regional Clinical Hospital"
city: Belgrade
country: Serbia
facility: Clinic for gastroenterohepatology
city: Belgrade
country: Serbia
facility: Clinical Hospital Center Zemun
city: Belgrade
country: Serbia
facility: University Hospital Center Bezaniska Kosa
city: Kragujevac
country: Serbia
facility: Clinical Center Kragujevac
city: Leskovac
country: Serbia
facility: General Hospital Leskovac
city: Nis
country: Serbia
facility: Clinical Center Nis
city: Zrenjanin
country: Serbia
facility: General Hospital Djordje Joanovic, Internal Deases Department, Gastroenterology
city: Huelva
country: Spain
facility: Hospital Juan Ramón Jimenez
city: Fatih
country: Turkey
facility: Bezmiâlem Vakıf Üniversitesi
city: Fatih
country: Turkey
facility: Istanbul Universitesi Istanbul Tip Fakultesi Gastroenteroloji Bilim Dali
city: Trabzon
country: Turkey
facility: Karadeniz Teknik Üniversitesi Tip Fakultesi
city: Dnipro
country: Ukraine
facility: Public Enterprise "Dnipropetrovsk regional clinical hospital named after I.I. Mechnikova", Department of Gastroenterology (Hepatology)
city: Ivano-Frankivs'k
country: Ukraine
facility: MNPE "Regional Clinical Hospital of Ivano-Frankivsk Regional Council", Gastroenterology Department, SHEI "Ivano-Frankivsk National Medical University", Chair of Internal Medicine #1
city: Ivano-Frankivs'k
country: Ukraine
facility: Ivano-Frankivsk City Clinical Hospital No. 1
city: Kharkiv
country: Ukraine
facility: Municipal Non-profit Enterprise "City Clinical Hospital #2 named after prof. O.O. Shalimova", of Kharkiv City Council, Proctology Department
city: Kharkiv
country: Ukraine
facility: Municipal Non-profit Enterprise of Kharkiv Regional Council "Regional Clinical Hospital", Gastroenterology Department
city: Kropyvnytskyi
country: Ukraine
facility: Private Enterprise Private Manufacturing Firm "Acinus", Treatment and diagnostic Centre
city: Kyiv
country: Ukraine
facility: Medical Center Medical Clinic Blagomed LLC
city: Kyiv
country: Ukraine
facility: Kyiv City Clinical Hospital #18, Proctology Department, National Medical University named after O.O.Bogomolets, Chair of Surgery #1
city: Kyiv
country: Ukraine
facility: Kyiv City Clinical Hospital #1, Therapeutics Department #2
city: Kyiv
country: Ukraine
facility: Medical Centre of Limited Liability Company "Medical Centre "Dopomoga plus""
city: Kyiv
country: Ukraine
facility: Shalimov's National Institute of surgery and transplantation
city: Kyiv
country: Ukraine
facility: Medical Centre of Limited Liability Company "Medical Centre "Consilium Medical", clinico-consultation department
city: Kyiv
country: Ukraine
facility: Kyiv Regional Clinical Hospital No 2
city: Lutsk
country: Ukraine
facility: Volyn Regional Clinical Hospital
city: Lviv
country: Ukraine
facility: Municipal Non-profit Enterprise of Lviv Regional Council "Lviv Regional Clinical Hospital", proctology department, Danylo Galytsky Lviv National Medical University, Chair of Surgery #1
city: Mykolaiv
country: Ukraine
facility: KARDIOKOM Ltd.
city: Uzhhorod
country: Ukraine
facility: Transcarpathian Regional Clinical Hospital named after Andriy Novaka, gastroenterology department
city: Vinnytsia
country: Ukraine
facility: Municipal Non-profit Enterprise "Vinnytsia Regional Clinical Hospital named after M.I. Pyrogova of Vinnytsia Regional Council, Regional Specialized Clinical Gastroenterological Center,
city: Vinnytsia
country: Ukraine
facility: 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
city: Zaporizhzhya
country: Ukraine
facility: Municipal Institution "Zaporizhzhska Regional Clinical Hospital" of Zaporizhzha Regional Council, gastroenterology department
city: Harrow
country: United Kingdom
facility: London North West University Healthcare NHS Trust (LNWH), St Mark's Hospital, R&D Department, Northwick Park Hospital
city: London
country: United Kingdom
facility: Barts Health NHS Trust, of Royal London Hospital
city: London
country: United Kingdom
facility: University College London Hospitals NHS Foundation Trust
city: Prescot
country: United Kingdom
facility: St Helens & Knowsley Teaching Hospitals NHS Trust, Whiston Hospital
city: Shrewsbury
country: United Kingdom
facility: University Hospitals Coventry and Warwickshire NHS Trust, University Hospital
city: Shrewsbury
country: United Kingdom
facility: Shrewsbury and Telford Hospitals NHS Trust, Royal Shrewsbury Hospital
city: Wolverhampton
country: United Kingdom
facility: The Royal Wolverhampton NHS Trust, New Cross Hospital
Study officials:
affiliation: Immunic Therapeutics
name: Andreas Muehler
role: STUDY_DIRECTOR
References: