AzTrials
AzTrials

Ulcerative ColitisPhase 2CALDOSE-1NCT03341962

Phase 2 Dose-finding IMU-838 for Ulcerative Colitis

A Phase 2 study testing IMU-838 in people with Ulcerative Colitis, run by Immunic AG at 131 sites in 19 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Ulcerative Colitis
What is being tested?
IMU-838
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
263 participants
Where
131 sitesin 19 countries
Study dates
15 Mar 2018to 16 Nov 2022
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Induction phase
  • Male and female patients, aged 18 - 80 years
  • UC diagnosed more than 3 months before Screening (Day-30) as documented in the medical chart
  • Previous treatment failure defined as:
  • 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
  • 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.)
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  • Active disease defined as
  • 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)
  • 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)
  • 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
  • Female patients must:
  • 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
  • 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 (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
  • Ability to understand and comply with study procedures and restrictions
  • 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)

Who cannot join

  • Gastrointestinal exclusion criteria
  • Diagnosis of Crohn's disease, inflammatory bowel disease type unclassified, ischemic colitis, microscopic colitis, radiation colitis or diverticular disease-associated colitis
  • Ileostomy, colostomy, or known fixed symptomatic stenosis of the intestine
  • History of colectomy with ileorectal anastomosis or ileal-pouch anal anastomosis or imminent need for colectomy (i.e. colectomy is being planned)
  • Active therapeutically uncontrollable abscess or toxic megacolon
  • Malabsorption or short bowel syndrome
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  • History of colorectal cancer or colorectal dysplasia (with the exception of dysplasia in polyps which have been removed)
  • Infectious disease exclusion criteria
  • 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
  • Treatment for intestinal pathogens other than C. difficile within 30 days prior to first randomization
  • 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
  • Any live vaccinations within 30 days prior to study drug administration except for the influenza vaccine
  • Other medical history and concomitant disease exclusion criteria
  • Known history of nephrolithiasis or underlying condition with a strong association of nephrolithiasis, including hereditary hyperoxaluria or hereditary hyperuricemia
  • Diagnosis or suspected liver function impairment which may cause, as assessed by the investigator, a potential for fluctuating liver function tests during this trial
  • Renal impairment i.e. estimated glomerular filtration rate (eGFR) ≤60 mL/min/1.73m²
  • Serum uric acid levels at Screening >1.2 x ULN (for women >6.8 mg/dL, for men >8.4 mg/dL)
  • History or clinical diagnosis of gout
  • Known or suspected Gilbert syndrome
  • Indirect (unconjugated) bilirubin ≥1.2 x ULN at Screening (i.e. ≥ 1.1 mg/dL)
  • 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
  • Use of any investigational product within 8 weeks or 5 x the respective half-life before first randomization, whatever is longer
  • Use of the following medications within 2 weeks before first randomization:
  • Tofacitinib
  • Methotrexate
  • Mycophenolate mofetil
  • Any calcineurin inhibitors (e.g. tacrolimus, cyclosporine, or pimecrolimus)
  • Oral systemic corticosteroids >20 mg/day prednisolone equivalent including beclomethasone dipropionate (at >5 mg/day) and budesonide (multi-matrix [MMX] at >9 mg/day)
  • Oral aminosalicylates (e.g. mesalazines) >4 g/day
  • Use of the following medications within 4 weeks before first randomization:
  • Use of intravenous corticosteroids
  • Use of thiopurines including azathioprine, mercaptopurine and 6-thioguanine
  • Use of any rectal and topical aminosalicylates and/or budesonide
  • 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
  • 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
  • Use of biologics as follows:
  • anti-tumor necrosis factor α antibodies (infliximab, adalimumab, golimumab, including their biosimilars) within 4 weeks before first randomization
  • vedolizumab and ustekinumab within 8 weeks before first randomization
  • Use of the DHODH inhibitors leflunomide or teriflunomide within 6 months before first randomization
  • Any use of natalizumab (Tysabri™) within 12 months before first randomization
  • 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
  • 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
  • Known hypersensitivity to DHODH inhibitors (teriflunomide, leflunomide) or any ingredient of the investigational product
  • Pregnancy or breastfeeding
  • History of drug or alcohol abuse during the past year
  • Concurrent participation in any other clinical trial using an investigational medicinal product or medical device
  • An employee of an investigator or sponsor or an immediate relative of an investigator
  • 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 *
  • 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
  • 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.

Trial locations and contacts

131 sites in 19 countries.

131 sites in 19 countries

Ukraine20 sites

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

    Dnipro, 49005

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

    Ivano-Frankivsk, 76008

  • Ivano-Frankivsk City Clinical Hospital No. 1

    Ivano-Frankivsk, 76018

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

    Kharkiv, 61037

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

    Kharkiv, 61201

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

    Kropyvnytskyi, 25006

  • Medical Center Medical Clinic Blagomed LLC

    Kyiv, 01001

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

    Kyiv, 01030

  • Kyiv City Clinical Hospital #1, Therapeutics Department #2

    Kyiv, 02091

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

    Kyiv, 02132

  • Shalimov's National Institute of surgery and transplantation

    Kyiv, 03680

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

    Kyiv, 04050

  • Kyiv Regional Clinical Hospital No 2

    Kyiv, 04073

  • Volyn Regional Clinical Hospital

    Lutsk, 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, 79010

  • KARDIOKOM Ltd.

    Mykolaiv, 08711

  • Transcarpathian Regional Clinical Hospital named after Andriy Novaka, gastroenterology department

    Uzhhorod, 88018

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

    Vinnytsia, 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, 21029

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

    Zaporizhzhya, 69600

Other trials in Ukraine

Poland18 sites

  • Centrum Usług Medycznych MaxMed

    Bochnia, 32700

  • Centrum Medyczne Pratia Gdynia

    Gdynia, 81338

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

    Karczew, 05480

  • Vita Longa Sp. z o.o.

    Katowice, 40748

  • GLOBE Badania Kliniczne Sp. z o.o.

    Kłodzko, 57300

  • Salve Medica Sp. z o.o. Spółka Komandytowa

    Lodz, 91211

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

    Łódz, 91034

  • Samodzielny Publiczny Szpital Kliniczny Nr 4 w Lublinie Oddział Gastroenterologii

    Lublin, 20954

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

    Nowy Targ, 34400

  • Etyka Ośrodek Badań Klinicznych

    Olsztyn, 10117

  • Ars Medical - Szpital, Ars Medical - Ambulatorium

    Piła, 64920

  • SOLUMED Centrum Medyczne

    Poznan, 60529

  • Niepubliczny Zakład Opieki Zdrowotnej Centrum Medyczne HCP - Lecznictwo Stacjonarne

    Poznan, 61485

  • Endoskopia Sp. z o.o.

    Sopot, 81756

  • Klinika Medifem

    Warsaw, 02-884

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

    Warsaw, 02679

  • Przychodnia Vistamed

    Wroclaw, 53149

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

    Wroclaw, 54204

Other trials in Poland

United States15 sites

  • McFarland Clinic, P.C.

    Ames, Iowa, 50010

  • Atlanta Gastroenterology Associates, LLC

    Atlanta, Georgia, 30308

  • First Street Surgical Hospital

    Bellaire, Texas, 77401

  • Commonwealth Clinical Studies

    Brockton, Massachusetts, 02302

  • Clinical Trials of South Carolina

    Charleston, South Carolina, 29406-7132

  • Alliance Medical Research, LLC

    Lighthouse PT, Florida, 33071

  • Axis Clinical Trials

    Los Angeles, California, 90036

  • Medley Research Associates

    Medley, Florida, 33166

  • Global Life Research LLC

    Miami, Florida, 33155-4630

  • Family Clinical Trials

    Pembroke Pines, Florida, 33026-3240

  • PMG Research of Salisbury, LLC

    Salisbury, North Carolina, 28144

  • Digestive Health Specialists

    Tacoma, Washington, 98405

  • Clinical Research Trials of Florida, Inc.

    Tampa, Florida, 33607

  • Del Sol Research Management, LLC

    Tucson, Arizona, 85710

  • Ventura Clinical Trials

    Ventura, California, 93003

Other trials in United States

Russia14 sites

  • Kazan State Medical University

    Kazan', 420012

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

    Krasnodar, 350072

  • Central Clinical Hospital of the Russian Academy of Sciences

    Moscow, 119435

  • Federal Medical Biophysical Center n.a. Burnazyan

    Moscow, 123098

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

    Moscow, 129110

  • Novosibirskiy Gastrocenter, LLC

    Novosibirsk, 630007

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

    Saint Petersburg, 191015

  • Hospital of Saint Martyr Elizaveta

    Saint Petersburg, 195257

  • Research Center Eco-Safety, LLC

    Saint Petersburg, 196143

  • Gastroenterological Center "Expert" LLC

    Saint Petersburg, 196620

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

    Saint Petersburg, 197101

  • City Hospital No. 5 - Sochi

    Sochi, 354207

  • Siberian State Medical University

    Tomsk, 634050

  • Regional State Autonomous Healthcare Institution "Tomsk Regional Clinical Hospital"

    Tomsk, 634063

Other trials in Russia

Croatia9 sites

  • General Hospital Bjelovar

    Bjelovar, 43000

  • Clinical Hospital Center Osijek

    Osijek, 31000

  • Clinical Hospital Center Rijeka

    Rijeka, 51000

  • Clinical Hospital Center Split

    Split, 21000

  • General Hospital Vukovar

    Vukovar, 32000

  • Clinical Hospital Center Zagreb

    Zagreb, 10000

  • Clinical Hospital Dubrava

    Zagreb, 10000

  • Polyclinic Solmed Zagreb

    Zagreb, 10000

  • Clinical Hospital Center Split

    Zagreb, 21000

Other trials in Croatia

Bulgaria8 sites

  • Multiprofile Hospital for Active Treatment Blagoevgrad AD

    Blagoevgrad, 2700

  • Mhat Byala

    Byala, 187100

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

    Kazanlak, 6100

  • Medical Center "Medconsult Pleven" OOD

    Pleven, 5800

  • Medical Center Exacta Medica

    Pleven, 5800

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

    Plovdiv, 4002

  • Medical Center "Hera" EOOD

    Sofia, 1510

  • Diagnostic-Consulting Center "Convex" EOOD

    Sofia, 1680

Other trials in Bulgaria

Czechia7 sites

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

    Havířov, 73601

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

    Hradec Králové, 50012

  • Artroscan s.r.o.

    Ostrava - Třebovice, 72200

  • FaraCol s.r.o. - Prague

    Prague, 10100

  • MEDICON a.s. - Poliklinika Budějovická Gastroenterologie

    Prague, 14000

  • Klinika ResTrial

    Prague, 14300

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

    Prague, 17004

Other trials in Czechia

Serbia7 sites

  • Clinic for gastroenterohepatology

    Belgrade, 11000

  • Clinical Hospital Center Zemun

    Belgrade, 11070

  • University Hospital Center Bezaniska Kosa

    Belgrade, 11080

  • Clinical Center Kragujevac

    Kragujevac, 34000

  • General Hospital Leskovac

    Leskovac, 16000

  • Clinical Center Nis

    Niš, 18000

  • General Hospital Djordje Joanovic, Internal Deases Department, Gastroenterology

    Zrenjanin, 34000

Other trials in Serbia

United Kingdom7 sites

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

    Harrow, HA1 3UJ

  • Barts Health NHS Trust, of Royal London Hospital

    London, E1 1BB

  • University College London Hospitals NHS Foundation Trust

    London, NW1 2PG

  • St Helens & Knowsley Teaching Hospitals NHS Trust, Whiston Hospital

    Prescot, L35 5DR

  • University Hospitals Coventry and Warwickshire NHS Trust, University Hospital

    Shrewsbury, CV2 2DX

  • Shrewsbury and Telford Hospitals NHS Trust, Royal Shrewsbury Hospital

    Shrewsbury, SY3 8XQ

  • The Royal Wolverhampton NHS Trust, New Cross Hospital

    Wolverhampton, WV10 0QP

Other trials in United Kingdom

Romania4 sites

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

    Bucharest, 10719

  • Spitalul Clinic Colentina, Sectia Gastroenterologie

    Bucharest, 20125

  • Institutul Clinic Fundeni, Sectia Clinica Gastroenterologie III

    Bucharest, 22328

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

    Timișoara, 300002

Other trials in Romania

Albania3 sites

  • Durres Regional Hospital

    Durrës, 2001

  • Regional Hospital of Shkoder

    Shkoder, 4001

  • University Hospital Center Mother Teresa

    Tirana, 1000

Other trials in Albania

Belarus3 sites

  • Gomel Regional Clinical Hospital

    Homyel, 246029

  • Republican Scientific and Practical Center for Radiation Medicine and Human Ecology

    Homyel, 246040

  • Vitiebsk State Order of Peoples' Friendship Medical University

    Vitebsk, 210009

Other trials in Belarus

Netherlands3 sites

  • Amsterdam UMC, locatie AMC

    Amsterdam, 1105 AZ

  • Albert Schweitzer Hospital

    Dordrecht, 3318 AT

  • Elisabeth-TweeSteden Hospital

    Tilburg, 5022 GC

Other trials in Netherlands

Portugal3 sites

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

    Coimbra, 3000-075

  • Hospital da Senhora da Oliveira - Guimarães, EPE

    Guimarães, 4835-044

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

    Santa Maria da Feira, 4520-211

Other trials in Portugal

Turkey (Türkiye)3 sites

  • Bezmiâlem Vakıf Üniversitesi

    Fatih, 34093

  • Istanbul Universitesi Istanbul Tip Fakultesi Gastroenteroloji Bilim Dali

    Fatih, 34093

  • Karadeniz Teknik Üniversitesi Tip Fakultesi

    Trabzon, 61080

Other trials in Turkey (Türkiye)

Bosnia and Herzegovina2 sites

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

    Banja Luka, 78000

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

    Mostar, 88000

Other trials in Bosnia and Herzegovina

Georgia2 sites

  • Academician Z.Tskhakaia West Georgia National Center of Interventional Medicine

    Kutaisi, 4600

  • LTD Unimedi Kakheti - Caraps Medline

    Tbilisi, 0159

Other trials in Georgia

North Macedonia2 sites

  • City General Hospita 8th September

    Skopje, 1000

  • University Clinic for Hematology - Skopje - Macedonian Hematology Association

    Skopje, 1131

Other trials in North Macedonia

Spain1 site

  • Hospital Juan Ramón Jimenez

    Huelva

Other trials in Spain

About this study

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

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).

Read the 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.

Being tested
IMU-838, Placebo
Keywords
Ulcerative Colitis, IMU-838, vidofludimus calcium
Medical subject headings
Colitis, Ulcerative

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IMU-838Drug

    Also called IM90838, vidofludimus calcium

    IMU-838 tablet

  • PlaceboDrug

    Also called Placebo (for IMU-838)

    Tablets manufactured to mimic IMU-838 tablets

Study groups in NCT03341962
Study groupRoleWhat they receive
10 mg IMU-838 (Induction)ExperimentalTwo 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.
Receives: Drug: IMU-838
30 mg IMU-838 (Induction)ExperimentalTwo 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.
Receives: Drug: IMU-838
45 mg IMU-838 (Induction)ExperimentalTwo 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.
Receives: Drug: IMU-838
placebo (Induction)Placebo comparatorThe placebo tablets will be identical to the IMU-838 tablets in terms of appearance, constitution of inactive ingredients, and packaging.
Receives: Drug: Placebo
10 mg IMU-838 (Maintenance)ExperimentalTwo 5 mg tablets once daily of IMU-838 until Week 50 or ulcerative colitis relapse.
Receives: Drug: IMU-838
30 mg IMU-838 (Maintenance)ExperimentalTwo 15 mg tablets once daily of IMU-838 until Week 50 or ulcerative colitis relapse.
Receives: Drug: IMU-838
placebo (Maintenance)Placebo comparatorThe 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).
Receives: Drug: Placebo
30 mg IMU-838 (Open-label)ExperimentalTwo 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
Receives: Drug: IMU-838

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Induction Phase: Symptomatic Remission and Endoscopic Healing at Week 10

    Composite endpoint: Proportion of patients with both, symptomatic remission (Mayo rectal bleeding subscore = 0, and Mayo stool frequency subscore of 0 or 1) and endoscopic healing (Modified Mayo endoscopy subscore of 0 or 1) at Week 10.

    All patients who were randomized to 30 mg/day and 45 mg/day were used for the assessment of the primary efficacy endpoint

    Measured: 10 weeks

Secondary outcomes (41)

  1. Induction Phase: Symptomatic Remission and Endoscopic Healing at Different Doses at Week 10

    Proportion of patients with both symptomatic remission and endoscopic healing at Week 10 (all individual IMU-838 doses were compared with one another and to placebo)

    Measured: 10 weeks

  2. Induction Phase: Symptomatic Remission

    Proportion of patients achieving symptomatic remission (Mayo rectal bleeding subscore = 0, and Mayo stool frequency subscore of 0 or 1) during the induction phase

    Measured: 22 weeks

  3. Induction Phase: Time to Achieving Symptomatic Remission

    Time to achieving symptomatic remission (Mayo rectal bleeding subscore = 0 and Mayo stool frequency subscore of 0 or 1) within the extended induction phase

    Measured: 22 weeks

  4. Induction Phase: Proportion of Patients With Clinical Response

    Proportion of patients with clinical response (decrease from Baseline in the full Mayo score of at least 3 points and at least 30%, with an accompanying decrease in the subscore for rectal bleeding of at least 1 point or an absolute subscore for rectal bleeding of 0 or 1) at Week 10

    Measured: 10 weeks

  5. Induction Phase: Proportion of Patients With Endoscopic Healing

    Proportion of patients with endoscopic healing (Modified Mayo endoscopy subscore of 0 or 1) at Week 10

    Measured: 10 weeks

  6. Induction Phase: Proportion of Patients With Symptomatic Response

    Proportion of patients with symptomatic response (≥1-point decrease from Baseline in Mayo PRO-2 score) during the induction phase (including extended induction phase)

    Measured: 22 weeks

  7. Induction Phase: Full Mayo Score

    Change in full Mayo Score from Baseline to Week 10. The full Mayo score is composed of 4 categories (bleeding, stool frequency, physician assessment, and endoscopic appearance) each rated from 0 to 3 that are added up to give a total score that ranges from 0 to 12. A higher score indicates a worse outcome.

    Measured: 10 weeks

  8. Induction Phase: Partial Mayo Score

    Change in partial mayo score over 10 or 22 weeks. The partial Mayo score includes only the non-invasive Mayo subscores, ie, stool frequency, rectal bleeding, and physician's global assessment (each rated from 0 to 3 that are added up to give a total score that ranges from 0 to 9). A higher score indicates a worse outcome.

    Measured: 22 weeks

  9. Induction Phase: Patient Reported Outcome (PRO)-2 Mayo Score

    Change in PRO-2 Mayo score over 10 or 22 weeks. Mayo PRO-2 score, ie, stool frequency and rectal bleeding score each rated from 0 to 3 that are added up to give a total score that ranges from 0 to 6. A higher score indicates a worse outcome.

    Measured: 22 weeks

  10. Induction Phase: Fecal Calprotectin (fCP)

    Time course of biomarker fCP in stool samples during extended induction phase

    Measured: 22 weeks

  11. Induction Phase: C-reactive Protein (CRP)

    Time course of biomarker CRP in blood samples during extended induction phase

    Measured: 22 weeks

  12. Safety: Adverse Events

    Incidence and Severity of AEs during the induction and maintenance phases

    Measured: 50 weeks

  13. Safety: Number of Participants With Clinically Significant Findings During Physical Examination

    The emergence of any clinically significant findings compared to screening captured during the induction and maintenance phases

    Measured: 50 weeks

  14. Safety: Body Weight

    Changes in body weight during the induction and maintenance phases

    Measured: 50 weeks

  15. Safety: Blood Pressure

    Changes in blood pressure (mm Hg) during the induction and maintenance phases

    Measured: 50 weeks

  16. Safety: Heart Rate

    Changes in heart rate (beats per minute) during the induction and maintenance phases

    Measured: 50 weeks

  17. Safety: 12-lead Electrocardiogram (ECG)

    Number of patients with clinically significant changes in ECG

    Measured: 50 weeks

  18. Safety: Hematology

    Number of participants with abnormal hematology laboratory values (treatment-emergent adverse events [TEAEs] related to hematological abnormalities)

    Measured: up to Week 50

  19. Safety: Blood Chemistry

    Number of participants with abnormal blood chemistry laboratory values (TEAES related to clinical chemistry abnormalities)

    Measured: 50 weeks

  20. Safety: Coagulation

    Number of participants with clinically significant abnormal coagulation laboratory values

    Measured: 10 weeks

  21. Safety: Urinalysis

    Number of participants with abnormal urinalysis laboratory values (TEAEs related to urinalysis)

    Measured: 50 weeks

  22. Safety: Micro Ribonucleic Acid-122 Expression

    Micro ribonucleic acid-122 (miR-122) expression (before first dose and 24 hours after first dose - foldchange of normalized expression values )

    Measured: 24 hours

  23. Pharmacodynamics (PK): IMU-838 Trough Level

    Measurement of pre-dose (trough) blood plasma levels of IMU-838 throughout the induction period

    Measured: Day 0, Day 1, Day 7, Week 2 and Week 10

  24. PK: IMU-838 Plasma Level

    Measurement of post-dose blood plasma levels of IMU-838 at Week 2

    Measured: 2 weeks

  25. PK: Area Under the Drug Concentration-time Curve (AUC) From Time Zero to 24 Hours (AUC0-24h)

    Single-dose PK measurement of AUC0-24h in a subset of patients in the open-label phase

    Measured: 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

  26. PK: AUC Time Zero to Last Measurable Concentration (AUC0-t)

    Single-dose PK measurement of AUC0-t in a subset of patients in the open-label phase

    Measured: 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

  27. PK: AUC Time Zero to Infinity (AUC0-inf)

    Single-dose PK measurement of AUC0-inf in a subset of patients in the open-label phase

    Measured: 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

  28. PK: Maximum Plasma Concentration (Cmax)

    Single-dose PK measurement of Cmax in a subset of patients in the open-label phase

    Measured: 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

  29. PK: Time to Cmax (Tmax)

    Single-dose PK measurement of Tmax in a subset of patients in the open-label phase

    Measured: 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

  30. Maintenance Phase: Proportion of Patients in Symptomatic Remission

    Proportion of patients in symptomatic remission (Mayo rectal bleeding subscore = 0, and Mayo stool frequency subscore of 0 or 1) by visit up to Week 50 in maintenance phase

    Measured: Week 14, Week 30, Week 50

  31. Maintenance Phase: Mayo PRO-2 Score

    Time course of Mayo PRO-2 score until Week 50. Mayo patient-reported outcome score, ie, stool frequency and rectal bleeding score each rated from 0 to 3 3 that are added up to give a total score that ranges from 0 to 6. A higher score indicates a worse outcome.

    Measured: 50 weeks

  32. Maintenance Phase: Time to Relapse

    Time to symptomatic ulcerative colitis (UC) relapse

    Measured: 50 weeks

  33. Maintenance Phase: Proportion of Patients Without Relapse

    Proportion of patients without symptomatic UC relapse until Week 50

    Measured: 50 weeks

  34. Maintenance Phase: fCP

    Timecourse of biomarker fCP in stool samples

    Measured: 50 weeks

  35. Maintenance Phase: CRP

    Timecourse of biomarker CRP in blood samples

    Measured: 50 weeks

  36. Maintenance Phase: Proportion of Patients With Endoscopic Healing

    Proportion of patients with endoscopic healing (Modified Mayo endoscopy subscore of 0 or 1) at Week 50 of maintenance phase

    Measured: 50 weeks

  37. Maintenance Phase: Proportion of Patients With Microscopic Healing

    Proportion of patients with microscopic healing (Geboes score of =< 3.1) at Week 50 of maintenance phase

    Measured: 50 weeks

  38. Maintenance Phase: Corticosteroid-free Remission

    Corticosteroid-free clinical remission (clinical remission and no receipt of systemic or local corticosteroids) at Week 50 in patients receiving corticosteroids at Baseline

    Measured: 50 weeks

  39. Open-label Phase: Symptom Control

    Proportion of patients with symptom control

    Measured: up to 4 years

  40. Open-label Phase: fCP

    Timecourse of biomarker fCP in stool samples. Visits were scheduled every 4 weeks (+/-7 days) until 50 weeks of total study participation (ie induction + extended induction, if applicable, maintenance + open-label part) and every 10 weeks (+/-7 days) thereafter. The visit schedule in the OLE after 50 weeks of overall study treatment was changed from a 10-week schedule to a 24 week (+/-14 days) schedule after Protocol Version 6.0 came into force.

    Because the study was terminated early, EoT varied between patients depending on when patients entered the study and the time a patient participated in the induction and maintenance phases before switching to the OLE.

    Measured: Baseline, Week 4 OLE, Week 8 OLE, EoT up to 4 years (variable)

  41. Open-label Phase: CRP

    Timecourse of biomarker CRP in blood samples. Visits were scheduled every 4 weeks (+/-7 days) until 50 weeks of total study participation (ie induction + extended induction, if applicable, maintenance + open-label part) and every 10 weeks (+/-7 days) thereafter. The visit schedule in the OLE after 50 weeks of overall study treatment was changed from a 10-week schedule to a 24 week (+/-14 days) schedule after Protocol Version 6.0 came into force.

    Because the study was terminated early, EoT varied between patients depending on when patients entered the study and the time a patient participated in the induction and maintenance phases before switching to the OLE.

    Measured: 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)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Nov 2017
  2. Study start15 Mar 2018
  3. Primary completion16 Nov 2022
  4. Study completion16 Nov 2022

Why it stopped: Considering the efficacy results of the induction phase (allowed use of corticosteroids as concomitant medication) in the study population and since IMU-838 did not show superiority over placebo, the OLE was prematurely closed by the sponsor.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
263 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03341962
Sponsor's protocol ID
P2-IMU-838-UC
Other IDs
P2-IMU-838-UC, 2017-003703-22, 2017
Acronym
CALDOSE-1
Status last verified
Feb 2024
First submitted
8 Nov 2017
Last updated
5 Mar 2024
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • D'Haens G, Stardelova KG, Sadiku E, Kizlova N, Skybalo S, Shehovtsova Y, Abramescu M, Vitt D, Kohlhof H, Muehler A. Vidofludimus Calcium in Patients With Moderate-to-Severe Ulcerative Colitis: A Randomized, Placebo-Controlled, Phase 2 Trial. Clin Transl Gastroenterol. 2025 Mar 1;16(3):e00813. doi: 10.14309/ctg.0000000000000813.

    PubMed 39791563

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing IMU-838 in people with Ulcerative Colitis, run by Immunic AG at 131 sites in 19 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 37 inclusion and 62 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 5 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 131 sites in Ukraine, Poland, United States, Russia, Croatia and 14 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 5 Mar 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Induction Phase: Symptomatic Remission and Endoscopic Healing at Week 10 (time frame: 10 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03341962, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Mar 2024.

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