Clinical trial NCT03178669: The Efficacy of Cobitolimod in Patients With Moderate to Severe Active Ulcerative Colitis
Official title: A Randomised Dose-Optimisation Study to Evaluate the Efficacy and Safety of Cobitolimod in Moderate to Severe Active Ulcerative Colitis Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Ulcerative Colitis
Keywords: Colitis, Ulcerative
Gastrointestinal Diseases
Inflammatory Bowel Disease
Immunomodulator Therapy
Glucocorticoids
Anti-Inflammatory Agents
Therapeutic uses
Kappaproct
IDX0150
DIMS0150
Lead sponsor: InDex Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2017-06-07
Enrollment: 213
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study was to evaluate efficacy of cobitolimod treatment at different dose levels and frequencies compared to placebo in patients with moderate to severe left-sided ulcerative colitis.

Detailed description: This was a Phase IIb study in patients with moderate to severe left-sided ulcerative colitis. Patients either received cobitolimod 31 mg, 125 mg or 250 mg at two occasions or 125 mg or placebo at four occasions during a 3-weeks period. To ensure blindness, patients received active treatment at two occasions and placebo at the other two occasions. Blood, stool, and tissue samples was collected at various time points throughout the study to evaluate safety and efficacy. Primary endpoint was evaluated at week 6.

Duration of participation for patients was approximately 12 weeks (from screening to final follow-up visit).

Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years old
* Established diagnosis of Ulcerative Colitis (UC)
* Moderately to severely active left sided UC assessed by central reading
* Current oral 5-Aminosalicylic Acid (5-ASA)/ Sulphasalazine (SP) use or a history of oral 5-ASA/SP use
* Current Glucocorticosteroids (GCS) use or history of GCS dependency, refractory, or intolerance
* Demonstrated an inadequate response, loss of response, or intolerance to at least one of the following agents:

  * Immunomodulators
  * Tumor Necrosis Factor alpha (TNF-α) inhibitors and/or anti-integrins

Exclusion Criteria:

* Suspicion of differential diagnosis
* Acute fulminant UC and/or signs of systemic toxicity
* UC limited to the rectum (disease which extend \<15 cm above the anal verge)
* History of malignancy
* History or presence of any clinically significant disorder
* Concomitant treatment with cyclosporine, methotrexate, tacrolimus, TNF-α inhibitors, anti-integrins or similar immunosuppressants and immunomodulators
* Treatment with rectal GCS, 5-ASA/SP or tacrolimus
* Long term treatment with antibiotics or non-steroidal anti-inflammatory drugs (NSAIDs)
* Serious active infection
* Gastrointestinal infections
* Currently receiving parenteral nutrition or blood transfusions
* Females who are lactating or have a positive serum pregnancy test
* Women of childbearing potential not using reliable contraceptive methods
* Concurrent participation in another clinical study
* Previous exposure to cobitolimod

Primary outcomes:
measure: Clinical Remission
timeFrame: 6 weeks after first treatment
Secondary outcomes:
measure: Modified Clinical Remission
timeFrame: Week 6
measure: Symptomatic Remission
timeFrame: Week 6
measure: Clinical Response
timeFrame: Week 6
measure: Endoscopic Remission
timeFrame: Week 6
measure: Histological Remission
timeFrame: Week 6
Other outcomes:
Locations:
city: Prague
country: Czechia
facility: 1
city: Amiens
country: France
facility: 2
city: Caen
country: France
facility: 3
city: Clichy
country: France
facility: 4
city: Grenoble
country: France
facility: 5
city: Nice
country: France
facility: 6
city: Pierre-Bénite
country: France
facility: 7
city: Saint-Étienne
country: France
facility: 8
city: Toulouse
country: France
facility: 9
city: Vandœuvre-lès-Nancy
country: France
facility: 10
city: Augsburg
country: Germany
facility: 11
city: Berlin
country: Germany
facility: 12
city: Erlangen
country: Germany
facility: 13
city: Hamburg
country: Germany
facility: 14
city: Hanover
country: Germany
facility: 15
city: Heidelberg
country: Germany
facility: 16
city: Leipzig
country: Germany
facility: 17
city: Lüneburg
country: Germany
facility: 18
city: Mannheim
country: Germany
facility: 19
city: München
country: Germany
facility: 20
city: Budapest
country: Hungary
facility: 21
city: Békéscsaba
country: Hungary
facility: 22
city: Debrecen
country: Hungary
facility: 23
city: Mosonmagyarovar
country: Hungary
facility: 24
city: Pécs
country: Hungary
facility: 25
city: Czestochowa
country: Poland
facility: 26
city: Kraków
country: Poland
facility: 27
city: Ksawerów
country: Poland
facility: 28
city: Lublin
country: Poland
facility: 29
city: Poznań
country: Poland
facility: 30
city: Sopot
country: Poland
facility: 31
city: Warszawa
country: Poland
facility: 32
city: Wrocław
country: Poland
facility: 33
city: Włocławek
country: Poland
facility: 32
city: Łódź
country: Poland
facility: 33
city: Cheboksary
country: Russian Federation
facility: 34
city: Ekaterinburg
country: Russian Federation
facility: 35
city: Kazan
country: Russian Federation
facility: 36
city: Kirov
country: Russian Federation
facility: 37
city: Moscow
country: Russian Federation
facility: 38
city: Novosibirsk
country: Russian Federation
facility: 39
city: Ryazan'
country: Russian Federation
facility: 40
city: Saint Petersburg
country: Russian Federation
facility: 41
city: Stavropol'
country: Russian Federation
facility: 42
city: Tver
country: Russian Federation
facility: 43
city: Ufa
country: Russian Federation
facility: 44
city: Belgrad
country: Serbia
facility: 45
city: Ferrol
country: Spain
facility: 46
city: Fuenlabrada
country: Spain
facility: 47
city: Madrid
country: Spain
facility: 48
city: Sevilla
country: Spain
facility: 49
city: Valencia
country: Spain
facility: 50
city: Uppsala
country: Sweden
facility: 51
city: Chernivtsi
country: Ukraine
facility: 52
city: Dnipropetrovs'k
country: Ukraine
facility: 53
city: Ivano-Frankivs'k
country: Ukraine
facility: 54
city: Kharkiv
country: Ukraine
facility: 55
city: Kiev
country: Ukraine
facility: 56
city: Luts'k
country: Ukraine
facility: 57
city: Lviv
country: Ukraine
facility: 58
city: Odesa
country: Ukraine
facility: 59
city: Sumy
country: Ukraine
facility: 60
city: Zaporizhzhya
country: Ukraine
facility: 61
city: Úzhgorod
country: Ukraine
facility: 62
Study officials:
affiliation: Friedrich-Alexander University Erlangen-Nuremberg
name: Raja Atreya
role: PRINCIPAL_INVESTIGATOR
References:
citation: Atreya R, Peyrin-Biroulet L, Klymenko A, Augustyn M, Bakulin I, Slankamenac D, Miheller P, Gasbarrini A, Hebuterne X, Arnesson K, Knittel T, Kowalski J, Neurath MF, Sandborn WJ, Reinisch W; CONDUCT study group. Cobitolimod for moderate-to-severe, left-sided ulcerative colitis (CONDUCT): a phase 2b randomised, double-blind, placebo-controlled, dose-ranging induction trial. Lancet Gastroenterol Hepatol. 2020 Dec;5(12):1063-1075. doi: 10.1016/S2468-1253(20)30301-0. Epub 2020 Oct 5.