NCT03178669: CONDUCT

The Efficacy of Cobitolimod in Patients With Moderate to Severe Active Ulcerative Colitis

Completed Phase 2 Results posted Last updated 1 February 2021

What this trial tests

Phase 2 trial testing cobitolimod in Ulcerative Colitis in 213 participants. Completed in 30 August 2019.

Timeline

21 June 2017

Primary endpoint
30 August 2019

30 August 2019

Quick facts

Lead sponsor	InDex Pharmaceuticals
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	213
Start date	21 June 2017
Primary completion	30 August 2019
Estimated completion	30 August 2019
Sites	64 locations across France, Russia, Ukraine, Serbia, Sweden, Germany, Poland, Hungary

Drugs / interventions tested

• cobitolimod — full drug profile →
• Placebo

Conditions studied

• Ulcerative Colitis — all drugs for Ulcerative Colitis →

Sponsor

InDex Pharmaceuticals — full company profile →

Who can join

18 and older, any sex, with Ulcerative Colitis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Clinical Remission Primary · 6 weeks after first treatment

Patients with clinical remission at Week 6 (yes=1, no=0), defined by Modified Mayo sub scores, i) rectal bleeding of 0, ii) stool frequency of 0 or 1 (with at least one point decrease from Baseline, Week 0), and iii) endoscopy score of 0 or 1 (excluding friability).

Group	Value	95% CI
Cobitolimod Dose 2x31 mg	5
Cobitolimod Dose 2x125 mg	2
Cobitolimod Dose 2x250 mg	9
Cobitolimod Dose 4x125 mg	4
Placebo	3

Modified Clinical Remission Secondary · Week 6

Patients with modified clinical remission at Week 6 (yes=1, no=0), defined by the Modified Mayo score ≤ 2 and sub scores, i) rectal bleeding of 0, ii) stool frequency of 0 or 1 (with at least one point decrease from Baseline, Week 0), iii) endoscopy score of 0 or 1 (excluding friability ) and iiii) physician´s global assessment (PGA) of 0 or 1

Group	Value	95% CI
Cobitolimod Dose 2x31 mg	5
Cobitolimod Dose 2x125 mg	1
Cobitolimod Dose 2x250 mg	7
Cobitolimod Dose 4x125 mg	3
Placebo	3

Symptomatic Remission Secondary · Week 6

Patients with symptomatic remission at Week 6 (yes=1, no=0), defined by the Mayo sub scores, i) rectal bleeding of 0, ii) stool frequency of 0 or 1 (with at least one point decrease from Baseline, Week 0), (patient reported outcome)

Group	Value	95% CI
Cobitolimod Dose 2x31 mg	10
Cobitolimod Dose 2x125 mg	11
Cobitolimod Dose 2x250 mg	13
Cobitolimod Dose 4x125 mg	10
Placebo	9

Clinical Response Secondary · Week 6

Patients with clinical response at Week 6 (yes=1, no=0), defined as clinical remission or a three point and ≥30 % decrease from Baseline, Week 0 in the sum of the Modified Mayo score, i) rectal bleeding, ii) stool frequency and iii) endoscopy score (excluding friability), iiii) physicians global assessment (PGA)

Group	Value	95% CI
Cobitolimod Dose 2x31 mg	17
Cobitolimod Dose 2x125 mg	18
Cobitolimod Dose 2x250 mg	20
Cobitolimod Dose 4x125 mg	15
Placebo	20

Endoscopic Remission Secondary · Week 6

Patients with endoscopic remission at Week 6 (yes=1, no=0), defined by the Modified Mayo endoscopic sub score of 0 or 1 (excluding friability)

Group	Value	95% CI
Cobitolimod Dose 2x31 mg	7
Cobitolimod Dose 2x125 mg	5
Cobitolimod Dose 2x250 mg	15
Cobitolimod Dose 4x125 mg	10
Placebo	12

Histological Remission Secondary · Week 6

Patients with histological remission at Week 6 (yes=1, no=0), defined by the Nancy histological index of grade 0 or 1

Group	Value	95% CI
Cobitolimod Dose 2x31 mg	4
Cobitolimod Dose 2x125 mg	5
Cobitolimod Dose 2x250 mg	8
Cobitolimod Dose 4x125 mg	7
Placebo	10

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse Event (AE) was collected from the date of signed informed consent. During the screening period up to first treatment only AEs related to a study specific procedures should be reported. AEs were reported up to follow up visit at Week 10 (from first treatment). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Cobitolimod Dose 2x31 mg

Serious: 2/40 (5%)

Deaths: 0/40

Cobitolimod Dose 2x125 mg

Serious: 0/43 (0%)

Deaths: 0/43

Cobitolimod Dose 2x250 mg

Serious: 4/42 (10%)

Deaths: 0/42

Cobitolimod Dose 4x125 mg

Serious: 2/42 (5%)

Deaths: 0/42

Placebo

Serious: 2/44 (5%)

Deaths: 1/44

Serious adverse events (6 terms)

Reaction	System	Cobitolimod Dose 2x31 mg	Cobitolimod Dose 2x125 mg	Cobitolimod Dose 2x250 mg	Cobitolimod Dose 4x125 mg	Placebo
Ulcerative colitis	Gastrointestinal disorders	—	—	—	—	—
Abdominal hernia	Gastrointestinal disorders	—	—	—	—	—
Wound Dehiscence	Injury, poisoning and procedural complications	—	—	—	—	—
Pruritus	Skin and subcutaneous tissue disorders	—	—	—	—	—
Rash erythematous	Skin and subcutaneous tissue disorders	—	—	—	—	—
Deep vein thrombosis	Vascular disorders	—	—	—	—	—

Other adverse events (5 terms — click to expand)

Reaction	System	Cobitolimod Dose 2x31 mg	Cobitolimod Dose 2x125 mg	Cobitolimod Dose 2x250 mg	Cobitolimod Dose 4x125 mg	Placebo
Ulcerative colitis	Gastrointestinal disorders	—	—	—	—	—
Headache	Nervous system disorders	—	—	—	—	—
Viral upper respiratory infection	Infections and infestations	—	—	—	—	—
Pyrexia	General disorders	—	—	—	—	—
Faecal calprotectin increased	Investigations	—	—	—	—	—

Most-reported serious reactions: Ulcerative colitis, Abdominal hernia, Wound Dehiscence, Pruritus, Rash erythematous, Deep vein thrombosis.

Data from ClinicalTrials.gov NCT03178669 adverse events section.

Sponsor's own description

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.

Publications & conference data

5 peer-reviewed publications reference this trial (live from Europe PMC):

1. The TLR9 Agonist Cobitolimod Induces IL10-Producing Wound Healing Macrophages and Regulatory T Cells in Ulcerative Colitis.
   Schmitt H, Ulmschneider J, Billmeier U, Vieth M, et al · · 2020 · cited 59× · PMID 31630153 · DOI 10.1093/ecco-jcc/jjz170
2. Cobitolimod for moderate-to-severe, left-sided ulcerative colitis (CONDUCT): a phase 2b randomised, double-blind, placebo-controlled, dose-ranging induction trial.
   Atreya R, Peyrin-Biroulet L, Klymenko A, Augustyn M, et al · · 2020 · cited 36× · PMID 33031757 · DOI 10.1016/s2468-1253(20)30301-0
3. Emerging Mechanisms of Innate Immunity and Their Translational Potential in Inflammatory Bowel Disease.
   Corridoni D, Chapman T, Ambrose T, Simmons A. · · 2018 · cited 31× · PMID 29515999 · DOI 10.3389/fmed.2018.00032
4. Oligonucleotides-A Novel Promising Therapeutic Option for IBD.
   Scarozza P, Schmitt H, Monteleone G, Neurath MF, et al · · 2019 · cited 24× · PMID 31068803 · DOI 10.3389/fphar.2019.00314
5. Intestinal Organoids as a Novel Complementary Model to Dissect Inflammatory Bowel Disease.
   Schulte L, Hohwieler M, Müller M, Klaus J. · · 2019 · cited 10× · PMID 31015842 · DOI 10.1155/2019/8010645