A Randomised Double-Blind Placebo-Controlled Phase III Clinical Study to Evaluate the Efficacy and Safety of Cobitolimod as an Induction and Maintenance Therapy in Participants With Moderate to Severe Active Left-Sided Ulcerative Colitis

The purpose of the study is to evaluate the efficacy of cobitolimod treatment compared to placebo in inducing clinical remission, in participants with moderate to severe active left-sided UC and to evaluate the efficacy of cobitolimod maintenance treatment compared to placebo in inducing or maintaining clinical remission at week 52, in participants with clinical response at week 6 after induction treatment with cobitolimod.

Start Date24 Nov 2021

Sponsor / Collaborator

Flerie AB

NCT05404074

/ Unknown statusPhase 1

Pharmacokinetics of Cobitolimod Enemas in Participants With Active Ulcerative Colitis

The purpose of the study is to evaluate the PK, safety and tolerability of cobitolimod ememas (500mg/50mL) given to participants with active left-sided UC.

Start Date22 Nov 2021

Sponsor / Collaborator

Flerie AB

NCT03178669

/ CompletedPhase 2

A Randomised Dose-Optimisation Study to Evaluate the Efficacy and Safety of Cobitolimod in Moderate to Severe Active Ulcerative Colitis Patients

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.

Start Date21 Jun 2017

Sponsor / Collaborator

Flerie AB

100 Clinical Results associated with Cobitolimod

100 Translational Medicine associated with Cobitolimod

100 Patents (Medical) associated with Cobitolimod

Literatures (Medical) associated with Cobitolimod

01 Jun 2025·Pharmacology Research & Perspectives

Comparative Efficacy of Different Targeted Therapies in Patients With Moderate‐to‐Severe Ulcerative Colitis: Systematic Review/Network Meta‐Analysis and Mechanistic Overview

Review

Author: Xu, Li ; Sun, Yingzhe ; Hu, Suying ; Pan, Pingting ; Hu, Fang ; Dai, Youran ; Yang, Wenhui ; Li, Qiushuang ; Liu, Shan

ABSTRACT:

Ongoing evaluations of targeted therapies for moderate‐to‐severe ulcerative colitis (UC) continue to unfold, with the emergence of novel drugs. However, head‐to‐head trials comparing these therapies are still lacking. The aim of this study is to investigate the therapeutic effects of targeted therapies in moderate‐to‐severe UC. The Cochrane Library, Web of Science, PubMed, and Embase were searched from the inception to November 12, 2024. Statistical analyses included multivariate random effects models and Bayesian modeling. Stratified and sensitivity analyses were also performed. Publication bias was assessed using funnel plots. Outcomes such as clinical response/remission, endoscopic remission, mucosal healing, quality of life, adverse events (AEs), and serious adverse events (SAEs) were used to quantify the relative therapeutic effects. Thirty‐three studies (33 reported on the induction phase; 13 reported on the maintenance phase) were identified. In the induction phase, Upadacitinib 45 mg demonstrated the highest efficacy in achieving clinical remission (OR 10.03; 95% CI, 4.83–20.80), clinical response (OR 7.96; 95% CI, 3.89–16.28), and mucosal healing rate (OR 8.91; 95% CI, 3.36–23.62). Cobitolimod 250 mg was the first‐ranked treatment (SUCRA, 92.67%) in Endoscopic remission. Vedolizumab 108 mg was the best dosage in reducing Adverse Events (AEs). The optimal dosage for reducing Serious Adverse Events (SAEs) was found to be Tulisokibart 1000/500 mg. During the maintenance phase, Etrasimod 2 mg/kg ranked first in clinical remission (OR 9.58; 95% CI, 2.82–32.59), and Upadacitinib 45 mg was superior in endoscopic remission. Additionally, the most effective medication for raising quality of life was Guselkumab 200 mg (OR 3.04; 95% CI, 1.70–5.40). Consequently, there is a need for further high‐quality research to conclusively determine the best therapeutic option.

01 Apr 2022·Alimentary pharmacology & therapeuticsQ1 · MEDICINE

Review article: emerging drug therapies in inflammatory bowel disease

Q1 · MEDICINE

Review

Author: Grossberg, Laurie B. ; Cheifetz, Adam S. ; Papamichael, Konstantinos

Summary:

Background:

The landscape of inflammatory bowel disease (IBD) treatment is rapidly expanding with the development of new therapeutic options.

Aim:

To review the mechanisms of action and the available clinical trial data on emerging drug therapies for IBD.

Methods:

Pubmed, Medline and Cochrane databases were queried up to July 2021 using keywords “inflammatory bowel disease,” “IBD,” “Crohn’s disease,” “ulcerative colitis” and “trial,” “phase” and “study.” In addition, we manually reviewed the grey literature including clinical trial registries and abstracts from major gastroenterology conferences in 2020 and 2021 to include pertinent information.

Results:

In ulcerative colitis (UC), phase 2b and/or phase 3 studies met primary endpoints for S1P receptor agonists (estrasimod, ozanimod), anti‐IL‐23 agent (mirikizumab), anti‐lymphocyte trafficking agents (ontamalimab, subcutaneous vedolizumab), JAK inhibitors (upadacitinib, filgotinib) and TLR9 agonist (cobitolimod). In Crohn’s disease (CD), anti‐IL‐23 agents (risankizumab, mirikizumab, guselkumab), JAK inhibitors (upadacitinib, filgotinib) and anti‐lymphocyte trafficking agents (ontamalimab, etrolizumab) met primary endpoints in randomised controlled clinical trials.

Conclusion:

Several new IBD drug therapies have positive efficacy and safety data in early clinical trials, and there are several drugs in the therapeutic pipeline. As more treatments for CD and UC are approved for clinical use, research to assess predictors of response to therapy and head‐to‐head trials is needed to inform providers on how to best position therapeutic options for patients with IBD.

01 Dec 2020·The lancet. Gastroenterology & hepatologyQ1 · MEDICINE

Cobitolimod for moderate-to-severe, left-sided ulcerative colitis (CONDUCT): a phase 2b randomised, double-blind, placebo-controlled, dose-ranging induction trial

Q1 · MEDICINE

Article

Author: Gasbarrini, Antonio ; Augustyn, Monica ; Reinisch, Walter ; Knittel, Thomas ; Bakulin, Igor ; Klymenko, Andrii ; Neurath, Markus F ; Atreya, Raja ; Kowalski, Jan ; Sandborn, William J ; Hébuterne, Xavier ; Peyrin-Biroulet, Laurent ; Miheller, Pal ; Slankamenac, Dusan ; Arnesson, Karin

BACKGROUND:

Cobitolimod is a topically administered, DNA-based oligonucleotide that activates Toll-like receptor 9 (TLR9), and previous research has shown clinical efficacy in patients with moderate-to-severe ulcerative colitis. Here we assessed the efficacy and safety of different dose regimens of cobitolimod for induction therapy in patients with moderate-to-severe, left-sided ulcerative colitis.

METHODS:

CONDUCT was a randomised, double-blind, five-arm, placebo-controlled, dose-ranging phase 2b study that recruited patients with moderate-to-severe, left-sided ulcerative colitis, with inadequate response to conventional or biological therapies, from 91 hospitals or outpatient clinics in 12 European countries. Eligible patients had a Mayo score of 6-12 with a centrally read endoscopic subscore (modified to exclude friability from grade 1) of 2 or higher and no individual subscore of less than 1, and confirmation of left-sided disease. Patients were randomised (1:1:1:1:1; block size of ten) via a computer-generated schedule and centralised interactive voice and web response system to receive rectal enemas of cobitolimod at 31 mg, 125 mg, or 250 mg at weeks 0 and 3 (2 × 31 mg, 2 × 125 mg, and 2 × 250 mg groups), cobitolimod at 125 mg at weeks 0, 1, 2, and 3 (4 × 125 mg group), or placebo. Randomisation was stratified by current glucocorticosteroid and previous tumour necrosis factor inhibitor treatment. Patients and all study personnel were masked to treatment allocation. The primary endpoint was the proportion of patients achieving clinical remission (Mayo subscores for rectal bleeding of 0, for stool frequency of 0 or 1 [with ≥1-point decrease from baseline], and for endoscopy of 0 or 1 [excluding friability]) at week 6. The primary analysis (based on intention to treat) and safety analysis were done in all randomly assigned patients who received at least one dose of active study drug or placebo. In this exploratory study, statistical tests were one-sided; p values of less than 0·10 were regarded as statistically significant, with no adjustment for multiplicity. This study is registered with ClinicalTrials.gov, NCT03178669, and is completed; the results here represent the final analysis.

FINDINGS:

213 patients were randomly assigned between June 30, 2017, and June 26, 2019. Of these, 211 patients received study treatment: 40 in the cobitolimod 2 × 31 mg group, 43 in the 2 × 125 mg group, 42 in the 4 × 125 mg group, 42 in the 2 × 250 mg group, and 44 in the placebo group. A greater proportion of patients were in clinical remission at week 6 in the cobitolimod 2 × 250 mg group than in the placebo group (nine [21%] of 42 patients vs three [7%] of 44; odds ratio [OR] 3·8 [80% CI 1·5-9·5]; one-sided p=0·025). We identified no significant difference in the proportion of patients with clinical remission in the cobitolimod 2 × 31 mg group (five [13%] of 40 patients; OR 2·0 [80% CI 0·7-5·5], p=0·18), 2 × 125 mg group (two [5%] of 43; 0·7 [0·2-2·2], p=0·66), or 4 × 125 mg (four [10%] of 42; 1·4 [0·5-3·9], p=0·33) compared with the placebo group. Treatment-emergent adverse events occurred in 21 (48%) patients in the placebo group, ten (25%) patients in the cobitolimod 2 × 31 mg group, 17 (40%) patients in the 2 × 125 mg group, 15 (36%) patients in the 4 × 125 mg group, and 18 (43%) patients in the 2 × 250 mg group. Severe adverse events occurred in eight (4%) of 211 patients (worsening of ulcerative colitis [seven patients] and abdominal hernia and wound dehiscence [one patient]). Ten patients (two [5%] in the placebo group, two [5%] in the cobitolimod 2 × 31 mg group, two [5%] in the 4 × 125 mg, and four [10%] in the 2 × 250 mg group) had a total of 13 serious adverse events; these were worsening of ulcerative colitis (eight events) and pruritus, rash, abdominal hernia, fascia dehiscence, and deep vein thrombosis (one event each). One patient in the placebo group died from total organ failure after receiving a colectomy for a serious adverse event of disease worsening.

INTERPRETATION:

Two topical administrations of cobitolimod 250 mg were well tolerated and more effective than placebo in inducing clinical remission 6 weeks after the start of treatment. TLR9 activation is a promising novel therapeutic target in ulcerative colitis and warrants further testing, with phase 3 trials of cobitolimod planned.

FUNDING:

InDex Pharmaceuticals.

News (Medical) associated with Cobitolimod

19 Jan 2024

·www.prnewswire.com

InDex Pharmaceuticals announces expected cash balance per March 31, 2024

STOCKHOLM, Jan. 19, 2024 /PRNewswire/ -- InDex Pharmaceuticals Holding AB (publ) ("InDex Pharmaceuticals") today announced that remaining commitments for the company have been quantified, and the expected cash balance per March 31, 2024, amounts to SEK 180-190 million. The amount includes all closing costs for the phase III program CONCLUDE, even though activities for closing the phase III program will continue also after March 31, 2024. The company will have additional operating costs required to fulfill obligations of a listed company after March 31, 2024 amounting to SEK 0.6-0.8 million per month. InDex Pharmaceuticals is currently looking at alternatives for the company's future. The company's cash and cash equivalents as of December 31, 2023, amounts to SEK 294 million. The concluding results from the terminated Induction Study 1 of the phase III program CONCLUDE are expected in the latter part of February 2024 and will be communicated at that timepoint. For more information: Jenny Sundqvist, CEO Phone: +46 8 122 038 50 E-mail: [email protected] Johan Giléus, CFO and deputy CEO Phone: +46 8 122 038 50 E-mail: [email protected] Publication This information is information that InDex Pharmaceuticals Holding AB (publ) is obliged to make public pursuant to the EU Market Abuse Regulation (MAR). The information was submitted for publication through the agency of the contact person set out above at 10.10 CET on January 19, 2024. This is an English translation of the Swedish press release. In case of discrepancies between the English translation and the Swedish press release, the Swedish press release shall prevail. Information in this press release is intended for investors. InDex Pharmaceuticals in brief InDex Pharmaceuticals has a vision to help patients with immunological diseases where there is a high unmet medical need. The company is focusing on the drug candidate cobitolimod, a first in class mode-of-action, with the aim to offer an effective and safe treatment option. Cobitolimod was being evaluated in the phase III program CONCLUDE for moderate to severe left-sided ulcerative colitis – a debilitating, chronic inflammation of the large intestine. InDex Pharmaceuticals is based in Stockholm, Sweden. The company's shares (ticker INDEX) are traded on Nasdaq First North Growth Market Stockholm. Redeye AB is the company's Certified Adviser. For more information, please visit . The following files are available for download:

Phase 3Financial Statement

19 Jan 2024

·www.biospace.com

InDex Pharmaceuticals announces expected cash balance per March 31, 2024

STOCKHOLM, Jan. 19, 2024 /PRNewswire/ -- InDex Pharmaceuticals Holding AB (publ) ("InDex Pharmaceuticals") today announced that remaining commitments for the company have been quantified, and the expected cash balance per March 31, 2024, amounts to SEK 180-190 million. The amount includes all closing costs for the phase III program CONCLUDE, even though activities for closing the phase III program will continue also after March 31, 2024. The company will have additional operating costs required to fulfill obligations of a listed company after March 31, 2024 amounting to SEK 0.6-0.8 million per month. InDex Pharmaceuticals is currently looking at alternatives for the company's future. The company's cash and cash equivalents as of December 31, 2023, amounts to SEK 294 million. The concluding results from the terminated Induction Study 1 of the phase III program CONCLUDE are expected in the latter part of February 2024 and will be communicated at that timepoint. For more information: Jenny Sundqvist, CEO Phone: +46 8 122 038 50 E-mail: jenny.sundqvist@indexpharma.com Johan Giléus, CFO and deputy CEO Phone: +46 8 122 038 50 E-mail: johan.gileus@indepharma.com Publication This information is information that InDex Pharmaceuticals Holding AB (publ) is obliged to make public pursuant to the EU Market Abuse Regulation (MAR). The information was submitted for publication through the agency of the contact person set out above at 10.10 CET on January 19, 2024. This is an English translation of the Swedish press release. In case of discrepancies between the English translation and the Swedish press release, the Swedish press release shall prevail. Information in this press release is intended for investors. InDex Pharmaceuticals in brief InDex Pharmaceuticals has a vision to help patients with immunological diseases where there is a high unmet medical need. The company is focusing on the drug candidate cobitolimod, a first in class mode-of-action, with the aim to offer an effective and safe treatment option. Cobitolimod was being evaluated in the phase III program CONCLUDE for moderate to severe left-sided ulcerative colitis – a debilitating, chronic inflammation of the large intestine. InDex Pharmaceuticals is based in Stockholm, Sweden. The company's shares (ticker INDEX) are traded on Nasdaq First North Growth Market Stockholm. Redeye AB is the company's Certified Adviser. For more information, please visit . The following files are available for download: View original content: SOURCE InDex Pharmaceuticals Company Codes: ISIN:SE0008966295, Stockholm:INDEX

Phase 3Financial Statement

22 Nov 2023

·www.fiercebiotech.com

Viatris-partnered ulcerative colitis drug fails interim phase 3 review, sending InDex's stock down 60%

Viatris paid $10 million for the Japanese rights to cobitolimod in May. InDex Pharmaceuticals may be struggling to think of reasons to be thankful. The Swedish biotech has rocked investors with news it is stopping a phase 3 ulcerative colitis trial early in response to lackluster efficacy, sending its share price down 60%. The study was testing cobitolimod, a TLR9 agonist that is delivered directly to the inflamed colon via an enema. InDex identified the approach as a way to quickly induce mucosal healing and relieve ulcerative colitis symptoms without the complications of systemic exposure and off-target effects. Management recently tipped the drug to generate blockbuster sales and landed a deal with Viatris in Japan. Optimism faded fast after the Swedish market closed Tuesday. InDex revealed an interim analysis of the first 133 patients found its phase 3 trial is unlikely to meet its primary endpoint. The analysis, which was designed to check for futility and to choose the best dose, prompted the independent data monitoring committee to recommend stopping the study. “This surprising and disappointing news confirms the complexity of the disease and the need for further research within this field, especially as moderate to severe ulcerative colitis is an indication with high unmet medical need for new treatment options,” InDex CEO Jenny Sundqvist said in a statement. “We will conduct a comprehensive analysis of all the study data before announcing next steps.” The induction stage of the trial was assessing the proportion of patients in clinical remission at Week 6, by which point patients had received two rounds of treatment with cobitolimod or placebo. No safety concerns emerged, but, based on an analysis of the first 30% of planned patients, neither dose was on course to improve on the remission rate achieved by placebo. Investors responded by sending InDex’s share price down 60% to 0.27 Swedish krona. The crash reflects the rapid revision of expectations for the biotech’s lead candidate. InDex predicted the therapy could claim 20% to 30% of the moderate to severe left-sided ulcerative colitis market, a share that would translate into sales in excess of $1 billion. The biotech’s efforts to persuade others of the promise of the program brought some successes. Viatris paid $10 million for the Japanese rights to the candidate in May as part of a deal that is worth up to $40 million in development and sales milestones. The upfront payment helped InDex increase its cash pile to 412.5 million Swedish krona ($39.5 million) by the end of June.

Phase 3Financial Statement

100 Deals associated with Cobitolimod

External Link

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Colitis, Ulcerative	Phase 3	Czechia	Flerie AB	01 Dec 2011
Colitis, Ulcerative	Phase 3	France	Flerie AB	01 Dec 2011
Colitis, Ulcerative	Phase 3	Germany	Flerie AB	01 Dec 2011
Colitis, Ulcerative	Phase 3	Hungary	Flerie AB	01 Dec 2011
Colitis, Ulcerative	Phase 3	Italy	Flerie AB	01 Dec 2011
Colitis, Ulcerative	Phase 3	Poland	Flerie AB	01 Dec 2011
Colitis, Ulcerative	Phase 3	United Kingdom	Flerie AB	01 Dec 2011
Brain Edema	Phase 1	Sweden	Flerie AB	-

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04985968 (CONCLUDE, Biospace) Manual	Phase 3	Colitis, Ulcerative	-	cobitolimod	mokmjpljmd(reggftgsjo) = cobitolimod is “unlikely” to meet the study’s primary endpoint ovqslitqxz (ndhkozuafy ) Not Met	Negative	23 Nov 2023
UEGW2023	Not Applicable	Colitis, Ulcerative	-	Cobitolimod enema 500 mg/50 ml	drzwwujkks(tnrbpfxjko) = ezqotobvdc wipwopmehl (ldnqnhnsrj ) View more	-	15 Oct 2023
NCT03178669 (CONDUCT, CTgov)	Phase 2	Colitis, Ulcerative	213	cobitolimod (Cobitolimod Dose 2x31 mg)	gvshpykdhm = dizcghotnc hayojzizww (hmksuyyyfq, txqrgouhdn - nxtugaxgfo) View more	-	01 Feb 2021
				cobitolimod (Cobitolimod Dose 2x125 mg)	gvshpykdhm = jwtplzkgpo hayojzizww (hmksuyyyfq, mqbpgditnk - tmiuzixsyu) View more
NCT03178669 (CONDUCT, Pubmed \| Lancet Gastroenterol Hepatol)	Phase 2	Colitis, Ulcerative	213	Cobitolimod 2 × 31 mg	vhtmkdxxoa(qwwhjzkqmk) = qsxtjomjdw nzpabaayjl (qmgaitgese )	Positive	01 Dec 2020
				Cobitolimod 2 × 125 mg	vhtmkdxxoa(qwwhjzkqmk) = lfnjhrwsie nzpabaayjl (qmgaitgese )
NCT03178669 (CONDUCT, UEGW2020)	Phase 2	Colitis, Ulcerative TLR9	211	Cobitolimod 2x31 mg	oajvmqxqcz(sxhjhxzhyu) = ttoplxllmz wsjamnehep (jrvexzdtct ) View more	Positive	11 Oct 2020
				Cobitolimod 2x125 mg	oajvmqxqcz(sxhjhxzhyu) = nmlokhnmfj wsjamnehep (jrvexzdtct ) View more
NCT01493960 (COLLECT, Pubmed \| Dig Liver Dis)	Phase 3	Colitis, Ulcerative	104	Cobitolimod	wfzlwhtoja(mtruzkkrhe) = utpmbaioas sqmdzpzlyj (vyjdoonvfi )	Positive	01 Oct 2018
				Placebo	wfzlwhtoja(mtruzkkrhe) = axfkveqwji sqmdzpzlyj (vyjdoonvfi )
NCT01493960 (COLLECT, CTgov)	Phase 3	Colitis, Ulcerative	131	Cobitolimod (Cobitolimod)	geifqzndwh = xrxycbpgzk mnaaddgmzy (gskwqpgtkq, iqgethhrtl - gqkqqggywz) View more	-	24 Jan 2018
				Placebo (Placebo)	geifqzndwh = tmddqkebqy mnaaddgmzy (gskwqpgtkq, fqvvmgarxb - tpzjukoevl) View more
NCT01493960 (Pubmed \| J Crohns Colitis) Manual	Phase 3	Colitis, Ulcerative	131	DIMS0150	ilmleadbiq(qfgrtwjmim) = dgwqjaoiyj eiiylmcmzm (amfgnewjez ) View more	Positive	01 Nov 2016
				Placebo	ilmleadbiq(qfgrtwjmim) = krxblyruxi eiiylmcmzm (amfgnewjez ) View more
ECCO2015	Phase 3	Colitis, Ulcerative Add-on	131	DIMS0150 (30 mg)	czsccjjklp(bhugffsqrv) = kgeikxbcij rtjifiiiuf (losgtpqckp ) View more	Positive	19 Jan 2015
				Placebo	czsccjjklp(bhugffsqrv) = dtjlokquiu rtjifiiiuf (losgtpqckp ) View more
UEGW2013	Not Applicable	Colitis, Ulcerative	-	DIMS0150 30 mg/50mL single dose	mylldsneah(yaxkcdunwj) = gbkcjkuoea ipoebaeucc (xcoxiaihkf )	-	01 Oct 2013

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