Highlights:
- Immuron proceeding to Phase 3 registration strategy with the FDA
- Travelan® topline clinical trial results demonstrate protective efficacy with single daily dose
- 36.4% protective efficacy against Enterotoxigenic Escherichia coli (ETEC) induced moderate to severe diarrhea was observed in the Travelan® group compared to the placebo group (primary endpoint)
- 66.7% protective efficacy against ETEC induced severe diarrhea was observed in the Travelan® group compared to the placebo group (secondary endpoint)
- 83.3% statistically significant reduction in the number of subjects in the Travelan® group requiring early antibiotic treatment post challenge compared to the placebo (secondary endpoint)
- 100% of the subjects requiring IV fluids post challenge were in the placebo (secondary endpoint)
- 55.6% reduction in the number of subjects experiencing adverse events associated with the ETEC challenge observed in the Travelan® group compared to the placebo group (secondary endpoint)
- Phase 2 clinical study data supports the excellent safety and tolerability profile of Travelan®
MELBOURNE, Australia, March 07, 2024 (GLOBE NEWSWIRE) -- Immuron Limited (ASX: IMC; NASDAQ: IMRN), an Australian based and globally integrated biopharmaceutical company is pleased to announce the interim topline results confirming that a single daily dose of Travelan® is effective in prevention of moderate to severe diarrhea following challenge with enterotoxigenic Escherichia coli (ETEC).
Immuron was awarded AU $4.8 (USD $3.43) million funding by the U.S. Department of Defense (ASX Announcement 12 January 2022) to perform a randomized double-blind placebo-controlled phase 2 controlled human infection model (CHIM) study to assist with evaluating a dosing regimen that is most suited to deployed US troops visiting developing countries. Healthy volunteers were recruited and randomly assigned to receive a single daily oral dose of 1200 mg of Travelan® or placebo. Dosing commenced 2 days prior to challenge with ETEC strain H10407 and continued for 7 days. ClinicalTrials.gov Identifier: NCT05933525.
This interim analysis summarizes the data for a total of 60 subjects who have completed the inpatient challenge component of this current clinical study. Last patients last visits are anticipated to commence in April this year and final clinical study report will be completed in H2 2024.
Having demonstrated protective efficacy in two published clinical studies (Otto et al., 2011), this Phase 2 study was designed to compare the preventative effects of once daily dosing to the current standard recommended treatment of three times daily dosing. To learn more about Phase 2 study design, read: U.S. Food and Drug Administration Step 3: Clinical Research
IMM-124E (Travelan®) will be the first product developed with Immuron’s platform technology to proceed into Phase 3 clinical trials. The underlying nature of Immuron’s platform technology enables the development of medicines across a large range of infectious diseases. The platform can be used to block viruses or bacteria at mucosal surfaces such as the Gastrointestinal tract and neutralize the toxins they produce. More information on Immuron’s platform technology can be found below.
Travelan® demonstrated clinical efficacy in preventing ETEC-attributable diarrhea in two previous CHIM studies (Table 1). These studies showed dosing 400 mg three times daily, resulted in 76.7% (p=0.007) to 90.9% (p=0.0005) protection (Otto et al., 2011).
This trial demonstrated protective efficacy* with once daily dosing even though the attack rate for this study was much lower than planned. The intended attack rate (percentage of subjects with ETEC-induced moderate- severe diarrhea) for this study was approximately 70%. The attack rate for the Placebo group of this study was only 37% (Table 2). Given the lower than planned attack rate, this current study is underpowered to appropriately detect a significant difference in moderate to severe ETEC attributed diarrhea in the Placebo group compared to the Treatment group. This makes the demonstration of protective efficacy and reduction in adverse events and diarrheal symptoms particularly noteworthy.
The company will now proceed to hold an end of Phase 2 meeting with the U.S Food and Drug Administration to discuss the pivotal Phase 3 registration strategy and planned clinical trials including recommended dosing to support a Biologics License Application (BLA) for Travelan® as a prophylactic medicine for Travelers’ Diarrhea. A preventative treatment that defends against infectious enteric diseases is a high priority objective for the U.S. Military.
Immuron is in the process of exploring non-dilutive funding opportunities for these Phase 3 clinical trials.
Topline results:
Travelan®, a first-in-class, oral antibody therapy, dosed once daily resulted in a reduction ETEC-induced moderate-severe diarrhea compared to placebo.
- ETEC-induced moderate to severe diarrhea was reduced by 36.4% in the Travelan® group compared to the placebo group
- Protective efficacy of once daily dosing shown to be approx. 50% as effective as the current recommended three times daily dosing regimen; this is a strong result given the lower than expected attack rate
- 66.7% protective efficacy against ETEC induced severe diarrhea was observed in the Travelan® group compared to the placebo group
- Statistically significant reduction of 83.3% in the subjects in the Travelan® group requiring early antibiotic treatment post challenge compared to the placebo
- For the subjects requiring intravenous rehydration post challenge 100% were in the placebo group and none were in the Travelan® group
- 55.6% reduction in the number of subjects experiencing adverse events post the ETEC challenge was observed in the Travelan® group compared to the Placebo group
Studies using the CHIM for a variety of different enteric pathogens suggest the greatest protection may be against more severe disease and in studies where the disease appears to be predominately mild, which appears to be the case in this study, the efficacy estimates can be lower than anticipated.
Table 1: Summary of current clinical study data
| Event post challenge | Travelan® n = 30 n (%) | Placebo n = 30 n (%) | Reduction in AEs or Symptoms (%) | P value | |
| Primary Endpoint | |||||
| Number (n) of subjects with ETEC-induced moderate- severe diarrhea | 7 (23.3%) | 11 (36.7%) | NA | 0.399 | |
| Protective efficacy [%]1 95% 2-sided Confidence Interval2 | 36.4%* (-79.8%, 79.1%) | ||||
| Secondary Endpoints - Safety and tolerability | |||||
| Number of subjects with an adverse event (AE) 95% 2-sided Confidence Interval2 | 4 (13.3%) (-3.8%, 37.1%) | 9 (30.0%) | 55.6% | 0.1172 | |
| Number of subjects with (AEs) fever, nausea, anorexia, or abdominal pain/cramps rated as moderate to severe 95% 2-sided Confidence Interval2 | 3 (10.0%) (-5.2%, 31.9%) | 7 (23.3%) | 57.1% | 0.1659 | |
| Secondary Endpoints – Degree to which a participant experiences diarrheal symptoms | |||||
| Number of subjects who experienced severe diarrhea 95% 2-sided Confidence Interval2 | 1 (3.3%) (-5.8%, 19.2%) | 3 (10.0%) | 66.7% | 0.3006 | |
| Number of subjects requiring early antibiotic treatment 95% 2-sided Confidence Interval2 | 1 (3.3%) (1.0%, 32.4%) | 6 (20.0%) | 83.3% | 0.0444 | |
| Number of subjects requiring IV fluids 95% 2-sided Confidence Interval2 | 0 (-0.7%, 20.7%) | 3 (10.0%) | 100.0% | 0.0756 | |
1 Fishers exact test and binomial distribution 2 Chi-square test
AE = Adverse event associated with the ETEC challenge
* Intent-to-treat analysis set defined as randomized subjects who received study medication and were challenged
Table 2: Comparison of clinical study data attack rates
| Event post challenge | Otto3 Study 1 Placebo n = 15 n (%) | Otto3 Study 2 Placebo n = 14 n (%) | Current Travelan® Study n = 30 n (%) |
| Number (n) of subjects with ETEC-induced moderate- severe diarrhea | 11 (73%) | 12 (86%) | 11 (37%) |
Immuron is investigating the impact of the lower than expected attack rate.
Immuron has filed a provisional patent application with the U.S. Patent Office including results from this trial.
This release has been authorized by the directors of Immuron Limited.
COMPANY CONTACT:
Steven Lydeamore
Chief Executive Officer
steve@immuron.com
About Immuron
Immuron Limited (ASX: IMC, NASDAQ: IMRN), is an Australian biopharmaceutical company focused on developing and commercializing orally delivered targeted polyclonal antibodies for the treatment of infectious diseases.
For more information visit: https://www.immuron.com.au/ and https://www.travelan.com
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