HEM1036 Phase 2 Study in Low Anterior Resection Syndrome

Study Overview
=================
Brief Summary
-----------------
Double-blind, randomized, placebo controlled phase 2 study to explore the efficacy and safety of HEM1036 in the treatment of subjects with LARS

Detailed Description
-----------------
The study will be conducted as a double-blind, randomized, placebo controlled phase 2 study to explore the efficacy and safety of HEM1036 in the treatment of subjects with LARS. Subjects will be males and females ≥18 and ≤75 years of age with LARS. Subjects must have a LARS score of >20 at the Screening Visit after sphincter preserving rectal resection surgery for the curative treatment of diagnosed rectal cancer.

Official Title
-----------------
A Phase 2, Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Efficacy and Safety of HEM1036 in Subjects With Low Anterior Resection Syndrome (LARS)

Conditions
-----------------
LARS - Low Anterior Resection Syndrome

Intervention / Treatment
-----------------
* Drug: Lactobacillus Fermentum
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male and female subjects ≥18 and ≤75 years old. Diagnosed with rectal cancer and undergone sphincter preserving rectal resection surgery. Completed curative treatment (rectal resection, systemic chemotherapy, hormonal therapy, immunotherapy, biologic therapy, radiotherapy, and stomy repairment) ≥6 months prior to Screening. Current LARS with a LARS score >20 at Screening. An Eastern Cooperative Oncology Group score 0 or 1 at Screening. No evidence of anastomotic leakage or severe stenosis. Capable of returning to study site for all study visits according to requirement of protocol and willing to comply with the policy, procedure, and restriction of the study. Capable of actively communicating with the investigator/study personnel and completing the study related documents. Body mass index is at least 18 kg/m2 but no more than 35 kg/m2. Exclusion Criteria: History of: Abdominoperineal resection surgery, Hartmann operation, colostomy, Transanal irrigation therapy for LARS within 2 weeks prior to Screening, Secondary operation with stoma, etc. Not completed stomy repairment done at rectal resection surgery. History of allergic or adverse responses to IP or Milk, yeast, soy. On systemic chemotherapy, hormonal therapy, immunotherapy, biologic therapy, or radiotherapy at the time of Screening. Any antibiotic use within 4 weeks before the first dose of the IP. Is currently participating or has participated in another study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of the IP. Tested positive for HIV antigen, Hepatitis B, C at screening Past or current alcohol or drug abuse history

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HEM1036 (Lactobacillus fermentum)<br>Daily dose of 1 × 10^10 colony-forming units divided in 2 equal doses as a powder for BID oral administration | Drug: Lactobacillus Fermentum<br>* Lactobacillus Fermentum<br>* Other names: HEM1036;|
| Placebo Comparator: Placebo<br>2g Powder for BID oral administration | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Low Anterior Resection Syndrome score from Baseline to 8 weeks | Higher score means worse outcome We will assess the change of LARS score at 8 weeks frome baseline. The change of LARS score of two treatment groups will be compared. | Baseline to 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in QoL(Quality of Life) score from Baseline to 8 weeks | Score 0-100(higher score means better outcome) | Baseline to 8 weeks | 
| Change in fecal microbiota composition assessed by alpha-diversity and differential abundance analysis |  | Baseline to 4, 8 weeks | 
| Change of fecal metabolites assessed by fecal analysis | Change of metabolites (including Total short-chain fatty acids, acetate, butyrate,propionate, lactate, bile acids in fecal samples) assessed by fecal analysis and all parameters will be presented as umol/g | Baseline to 4, 8 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
LARS - Low Anterior Resection Syndrome, Probiotics, Colorectal Cancer