Safety and Activity of ORE1001 in Subjects With Ulcerative Colitis

Study Overview
=================
Brief Summary
-----------------
A clinical trial is being conducted to test the effects of a potential new treatment in patients with ulcerative colitis. Study participants will be given capsules containing either ORE1001 or a matching placebo capsule and will take the medicine by mouth for six weeks. Study participants will be asked to visit clinic sites where they will be asked questions about their ulcerative colitis. Small samples of blood will be be drawn at study visits to monitor the participant's health and a tiny sample of tissue will be taken in an endoscopy at two times to determine whether the disease is getting better or worse.

Detailed Description
-----------------
This is a Phase Ib/IIa prospective, multicenter, double blind, randomized, placebo controlled, clinical study to evaluate the safety, tolerability and pilot therapeutic activity of ORE1001, administered as capsules by mouth, for 6 weeks in subjects with Ulcerative Colitis. Eligible subjects will be randomly assigned to either ORE1001 or placebo, respectively. Sigmoidoscopies with biopsies will be performed at the first treatment visit and week 6. Subjects will be instructed to self-administer the study drug on an outpatient basis and will be scheduled to return for clinical evaluation on weeks 2, 4, 6 and between Weeks 10-12.

Official Title
-----------------
A Randomized, Double-Blind, Placebo-Controlled Pilot Study of the Safety and Therapeutic Activity of ORE1001 in Subjects With Ulcerative Colitis

Conditions
-----------------
Mild to Moderate Ulcerative Colitis

Intervention / Treatment
-----------------
* Drug: ORE1001
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subject has a documented diagnosis of mild to moderate Ulcerative Colitis, as demonstrated clinically and by endoscopy at Visit 2. Baron score greater than or equal to 2 at baseline. Truelove-Witt (modified) score of 14 or less. At least 6 months duration of disease At baseline the subject should have either stable disease or stable disease requiring 5-ASA treatment If on a 5-ASA treatment, subject must have been on stable dose for at least two weeks prior to screening and is expected to continue on that dose until the study is completed Subject has normally functioning major organ systems (aside from gastrointestinal tract) as indicated by medical history, vital signs, physical exam and clinical laboratories (including hematology, coagulation, chemistries and urinalysis). Male or female subjects 18-70 years old Subject has provided voluntary written informed consent to participate in this study. Subject may be of child-bearing potential, but is not pregnant, nursing, or planning a pregnancy for the duration of the study and has a negative pregnancy test prior to enrollment. Subject agrees to use a medically-acceptable form of contraception from screening through 30 days after the final dose of study drug. Female partners of male subjects enrolled into this study are also recommended to use an acceptable method of birth control. Males must agree to not donate sperm during the entire study and for 90 days after the last dose of study drug. Exclusion Criteria: A clinically significant medical history, medical finding or an ongoing medical or psychiatric condition which, in the opinion of the Investigator, could jeopardize the safety of the subject, impact the validity of the study results, or interfere with the completion of treatment according to this protocol. Subject has an ALT or serum creatinine greater than 1.5 times the upper limit of normal range for the reference lab at screening. Subject who, in the opinion of the investigator, is febrile at screening. Subject had used the following treatments for IBD: steroids or any or biologic immunomodulators or any topical treatments (e.g. enemas) within the last 4 weeks prior to baseline, immunosuppressants or antimetabolites within the preceding 6 weeks, antibiotic use within the previous 7 days or chronic use of any anti-inflammatory drugs (except aminosalicylates) within 7 days. History of illicit drug abuse or positive urine screen for drugs of abuse or history of alcohol abuse if acknowledged at the screening visit or noted in the subject's medical record at screening. Subject has a positive blood screen for HIV, Hepatitis B (HBsAg), or Hepatitis C. Subject has evidence of infectious colitis, e.g., Clostridium difficile, Amoebiasis, Giardia lamblia by stool examination of at screening. Subject has evidence for gastrointestinal parasites as per stool ova and parasites testing at screening. Subject has evidence of tuberculosis by blood interferon gamma release assay at screening. Any uncontrolled, intercurrent illness (e.g., active infection). History of gastrointestinal cancer. Abdominal surgery or any major surgery within the preceding 28 days of the screening visit.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active study drug<br>ORE1001 300 mg oral capsules | Drug: ORE1001<br>* Oral capsules containing 300 mg of the active, study drug<br>* Other names: GL1001;|
| Placebo Comparator: Placebo control<br>300 mg oral capsules containing placebo material | Drug: Placebo<br>* placebo capsules<br>* Other names: matched placebo;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The safety and tolerability of ORE1001 in subjects with ulcerative colitis as demonstrated by the frequency and severity of adverse events |  | 6 Week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the modified Baron Score from Baseline to Week 6 |  | 6 Week | 
| Change in the Ulcerative Colitis Clinical Score from Baseline |  | 6 Week | 
| Change in the partial Mayo Score fom baseline |  | 6 week | 
| Calprotectin concentrations |  | 6 week | 
| Riley Acute Inflammation Scale (histology) |  | 6 week | 
| Clinical remission |  | Week 6 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
IBD, Ulcerative colitis