Study of Bacteroides Thetaiotaomicron in Young People Aged 16 to 18 Years With Stable Crohn's Disease

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety and tolerability of Bacteroides thetaiotaomicron (Thetanix®)) capsules in young people aged 16 to 18 years with stable Crohn's disease.

Detailed Description
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This study is a single (Part A) and multiple (Part B) dose study. Following informed consent and screening, 10 eligible subjects will receive a single dose of Thetanix or placebo in the clinic. A Safety Review Committee will review the safety data up to Day 7 from these first ten subjects and determine if it is appropriate to continue into Part B in which 10 subjects will receive 15 doses of Thetanix or placebo in a twice daily dosing regimen over 7.5 days. In both parts of the study, 8 of the 10 subjects will randomly receive Thetanix and 2 subjects will randomly receive placebo. Each dose consists of three capsules. Subjects in Part B will receive the first and last dose in the clinic and will take 13 doses at home. While at home, subjects will be required to answer questions about their health, record their body temperature and when they take the capsules in an electronic diary. Subjects developing a fever will undergo further assessments, including blood cultures. Subjects will provide stool samples for analysis of microbiota and faecal calprotectin.

Official Title
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A Randomised, Double-blind, Placebo-controlled Study to Assess the Safety and Tolerability of Bacteroides Thetaiotaomicron in Young People Aged 16 to 18 Years With Stable Crohn's Disease

Conditions
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Crohn's Disease

Intervention / Treatment
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* Other: Thetanix
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects aged 16 to 18 years inclusive, with confirmed diagnosis of Crohn's disease who are currently in clinical remission* in the opinion of the investigator and who are otherwise healthy. Subjects who are able and willing to give written informed consent to participate. If applicable, a parent/carer may also give consent to their participation. Exclusion Criteria: Subjects who are pregnant or breastfeeding. Subject who are experiencing an exacerbation at the time of screening or up to the time of the first dose. Subjects who have undergone previous surgery for resection of bowel. Subjects who have fistulisation. Subjects who have had a significant change in their immune-modulating maintenance medication in the 3 months prior to screening and/or the start of dosing. Subjects who have taken systemic steroids in the last 3 months. Subjects who are unable to take any oral feeding. Subjects with feeding gastrostomies. Subjects who have non-food dietary supplementation for any reason changed within 1 month prior to dosing. Subjects who have received monoclonal antibodies in the 6 months prior to dosing. Subjects who have received antibiotics or probiotic dietary supplementation in the two weeks before dosing. Subjects who have received foods with probiotics e.g. yoghurts will be permitted to volunteer for the study. Subjects who are receiving exclusive enteral feeding or have completed a course of exclusive enteral feeding in the 3 months prior to dosing. Subjects with concomitant autoimmune diseases. Female Subjects of child bearing potential unwilling to use effective contraception from the signing of the consent form until completion of two periods after the last dose. An effective method of birth control is defined as one which results in a low failure rate (i.e. less than 1% per year) when used consistently and correctly such as sterilisation, implants, injectables, combined oral contraceptives, Intrauterine Device (IUD), condoms, occlusive caps (cervical/vault caps) with spermicidal foam/gel/film/cream/pessary. True sexual abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject. Subjects with clinically significantly, in the opinion of the investigator, elevated platelets, white cell count, C-reactive protein, erythrocyte sedimentation rate (ESR), low albumin or haemoglobin. Subjects who are positive for the following viruses: HIV, hepatitis B and hepatitis C. Subjects who smoke cigarettes or use other tobacco or nicotine containing products, including e-cigarettes. Subjects who have a known sensitivity to any of the constituents of the investigational medicinal compound. Diastolic blood pressure <50 or >90 mmHg, a systolic blood pressure <100 or >150 mmHg, a pulse <40 or >100 beats per minute (bpm) after resting for 5 minutes. Subjects with clinically significantly abnormal ECGs or structural cardiac abnormalities e.g. valvular heart disease, patent foramen ovale. BMI Z SCORE less than -2.6 or greater than 2.6 (0 ± 2.6); i.e. below the 2nd centile or greater than the 98th centile. Any condition that, in the opinion of the Investigator, might interfere with the primary study objective. Subjects allergic to metronidazole and co-amoxiclav

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Thetanix<br>In Part A, 8 subjects will receive a single dose and in Part B, 8 subjects will receive twice daily doses for 7.5 days (a total of 15 doses). Each dose consists of three capsules | Other: Thetanix<br>* Thetanix is an encapsulated lyophilised formulation of a pure culture of Bacteroides thetaiotaomicron with excipients.<br>* Other names: B. theta;|
| Placebo Comparator: Placebo<br>In Part A, 2 subjects will receive a single dose and in Part B, 2 subjects will receive twice daily doses for 7.5 days (a total of 15 doses). Each dose consists of three capsules. | Other: Placebo<br>* Placebo is encapsulated microcrystalline cellulose without Bacteroides thetaiotaomicron.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment emergent adverse events | The change from baseline will be assessed at Day 7 (Part A) and at Day 14 (Part B). Part A and Part B will be analysed separately as they are of different duration. The primary endpoint for each part is taken as 7 days after the last dose. | Part A (single dose): Day 7. Part B (15 doses over 7.5 days): Day 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Physician Global Assessment | Change in Physician Global Assessment | Part B: Day 14 | 
| Weighted Paediatric Crohn's Disease Activity Index | Change in Weighted Paediatric Disease Activity Index | Part B; Day 14 | 
| The number of subjects with abnormal clinically and non-clinically significant or out of expected range tests. | Tests include: Serum biochemistry and haematology; physical examinations, blood pressure, pulse rate, respiratory rate and oral temperature, weight, height, ECG parameters. | Part A: Day 7; Part B: Day 14 | 
| Part A: Faecal Microbiome Part B Microbiome and faecal calprotectin concentrations | Stool samples will be collected and analysed for faecal calprotectin and microbial communities with specific interest in B. theta. | Part B: Day 14 |