A Pilot Study of GWP42003 in the Symptomatic Treatment of Ulcerative Colitis (GWID10160)

• Clinical Efficacy Blood Sample Measurements [ Time Frame: Baseline to end of treatment (10 weeks treatment period) ] [ Designated as safety issue: No ]
  Serum C-Reactive protein (CRP) Serum Cytokines (IL-6, IL-2 & TNF-α)
• Clinical Efficacy Stool Sample Measurements [ Time Frame: Baseline to end of treatment (10 weeks treatment period) ] [ Designated as safety issue: No ]
  Stool sample for faecal inflammatory marker calprotectin
• Clinical Body Weight Assessment [ Time Frame: Baseline to end of treatment (10 weeks treatment period) ] [ Designated as safety issue: No ]
  Body weight measurement
• Clinical Assessments [ Time Frame: Baseline to end of treatment (10 weeks treatment period) ] [ Designated as safety issue: No ]
  • IBDQ
  • SGIC
  • PGAS
  • MAYO Score
• Ulcerative Colitis symptom measures [ Time Frame: Baseline to end of treatment (10 weeks treatment period) ] [ Designated as safety issue: No ]
  • Pain (NRS)
  • Rectal bleeding (NRS)
  • Stool frequency (NRS)

Ulcerative Colitis is an inflammatory bowel disease effecting large amounts of the population. The most common treatment for this condition is 5-ASA, however patients failing to respond to this and incurring a flare up are often escalated to steroidal treatments.

This study is being conducted by GW Pharma Ltd as a pilot study in order to determine the efficacy and safety of GW42003 (150mg - 250mg twice daily), compared with placebo, by the percentage of participants achieving remission quantified as a MAYO score of 2 or less (with no subscore > 1) after 10 weeks treatment.

This is the first study to determine whether the study medication has a positive benefit for subjects on their ulcerative colitis symptom control,as well as effects on inflammatory marker cytokines (plasma TNFα, Il-2, Il-6), CRP, faecal inflammatory marker (calprotectin), stool frequency (NRS), rectal bleeding (NRS), pain (NRS). In addition, various IBD questionnaires are being implemented in the study to observe further benefits on the study medication, compared with placebo.

This study will be a multi-centre, randomised, double-blind, placebo-controlled, parallel-group pilot study. There will be two parallel groups of participants (150mg-250mg GWP42003 and placebo, twice daily), with a treatment duration of 10 weeks as well as a 7 day baseline period and one week follow-up. The two treatment groups of 150mg-250mg GWP42003 and placebo will be randomised equally into a 1:1 ratio, with 31 participants in the active IMP group and 31 participants allocated placebo treatment.

In order to be eligible for enrollment in this study, subjects will need to be aged 18 years and above and be clinically diagnosed with with mild or moderate ulcerative colitis and on a fixed dose of 5-ASA treatment and have been on a stable dose for at least 2 weeks prior to screening.

Eligible subjects will enter the study at a screening visit (Visit 1) and commence a baseline period. Each subject will have a MAYO (including endoscopy) assessment conducted to confirm eligibility. If eligible, the subject will be randomised into the 10-week treatment phase. There are a total of 6 visits in the study.

• Drug: GWP42003
  1-5 capsules taken twice daily, 10 week treatment period.
• Drug: Placebo
  1-5 capsules taken, twice daily. 10 week treatment period.

• Active Comparator: GWP42003
  (150-250mg, BD)
  Intervention: Drug: GWP42003
• Placebo Comparator: Placebo
  Intervention: Drug: Placebo

Inclusion Criteria:

• Male or female participants aged 18 years or above;
• Participant diagnosed with mild to moderate ulcerative colitis and on a fixed dose of 5-ASA treatment and have been on a stable dose for at least 2 weeks prior to screening;
• Participants at screening (Visit 1) and baseline (Visit 2) with a MAYO assessment score of greater than or equal to 4 (≥ 4) but less than or equal to 10 (≤ 10) and with an endoscopy score of at least 1 (≥ 1) , following an adequate exposure to oral and/ or topical 5-ASA, in the opinion of the investigator;
• In the opinion of the investigator, capable of complying with the study requirements and completing the study;
• Willing and able to give informed consent;
• Willing to allow his or her primary care practitioner and consultant, if appropriate, to be notified of participation in the study;

Exclusion Criteria:

• Severe ulcerative colitis (MAYO score of greater than 10 (> 10));
• Ulcerative colitis only affecting the rectum i.e. Proctitis
• Gastrointestinal infection evident from stool culture and testing for clostridium difficile toxin (in the opinion of the investigator);
• Previous non-responders to mono or polyclonal anti-Tumour Necrosis Factor antibodies;
• Female participant who is pregnant, lactating or planning pregnancy during the course of the study and for 3 months from the date of last dose;
• Female participants of child bearing potential, unless willing to use two forms of contraception, one of which must be a barrier contraception (e.g. female condom or occlusive cap (diaphragm or cervical vault/caps) with spermicide) during the study and for 3 months from the date of last dose (however a male condom should not be used in conjunction with the female condom);
• Male participants whose partner is of child bearing potential, unless willing to use an appropriate barrier method of contraception (condom and spermicide) in addition to having their female partner use another form of barrier contraception (e.g. occlusive cap (diaphragm or cervical vault/caps) with spermicide) during the study and for 3 months from date of last dose (however a male condom should not be used in conjunction with a female condom);
• Travel outside the country of residence planned during the treatment phase of the study;
• Received an Investigational Medicinal Product (IMP) within 30 days prior to the screening visit;
• In the opinion of the investigator, is not considered to be suitable for the study;
• Any other significant disease or disorder which, in the opinion of the investigator, may either put the participant at risk because of participation in the study, may influence the result of the study, or the participant's ability to participate in the study;
• Following a physical examination, the participant has any abnormalities that, in the opinion of the investigator would prevent the participant from safe participation in the study;
• Unwilling to abstain from donation of blood during the study;
• Participants previously randomised into this study.