A STUDY TO INVESTIGATE THE EFFICACY AND SAFETY OF TREATMENT WITH LYC-30937-EC IN PATIENTS WITH ULCERATIVE COLITIS

Phase 1

• Conditions: lcerative Colitis; MedDRA version: 20.1Level: LLTClassification code 10045365Term: Ulcerative colitisSystem Organ Class: 100000004856; Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

• Registration Number: EUCTR2016-000518-31-PL
• Lead Sponsor: ycera Corp.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2016-08-19
• Last Update Posted: 30 April 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

1. Consenting adults aged 18–75 years.
2. Have had UC diagnosed at least 6 months prior to screening and with a minimum disease extent of = 15 cm from the anal verge. The diagnosis of UC must be confirmed by endoscopic and histologic evidence (histology may be confirmed at screening based on biopsy collection during the screening colonoscopy with histological evaluation done by the site).
3. Have active UC defined as a TMS of 4–11 (inclusive) with endoscopic subscore of = 2 and rectal bleeding subscore of = 1 at screening.
4. Male and females subjects of childbearing potential must agree to use adequate birth control measures during the study. Female subjects of child bearing potential must use two highly effective forms of contraception, unless surgically sterilized, partner has had a vasectomy, or they will be abstinent, during study participation and for 30 days after their last dose of study drug. Highly effective methods of birth control in this study include: intrauterine device, hormonal contraceptives (oral patch, long acting injectable, implant), double-barrier method (condom or diaphragm with spermicide), or abstinence during study participation and for 30 days after their last dose of study drug. (Post-menopausal defined as lack of menses for = 6 months prior to screening confirmed with serum FSH > 25 mIU/mL at screening.)
5. If currently receiving any of the following UC treatments the duration and dose prior to the screening endoscopy must be as specified below and a stable dose should be maintained throughout the double-blind trial:
a. Oral aminosalicylates (eg, mesalamine, sulfasalazine, olsalazine, balsalazide) for
= 6 weeks with the dose stable for = 3 weeks prior to the Screening endoscopy (eg, if recently tapered off corticosteroid).
b. Prednisone (dose = 20 mg daily) or equivalent for = 4 weeks and receiving a stable dose for = 2 weeks prior to the screening endoscopy.
c. Thiopurines (azathioprine or 6-mercaptopurine) provided the dose has been stable for = 8 weeks prior to the screening endoscopy.
6. If oral aminosalicylates (ASA) or corticosteroids have been recently discontinued, they must have been stopped for = 2 weeks prior to the screening endoscopy (eg, if recently tapered off corticosteroid). If a thiopurine has recently been discontinued it must have been stopped = 4 weeks prior to the screening endoscopy.
7. Ability to provide written informed consent and to be compliant with the schedule of events.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 80
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 40

Exclusion Criteria

1. Known mitochondrial disorder.
2. History of CD or indeterminate colitis or the presence or history of a fistula consistent with CD.
3. History of bleeding disorders (eg, complement disorders, hemophilia, history of uncontrolled bleeding).
4. Severe extensive disease that in physician judgment the subject is likely to require colonic surgery during the 8 week double-blind course (eg, fulminant colitis, toxic megacolon, bowel perforation, evidence of an acute abdomen).
5. Positive test for Clostridium (C.) difficile, positive stool culture for enteric pathogens (eg, Salmonella, Shigella, Campylobacter), or presence of ova or parasites at screening.
Note that C. difficile may be treated and the subject may be retested for screening after
he/she completed this treatment.
6. Any of the following laboratory abnormalities:
a. liver function tests > 1.5 x the upper limit of normal (ULN) or direct bilirubin > 1.5 x ULN.
b. hemoglobin < 8.5 g/dl (international system units [SI]: < 85 g/L).
c. neutrophils < 1500/mm3 (SI: < 1.5 x 109/L).
d. white blood cell (WBC) count < 3,000/mm3 (SI: < 3.0 x 109/L).
e. Platelets < 80,000 mm3 (SI: 80 x 109/L).
f. international normalized ratio (INR) > 1.5.
g. serum creatinine > 1.4 mg/dL for women or > 1.6 mg/dL for men.
7. Treatment with non-thiopurine immunosuppressant agents within 4 weeks prior to screening endoscopy (eg, cyclosporine, methotrexate, tacrolimus, sirolimus, or mycophenolate mofetil) [MMF]
8. Pregnancy, lactation, or a positive serum beta human chorionic gonadotropin (hCG) at
screening. Female subjects should not be planning to become pregnant while enrolled in the trial.
9. Clinically relevant hepatic, neurological, pulmonary, ophthalmological, gastrointestinal, endocrine, psychiatric, or other major systemic disease making implementation of the protocol or interpretation of the study difficult or that would put the subject at risk by participating in the study.
10. History of uveitis within the 12 months prior to initiation of screening procedures.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective will be to assess the efficacy of LYC-30937-EC in inducing remission compared with placebo in subjects with active UC over a treatment duration of 8 weeks.;Secondary Objective: The secondary objectives will be to evaluate the safety, tolerability, plasma tissue PK of LYC-30937-EC compared with placebo in subjects with active UC.;Primary end point(s): The proportion of subjects who achieve a clinical remission at Week 8 using the modified Mayo score (MMS). Clinical remission is defined as Mayo stool frequency subscore of =1, Mayo rectal bleeding subscore of 0 and Mayo endoscopy subscore of =1. ;Timepoint(s) of evaluation of this end point: At week 8 of participation of a subject.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): • The proportion of subjects who achieve clinical remission at Week 8 using the total Mayo score (TMS), defined as a Mayo score of =2, with no individual score >1, and rectal bleeding score of 0; <br>• The proportion of subjects with a clinical response at Week 8, defined as a reduction from Baseline MMS of =2 points and =25%, and a decrease from baseline in rectal bleeding subscore of =1 point or an absolute rectal bleeding subscore of =1 point;<br>• The proportion of subjects with a clinical response at Week 8, defined as a reduction from Baseline in TMS of =3 points and =30%, and a decrease from Baseline in rectal bleeding subscore of =1 point or an absolute rectal bleeding subscore of =1 point;<br>• The change from baseline TMS at Week 8;<br>• The change from baseline to Week 8 in fecal calprotectin.;Timepoint(s) of evaluation of this end point: At week 8 of participation of a patient.