A multi-centre, double-blind, placebo controlled, parallelgroup, proof of concept study to evaluate the efficacy,safety and tolerability of KRP203 in subjects withmoderately active refractory ulcerative colitis

Phase 1

• Conditions: lcerative colitis; MedDRA version: 14.0Level: LLTClassification code 10045365Term: Ulcerative colitisSystem Organ Class: 10017947 - Gastrointestinal disorders

• Registration Number: EUCTR2010-019970-33-BE
• Lead Sponsor: ovartis Services AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-09-20
• Last Update Posted: 21 August 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 72

Inclusion Criteria

1.Written informed consent must be obtained before any assessment is performed.
2.Males and females 18-65 years of age with an established diagnosis of ulcerative colitis are eligible for the study.
3.Subjects must have active disease with a Partial Mayo Score between 5 and 9 (inclusive), with a score of at least 2 on either stool frequency or rectal bleeding and a Modified Baron Score of at least 2 upon endoscopic examination with the disease extending at least 25 cm from the anal verge.
4.Subjects must have responded inadequately to conventional therapy with oral 5-ASA prior to screening. Inadequate response is considered to be any of the following:
a.Active disease despite induction therapy with 5-ASA agents where adequate therapy is considered with an oral 5-ASA (mesalamine 2– 4.8 g/day, sulfasalazine 4–6 g/day, balsalazide 6-7.5 g/day or olsalazine 1.5–3 g/day) administered for at least 2 weeks.
b.Intolerance to oral 5-ASAs.
5.Female patients may be included in the study according to the following:
a.Female patients of child bearing potential must be using two highly effective methods of contraception (one primary and one secondary), from the time of screening and for the duration of the study, through Study Completion and for two (2) months after study completion. Period abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
Primary contraception forms:
•Hormonal contraception (combination oral contraceptives, hormonal transdermal patch, combined injected hormones, injected single hormone, implanted hormones, or hormonal vaginal ring)
•Tubal sterilization
•Partner's vasectomy
•Intrauterine device (eg: synthetic progestin containing IUDs, IUD copper T380)
Secondary contraception forms:
•Male latex condom
•Diaphragm
•Cervical cap
b.Postmenopausal females must have had no regular menstrual bleeding for at least one (1) year prior to initial dosing. Menopause will be confirmed by a plasma FSH level of >40 IU/L at screening.
c.Female patients who report surgical sterilization must have had the procedure at least six (6) months prior to initial dosing. Surgical sterilization procedures should be supported with clinical documentation made available to the sponsor and noted in the Relevant Medical History / Current Medical Conditions section of the CRF.
d.All female patients must have negative pregnancy test results at Screening.
6.Male subjects must agree to comply with two highly effective contraceptive methods comprising a barrier method (condom or occlusive cap plus spermicidal) for up to the last drug administration, and refrain from fathering a child for at least two (2) months following the last study drug administration. Periodic abstinence and withdrawal are not acceptable methods of contraception.
7.Patients must be able to communicate well with the Investigator, to understand and comply with the requirements of the study and to understand and sign the written informed consent.

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
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1.Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment
2.Pregnant or nursing (lactating) women
3.Subjects who have been treated with
a.Anti-TNF a or biological therapy and cyclophosphamide with 3 months prior to randomization
b.Rituximab or other immunosuppressive treatments with effects potentially lasting over 6 months, within 12 months prior to randomization.
c.a dose of = 1 mg prednisone or equivalent per body kg weight in the last 8 weeks prior to randomization.
4.Ongoing treatment with cyclosporine, methotrexate, azathioprine, 6-mercaptoprine, tacrolimus or rectally administered corticosteroid or 5-aminosalicylate containing medication. Eligible subjects must have stopped cyclosporine, methotrexate, azathioprine, 6-mercaptoprine and tacrolimus at least 4 weeks and antibiotics and rectal or topical therapy at least 1 week prior to randomization.
5.A history of macular edema, diabetic retinopathy, uveitis, central serious retinopathy, retinal vein occlusion, or any other eye disease that increases the risk of macular edema.
6.History or evidence abnormal cardiovascular conditions
7.Any of the following pulmonary conditions:
a.pulmonary fibrosis or any severe respiratory disease
b.tuberculosis, except for history of successfully treated tuberculosis or history of prophylactic treatment after positive PPD skin reaction
c.patients receiving chronic (daily) therapies for asthma
d.patients with any other types of clinically significant bronchoconstrictive disease
8.Uncontrolled diabetes mellitus
9.Repeated and confirmed laboratory findings showing:
a.known history of alcohol abuse, chronic liver or biliary disease
b.total bilirubin greater than the upper limit of the normal range (ULN) unless in context of Gilbert’s syndrome
c.conjugated bilirubin greater than the ULN
d.alkaline phosphatase (AP) greater than 1.5 x ULN
e.AST (SGOT), ALT (SGPT) greater than 1.5 x ULN
f.gamma-glutamyl-transferase (GGT) greater than 2 x ULN
g.serum creatinine greater than 1.5 times the upper limit of normal range
h.total white blood cell count (WBC) outside the range of 3,000 – 12,000 /µL. Subjects with mild leukocytosis (WBC not higher than 15,000 /µL) may be eligible, if the elevated WBC, according to the Investigator, is attributable to corticosteroid therapy and other causes such as hematological or infectious diseases can be excluded.
i.platelets <100,000/µL
j.Hemoglobin less 9 g/dL and/or other signs of severe anemia.
k.lymphocyte count <800/mm3 (<800 / µL)
10.Subjects who have been diagnosed with primary sclerosing cholangitis are excluded from the study.
11.History or presence of a significant renal disease
12.Clinical signs and symptoms of toxic megacolon
13.Positive alcohol or drug abuse test at screening.
14.Donation or loss of 400 mL or more of blood within 8 weeks prior to dosing or longer if required by local regulation.
15.Have received any live or live attenuated vaccines (including for varicella-zoster virus or measles) within 2 months prior to randomization.
16.Significant illness within the two weeks prior to dosing or any active systemic infection or medical condition that may require treatment or therapeutic intervention during the study.
17.Current history of active systemic bacterial, viral or fungal infections
18.Diagnosis of AIDS, Hepatitis B, Hepatitis C infection defined as a positive HIV antibody, Hepatitis B surface antigen or He

Study & Design

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