Overview

Phase II Study of Hemay005 in Patients With Active Ulcerative Colitis

Status:
Not yet recruiting
Trial end date:
2024-09-30
Target enrollment:
0
Participant gender:
All
Summary
This study adopts a multicenter, randomized, double-blind, low--high dose groups and placebo parallel controlled clinical study design. After screening, patients with active ulcerative colitis who meet the inclusion criteria and do not meet the exclusion criteria will be randomized by 1:1:1 to Hemay005 45 mg BID group, 60 mg BID group or placebo group, with proposed 36 patients in each group. All patients will enter a 12-w eek double-blind inductive treatment period. All randomized subjects who have received the investigational drug should be subjected to a 4-week observation after the end of treatment.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Ganzhou Hemay Pharmaceutical Co., Ltd
Treatments:
Hemay005
Criteria
Inclusion Criteria:

- Willing to participate in the trial and signing the informed consent forms;

- Age ≥18 years old, male or female;

- Diagnosed as ulcerative colitis (UC) ≥ 3 months at screening with clinical
manifestations and evidence of endoscopy and confirmed by histopathological reports;

- Expansion of the affected bowel segment beyond the rectum confirmed on endoscopy
(affected bowel segment≥15cm);

- Moderate to severe ulcerative colitis with Modified Mayo clinical score (MMCS)≥ 4
points and ≤9 points, the Endoscopy subscore ≥ 2 points within 14 days before
randomization and Stool Frequency subscore ≥ 1 point;

- UC treatment failure or intolerance (intolerance is defined as the discontinuation of
drug use due to adverse reactions judged by the investigators) experienced by patients
using at least one of the following:

Oral administration of sulfasalazine (SASP) and/or 5-aminosalicylic acid (5-ASA); Oral
administration of corticosteroids; Azathioprine or 6-mercaptopurine; Anti-TNF-α treatment:
infliximab or adalimumab, etc.; - If the patient is using the following drugs to treat
ulcerative colitis at the time of screening, it is necessary to receive stable treatment
during the screening period and the following requirements during the study period are as
follows: Oral administration of sulfasalazine (SASP) and/or 5-aminosalicylic acid (5-ASA)
maintaining stable for at least ≥ 2 weeks prior to endoscopy during the screening period
and maintaining stable during the study period; and/or Oral administration of low-dose
corticosteroids (≤25 mg/d prednisolone or equivalent drug dose) maintaining stable for at
least ≥ 2 weeks prior to endoscopy during the screening period;

- At least one of the following effective contraceptive methods should be adopted for
female patients with fertility and male patients who have not undergone vasectomy during
the entire study period from the date of signing the informed consent to 3 months after the
last dose. Acceptable contraceptive methods in this study include: a. abstinence; b.
hormones (oral intake, patch, ring, injection, implantation) combined with male condoms.
This measure must be applied at least 30 days prior to the first administration of
investigational drug, otherwise another acceptable method of contraception must be used; c.
intra-uterine device (IUD) combined with male condoms; d. barrier method (diaphragm,
cervical cap, sponge) combined with male condoms; exceptional circumstances: a) females who
have been menopausal for 5 years and more, and b) surgical sterilization (proof should be
provided).

Exclusion Criteria:

- Pregnant or lactating women, or women or men whose partners planning to become
pregnant during the study;

- Knownto be allergic to any component of Hemay005 tablets (the main component is
hemay005, and the main excipients are mannitol, low substituted hydroxypropyl
cellulose, croscarmellose sodium and magnesium stearate);

- Patients with suspected or confirmed Crohn's disease, undiagnosed types of colitis,
fulminant colitis, toxic megacolon, microscopic colitis, ischemic colitis or
radioactive colitis based on medical history and endoscopy and/or histological
results;

- Patients with active EBV and/or CMV infection (EBV antibody IgM and/or EBV DNA
positive); CMV antibody IgM and/or CMV DNA positive);

- Patients with the disease confined to the rectum (ulcerative proctitis) according to
the endoscopy during screening;

- Patients who have undergone surgical treatment for ulcerative colitis or who require
surgery during the study;

- Patients with active infection or positive pathogen test at the time of screening, and
determined by the investigator to increase the risk of the subject, except for those
with negative repeat test results and no symptoms of persistent infection (if time
permits, during screening treatment and repeat testing);

- Patients receiving the following treatments:

Patients who have used azathioprine/6-mercaptopurine, methotrexate within 7 days before
randomization; Patients who have used cyclosporine, mycophenolate mofetil,
tacrolimus/sirolimus within 4 weeks before randomization; Patients who have used interferon
within 8 weeks before randomization; Patients who have received anti-TNF-α treatment within
8 weeks before randomization; Intravenous corticosteroids or rectal administration of
corticosteroids or rectal administration of 5-ASA within 2 weeks prior to randomization;
Patients who have used thalidomide within 8 weeks before randomization;Patients who have
received antibiotic treatment within 1 week before randomization;

- Patients with active infection and judged by the investigator to increase the risk of
the subjects;

- Patients with a history of TB or active TB (Investigator-judged signs or symptoms of
active tuberculosis at screening):

Screening was permitted if patients had a history of tuberculosis and had been cured by
investigator assessment for at least 3 years prior to randomization; subjects with a
negative T-cell test for tuberculosis infection (T-SPOT) at screening can be included in
this study. Subjects who are T-SPOT positive during the screening period need to undergo
tuberculosis-related clinical examinations (Tuberculosis-related clinical work performed
within 12 weeks prior to randomization can be used directly for evaluation), if the
tuberculosis-related clinical examination confirmed active tuberculosis, the subjects will
not be eligible for this study. Subjects can be included in this study if the
tuberculosis-related clinical examination confirms inactive tuberculosis. If the research
center cannot perform T-SPOT test, TB screening by QuantiFERON-TB Gold test kit can also be
accepted. The treatment of QuantiFERON-TB-Gold screening results is the same as that of
T-SPOT.

- Patients with hemoglobin <8 g/dL or hematocrit <30%, white blood cells <3.0 × 10^9/L
or neutrophils <1.2 × 10^9/L, platelets <100 × 10^09/L at screening;

- Total bilirubin (TBIL), aspartate aminotransferase (AST) or alanine aminotransferase
(ALT) ≥ 2 upper limits of normal (ULN) at screening;

- Glomerular filtration rate (eGFR) ≤ 40 ml/min;

- Patients with hereditary immunodeficiency disease;

- Patients with a history of lymphoproliferative disorders (e.g. EBV-related
lymphoproliferative disorders), or with lymphoma, leukemia, myeloproliferative
disease, multiple myeloma;

- Lymphocyte apheresis or selective mononuclear granulocyte apheresis was performed
within 12 months before the screening or is planned to be performed during the study;

- Patients with malignant tumor or with a history of malignancy other than well-treated
or resected basal cell or squamous cell skin cancer;

- Patients with conditions that may affect oral drug absorption, e.g. gastrectomy or
clinically significant diabetes-related gastrointestinal disorders, or specific types
of obesity surgery such as gastric bypass, however, patients only subjected to the
division of the stomach into independent chambers, like gastric banding, will not be
excluded;

- Patients with previous surgery on small intestine or colon and with evidence of
colonic dysplasia or intestinal stenosis;

- Patients with chronic hepatitis B virus (HBV) infection (hepatitis B surface antigen
(HBsAg), hepatitis B surface antibody (HBsAb) and hepatitis B core antibody (HBcAb)
should be assessed for all patients during screening: patients with positive hepatitis
B surface antigen (HBsAg) will be excluded; patients with HBsAg (negative), HBsAb
(negative or positive) and HBcAb (positive) should be tested for HBV-DNA, and if the
HBV-DNA result is positive, patient will be excluded; if the HBV-DNA result is
negative, patients can be enrolled in the study.), chronic hepatitis C virus (HCV)
infection (patients with positive hepatitis C virus antibody (HCVAb) excluded) or
human immunodeficiency virus (HIV) infection (patients with positive human
immunodeficiency virus (HIV) antibody excluded) or Syphilis (TP) infection (excluded
patients with Treponema pallidum antibody (Anti-TP) positive);

- Patients receive any live vaccine at present or has received any live vaccine within 8
weeks prior to randomization, or have been vaccinated against COVID-19 within 14 days
prior to randomization;

- Use of cytochrome P450 enzyme inducers (such as rifampicin, phenobarbital,
dexamethasone, isoniazid, carbamazepine, etc.) within 14 days before screening;

- Suicidal behavior (including active attempts, interrupted attempts, or attempted
attempts) or suicidal thoughts within the past 6 months;

- Other conditions that the investigator judges as unsuitable to participate in the
study.