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出境医 / 临床实验 / Phase II Study of Hemay007 in Patients With Active Ulcerative Colitis

Phase II Study of Hemay007 in Patients With Active Ulcerative Colitis

Study Description
Brief Summary:
This study adopts a multicenter, randomized, double-blind, low-medium-high dose group 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 1:1:1:1 to Hemay007 400 mg BID group, 800 mg QD group, 600 mg BID group or placebo group, with proposed 72 cases in each group. After 12 weeks of double-blind inductive treatment period, the patients will enter the Hemay007 open treatment period of 12 weeks when Hemay007 600 mg BID will be used as the medication regimen. All randomized subjects who have received the investigational drug should be subjected to a 4-week observation after the end of treatment.

Condition or disease Intervention/treatment Phase
Ulcerative Colitis Drug: Hemay007 Drug: Placebo Phase 2

Detailed Description:
his study adopts a multicenter, randomized, double-blind, low-medium-high dose group 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 1:1:1:1 to Hemay007 400 mg BID group, 800 mg QD group, 600 mg BID group or placebo group, with proposed 72 cases in each group. After 12 weeks of double-blind inductive treatment period, the patients will enter the Hemay007 open treatment period of 12 weeks when Hemay007 600 mg BID will be used as the medication regimen. All randomized subjects who have received the investigational drug should be subjected to a 4-week observation after the end of treatment.
Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 70 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Double-blind, Placebo Parallel Controlled Clinical Study on the Effecacy and Safety of Different Dosing Regimens of Hemay007 in Patients With Active Ulcerative Colitis
Actual Study Start Date : August 13, 2019
Estimated Primary Completion Date : December 31, 2021
Estimated Study Completion Date : December 31, 2021
Arms and Interventions
Arm Intervention/treatment
Active Comparator: Hemay007 400 mg BID group
Patients will orally take Hemay007 tablets 400 mg BID for 12 weeks.
Drug: Hemay007
Hemay007 will be orally administered.

Active Comparator: Hemay007 800 mg QD group
Patients will orally take Hemay007 tablets 800 mg QD for 12 weeks.
Drug: Hemay007
Hemay007 will be orally administered.

Active Comparator: Hemay007 600 mg BID group
Patients will orally take Hemay007 tablets 600 mg BID for 12 weeks.
Drug: Hemay007
Hemay007 will be orally administered.

Placebo Comparator: placebo group
Patients will orally take placebo tablets for 12 weeks.
Drug: Placebo
Placebo

Outcome Measures
Primary Outcome Measures :
  1. clinical response [ Time Frame: 12-week ]
    12-week clinical response rate Definition of clinical response: defined as full Mayo score decreased by ≥ 3 points compared with baseline and lowered by ≥ 30% compared with baseline, combined with the rectal bleeding subscore decreased by ≥ 1 point compared with baseline, or the absolute value of rectal bleeding subscore ≤ 1 point.


Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Willing to participate in the trial and signing the informed consent forms;
  • Age ≥18 years old and ≤70 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;
  • Active ulcerative colitis with full Mayo score ≥ 4 points, and the subscore "endoscopic findings" in the Mayo endoscopic score within 14 days before randomization ≥ 2 points;
  • 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 planning to become pregnant during the study;
  • Knownto be allergic to any component of Hemay007 tablets (the main component is hemay007, and the main excipients are microcrystalline cellulose, pregelatinized starch, croscarmellose sodium, 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 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;
  • Patientswith evidence of pathogenic intestinal infection;
  • 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 positive mycobacterium tuberculosis or potential mycobacterium tuberculosis infection, i.e. patients conforming to any one of the following definitions will be excluded: QuantiFERON®-TB Gold (QFT-G) or T-SPOT.TB test positive or purified protein derivative (PPD) skin test induration result ≥ 5 mm (within 3 months before screening); Chest imaging examination indicating positive tuberculosis (TB) infection lesion within 3 months prior to screening; History of latent or active TB infection;

  • 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;
  • Patients previously receiving drugs or treatment depleting lymphocytes (e.g. alemtuzumab, alkylating agents (e.g. cyclophosphamide or chlorambucil), total lymph node radiotherapy, etc.), however, patients can be enrolled if they used rituximab or other selective B lymphocyte depleting drugs more than one year before screening;
  • Lymphocyte apheresis or selective mononuclear granulocyte apheresis was performed within 12 months before the screening or is planned to be performed during the study;
  • The electrocardiogram during the screening period is abnormal and clinically significant, with the safety risk possibly increasing judged by the investigator;
  • Blood donation ≥500 ml within 2 months before randomization;
  • 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; [21] 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);
  • Varicella, herpes zoster or other serious viral infections within 6 weeks prior to screening;
  • Patients receive any live vaccine at present or has received any live vaccine within 8 weeks prior to randomization;
  • Major organ transplantation (e.g. heart, lung, kidney, liver) or hematopoietic stem cell/bone marrow transplantation;
  • Application of other drugs or devices of research nature within 3 months prior to randomization;
  • Patients with primary sclerosing cholangitis;
  • History of alcohol or drug abuse;
  • Other conditions that the investigator judges as unsuitable to participate in the study.
Contacts and Locations

Locations
Show Show 25 study locations
Sponsors and Collaborators
Tianjin Hemay Pharmaceutical Co.,Ltd
Investigators
Layout table for investigator information
Principal Investigator: Xiaowei Liu, M.D. XiangYa Hospital CentralSouth University
Tracking Information
First Submitted Date  ICMJE April 27, 2019
First Posted Date  ICMJE June 6, 2019
Last Update Posted Date June 3, 2021
Actual Study Start Date  ICMJE August 13, 2019
Estimated Primary Completion Date December 31, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 5, 2019)
clinical response [ Time Frame: 12-week ]
12-week clinical response rate Definition of clinical response: defined as full Mayo score decreased by ≥ 3 points compared with baseline and lowered by ≥ 30% compared with baseline, combined with the rectal bleeding subscore decreased by ≥ 1 point compared with baseline, or the absolute value of rectal bleeding subscore ≤ 1 point.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase II Study of Hemay007 in Patients With Active Ulcerative Colitis
Official Title  ICMJE A Multicenter, Randomized, Double-blind, Placebo Parallel Controlled Clinical Study on the Effecacy and Safety of Different Dosing Regimens of Hemay007 in Patients With Active Ulcerative Colitis
Brief Summary This study adopts a multicenter, randomized, double-blind, low-medium-high dose group 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 1:1:1:1 to Hemay007 400 mg BID group, 800 mg QD group, 600 mg BID group or placebo group, with proposed 72 cases in each group. After 12 weeks of double-blind inductive treatment period, the patients will enter the Hemay007 open treatment period of 12 weeks when Hemay007 600 mg BID will be used as the medication regimen. All randomized subjects who have received the investigational drug should be subjected to a 4-week observation after the end of treatment.
Detailed Description his study adopts a multicenter, randomized, double-blind, low-medium-high dose group 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 1:1:1:1 to Hemay007 400 mg BID group, 800 mg QD group, 600 mg BID group or placebo group, with proposed 72 cases in each group. After 12 weeks of double-blind inductive treatment period, the patients will enter the Hemay007 open treatment period of 12 weeks when Hemay007 600 mg BID will be used as the medication regimen. All randomized subjects who have received the investigational drug should be subjected to a 4-week observation after the end of treatment.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Ulcerative Colitis
Intervention  ICMJE
  • Drug: Hemay007
    Hemay007 will be orally administered.
  • Drug: Placebo
    Placebo
Study Arms  ICMJE
  • Active Comparator: Hemay007 400 mg BID group
    Patients will orally take Hemay007 tablets 400 mg BID for 12 weeks.
    Intervention: Drug: Hemay007
  • Active Comparator: Hemay007 800 mg QD group
    Patients will orally take Hemay007 tablets 800 mg QD for 12 weeks.
    Intervention: Drug: Hemay007
  • Active Comparator: Hemay007 600 mg BID group
    Patients will orally take Hemay007 tablets 600 mg BID for 12 weeks.
    Intervention: Drug: Hemay007
  • Placebo Comparator: placebo group
    Patients will orally take placebo tablets for 12 weeks.
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: May 31, 2021)
70
Original Estimated Enrollment  ICMJE
 (submitted: June 5, 2019)
288
Estimated Study Completion Date  ICMJE December 31, 2021
Estimated Primary Completion Date December 31, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Willing to participate in the trial and signing the informed consent forms;
  • Age ≥18 years old and ≤70 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;
  • Active ulcerative colitis with full Mayo score ≥ 4 points, and the subscore "endoscopic findings" in the Mayo endoscopic score within 14 days before randomization ≥ 2 points;
  • 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 planning to become pregnant during the study;
  • Knownto be allergic to any component of Hemay007 tablets (the main component is hemay007, and the main excipients are microcrystalline cellulose, pregelatinized starch, croscarmellose sodium, 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 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;
  • Patientswith evidence of pathogenic intestinal infection;
  • 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 positive mycobacterium tuberculosis or potential mycobacterium tuberculosis infection, i.e. patients conforming to any one of the following definitions will be excluded: QuantiFERON®-TB Gold (QFT-G) or T-SPOT.TB test positive or purified protein derivative (PPD) skin test induration result ≥ 5 mm (within 3 months before screening); Chest imaging examination indicating positive tuberculosis (TB) infection lesion within 3 months prior to screening; History of latent or active TB infection;

  • 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;
  • Patients previously receiving drugs or treatment depleting lymphocytes (e.g. alemtuzumab, alkylating agents (e.g. cyclophosphamide or chlorambucil), total lymph node radiotherapy, etc.), however, patients can be enrolled if they used rituximab or other selective B lymphocyte depleting drugs more than one year before screening;
  • Lymphocyte apheresis or selective mononuclear granulocyte apheresis was performed within 12 months before the screening or is planned to be performed during the study;
  • The electrocardiogram during the screening period is abnormal and clinically significant, with the safety risk possibly increasing judged by the investigator;
  • Blood donation ≥500 ml within 2 months before randomization;
  • 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; [21] 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);
  • Varicella, herpes zoster or other serious viral infections within 6 weeks prior to screening;
  • Patients receive any live vaccine at present or has received any live vaccine within 8 weeks prior to randomization;
  • Major organ transplantation (e.g. heart, lung, kidney, liver) or hematopoietic stem cell/bone marrow transplantation;
  • Application of other drugs or devices of research nature within 3 months prior to randomization;
  • Patients with primary sclerosing cholangitis;
  • History of alcohol or drug abuse;
  • Other conditions that the investigator judges as unsuitable to participate in the study.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03977480
Other Study ID Numbers  ICMJE HM007UC2S01
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Tianjin Hemay Pharmaceutical Co.,Ltd
Study Sponsor  ICMJE Tianjin Hemay Pharmaceutical Co.,Ltd
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Xiaowei Liu, M.D. XiangYa Hospital CentralSouth University
PRS Account Tianjin Hemay Pharmaceutical Co.,Ltd
Verification Date May 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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