Hemay005 for the Treatment of Chinese Moderately to Severely Active Ulcerative Colitis
A Phase III, Multicenter, Double-Blind, Placebo-Controlled, Re-randomized Study To Assess the Efficacy and Safety With Hemay005 Tablets in Chinese Patients With Moderately to Severely Active Ulcerative Colitis
調査の概要
詳細な説明
This study is a phase 3, multicenter, randomized, double-blinded, placebo-controlled, parallel-group study to examine the efficacy, safety of Hemay005 in induction and maintenance therapy in Chinese patients with moderately or severely active ulcerative colitis. The study consists of two independent phases: an 12-week Induction Phase (might including an 12-week Extended Induction phase, depending on the participant status by the end of the induction treatment) and a 40-week Maintenance Phase. Screening period will be up to 5 Weeks.
In the Induction Phase, participants will be randomized 2:1 to receive either Hemay005 (twice daily) or placebo for 12 weeks. The randomization will be stratified by: exposed to advanced therapy (yes/no); disease severity (modified Mayo score of 5-6 or 7-9) and baseline corticosteroid use (yes/no). Participants who have not show clinical response (either receive Hemay005 or placebo) by week 12 will undergo an extended 12-week induction treatment with Hemay005.
After completing the Induction Phase (or the Extended Induction Phase), participants with response are eligible to go to the Maintenance Phase. Participants with a response to Hemay005 by week 12 of the Induction Phase and those with a response by the end of the Extended Induction Phase) will be randomized 1:1 to receive either Hemay005 (twice daily) or placebo for 40 weeks. Randomization will be stratified by corticosteroid use at the start date of Maintenance Phase (yes/no) and clinical remission status by the end of Induction Phase (yes/no). Participants who are assigned to placebo during the Induction Phase and have demonstrated a clinical response will continue to receive blinded placebo during the Maintenance Phase. Participants who have not showed a clinical response by week 12 of the Induction Phase but have a response to Hemay005 by the end of the Extended Induction Phase will continue to receive blinded Hemay005 during the Maintenance Phase.
During the Maintenance Phase, participants who are demonstrated loss of response will be eligible to go to the open-label treatment phase and treated with Hemay005. The total duration of open-label treatment phase will not exceed 40 weeks since the participant enrolled into the Maintenance Phase.
研究の種類
入学 (推定)
段階
- フェーズ 3
連絡先と場所
研究連絡先
- 名前:Han Hai
- 電話番号:86-22-24929530
- メール:haihan@hemay.com.cn
研究場所
-
-
-
Guangzhou、中国
- The First Affiliated Hospital,Sun Yat-sen University
-
主任研究者:
- Baili Chen
-
コンタクト:
- Minhu Chen, M.D
- 電話番号:86-020-87755766
- メール:chenminhu@vip.163.com
-
Guangzhou、中国
- The Sixth Affiliated Hospital,Sun Yat-sen University
-
コンタクト:
- Xiang Gao, M.D
- 電話番号:86-020-38254000
-
主任研究者:
- Xiang Gao, M.D
-
-
参加基準
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
説明
Inclusion Criteria:
- Men or women 18 to 80 years of age, inclusive, at the time of consent.
- Voluntarily to give written informed consent.
- Diagnosed with UC established at least 3 months prior to screen visit. The diagnosis must be confirmed by clinical and endoscopic evidence, corroborated by a histopathology report.
- Active UC confirmed by endoscopy, classified as Montreal E2 or E3.
- Moderately to severely active UC, defined as mMS of 5 to 9 points, including a MES of at least 2 (confirmed through centrally read endoscopy) and a SFS of at least 1 and a RBS of at least 1. The endoscopy should be performed within 14 days prior to randomization.
Demonstrated inadequate response, loss of response and/or intolerance to at least one of the following UC therapies:
A) Conventional therapies, including oral 5-aminosalicylic acid (5-ASA) compounds, corticosteroids, immunoregulatory agents.
B) Advanced therapies: biologics (including but not limit to antitumor necrosis factor alpha (TNFα) antibodies, anti-integrin antibodies, anti-interleukin 12/23 antibodies) and small molecule therapies(including but not limit to JAK inhibitors, S1P receptor modulators) Note: The medication used to qualify the subject for entry into this category must be approved for the treatment of UC in the country of use and the subject must have received an adequate course of therapy based on local guidelines for that therapy.
- For female participants of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use adequate contraception and agreement to refrain from egg donation or undergo fertility treatment during the treatment period and for 30 days after the final dose of Hemay005. For male participants: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agree to refrain from donating sperm during the treatment period and for 30 days after the final dose of Hemay005.
Exclusion Criteria:
- Current diagnosis of CD, abdominal/intrabdominal/perianal fistula and/or abscess, indeterminant colitis, IBD-unclassified, microscopic colitis, ischemic colitis, infectious colitis, radiation colitis, or active diverticular disease.
Severe UC as evidenced by any of the following:
A) Hospitalization for the treatment of UC ≤ 2 weeks prior to screening or, in the physician's judgement, is likely to require hospitalization for medical care or surgical intervention of any kind for UC during the study.
B)Current evidence of fulminant colitis, toxic megacolon, or recent history (within 6 months) of toxic megacolon, or bowel perforation.
C)Prior history of subtotal, or total colectomy.
- Past or current evidence of any gastrointestinal malignancy, either prior to or at the time of screening. History of malignancy within 5 years prior to screening visit, with the exception of malignancies adequately treated with resection for non-metastatic basal cell or squamous cell cancer or in situ cervical cancer.
- Past or current evidence of definite low-grade or high-grade colonic dysplasia or adenomas or neoplasia not completely removed.
- Significant uncontrolled medical comorbidity (such as cardiac, pulmonary, renal, hepatic, endocrine, ), psychiatric, or other condition that in the opinion of the investigator, would confound the study results, compromise patient safety, interfere with the potential participant's provision of informed consent, or compliance with trial procedures.
- Evidence of infection with Clostridioides difficile (C. difficile; formerly known as Clostridium difficile), cytomegalovirus (CMV), human immunodeficiency virus (HIV), Hepatitis B (HBV), Hepatitis C (HCV).
- Evidence of active tuberculosis (TB).
- Any condition that would preclude endoscopic evaluation.
- Either received protocol-specified prohibited medicines prior to baseline endoscopy and/ or randomization, or have not be washed out sufficiently due to the protocol before baseline endoscopy and/ or randomization.
研究計画
研究はどのように設計されていますか?
デザインの詳細
- 主な目的:処理
- 割り当て:ランダム化
- 介入モデル:並列代入
- マスキング:4倍
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的:Induction Treatment Arm
60mg, administratered orally, twice daily
|
Participants receive treatment with Hemay005 tablet during the Induction Phase (week I-0~I-12).
Participants receive treatment with Hemay005 tablet during the Maintenance Phase (week M-0~M-40).
|
|
プラセボコンパレーター:Induction Comparator Arm
matching tablet, administratered orally, twice daily
|
Participants receive treatment with placebo tablet during the Induction Phase (week I-0~I-12).
Participants receive treatment with placebo during the Maintenance Phase (week M-0~M-40).
|
|
実験的:Maintenance Treatment Arm
60mg, administratered orally, twice daily
|
Participants receive treatment with Hemay005 tablet during the Induction Phase (week I-0~I-12).
Participants receive treatment with Hemay005 tablet during the Maintenance Phase (week M-0~M-40).
|
|
プラセボコンパレーター:Maintenance Comparator Arm
matching tablet, administratered orally, twice daily
|
Participants receive treatment with placebo tablet during the Induction Phase (week I-0~I-12).
Participants receive treatment with placebo during the Maintenance Phase (week M-0~M-40).
|
この研究は何を測定していますか?
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Induction Phase: Percentage of Participants With Clinical Remission at Week 12.
時間枠:Induction Phase Week 12
|
Clinical remission is based on the Modified Mayo Score (mMS).
The Modified Mayo Score (mMS) consists of Rectal Bleeding Subscore (RBS), Stool Frequency Subscore (SFS) and Mayo Endoscopic Subscore (MES).
Each subscore ranges from 0 to 3 and a total mMS ranging from 0 to 9, with higher scores indicating more severe disease.
Clinical remission is defined as a SFS of 0 or 1 with a decrease of at least 1 from baseline , and a RBS of 0, and a MES of 0 or 1 without friability.
|
Induction Phase Week 12
|
|
Maintenance Phase: Percentage of Participants With Clinical Remission at Week 40.
時間枠:Maintenance Phase: Week 40
|
Clinical remission is defined as a SFS of 0 or 1 with a decrease of at least 1 from baseline , and a RBS of 0, and a MES of 0 or 1 without friability.
|
Maintenance Phase: Week 40
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Induction Phase: Percentage of Participants With Endoscopic Improvement at Week 12.
時間枠:Induction Phase: At Week 12
|
Endoscopic Improvement is based on the Mayo Endoscopic Subscore (MES).
The MES ranges from 0 to 3, with higher scores indicating more severe disease.
Endoscopic Improvement is defined as MES of 0 or 1(without friability).
|
Induction Phase: At Week 12
|
|
Induction Phase: Percentage of Participants With Completely Symptomatic Remission at Week 12.
時間枠:At Week 12
|
Complete Symptomatic Remission is defined as a SFS of 0 and a RBS of 0.
|
At Week 12
|
|
Induction Phase: Percentage of Participants With Symptomatic Remission at Week 12.
時間枠:At Week 12
|
Symptomatic Remission is defined as a SFS of 0 or 1 with a decrease of at least 1 from baseline and a RBS of 0.
|
At Week 12
|
|
Induction Phase: Percentage of Participants With Clinical Response at Week 12.
時間枠:At Week 12
|
Clinical response is based on the Modified Mayo Score (mMS).
The Modified Mayo Score (mMS) consists of Rectal Bleeding Subscore (RBS), Stool Frequency Subscore (SFS) and Mayo Endoscopic Subscore (MES).
Each subscore ranges from 0 to 3 and a total mMS ranging from 0 to 9, with higher scores indicating more severe disease.
Clinical Response is defined as a decrease in mMS of at least 2 points and 30% from baseline and either a decrease of at least 1 in RBS or a RBS of 0 or 1.
|
At Week 12
|
|
Induction Phase: Percentage of Participants With Endoscopic Response at Week 12.
時間枠:At Week 12
|
Endoscopic Response is defined as a decrease of at least 1 in MES from baseline.
|
At Week 12
|
|
Induction Phase: Percentage of Participants With Symptomatic Response at Week 12.
時間枠:At Week 12
|
Symptomatic Response is defined as a a decrease of ≥30% in the sum of RBS and SFS from baseline.
|
At Week 12
|
|
Maintenance Phase: Percentage of Participants With Endoscopic Improvement at Week 40.
時間枠:At Week 40
|
Endoscopic Improvement is defined as MES of 0 or 1 (without friability).
|
At Week 40
|
|
Maintenance Phase: Percentage of Participants with a Clinical Remission both at Week 12 of Induction Phase and Week 40 of Maintenance Phase.
時間枠:At Week 40
|
Clinical remission is defined as a SFS of 0 or 1 with a decrease of at least 1 from baseline , and a RBS of 0, and a MES of 0 or 1 without friability.
|
At Week 40
|
|
Maintenance Phase: Percentage of Participants With Steroid-free Clinical Remission at Week 40.
時間枠:At Week 40
|
Steroid-free Clinical Remission is defined as achieving clinical remission and have not used corticosteroids to treat UC for at least 8 weeks.
|
At Week 40
|
|
Maintenance Phase: Percentage of Participants With Endoscopic Response at Week 40.
時間枠:At Week 40
|
Endoscopic Response is defined as a decrease of at least 1 in MES from baseline.
|
At Week 40
|
|
Maintenance Phase: Percentage of Participants with a Clinical Response both at Week 12 of Induction Phase and Week 40 of Maintenance Phase.
時間枠:At Week 40
|
Clinical Response is defined as a decrease in mMS of at least 2 points and 30% from baseline and either a decrease of at least 1 in RBS or a RBS of 0 or 1.
|
At Week 40
|
|
Maintenance Phase: Percentage of Participants With Complete Symptomatic Remission.
時間枠:Maintenance Phase: At Week 8, Week 16, Week 24, Week 32, Week 40.
|
Complete Symptomatic Remission is defined as a SFS of 0 and a RBS of 0.
|
Maintenance Phase: At Week 8, Week 16, Week 24, Week 32, Week 40.
|
|
Maintenance Phase: Percentage of Participants With Symptomatic Remission.
時間枠:Maintenance Phase: At Week 8, Week 16, Week 24, Week 32, Week 40.
|
Symptomatic Remission is defined as a SFS of 0 or 1 with a decrease of at least 1 from baseline and a RBS of 0.
|
Maintenance Phase: At Week 8, Week 16, Week 24, Week 32, Week 40.
|
|
Maintenance Phase:Percentage of Participants With Symptomatic Response.
時間枠:Maintenance Phase: At Week 8, Week 16, Week 24, Week 32, Week 40.
|
Symptomatic Response is defined as a a decrease of ≥30% in the sum of RBS and SFS from baseline.
|
Maintenance Phase: At Week 8, Week 16, Week 24, Week 32, Week 40.
|
その他の成果指標
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Change of calprotectin from baseline.
時間枠:At Week 12 of Induction Phase and Week 40 of Maintenance Phase.
|
At Week 12 of Induction Phase and Week 40 of Maintenance Phase.
|
|
|
Among participants with abnormal calprotectin at baseline, percentage of participant with normalized calprotectin.
時間枠:At Week 12 of Induction Phase and Week 40 of Maintenance Phase.
|
At Week 12 of Induction Phase and Week 40 of Maintenance Phase.
|
|
|
Change of modified Mayo score from baseline.
時間枠:At Week 12 of Induction Phase and at Week 40 of Maintenance Phase.
|
The Modified Mayo Score (mMS) consists of Rectal Bleeding Subscore (RBS), Stool Frequency Subscore (SFS) and Mayo Endoscopic Subscore (MES).
Each subscore ranges from 0 to 3 and a total mMS ranging from 0 to 9, with higher scores indicating more severe disease.
|
At Week 12 of Induction Phase and at Week 40 of Maintenance Phase.
|
|
Change of partial modified Mayo score from baseline.
時間枠:Induction Phase: At Week 2, Week 4, Week 8, Week 12. Maintenance Phase: At Week 8, Week 16, Week 24, Week 32, Week 40.
|
The partial modified Mayo Score (pmMS) consists of Rectal Bleeding Subscore (RBS) and Stool Frequency Subscore (SFS).
Both RBS and SFS range from 0 to 3, with higher scores indicating more severe disease.
|
Induction Phase: At Week 2, Week 4, Week 8, Week 12. Maintenance Phase: At Week 8, Week 16, Week 24, Week 32, Week 40.
|
|
Change of IBDQ score from baseline.
時間枠:At Week 12 of Induction Phase and at Week 40 of Maintenance Phase.
|
The Inflammatory Bowel Disease Questionnaire (IBDQ) is used to assess health-related quality of life (HRQoL) in patients with ulcerative colitis.
It consists of 32 questions evaluating bowel and systemic symptoms, as well as emotional and social functions.
Each question is answered on a scale from 1 (worst) to 7 (best).
The total score ranges from 32 to 224 with higher scores indicating better health-related quality of life.
A positive change from Baseline indicates improvement.
|
At Week 12 of Induction Phase and at Week 40 of Maintenance Phase.
|
|
Among participants with abnormal C-reactive protein at baseline, percentage of participant with normalized C-reactive protein.
時間枠:At Week 12 of Induction Phase and at Week 40 of Maintenance Phase.
|
At Week 12 of Induction Phase and at Week 40 of Maintenance Phase.
|
|
|
Incidence and Severity of Adverse Events, Serious Adverse Events, Adverse Events Leading to Discontinuation, Adverse events of Special Interest.
時間枠:From Week 0 of Induction Phase to Week 40 of Maintenance Phase
|
From Week 0 of Induction Phase to Week 40 of Maintenance Phase
|
協力者と研究者
捜査官
- 主任研究者:Minhu Chen, M.D、First Affiliated Hospital, Sun Yat-Sen University
研究記録日
主要日程の研究
研究開始 (推定)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。