NCT07374471招募中1 期
A Phase 1b/2a, Multicenter, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of MB-001 in Participants With Moderately to Severely Active Ulcerative Colitis
Mage Biologics1 个研究点 分布在 1 个国家目标入组 100 人开始时间: 2026年4月1日最近更新:
干预措施
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Incidence of adverse events
研究概览
简要总结
The goal of this clinical trial is to learn if MB-001, an oral biologic, is able to treat patients with ulcerative colitis. Participants will be asked to take MB-001 or a matching placebo once-daily for a period of 12 weeks. Researchers will compare MB-001 to placebo to investigate its effects on clinical symptoms as well as endoscopic and histopathological findings. Patients will be offered open-label extension for another 12 weeks following the double-blind, placebo-controlled part of the study. Participants will keep a daily diary to record their symptoms and will have up to nine clinic visits.
详细描述
This double-blind, placebo controlled clinical trial is intended to study the effects of oral MB-001 in patients with moderately to severely active ulcerative colitis. The primary objectives of the study are to assess safety and efficacy. Secondary and exploratory endpoints are endoscopic response, histological response, pharmacokinetics, and pharmacodynamic changes compared to baseline.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Nonpregnant, nonlactating adults with a diagnosis of UC extending ≥ 15 cm from the anal verge, established at least 3 months prior to Screening by clinical and endoscopic evidence of UC (colonoscopy or flexible sigmoidoscopy) and confirmed by histology.
- •Moderately to severely active UC, defined as an mMS of 5 to 9, inclusive, with MES of at least 2 and RB subscore of at least
- •At Screening, a colonoscopy will be required if the participant has had extensive colitis or pancolitis of > 8 years duration or left-sided colitis of > 12 years duration but has not had a colonoscopy within 1 year of the initial Screening visit. If the participant has had a colonoscopy within 1 year of the initial Screening date, a flexible sigmoidoscopy may be used instead.
- •Demonstrated, in the opinion of the investigator, an inadequate response, loss of response, or intolerance/medical contraindication to at least 1 of the following treatments at doses approved for the treatment of UC:
- •Oral 5-ASA compounds or sulfasalazine
- •Oral corticosteroids (eg, prednisone, budesonide)
- •Immunosuppressants (eg, AZA, 6-MP, MTX)
- •An approved anti-integrin antibody (eg, vedolizumab)
- •An approved anti-IL-12/23 antibody (eg, ustekinumab)
- •An approved anti-IL-23 p19 antibody (eg, risankizumab, guselkumab, or mirikizumab)
- •An approved S1PR modulator (eg, ozanimod or etrasimod) Note: Participants who have had an inadequate response to more than 1 advanced therapy (eg, anti-integrin, anti-IL 12/23, IL-23 p19 antibody, or S1PR modulator) are not eligible (see Exclusion Criterion #15).
- •Participant may be receiving a therapeutic dosage of the following drugs:
- •Oral 5-ASA compounds or sulfasalazine, prescribed dose must be stable for at least 2 weeks before Screening endoscopy or stopped at least 2 weeks prior to Screening endoscopy
- •Oral corticosteroids - prednisone (max. 20 mg/day) (or equivalent) or budesonide (max. 9 mg/day) and have been at a stable dose for at least 2 weeks prior to Screening endoscopy or stopped at least 2 weeks prior to Screening endoscopy
- •Immunosuppressants (AZA, 6-MP, MTX) if the prescribed dose has been stable for at least 8 weeks before Screening endoscopy or stopped at least 8 weeks prior to Screening endoscopy
- •Is eligible to participate if not pregnant or breastfeeding, and the following conditions apply:
- •Of childbearing potential and using an acceptable contraceptive method during treatment with the IMP and for a minimum until 28 days after the last dose of IMP. The investigator should evaluate the potential or contraceptive method failure (eg, noncompliance, recently initiated) in relationship to the first dose of IMP. AND
- •Must have a negative highly sensitive pregnancy test as required by local regulations within 24 hours before the first dose of IMP,
- •Must agree not to donate eggs (ova, oocytes) for the purpose of assisted reproduction during the study and for a period of 28 days after receiving the last dose of IMP.
- •Able to participate fully in all aspects of this clinical trial. Full comprehension of consent language and informed consent must be obtained from the participant, or the participant's legally acceptable representative.
排除标准
- •The following complications:
- •Acute severe ulcerative colitis, defined by at least 6 bloody diarrhea/day AND any 1 of the following criteria: pulse > 90 beats/min, temperature > 37.8°C, hemoglobin < 105 g/l, erythrocyte sedimentation rate > 30 mm/h, or C-reactive protein > 30 mg/l, or in the investigator's opinion, hospitalization for the treatment of UC may be imminent
- •Previous extensive colonic resection (subtotal or total colectomy)
- •Short bowel syndrome
- •Ileostomy, colostomy, ileoanal pouch, fistulae, or known fixed symptomatic stenosis of the intestine
- •Toxic megacolon or recent history (within less than 6 months) of toxic megacolon or bowel perforation
- •Diagnosis of CD or the presence or history of a fistula consistent with CD, indeterminate colitis, ischemic colitis, NSAID-induced colitis, idiopathic colitis (ie, colitis not consistent with UC), radiation colitis, microscopic colitis, infectious colitis, colonic mucosal dysplasia, or untreated bile acid malabsorption.
- •Primary sclerosing cholangitis with uncontrolled liver function
- •Malignancies or history of malignancy within 5 years of Screening (including solid tumors and hematological malignancies), except for adequately treated or completely excised nonmetastatic basal cell carcinoma, squamous cell carcinoma of the skin, or cervical carcinoma in situ.
- •History of adenomatous polyps, unless removed.
- •History of lymphoproliferative disease, including lymphoma, or signs and symptoms suggestive of possible lymphoproliferative disease, such as lymphadenopathy and/or splenomegaly.
- •Class III or IV cardiovascular morbidity.
- •Clinically significant abnormal vital signs, physical examination, or 12-lead ECG at Screening or Day 1 (prolonged QTc using Fredericia's formula [> 460 ms for males and > 470 ms for females]), or conditions leading to additional risk for QT prolongation (eg, congenital long-QT syndrome). Participants with electrolyte abnormalities such as hypokalemia and hypomagnesemia that would increase the risk of QT prolongation should be corrected prior to randomization (an ECG may be repeated after electrolyte correction for determining eligibility, if needed).
- •History of bleeding disorders (eg, complement disorders, hemophilia, history of uncontrolled bleeding).
- •History of any major neurological disorders including stroke, epilepsy, or demyelinating or neurodegenerative disease.
- •Increased risk of infectious complications (eg, recent pyogenic infection, any congenital or acquired immunodeficiency [eg, HIV infection], or past organ or stem cell transplantation).
- •Systemic or opportunistic infections:
- •A positive diagnostic TB test at Screening (defined as a positive QuantiFERON(R) test). In cases where the QuantiFERON(R) test is indeterminate, the participant may have the test repeated once and if their second test is negative, they will be eligible. In the event a second test is also indeterminate, or QuantiFERON(R) is unavailable, the investigator has the option to perform a PPD skin test. If the PPD reaction is < 5 mm, then the participant is eligible. If the reaction is at least 5 mm, or PPD testing is not done, the participant is not eligible. An exception is made for participants with a history of latent TB who are currently receiving treatment for latent TB, will initiate treatment for latent TB before the first dose of IMP, or have documentation of completing appropriate treatment for latent TB within 3 years prior to the first dose of IMP.
- •A positive test for HBV, as defined by the presence of HBsAg or HBcAb test. Note: If a participant tests negative for HBsAg, but positive for HBcAb, the participant would be considered eligible if no HBV DNA is present, confirmed by HBV DNA polymerase chain reaction reflex testing performed by the central laboratory.
- •A positive test for HCV, as defined by a positive HCVAb test and detectable HCV RNA. Note: Participants who are HCVAb positive without evidence of HCV RNA may be considered eligible (spontaneous viral clearance or previously treated and cured [defined as no evidence of HCV RNA at least 12 weeks prior to randomization]).
- •Evidence of Clostridioides difficile toxin or treatment for C. difficile infection, or other intestinal bacterial pathogen, within 4 weeks prior to Screening.
- •Clinically active cytomegalovirus infection.
- •Any other clinically significant extra-intestinal infection or opportunistic, chronic, or recurring infection within 6 months prior to randomization, including, but not limited to infections requiring IV antibiotics, hospitalization, or prolonged treatment.
- •History of opportunistic infections.
- •Autoimmune disorders that may require treatment with immunosuppressant therapy.
- •Any of the following laboratory abnormalities during the screening period. If values are initially outside the prescribed limits, the evaluation may be repeated once within the screening period to determine eligibility:
- •Hemoglobin level: < 8.0 g/dL
- •Absolute white blood cell count: < 3.0 x 109/L
- •Absolute lymphocyte count: < 0.5 x 109/L
- •Absolute neutrophil count: < 1.5 x 109/L
- •Platelet count: < 100 x 109/L or > 1200 x 109/L
- •Alanine aminotransferase or aspartate aminotransferase: > 2.5 x ULN
- •Alkaline phosphatase: > 2.5 x ULN
- •Bilirubin: > 1.5 x ULN
- •Participants who had an inadequate response to > 1 of the following treatments: vedolizumab, ustekinumab, anti-IL-23 p19 antibodies, or S1PR modulators for UC.
- •Participants who had an inadequate response or loss of response to TNF inhibitors or JAK inhibitors.
- •Participants taking the following medical therapies for UC:
- •Any biologic therapy (eg, anti-integrins, anti-ILs) within 8 weeks or 5 half-lives (whichever is longer) prior to randomization
- •S1PR modulators within 4 weeks or 5 half-lives (whichever is longer) prior to randomization
- •IV antibiotics within 8 weeks prior to randomization or expected to receive IV antibiotics during the conduct of the study
- •Any rectal therapy for treatment of UC within 2 weeks prior to Screening endoscopy
- •NSAIDs as long-term treatment, defined as use for at least 4 days a week each month (> 100 mg daily or acetaminophen and aspirin > 325 mg daily)
- •Any medicinal product, herbal medication, or natural health product which might interfere with peristalsis within 2 weeks prior to randomization.
- •Participants unwilling to withhold protocol-prohibited medications during the study.
- •Fecal microbiota transplant (includes human microbiota-based therapeutics) within 4 weeks prior to randomization.
- •Vaccination with a live or live-attenuated vaccine within 4 weeks prior to randomization, or planned vaccination during conduct of the study.
- •Any major surgery, in the investigator's opinion, performed within 8 weeks prior to randomization or planned during the study (ie, any surgical procedure requiring general anesthesia).
- •Concurrent or previous participation in another clinical trial and received investigational therapy within 4 weeks or 5 half-lives (whichever is longer) prior to randomization.
- •Prior enrolment in the current study and had received IMP.
- •History of excessive alcohol or drug abuse that, in the opinion of the investigator, may interfere with the participant's ability to comply with the study procedures.
- 另有 4 项未显示
研究组 & 干预措施
Matching placebo
Placebo Comparator
干预措施: Matching placebo to MB-001 (Biological)
MB-001 capsules
Experimental
oral capsule formulation
干预措施: MB-001 (Biological)
结局指标
主要结局
Incidence of adverse events
时间窗: From study start until 4 weeks after end of treatment
All adverse events and serious adverse events will be collected from the signing of the ICF until the safety follow-up visit
Changes in laboratory parameters: Platelet count
时间窗: Week 12
Changes in laboratory parameter: Hemoglobin
时间窗: Week 12
Changes in laboratory parameter: Hematocrit
时间窗: Week 12
Changes in laboratory parameter: Red Blood Cell (RBC) count
时间窗: Week 12
Changes in laboratory parameter: Prothrombin time
时间窗: Week 12
Number of participants with abnormal laboratory tests results
时间窗: Week 12
Blood urea nitrogen, potassium, creatinine, creatinine phosphokinase, sodium, calcium, glucose, uric acid, AST/serum glutamic-oxaloacetic transaminase, ALT/serum glutamic-pyruvic transaminase, Gamma-glutamyl transferase/transpeptidase, alkaline phosphatase, bilirubin, protein, triglycerides, cholesterol, high-density lipoprotein, low-density lipoprotein
Number of participants with abnormal urinalysis results
时间窗: Week 12
Specific gravity, pH, colour, glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocyte esterase
Proportion of participants achieving clinical remission
时间窗: Week 12
Defined by a modified Mayo Score (mMS) of not more than 2 with a Mayo endoscopic subscore (MES) not more than 1, rectal bleeding (RB) subscore of 0, and stool frequency (SF) subscore not more than 1. The mMS ranges from 0 to 9. Higher values are worse.
次要结局
- Proportion of participants achieving endoscopic improvement(Week 12)
- Proportion of participants achieving endoscopic remission(Week 12)
- Proportion of participants achieving histologic remission(Week 12)
- Proportion of participants achieving histologic-endoscopic mucosal improvement(Week 12)
- Proportion of participants achieving mucosal healing(Week 12)
研究者
研究点 (1)
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