A Sub Study to Investigate the Safety and Tolerability of Aletekitug in Participants With Moderate To Severe Ulcerative Colitis

Официальное название

A Phase 1b, Non-Randomized, Open-Label, Repeat-Dose, Single Center Study to Investigate the Safety and Tolerability of Aletekitug in Advanced Therapy Naïve Participants With Moderate to Severe Ulcerative Colitis

Обзор

This goal of this sub-study is to learn how safe and tolerable the study drug, aletekitug (anti-IL-18), in participants with moderately to severely active ulcerative colitis (UC). This study is the sub-study of the platform trial.

Вмешательства

• Биопрепарат Aletekitug
  Aletekitug will be administered.

Первичные конечные точки

• Number of Participants with Adverse events (AEs) [Срок оценки: Up to 34 weeks [End of sub-study (EOSS)]]
• Number of Participants with Serious AEs (SAEs) [Срок оценки: Up to 34 weeks (EOSS)]
• Number of Participants who Discontinue Study Intervention due to AEs [Срок оценки: Up to 34 weeks (EOSS)]
• Number of Participants with Clinically Significant Changes in Laboratory Readings [Срок оценки: Up to 34 weeks (EOSS)]
• Number of Participants with Clinically Significant Changes in Vital Signs [Срок оценки: Up to 34 weeks (EOSS)]
• Number of Participants with Clinically Significant Changes in 12-lead Electrocardiogram (ECG) Readings [Срок оценки: Up to 34 weeks (EOSS)]

Критерии участия

Критерии включения

• Diagnosis of UC for greater than or equal (>=) 3 months before screening. Appropriate documentation of endoscopy and biopsy results consistent with the diagnosis of UC must be available.
• Active UC with a modified Mayo score (mMS) of 5 to 9 points and endoscopy sub score of 2 to 3 within 14 days before baseline biopsy collection.
• Active disease beyond the rectum (greater than \[>\]15 centimeter \[cm\] of active disease from the anal verge at the screening colonoscopy).
• Documentation of a surveillance colonoscopy (performed according to local standard) within 12 months before screening (may be performed during screening) for participants with pancolitis of >8 years duration or left-sided colitis of >12 years duration, or primary sclerosing cholangitis
• Demonstrated an inadequate response to, loss of response to, or intolerance to conventional therapy (e.g., oral 5- aminosalicyclic acid \[5-ASA\] compounds, corticosteroids, thiopurines).
• May have been receiving a conventional therapy if the prescribed dose has been stable for the required time period before the screening endoscopy.
• Must meet contraception requirements if a female participant is a woman of childbearing potential (WOCBP)

Критерии исключения

• Participants with current diagnosis of Crohn's disease (CD) or Inflammatory bowel disease-unclassified (IBD-U) or a history of radiation colitis, microscopic colitis or ischemic colitis. Have currently known complications of UC such as fulminant colitis, or toxic megacolon, stoma, or stricture/stenosis within the small bowel or colon.
• Have prior history of dysplasia of the gastrointestinal tract or found to have dysplasia, other than completely removed low-grade dysplastic lesions, in any biopsy performed during the screening endoscopy.
• Have a history of malignant neoplasm within the last 5 years.
• Have history of lymphoproliferative disorder, including lymphoma, or signs and symptoms suggestive of possible lymphoproliferative disease
• Have any active, chronic, or recurrent infections based on the investigator's assessment.
• Have history of opportunistic infections within 1 year of screening
• Have history or presence of significant medical illness including but not limited to cardiovascular, respiratory, gastrointestinal (excluding UC), hepatic, renal, endocrine, hematologic, neurological, and psychiatric disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention or interfering with the interpretation of the data.
• Have evidence of active or latent Tuberculosis (TB) as documented by medical history, examination, and TB testing at Screening:
• Have significant allergies to humanized monoclonal antibodies.
• Have clinically significant multiple or severe drug allergies, intolerance to topical corticosteroids, or severe post-treatment hypersensitivity reactions
• Have had previous colectomy (total or subtotal), or any other manifestation that might require surgery while enrolled in the trial.
• Have ostomy or ileoanal pouch.
• Have received any of the following for treatments of UC:

• Immunomodulatory medications, including cyclosporine, tacrolimus, mycophenolate mofetil, thalidomide, within 4 weeks before screening endoscopy.
• Topical (rectal) treatment of 5-ASA or corticosteroid enemas/suppositories within 2 weeks of screening endoscopy.
• Have received approved or investigational advanced therapy (Ats) (i.e., biologics or small molecules including biosimilars).
• Interferon therapy within 8 weeks before screening endoscopy.
• Agents that deplete B- or T-cells (e.g., rituximab) within 12 months of baseline. Participants remain excluded if there is evidence of persistent targeted lymphocyte depletion at the time of screening endoscopy.
• Had Clostridium difficile infection within 30 days of screening endoscopy or have a positive test result at screening, or other intestinal pathogen within 30 days before screening endoscopy.
• Participant must not have signs of an ongoing infection related to an intestinal pathogen.
• In the investigator's opinion, any clinically significant abnormalities of laboratory results from chemistry, hematology or urinalysis tests obtained at the screening visit that cannot be attributed to the underlying moderate-to-severe UC.
• Pregnant or breastfeeding women, or women planning to become pregnant or breastfeed during the study.
• Positive for hepatitis B or C, HIV (Human Immunodeficiency Virus), as assessed by method available at each site;
• Uncontrolled hypertension (i.e., blood pressure consistently measures >=140/90 millimeters of mercury (mmHg) while actively taking 1 or more antihypertensive medications).

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07747480 · 300227 Sub-study 1

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗