Clinical Trials

Inclusion Criteria

Inclusion Criteria apply to both Study 1 and Study

Type of Participant and Disease Characteristics

• Has had UC (from onset of symptoms) for at least 3 months before randomization. Diagnosis should be confirmed by documented endoscopy and histology in order to be eligible for study participation. For participants with no documented confirmation of UC diagnosis or if previous diagnosis is not deemed conclusive, UC diagnosis must be confirmed (by local histology report) at time of Screening endoscopy. A note of “chronic inflammation” or “ulcerative colitis” (or equivalent) on the histology report is acceptabl
• Has moderately to severely active UC as defined by MMS (RBS + SFS + ES) of 5 to 9, inclusive, with an ES ≥ 2 points (confirmed by BICR).
• Has a weight ≥ 40 kg.
• Satisfies at least 1 of the following criteria: a. Has had an inadequate response^1 or loss of response^2 to 1 or more of the following treatments:
  • Oral prednisone ≥ 40 mg/day (or equivalent) or budesonide ≥ 9 mg/day or equivalent or beclomethasone ≥ 5 mg/day for at least 2 weeks;
  • Immunomodulators (AZA ≥ 2 mg/kg/day or 6-MP ≥ 1.0 mg/kg/day [or a lower dose but with documentation of a therapeutic concentration of 6-thioguanine nucleotide]) for at least 8 weeks;
    • Note: A lower dosage of 6-MP or AZA is acceptable if local guidelines specify a different treatment regimen. See Appendix 7 for country-specific requirements.
  • Oral aminosalicylates (eg, mesalamine, sulfasalazine, olsalazine, balsalazide) at the appropriate local labeled dose and duration. Note: Participants who have an inadequate response or loss of response only to aminosalicylates may be eligible to participate in the study only in those countries where approved by local agency and ethical committee;
  • Advanced therapy^3 for UC having completed at least the induction regimen at ≥ the approved labeled doses:
    • An anti-TNF agent;
    • An anti-integrin (eg, vedolizumab);
    • A JAK inhibitor (eg, tofacitinib, upadacitinib, or filgotinib);
    • An anti-IL-23 or anti-IL-12/23 for UC (eg, ustekinumab);
    • A S1PR modulator (eg, ozanimod);
    • See Appendix 7 for country-specific requirements.
  • Notes:
    • ^1 Inadequate response: Signs and symptoms of persistently active disease (per investigator discretion) despite completing ≥ the regimen and ≥ treatment duration specified for corticosteroids, immunomodulators, and aminosalicylates;
    • ^2 Loss of response: Recurrence of signs and symptoms of active disease (per investigator discretion) after initial improvement despite continuing the following medications for ≥ the required treatment duration using ≥ the required dosing regimens;
    • ^3 For definitions on inadequate response or loss of response to advanced therapies, see Appendix 9; OR
  • Corticosteroid dependence as defined as follows:
    • Failure to successfully taper to < 10 mg/day of prednisone or equivalent or < 6 mg/day of budesonide or < 5 mg/day of beclomethasone, (ie, had a flare of disease) within 3 months of starting therapy, or if relapse occurs within 3 months of stopping corticosteroids; OR
  • Has been intolerant to 1 or more of the above-mentioned treatments (eg, unable to achieve therapeutic doses or treatment durations because of dose limiting adverse effects:
    • Advanced therapies: Refer to Appendix 9 for more details on intolerance to advanced therapies;
    • Corticosteroids: Dose limiting treatment-related adverse effects may include but are not limited to infections, hyperglycemia, osteoporosis, insomnia, or psychosis;
    • Immunomodulators: Dose limiting treatment-related adverse effects may include but are not limited to infection, nausea/vomiting, fatigue, bone marrow suppression, or hepatotoxicity.
• Is on treatment with any of the following allowable drugs during the study and meets drug stabilization requirements, as applicable:
  • Oral corticosteroid treatment must be equivalent of ≤ 20 mg prednisone or ≤ 9 mg budesonide or beclomethasone ≤ 5 mg daily at a stable dose for at least 2 weeks before randomization;
  • Oral aminosalicylates should be at a stable dose for at least 2 weeks before randomization;
  • AZA, 6-MP, or MTX (≤ 15 mg/week) should be at a stable dose for at least 4 weeks before randomization.

Demographics

• Is an individual of any sex/gender, from 16 to 75 years of age, inclusive, at the time of providing the informed consent (and assent, if applicable):
  • Note: Adolescent individuals ≥ 16 and < 18 years of age who meet the definition of Tanner Stage 5 (Appendix 14) can participate in Study 1 or Study 2 if approved by the country or regulatory/health authority. If these approvals are not granted, only individuals ≥ 18 years of age can be eligible for these studies. See Appendix 7 for country-specific requirements.

Assigned Male Sex at Birth

• If capable of producing sperm, the participant agrees to the following during the intervention period and for at least the time needed to eliminate study intervention after the last dose of study intervention. The length of time required to continue contraception after the last dose of study intervention is 12 weeks:
  • Abstains from penile-vaginal intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agrees to remain abstinent; OR
  • Uses contraception as detailed below unless confirmed to be azoospermic (vasectomized or secondary to medical cause, documented from the site personnel’s review of the participant’s medical records, medical examination, or medical history interview) as detailed below:
    • Uses a penile/external condom when having penile-vaginal intercourse with a nonparticipant of childbearing potential who is not currently pregnant and should also be advised of the benefit for that partner to use an additional method of contraception, as a condom may break or leak:
      • Note: Participants capable of producing ejaculate whose partner is pregnant or breastfeeding must agree to use penile/external condom during each episode of sexual activity in which the partner is at risk of drug exposure via ejaculate.
    • Contraceptive use by participants capable of producing sperm should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study interventions are more stringent than the requirements above, the local label requirements are to be followed.

Assigned Female Sex at Birth

• A participant assigned female sex at birth is eligible to participate if not pregnant or breastfeeding, and at least one of the following conditions applies:
  • Is not a POCBP; OR
  • Is a POCBP; and:
    • Uses an acceptable contraceptive method, or is abstinent from penile-vaginal intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis), as described in Appendix 5 during the intervention period and for at least 12 weeks after the last dose of study intervention. The investigator should evaluate the potential for contraceptive method failure (ie, noncompliance, recently initiated) in relationship to the first dose of study intervention. Contraceptive use by POCBPs should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study interventions are more stringent than the requirements above, the local label requirements are to be followed;
    • Has a negative highly sensitive pregnancy test (urine or serum) as required by local regulations within 24 hours (for a urine test) or 72 hours (for a serum test) before the first dose of study intervention. If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive. Additional requirements for pregnancy testing during and after study intervention are in Section 8.3.7;
    • Medical history, menstrual history, and recent sexual activity has been reviewed by the investigator to decrease the risk for inclusion of a POCBP with an early undetected pregnancy.

Informed Consent/Assent

• For participants ≥ 18 years of age: The participant (or legally acceptable representative) has provided documented informed consent for the study. The participant may also provide consent for FBR and/or the PK Subpopulation (Study 1 only). However, the participant may participate in the study without participating in FBR and/or the PK Subpopulation (Study 1 only). See Appendix 7 for country-specific requirements.
• For participants ≥ 16 to < 18 years of age: Has a legally acceptable representative who provides documented informed consent and the participant provides documented informed assent. The legally acceptable representative may also provide documented informed consent and the participant may also provide documented informed assent for FBR and/or the PK Subpopulation (Study 1 only). See Appendix 7 for country-specific requirements.

Exclusion Criteria:

Exclusion Criteria apply to both Study 1 and Study 2. An individual must be excluded from the study if the individual meets any of the following criteria:

Medical Conditions

• Has a diagnosis of CD or indeterminate colitis (IBD-undefined) or other types of colitis or enteritis that may confound efficacy assessment.
• Has a current diagnosis of fulminant colitis and/or toxic megacolon.
• Has UC limited to the rectum (ie, must have evidence of UC extending beyond the rectosigmoid junction, which is ~10 cm from the anal margin).
• Has a current or impending need for colostomy or ileostomy.
• Has had a total proctocolectomy or partial colectomy.
• Has received fecal microbial transplantation within 4 weeks before randomization.
• Has been hospitalized for the treatment of UC within 2 weeks before Screening.
• Has prior or current evidence of definite low-grade or high-grade colonic dysplasia including dysplasia identified during the Screening colonoscopy that has not been completely removed.
• Has any active or serious infections without resolution after adequate treatment (excluding fungal infections of nail beds or localized oral herpes), including but not limited to:
  • Infections requiring IV or intramuscular anti-infectives or hospitalization within 4 weeks before randomization;
  • Infections requiring oral anti-infective treatment within 2 weeks before randomization (except latent TB identified during Screening requiring complete course of medication during the study);
  • Chronic infection requiring ongoing antimicrobial treatment (eg, chronic pyelonephritis, osteomyelitis, bronchiectasis).
• Has had a herpes zoster reactivation or cytomegalovirus that resolved less than 8 weeks before Screening.
• Has a transplanted organ which requires continued immunosuppression.
• Has a history of cancer (except fully treated non-melanoma skin cell cancers or cervical carcinoma in situ after complete surgical removal) within the last 5 years. Participants who have had diagnostic evaluation suggestive of malignancy (eg, chest or breast imaging), and in whom the possibility of malignancy cannot be reasonably excluded following additional clinical assessments, are excluded.
• Is known to be infected with HBV, HCV, or HIV:
  • Participants with positive HBsAg are excluded from the study. Participants with negative HBsAg and positive HBcAb must have further testing for HBV-DNA. Participants with HBV-DNA ≥ LLOQ are not eligible for the study. Participants with HBV-DNA < LLoQ are eligible. See Appendix 7 for country-specific requirements.   
• Participants with positive HCV Abs at Screening must have further testing for HCV RNA. Participants with HCV RNA ≥ LLOQ are not eligible for the study. Participants with positive HCV Abs but HCV RNA < LLOQ are eligible. 
• Participants with a history of HIV infection or have a positive Ab test are not eligible for the study.
• Has evidence of active TB, latent TB not successfully treated (per local guidelines), or inadequately treated TB (for participants with history of TB) as evidenced by one of the following:
  • Positive QuantiFERON test or equivalent test:
    • Note: If a participant had a TB interferon gamma release assay such as QuantiFERON-TB Gold, T-SPOT TB, or PPD test within 3 months before Screening and source documentation is available, QuantiFERON test does not need to be performed at Screening provided nothing has changed in the participant’s medical history to warrant a repeat test. If the past test was PPD, it must be read by a licensed health care professional between 48 and 72 hours after administration; a reaction of ≥ 5 mm is considered a positive reaction. The result should be reported in mm; the absence of induration should be recorded as “0 mm”, not “negative”;
    • Note: If the QuantiFERON-TB test is indeterminate, a second test should be performed through the central laboratory or local TB interferon gamma release assay test such as QuantiFERON-TB Gold or T-SPOT TB. If the second test is positive, the participant is considered to be positive. If the second test is negative, the participant is considered to be negative.
  • Positive findings of active TB on chest x-ray (or CT scan if locally required):
    • Note: Chest x-ray is not required if the participant had a previous normal chest x-ray per local standard of care or chest CT within 3 months before Screening, provided all source documentation is available and nothing has changed in the participant’s medical history to warrant a repeat test;
    • Note: For participants with a history of active or latent TB, documentation of treatment must be provided to the Investigative site. Participants who are fully treated per local standard of care are eligible for the study. These participants do not require QuantiFERON testing. Chest x-ray is still required at Screening; normal chest x-ray or CT within 3 months before Screening is acceptable.
  • Latent TB not successfully treated (per local guidelines):
    • Note: For participants with a positive TB Screening test indicative of latent TB to be eligible for study enrollment: 1) confirmed negative for active TB infection; 2) an appropriate course of intervention for latent TB (per local guidelines) ≥ 2 weeks before randomization (unless deemed unnecessary by a pulmonary or infectious disease specialist), and 3) no evidence of active TB on chest x-ray (or CT scan if locally required) during Screening;
    • Note: Repeated indeterminate result from TB testing deemed likely due to concomitant steroid use is not exclusionary if there is documentation of lack of risk factors for TB and participant does not live in area where TB is endemic. Refer to Appendix 7 for country-specific requirements.
• Has confirmed or suspected COVID-19 infection: 
  • Note: Participants with recent confirmed or suspected COVID-19 infection may participate under the following conditions:
    • Participants with COVID-19 infection confirmed by a PCR or an antigen test:
      • For asymptomatic participants, randomization must be at least 10 days after the positive COVID-19 test;
      • For symptomatic participants, randomization must be at least 10 days after onset of symptoms and at least 3 days after resolution of fever without the use of feverreducing medications, and the participant must have a clinically meaningful improvement in symptoms.
    • Participants with suspected COVID-19 infection:
      • For participants with signs/symptoms suggestive of COVID-19 infection, a molecular (ie, PCR) test must be performed to rule out COVID-19 infection before randomization; OR
      • Randomization must be at least 10 days after onset of symptoms and at least 3 days after resolution of fever without the use of fever-reducing medications, and the participant must have clinically meaningful improvement in symptoms.
• Has a history of drug or alcohol abuse within 6 months before Screening (can be participant-reported).
• Has had major surgery within 3 months before Screening or has a major surgery (ie, requiring general anesthesia) planned during the study.
• Has a concurrent clinically significant disease or clinically relevant laboratory abnormalities, or a history of any illness or medical condition that, in the opinion of the investigator, might confound the results of the study or poses an additional risk to the participant by their participation in the study.

Prior/Concomitant Therapy

• Is currently receiving or is planning to receive total parenteral nutrition at any time during study treatment.
• Has received UC-related antibiotics and has not been on stable doses for at least 14 days before randomization or has discontinued these medications within 14 days of randomization.
• Requires treatment with a therapy that does not adhere to the guidance parameters specified in Sections 6.5.1 and 6.5.2.
• Has received prohibited medications within the specified timeframes before randomization (Table 1). These medications are also prohibited during the study.
• Has had prior exposure to MK-7240 or another anti-TL1A Ab.

Prior/Concurrent Clinical Study Experience

• Has participated in another investigational clinical study within 8 weeks or 5 half-lives of the investigational drug (whichever is longer) (see Table 1 for prohibited period) before randomization. This window will be derived from the date of the last dose of study medication taken in the previous study. Participants enrolled in observational/noninterventional studies may be included.

Diagnostic Assessments

• Stool positive for pathogens (eg, Clostridioides difficile toxin, pathogenic Escherichia coli, Salmonella species, Shigella species, Campylobacter species, Yersinia species) as well as ova and parasites at Screening. Note: Participants who are positive for enteric pathogens at Screening, and who are considered screen failures, may be rescreened after complete resolution of the infection following discussion with the Sponsor. Specific details on the rescreening visit requirements are in Section 8.12.1.
• Has Screening laboratory test results within the following parameters:
  • Hemoglobin < 8.0 g/dL (80 g/L);
  • White blood cell count < 3,500/mm^3 (3.5 × 10^9 /L):
  • Absolute neutrophil count < 1,000/mm^3 (1.0 × 10^9 /L);
  • Absolute lymphocyte count < 500/mm^3 (0.5 × 10^9 /L);
  • Platelets < 100,000/mm^3 (100 × 10^9 /L);
  • > 2.0 × ULN of any of the following: ALT, AST, ALP, or > ULN total bilirubin (> 1.5 × ULN total bilirubin if known Gilbert’s syndrome).

Other Exclusions

• Known allergies, hypersensitivity, or intolerance to MK-7240 or its excipients, or another anti-TL1A Ab. Note: Refer to the IB for details regarding excipients for MK-7240.
• Is or has an immediate family member (eg, spouse, parent/legal guardian, sibling, or child) who is investigational site or Sponsor staff directly involved with this study.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Eligibility last updated 1/4/24. Questions regarding updates should be directed to the study team contact.