Randomized, double-blind, placebo-controlled phase 3 study program to assess the efficacy and safety of MK-7240 in participants with moderately to severely active ulcerative colitis (MK-7240-001)

Zusammenfassung der Studie

The study program is aimed at patients with ulcerative colitis who are in a phase of moderately to severely active ulcerative colitis at the time of entry into the study. The study program includes 2 studies. Participants take part in either study 1 or study 2. In both studies, the efficacy and safety of an experimental drug, MK-7240, are investigated compared to placebo in patients with moderately to severely active ulcerative colitis. A placebo looks visually like the drug being studied but contains no active ingredient. If MK-7240 is effective, a reduction in inflammation in the intestine should be observed, and the symptom-free phases should last longer. Study 1 includes 3 treatment periods: - a first “induction period” lasting 3 months - a subsequent “maintenance period” lasting 9 months - and an “extension period” lasting approximately 3 years. Study 2 includes 2 treatment periods: - an “induction period” lasting 3 months - and an “extension period” lasting 3 years The administration of MK-7240 during the “maintenance period” and the “extension period” aims to maintain the symptom-free phase for as long as possible. Participants who do not respond to the study medication (MK-7240 or placebo) during the induction or maintenance period, or whose condition worsens, have the opportunity to receive the experimental drug MK-7240 in both studies (known as re-induction). In re-induction, both the study doctor and the participant know that the participant is receiving MK-7240. In study 1, approximately 720 patients will participate worldwide, about 4 in Switzerland. In study 2, approximately 300 patients will participate worldwide. In Switzerland, about 2 patients will participate in study 2.

(BASEC)

Untersuchte Intervention

Study 1:

After a detailed explanation and the participant's consent, a maximum 5-week screening phase (pre-study phase) is conducted. During this phase, it is carefully checked whether the participant meets all criteria for study participation.

Participants who meet all criteria for study participation are then randomly assigned by computer to one of 4 treatment groups (ratio 1:1:1:1).

Groups 1-3 receive MK-7240 in different amounts, while group 4 receives only placebo. A placebo looks visually like the drug being studied but contains no active ingredient.

This study is a so-called “double-blind” study. This means that neither the study doctor nor the participants know which group they have been assigned to.

Induction period:

During the induction period, all participants receive the assigned study medication (MK-7240 or placebo) through a needle in the arm. This is called an intravenous (i.v.) infusion. The induction period lasts approximately 3 months and includes 5 study visits. Each study visit lasts 2-3 hours.

Maintenance period:

In the subsequent maintenance period, all participants receive the assigned study medication as an injection using a pen (auto-injector) into the skin.

The maintenance period lasts approximately 9 months. During this time, participants self-inject the study medication every 2 weeks. During the 9 months, 8 study visits are planned, each lasting 1-2 hours.

Re-induction:

Participants who do not respond to the study medication during the maintenance period or who experience a worsening of symptoms have the opportunity to receive MK-7240 for approximately 3 months as an intravenous infusion (known as re-induction), regardless of group assignment. During the 3-month re-induction period, 5 study visits are planned, each lasting 2-3 hours.

Extension period:

Participants who respond to the study medication during the induction and maintenance periods or during re-induction can transition to the “extension period.” A computer decides how frequently the study medication will be administered.

The extension period is again double-blind, meaning that neither the study doctor nor the participants know how frequently they receive MK-7240.

The extension period lasts approximately 3 years, during which study visits are scheduled every 4 to 12 weeks. Each study visit lasts 1-2 hours.

Follow-up period:

After each treatment period, a follow-up period of approximately 3 months occurs, during which 3 study visits are planned. These last approximately 1 hour each.

During the study visits, the study medication can be administered, and various measures and examinations can be performed, e.g.: imaging procedures such as X-rays, colonoscopy with tissue sampling, collection of blood, stool, saliva, or urine samples, physical examination including checking vital signs (pulse, blood pressure, etc.). Additionally, participants are asked to record daily information about their current symptoms of ulcerative colitis in an electronic diary.

Study 2:

After a detailed explanation and the participant's consent, a maximum 5-week screening phase (pre-study phase) is conducted. During this phase, it is carefully checked whether the participant meets all criteria for study participation.

Participants who meet all criteria for study participation are then randomly assigned to one of 3 treatment groups (ratio 1:1:1):

Groups 1 and 2 receive MK-7240, while group 3 receives placebo.

A placebo looks visually like the drug being studied but contains no active ingredient.

This study is a so-called “double-blind” study. This means that neither the study doctor nor the participants know which group they have been assigned to and thus do not know whether they are receiving MK-7240 or placebo.

Induction period:

During the induction period, all participants receive the assigned study medication (MK-7240 or placebo) through a needle in the arm. This is called an intravenous (i.v.) infusion. The induction period lasts approximately 3 months and includes 5 study visits. Each study visit lasts 2-3 hours.

Re-induction:

Participants who do not respond to the study medication or who experience a worsening of symptoms have the opportunity to receive MK-7240 for approximately 3 months as an intravenous infusion (known as re-induction), regardless of group assignment. During the 3-month re-induction period, 5 study visits are planned, each lasting 2-3 hours.

Extension period:

Participants who respond to the study medication during the induction and maintenance periods or during re-induction can transition to the “extension period.” A computer decides how frequently the study medication will be administered.

The extension period is again double-blind, meaning that neither the study doctor nor the participants know how frequently they receive MK-7240.

The extension period lasts approximately 3 years, during which study visits are scheduled every 4 to 12 weeks. Each study visit lasts 1-2 hours.

Follow-up period:

After each treatment period, a follow-up period of approximately 3 months occurs, during which 3 study visits are planned. These last approximately 1 hour each.

During the study visits, the study medication can be administered, and various measures and examinations can be performed, e.g.: imaging procedures such as X-rays, colonoscopy with tissue sampling, collection of blood, stool, saliva, or urine samples, physical examination including checking vital signs (pulse, blood pressure, etc.). Additionally, participants are asked to record daily information about their current symptoms of ulcerative colitis in an electronic diary.

(BASEC)

Untersuchte Krankheit(en)

Ulcerative colitis is a chronic, recurrent disease that usually occurs in flares. This means that the intestinal mucosa is inflamed in phases and then recovers. Approximately 5 million people worldwide are affected by the disease. Due to the chronic inflammation of the colon and rectum, there may be recurrent diarrhea with increased mucus and blood admixtures and a constant urge to defecate. Often, severe, cramping abdominal pain occurs before defecation, which improves after evacuation. In severe cases, bleeding may occur in the intestine and ulcers may form. The long-term risk of colorectal cancer is increased compared to unaffected individuals. The exact causes of the disease are not yet fully understood. One possible factor is a malfunction of the immune system. When the immune system tries to fend off an invading virus or bacterium, it mistakenly attacks healthy cells in the digestive tract. As a result of this constant and exaggerated activity of the immune system, a chronic inflammation develops, which manifests in the typical symptoms of the disease. The standard treatment of ulcerative colitis involves alleviating symptoms and, depending on the severity of the symptoms, using anti-inflammatory medications, such as corticosteroids or medications that suppress the immune system. However, these medications are only partially suitable for long-term therapy due to possible side effects and resistances and require a combination of different medications as well as frequent therapy changes. In individuals with ulcerative colitis, a certain pro-inflammatory substance produced by the body, called TL1A, is detectable in elevated amounts in the blood and in the intestinal wall. TL1A is therefore associated with the onset of inflammation in the intestine and with the scarring of the inflamed intestinal mucosa, as occurs in ulcerative colitis. The experimental drug MK-7240 investigated in this study is an antibody that binds to TL1A and aims to reduce its effect in the body. Thus, a reduction of inflammation in the intestine and scarring of the inflamed intestinal mucosa is hoped for.

(BASEC)

Sponsor

MSD Merck Sharp & Dohme AG, Luzern

(BASEC)

Name der bewilligenden Ethikkommission (bei multizentrischen Studien nur die Leitkommission)

Ethikkommission Zürich

(BASEC)

Datum der Bewilligung durch die Ethikkommission

22.12.2023

(BASEC)

Ergebnisse der Studie