Randomized, double-blind, placebo-controlled phase 3 study program to assess the efficacy and safety of MK-7240 (Tulisokibart) in participants with moderately to severely active Crohn's disease
Zusammenfassung der Studie
The study program is aimed at patients with Crohn's disease who are in a phase of moderately to severely active Crohn's disease at the time of entry into the study. The study program includes two studies. Participants take part in either study 1 or study 2. Recruitment for study 2 can be initiated when either study 1 has reached the target number of participants with advanced therapeutic experience or when study 1 is completed. In both studies, the efficacy and safety of an experimental drug, MK-7240, is investigated compared to placebo in patients with moderately to severely active Crohn's disease. A placebo looks visually like the drug being studied but contains no active ingredient. If MK-7240 is effective, improvements in symptoms of Crohn's disease should be observed and symptom-free phases should last longer. Study 1 includes 3 treatment periods: - a first
(BASEC)
Untersuchte Intervention
In study 1, approximately 720 patients will participate worldwide, in study 2 approximately 480 patients. Therefore, a total of about 14 patients will participate in the two studies in Switzerland. Study 1: After detailed information and consent from the participant, a maximum 5-week screening phase (pre-study phase) is conducted. It is then checked whether the participant meets all the criteria for study participation. Participants who meet all the criteria for study participation will then be randomly assigned by computer to one of 4 treatment groups (ratio 1:1:1:1): Groups 1-3 receive MK-7240 in different amounts, 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 physician 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 study medication is administered 4 times over a period of 3 months. 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. This is called a subcutaneous injection. The study medication is administered by the patient himself every 2 weeks for approximately 9 months. During the 9 months, 7 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 whose symptoms worsen have the opportunity, regardless of group assignment, to receive MK-7240 for approximately 3 months as an intravenous infusion (so-called re-induction). During the 3-month re-induction period, 5 study visits are planned, each lasting 2-3 hours. The re-induction is not blinded, meaning both the study physician and the participant know that the participant is receiving MK-7240. However, the group assignment for the induction and maintenance periods remains double-blind. Extension period: Participants who respond to the study medication during the induction and maintenance periods or during re-induction can move to the "extension period". A computer decides how frequently the study medication (MK-7240 or placebo) will be administered. The study medication will continue to be administered every 2 weeks as a subcutaneous injection. The extension period is again double-blind, meaning that neither the study physician nor the participants know how frequently they receive MK-7240 or placebo. The extension period lasts approximately 3 years, during which 15 study visits are planned. The study visits last 1-2 hours each. Follow-up period: After the treatment period, a follow-up period of approximately 3 months occurs, meaning that participation in study 1 lasts a maximum of approximately 4 years and 7 months. One study visit is planned during the follow-up period. This lasts approximately 1 hour. 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.). In addition, participants are asked to record daily information about the current symptoms of Crohn's disease in an electronic diary. Study 2: After detailed information and consent from the participant, a maximum 5-week screening phase (pre-study phase) is conducted. It is then checked whether the participant meets all the criteria for study participation. Participants who meet all the criteria for study participation will then be randomly assigned to one of 3 treatment groups (ratio 1:1:1): Groups 1 and 2 receive MK-7240, group 3 receives placebo. Groups 1 and 2 differ in the amount of MK-7240 administered. This study is a so-called "double-blind" study. This means that neither the study physician nor the participants know which group they have been assigned to and therefore 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 study medication is administered 4 times over a period of 3 months. Each study visit lasts 2-3 hours. Re-induction: Participants who do not respond to the study medication during the induction period or whose symptoms worsen have the opportunity, regardless of group assignment, to receive MK-7240 for approximately 3 months as an intravenous infusion (so-called re-induction). The re-induction is not blinded, meaning both the study physician and the participant know that the participant is receiving MK-7240. 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 period or during re-induction can move to the "extension period". A computer decides whether the participant receives only MK-7240 or whether they receive MK-7240 or placebo alternately. The study medication (MK-7240 or placebo) will continue to be administered every 2 weeks by the patient themselves, as a subcutaneous injection. The extension period lasts approximately 3 years, during which 15 study visits are planned. The study visits last 1-2 hours each. The extension period is again double-blind, meaning that neither the study physician nor the participants know how frequently they receive MK-7240. Follow-up period: After the treatment period, a follow-up period of approximately 3 months occurs, meaning that participation in study 2 lasts a maximum of approximately 3 years and 10 months. 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.). In addition, participants are asked to record daily information about the current symptoms of Crohn's disease in a diary.
(BASEC)
Untersuchte Krankheit(en)
Crohn's disease is a chronic inflammatory bowel disease that can affect all parts of the gastrointestinal tract from the mouth to the anus. The disease is characterized by symptoms such as abdominal pain, diarrhea, fatigue, weight loss, and fever. Symptoms often occur in irregular flares. The chronic course of the disease can lead to complications such as fistulas, strictures, obstructions, perforations, anal fissures, and abscesses. The exact cause of Crohn's disease is unknown, but it is believed that a combination of a dysregulated immune system, genetic factors, changes in gut flora, and environmental influences leads to an excessive and abnormal immune response in the intestine. Crohn's disease occurs slightly more frequently in women than in men, and the risk of the disease may be higher in industrialized countries. The disease can affect people of any age, but it is most commonly seen in the third decade of life, between the ages of 20 and 30. The standard treatment for Crohn's disease aims to relieve clinical symptoms, prolong symptom-free phases, and prevent further inflammation. This is usually achieved through anti-inflammatory medications such as corticosteroids or through medications that suppress the immune system. However, due to possible side effects and resistances, these medications are only partially suitable for long-term therapy and often require a combination of different medications and frequent therapy changes. In individuals with Crohn's disease, 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. 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. TL1A is associated with the onset of inflammation in the intestine and the scarring of the inflamed intestinal mucosa. By blocking TL1A, it is hoped to reduce inflammation in the intestine and scarring of the intestinal mucosa.
(BASEC)
- Male or female study participants aged 18 to 75 years with confirmed Crohn's disease - Moderately to severely active Crohn's disease - Insufficient response or decreased response over time to at least one standard therapy (BASEC)
Ausschlusskriterien
- Patients with ulcerative colitis, unclear Crohn's disease, or another inflammatory bowel disease - Patients with ongoing complications of Crohn's disease: o abscess (abdominal or peri-anal) o symptomatic strictures or stenosis o previous colectomy o severe inflammation with significant colonic dilation (toxic megacolon) - Surgical bowel resection within 3 months prior to the pre-study phase (BASEC)
Studienstandort
Basel, Bern, St Gallen, Zürich
(BASEC)
Sponsor
MSD Merck Sharp & Dohme AG, Lucerne
(BASEC)
Kontakt für weitere Auskünfte zur Studie
Kontaktperson Schweiz
Klaudia Georgi
+41 58 618 33 88
klaudia.georgi@cluttermsd.comMSD Merck Sharp & Dohme AG, Lucerne
(BASEC)
Wissenschaftliche Auskünfte
Merck Sharp & Dohme LLC,
1-888-577-8839
klaudia.georgi@cluttermsd.com(ICTRP)
Name der bewilligenden Ethikkommission (bei multizentrischen Studien nur die Leitkommission)
Ethikkommission Zürich
(BASEC)
Datum der Bewilligung durch die Ethikkommission
09.08.2024
(BASEC)
ICTRP Studien-ID
NCT06430801 (ICTRP)
Offizieller Titel (Genehmigt von der Ethikkommission)
MK-7240-008: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Program to Evaluate the Efficacy and Safety of Tulisokibart in Participants with Moderately to Severely Active Crohn’s Disease (BASEC)
Wissenschaftlicher Titel
A Phase 3, Randomized, Double-Blind, Placebo-Controlled Program to Evaluate the Efficacy and Safety of Tulisokibart in Participants With Moderately to Severely Active Crohn's Disease (ICTRP)
Öffentlicher Titel
A Study to Evaluate the Efficacy and Safety of Tulisokibart (MK-7240) in Participants With Moderate to Severe Crohn's Disease (MK-7240-008) (ICTRP)
Untersuchte Krankheit(en)
Crohn's Disease (ICTRP)
Untersuchte Intervention
Drug: IV TulisokibartDrug: SC TulisokibartOther: IV PlaceboOther: SC Placebo (ICTRP)
Studientyp
Interventional (ICTRP)
Studiendesign
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor). (ICTRP)
Ein-/Ausschlusskriterien
The main inclusion and exclusion criteria include but are not limited to the following:
Inclusion Criteria:
- Has had a diagnosis of CD at least 3 months before study.
- Has moderately to severely active CD.
- Demonstrated inadequate response, loss of response, or intolerance to one or more of
the following categories of drugs: oral locally acting steroids, systemic steroids,
immunomodulators, biologic and/or small molecule advanced therapies.
- Adolescent participants =16 and <18 years of age can participate if approved by the
country or regulatory/health authority.
Exclusion Criteria:
- Has diagnosis of ulcerative colitis (UC) or indeterminate colitis.
- Has CD isolated to the stomach, duodenum, jejunum, or perianal region, without
colonic and/or ileal involvement.
- Currently has any of the following complications of CD: suspected or diagnosed with
intra-abdominal or perianal abscess, known symptomatic stricture or colonic stenosis
not passable in endoscopy, fulminant colitis, toxic megacolon, or any other
manifestation that might require surgery while enrolled in the study.
- Has current stoma or need for colostomy or ileostomy.
- Is missing >2 segments of the following 5 segments: terminal ileum, right colon,
transverse colon, sigmoid and left colon, and rectum.
- Has been diagnosed with short gut or short bowel syndrome, or any other uncontrolled
chronic diarrhea besides Crohn's disease.
- Has surgical bowel resection within 3 months of study.
- Has prior or current gastrointestinal dysplasia.
- Has chronic infection requiring ongoing antimicrobial treatment.
- Has a history of cancer (except fully treated non-melanoma skin cell cancers or
cervical carcinoma in situ after complete surgical removal) and is disease free for
<5 years.
- Is infected with Hepatitis B virus (HBV), Hepatitis C virus (HCV), or human
immunodeficiency virus (HIV).
- Has active tuberculosis.
- Has confirmed or suspected coronavirus disease of 2019 (COVID-19) infection.
- Prior exposure to tulisokibart (MK-7240, PRA023) or another anti-TL1A antibody. (ICTRP)
nicht verfügbar
Primäre und sekundäre Endpunkte
Study 1 [US/FDA Only]: Percentage of Participants Achieving Clinical Remission per Crohn's Disease Activity Index (CDAI) Score at Week 52;Study 1 [EU/EMA Only]: Percentage of Participants Achieving Clinical Remission per Stool Frequency and Abdominal Pain Score at Week 52;Study 1: Percentage of Participants Achieving Endoscopic Response at Week 52;Study 1: Percentage of Participants Achieving Clinical Remission per CDAI Score at Week 12;Study 1: Percentage of Participants Achieving Clinical Remission per Stool Frequency and Abdominal Pain Score at Week 12;Study 1: Percentage of Participants Achieving Endoscopic Response at Week 12;Study 2 [US/FDA Only]: Percentage of Participants Achieving Clinical Remission per CDAI Score at Week 12;Study 2 [EU/EMA Only]: Percentage of Participants Achieving Clinical Remission per Stool Frequency and Abdominal Pain Score at Week 12;Study 2: Percentage of Participants Achieving Endoscopic Response at Week 12 (ICTRP)
Study 1: Percentage of Participants Who Experienced an Adverse Event (AE);Study 1: Percentage of Participants who Discontinue Study Intervention due to an AE;Study 1 [US/FDA Only]: Percentage of Participants Achieving Clinical Remission per Stool Frequency and Abdominal Pain Score at Week 12;Study 1 [EU/EMA Only]: Percentage of Participants Achieving Clinical Remission per CDAI Score at Week 12;Study 1: Percentage of Participants with Decrease of =100 Points in CDAI Score from Baseline to Week 12;Study 1: Mean Change from Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) Score at Week 12;Study 1: Percentage of Participants Achieving Endoscopic Remission at Week 12;Study 1 and 2: Percentage of Participants in Diagnostic Assay Positive (Dx+) Subpopulation Achieving Clinical Remission per CDAI at Week 12;Study 1 and 2: Percentage of Participants in Diagnostic Assay Positive (Dx+) Subpopulation Achieving Endoscopic Response at Week 12;Study 1 [US/FDA Only]: Percentage of Participants Achieving Clinical Remission per Stool Frequency and Abdominal Pain Score at Week 52;Study 1: Percentage of Participants Achieving Clinical Remission per CDAI Score at Week 52;Study 1: Percentage of Participants with Decrease of =100 Points in CDAI Score from Baseline to Week 52;Study 1: Percentage of Participants Achieving Endoscopic Remission at Week 52;Study 1: Percentage of Participants Achieving Sustained Clinical Remission per CDAI at Both Week 12 and Week 52;Study 1: Percentage of Participants Achieving Corticosteroid-Free Clinical Remission per CDAI Score at Week 52;Study 1: Percentage of Participants Achieving Corticosteroid-Free Clinical Remission per Stool Frequency and Abdominal Pain Score at Week 52;Study 1: Percentage of Participants Achieving Clinical Remission per Stool Frequency, Abdominal Pain Score, and Endoscopic Remission at Week 52;Study 1: Percentage of Participants Achieving Clinical Remission per CDAI and Endoscopic Remission at Week 52;Study 1: Mean Change from Baseline in FACIT-Fatigue Score at Week 52;Study 1: Mean Change from Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Score at Week 52;Study 1: Percentage of Participants with Ulcer-Free Endoscopy at Week 52;Study 2: Percentage of Participants Who Experienced an AE;Study 2: Percentage of Participants who Discontinue Study Intervention due to an AE;Study 2 [US/FDA Only]: Percentage of Participants Achieving Clinical Remission per Stool Frequency and Abdominal Pain Score at Week 12;Study 2 [EU/EMA Only]: Percentage of Participants Achieving Clinical Remission per CDAI Score at Week 12;Study 2: Percentage of Participants with Decrease of =100 Points in CDAI Score from Baseline to Week 12;Study 2: Mean Change from Baseline in FACIT-Fatigue Score at Week 12;Study 2: Percentage of Participants Achieving Endoscopic Remission at Week 12;Study 2: Mean Change from Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Score at Week 12;Study 2: Percentage of Participants with Decrease of =100 Points in CDAI Score from Baseline to Week 6;Study 2: The percentage of Participants with Ulcer-Free Endoscopy at Week 12 (ICTRP)
Registrierungsdatum
nicht verfügbar
Einschluss des ersten Teilnehmers
nicht verfügbar
Sekundäre Sponsoren
nicht verfügbar
Weitere Kontakte
Medical Director;Toll Free Number, Trialsites@msd.com, 1-888-577-8839, Merck Sharp & Dohme LLC, (ICTRP)
Sekundäre IDs
MK-7240-008, 2023-508636-61, U1111-1298-6080, jRCT2031240196, 7240-008 (ICTRP)
Angaben zur Verfügbarkeit von individuellen Teilnehmerdaten
nicht verfügbar
Weitere Informationen zur Studie
https://clinicaltrials.gov/ct2/show/NCT06430801 (ICTRP)
Ergebnisse der Studie
Zusammenfassung der Ergebnisse
nicht verfügbar
Link zu den Ergebnissen im Primärregister
nicht verfügbar