MedPath

VECTORS - A Study to Evaluate Transmural Healing as a Treatment Target in Crohn's Disease

Phase 4
Recruiting
Conditions
Crohn Disease
Moderately to Severely Active Crohn's Disease
Disease Crohn
Interventions
Biological: Vedolizumab
Registration Number
NCT06257706
Lead Sponsor
Alimentiv Inc.
Brief Summary

Transmural healing (TMH) is recognized as a potentially important measure of Crohn's disease (CD) activity but not a formal target. Observational studies suggest that TMH may be associated with better long-term outcomes. The study will evaluate TMH using noninvasive intestinal ultrasound (IUS), a patient-friendly technique that can be performed routinely in clinical practice. The aim of the study is to determine if treating to a target of corticosteroid-free (CS-free) IUS outcomes + clinical symptoms + biomarkers is superior to a target of clinical symptoms + biomarkers alone in achieving CS-free endoscopic remission measured by the Simple Endoscopic Score for Crohn's Disease (SES-CD).

Qualified participants will be randomly assigned in a 1:1 ratio to one of 2 different target treatment groups.

Group 1: Participants will be treated over 48 weeks to achieve a target of corticosteroid-free IUS-based outcomes + clinical remission + biomarker remission. At Week 22 and 30, the IUS-based component of the target will be IUS response and at Week 38, the final treatment target will be TMH. Group 2: Participants will be treated over 48 weeks to achieve a target of corticosteroid-free clinical remission + biomarker remission.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
304
Inclusion Criteria

Participants must meet all of the following criteria for enrolment into the study:

  1. Adults aged 18 to 80 years, inclusive, at the time of consent;

  2. Moderately-to-severely active CD at baseline defined by a CDAI score of 220 to 450 inclusive and SES-CD, excluding the presence of narrowing component, ≥6 (or ≥4 for participants with isolated ileal disease);

  3. CRP of ≥5 mg/L and/or FCal ≥250 μg/g at Screening;

  4. BWT on IUS of >4.0 mm in the ileum or any colonic segment (excluding the rectum);

  5. Biologic-naïve or have previous exposure to no more than 1 advanced therapeutic compound (approved biologic or small molecule drug) for the treatment of their CD. Note: only approximately 15% to 30% of the enrolled population will have had prior exposure to an advanced therapeutic;

  6. Participants may continue stable dose (initiated at least 4 weeks prior to Screening) of 5-ASA for CD;

  7. Persons of childbearing potential must have a negative serum pregnancy test prior to randomization and must use a highly effective method of contraception throughout the study.

    Females unable to bear children must have documentation of such in the source records;

  8. Able to participate fully in all aspects of this clinical trial;

  9. Written informed consent must be obtained and documented.

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Exclusion Criteria

Participants who exhibit any of the following conditions are to be excluded from the study:

  1. Current or previous treatment with vedolizumab, etrolizumab, or natalizumab;
  2. Previously exposed to 2 or more compounds of an advanced therapeutic compound (approved biologic or small molecule drug) for the treatment of their CD;
  3. Change to oral corticosteroid therapy dosing within 2 weeks prior to randomization or a corticosteroid dose of >40 mg of prednisone or equivalent at randomization;
  4. Only have inflammation proximal to the terminal ileum that cannot be reached by ileocolonoscopy;
  5. Have a CD complication, such as symptomatic strictures in the small bowel with >3 cm prestenotic dilatation on any imaging modality, requiring procedural intervention;
  6. Previous extensive colonic resection or missing >2 segments out of 5 (terminal ileum, right colon, transverse colon, sigmoid and left colon, and rectum), ileorectal anastomosis, or a proctocolectomy;
  7. Ostomy or ileoanal pouch;
  8. Short bowel syndrome;
  9. Fibrotic only stricture in the ileum or colon without evidence of active inflammation (in the investigator's judgment), including any impassable stenosis;
  10. Abscess >2 cm, detected incidentally by IUS, but participants with draining fistulas are not excluded;
  11. Serious underlying disease other than CD that, in the opinion of the investigator, may interfere with the participant's ability to participate fully in the study or would compromise participant safety;
  12. Positive stool test for Clostridioides difficile infection (as demonstrated by positive toxin);
  13. Known HIV or hepatitis B or C infection. If a negative test result is available in the 12 months prior to randomization, retesting is not required;
  14. Known active or latent tuberculosis (TB); if a negative test result is available in the 12 months prior to randomization, confirmatory testing (per standard of care) is not required before randomization;
  15. Other systemic or opportunistic infection (including cytomegalovirus), any other clinically significant extraintestinal infection, or recurring infection within 6 months of randomization;
  16. Has active cerebral/meningeal disease, signs, symptoms, or any history of progressive multifocal leukoencephalopathy (PML) prior to randomization;
  17. Hypersensitivity, allergy, or intolerance to any excipient of vedolizumab or any other contraindication to vedolizumab;
  18. Active severe infection such as sepsis, cytomegalovirus, listeriosis, or opportunistic infection;
  19. Unwillingness to withhold protocol-prohibited medications during the trial;
  20. Concurrent or previous participation in another clinical trial and received any investigational therapy within 30 days or 5 half-lives (whichever is longer) prior to randomization;
  21. History of alcohol or drug abuse that in the opinion of the investigator may interfere with the participant's ability to comply with the study procedures;
  22. Prior enrolment in the current study and had received study treatment;
  23. Pregnant, lactating, or intending to become pregnant/impregnate a partner before, during, or within 18 weeks after the last dose; or intending to donate ova or sperm during such time period;
  24. Vaccination with a live or live-attenuated vaccine within 4 weeks prior to randomization, or planned vaccination with a live or live-attenuated vaccine during participation in the study;
  25. Any person performing mandatory military service, deprived of liberty, in a residential care setting, or any person who, due to a judicial decision, cannot take part in clinical studies;
  26. The person is an immediate family member, study site employee, or is in a dependent relationship with a study site employee who is involved in conduct of this study (e.g., spouse, parent, child, sibling).
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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Group 1: Corticosteroid-free IUS-based outcomes + clinical remission + biomarker remissionVedolizumabGroup 1 will be treated over 48 weeks to achieve a target of corticosteroid-free IUS-based outcomes + clinical remission + biomarker remission. At Week 22 and 30, the IUS-based component of the target will be IUS response and at Week 38, the final treatment target will be TMH.
Group 2: Corticosteroid-free clinical remission + biomarker remission.VedolizumabGroup 2 will be treated over 48 weeks to achieve a target of corticosteroid-free clinical remission + biomarker remission.
Primary Outcome Measures
NameTimeMethod
Percentage of participants with Corticosteroid-free Endoscopic remission in group 1 and group 2 at week 48week 48

Corticosteroid-free is defined as not using corticosteroids at the time of the assessment. Endoscopic remission is defined by a total Simple Endoscopic Score for CD (SES-CD) ≤4 and at least a 2-point reduction versus baseline with no subscore greater than 1 in any individual variable. The SES-CD scores 4 endoscopic items (ulcer size, proportion of ulcerated surface, proportion of the surface area affected by any disease lesion, and stenosis) from 0 to 3, with higher scores representing more severe endoscopic disease activity. Each variable is scored for the 5 intestinal segments (ileum, right colon, transverse colon, left colon, and rectum) and summed to provide the total variable score. The sum of each variable score ranges from 0 to 15, except for stenosis (ranges from 0 to 11), because 3 represents a stenosis through which a colonoscope cannot be passed and therefore, can only be observed once. Total SES-CD score is then calculated by summing the item scores (range, 0-56 points).

Secondary Outcome Measures
NameTimeMethod
Percentage of participants with Corticosteroid-free Transmural healing (TMH)+Endoscopic remission+Clinical remission in group 1 and group 2 at week 48week 48

Transmural healing is defined by Bowel wall thickness (BWT) ≤3.0 mm and color Doppler signal (CDS) 0 in all evaluable segments assessed by Intestinal Ultrasound.

Endoscopic remission is defined by achievement of a total Simple Endoscopic Score for CD (SES-CD) ≤4 and at least a 2-point reduction versus baseline with no subscore greater than 1 in any individual variable. The SES-CD assesses 4 endoscopic variables: the size of ulcers, ulcerated surface, affected surface, and presence of narrowing. Each variable score ranging from 0 to 3. The total SES-CD score is calculated using the sum of all parameter scores in 5 segments: terminal ileum, right colon, transverse colon, left colon, and rectum.

Clinical Remission is defined by achievement of Crohn's Disease Activity Index (CDAI) \<150.

CDAI consists of eight factors, each summed after adjustment with a weighting factor. Total score ranges from 0 to 600 points. Higher scores indicate more severity.

Percentage of participants with Corticosteroid-free IUS response+Endoscopic remission+Clinical Remission in group 1 and group 2 at week 48week 48

IUS response is defined by reduction from baseline of 25% in Bowel Wall thickness (BWT) assessed by Intestinal Ultrasound (IUS).

Endoscopic remission is defined by achievement of a total Simple Endoscopic Score for CD (SES-CD) ≤4 and at least a 2-point reduction versus baseline with no subscore greater than 1 in any individual variable.

Clinical Remission is defined by achievement of Crohn's Disease Activity Index (CDAI) \<150.

The CDAI consists of 8 items including physical examination items, extraintestinal manifestations, the hematocrit, and PRO measures as recorded in the participant diary card for the 7 days prior to the clinic visit. Each item is multiplied by a weighting factor and summed to give a total CDAI score, ranging from 0 to over 600 points, with higher scores representing more severe disease activity.

Percentage of participants with Corticosteroid-free clinical remission in group 1 and group 2 at Week 14, Week 22 and Week 48.week 14, week 22 and week 48

Corticosteroid-free is defined as not using corticosteroids for treatment of CD at the time of the assessment.

Clinical Remission is defined by achievement of Crohn's Disease Activity Index (CDAI) \<150.

The CDAI consists of 8 items including physical examination items, extraintestinal manifestations, the hematocrit, and PRO measures as recorded in the participant diary card for the 7 days prior to the clinic visit. Each item is multiplied by a weighting factor and summed to give a total CDAI score, ranging from 0 to over 600 points, with higher scores representing more severe disease activity.

Percentage of participants with Corticosteroid-free Endoscopic remission+Clinical Remission in group 1 and group 2 at week 48week 48

Endoscopic remission is defined by achievement of a total Simple Endoscopic Score for CD (SES-CD) ≤4 and at least a 2-point reduction versus baseline with no subscore greater than 1 in any individual variable. The SES-CD scores 4 endoscopic items (ulcer size, proportion of ulcerated surface, proportion of the surface area affected by any disease lesion, and stenosis) from 0 to 3. Each variable is scored for the 5 intestinal segments (ileum, right colon, transverse colon, left colon, and rectum) and summed to provide the total variable score. Total SES-CD score is then summed up the item scores (range, 0-56 points).

Clinical Remission is defined by Crohn's Disease Activity Index (CDAI) \<150. CDAI consists of eight factors, each summed after adjustment with a weighting factor. Total score ranges from 0 to 600 points. Higher scores indicate more severity.

Percentage of participants with Corticosteroid-free endoscopic response+Clinical response in group 1 and group 2 at week 48week 48

Endoscopic response is defined by Reduction in total Simple Endoscopic Score for CD (SES-CD) ≥50% from baseline. The SES-CD scores 4 endoscopic items (ulcer size, proportion of ulcerated surface, proportion of the surface area affected by any disease lesion, and stenosis) from 0 to 3, higher scores indicate more severity. Each variable is scored for the 5 intestinal segments (ileum, right colon, transverse colon, left colon, and rectum) and summed to provide the total variable score. The sum of each variable score ranges from 0 to 15, except for stenosis, where it ranges from 0 to 11. Total SES-CD score is then calculated by summing the item scores (range, 0-56 points).

Clinical Response is defined by Crohn's Disease Activity Index (CDAI) decrease of ≥100 points from baseline. CDAI consists of eight factors, each summed after adjustment with a weighting factor. Total score ranges from 0 to 600 points. Higher scores indicate more severity.

Percentage of participants with Corticosteroid-free Clinical Response in group 1 and group 2 at week 14, week 22 and week 48week 14, week 22 and week 48

Corticosteroid-free is defined as not using corticosteroids for treatment of CD at the time of the assessment.

Clinical Response is defined by Crohn's Disease Activity Index (CDAI) decrease of ≥100 points from baseline. The CDAI consists of 8 items including physical examination items, extraintestinal manifestations, the hematocrit, and PRO measures as recorded in the participant diary card for the 7 days prior to the clinic visit. Each item is multiplied by a weighting factor and summed to give a total CDAI score, ranging from 0 to over 600 points, with higher scores representing more severe disease activity.

Percentage of participants with Corticosteroid-free endoscopic response in group 1 and group 2 at week 48week 48

Corticosteroid-free is defined as not using corticosteroids for treatment of CD at the time of the assessment Endoscopic response is defined by Reduction in total Simple Endoscopic Score for CD (SES-CD) ≥50% from baseline. The SES-CD scores 4 endoscopic items (ulcer size, proportion of ulcerated surface, proportion of the surface area affected by any disease lesion, and stenosis) from 0 to 3, with higher scores representing more severe endoscopic disease activity. Each variable is scored for the 5 intestinal segments (ileum, right colon, transverse colon, left colon, and rectum) and summed to provide the total variable score. The sum of each variable score ranges from 0 to 15, except for stenosis, where it ranges from 0 to 11, because 3 represents a stenosis through which a colonoscope cannot be passed and therefore, can only be observed once. Total SES-CD score is then calculated by summing the item scores (range, 0-56 points).

SES-CD total score and corresponding change from baseline to Week 48 in group 1 and group 2week 48

The SES-CD scores 4 endoscopic items (ulcer size, proportion of ulcerated surface, proportion of the surface area affected by any disease lesion, and stenosis) from 0 to 3, with higher scores representing more severe endoscopic disease activity. Each variable is scored for the 5 intestinal segments (ileum, right colon, transverse colon, left colon, and rectum) and summed to provide the total variable score. The sum of each variable score ranges from 0 to 15, except for stenosis, where it ranges from 0 to 11, because 3 represents a stenosis through which a colonoscope cannot be passed and therefore, can only be observed once. Total SES-CD score is then calculated by summing the item scores (range, 0-56 points).

Crohn's Disease Activity Index(CDAI) total score and corresponding change from baseline during follow-up (Week 6, Week 14, Week 22, Week 30, Week 38, Week 48, Week 64, Week 80, Week 96) in group 1 and group 2week 6, week 14, week 22, week 30, week 38, week 48, week 64, week 80, week 96

Crohn's Disease Activity Index (CDAI) consists of 8 items including physical examination items, extraintestinal manifestations, the hematocrit, and PRO measures as recorded in the participant diary card for the 7 days prior to the clinic visit. Each item is multiplied by a weighting factor and summed to give a total CDAI score, ranging from 0 to over 600 points, with higher scores representing more severe disease activity.

Percentage of participants with Transmural healing (TMH) in group 1 and group 2 at week 48week 48

Transmural Healing (TMH) is defined by Bowel wall thickness (BWT) ≤3.0 mm and color Doppler signal (CDS) 0 in all evaluable segments assessed by Intestinal Ultrasound

Percentage of participants with Intestinal Ultrasound (IUS) response in group 1 and group 2 at Week 48week 48

IUS response is defined by reduction from baseline of 25% in Bowel Wall thickness (BWT) assessed by Intestinal Ultrasound (IUS)

Bowel Wall Thickness (BWT) measured by Intestinal Ultrasound (IUS) in mm and corresponding change from baseline at Week 48 in group 1 and group 2.week 48
International Bowel Ultrasound Segmental Activity Score (IBUS-SAS) (per segment as well as total) and corresponding change from baseline at Week 48 in group 1 and group 2week 48

International Bowel Ultrasound Segmental Activity Score (IBUS-SAS) is a 0-100 numerical activity index for Crohn's disease calculated from four Intestinal Ultrasound (IUS) parameters

Bowel Wall Thickness (BWT) measured by Intestinal Ultrasound (IUS) in mm and corresponding change from baseline at week 14, week 22, week 30, week 38, and week 48 in group 1week 14, week 22, week 30, week 38, week 48
Color Doppler signal (CDS) and corresponding change from baseline at Week 48 in group 1 and group 2.week 48
Percentage of participants with Transmural healing (TMH) at week 14, week 22, week 30, week 38, and week 48 in group 1week 14, week 22, week 30, week 38, week 48

Transmural Healing (TMH) is defined by Bowel wall thickness (BWT) ≤3.0 mm and color Doppler signal (CDS) 0 in all evaluable segments assessed by Intestinal Ultrasound

Percentage of participants with Intestinal Ultrasound (IUS) response at week 14, week 22, week 30, week 38, and week 48 in group 1week 14, week 22, week 30, week 38, week 48

IUS response is defined by reduction from baseline of 25% in Bowel Wall thickness (BWT) assessed by Intestinal Ultrasound (IUS)

Color Doppler signal (CDS) and corresponding change from baseline at week 14, week 22, week 30, week 38, and week 48 in group 1week 14, week 22, week 30, week 38, week 48
International Bowel Ultrasound Segmental Activity Score (IBUS-SAS) (per segment as well as total) and corresponding change from baseline at week 14, week 22, week 30, week 38, and week 48 in group 1week 14, week 22, week 30, week 38, week 48

International Bowel Ultrasound Segmental Activity Score (IBUS-SAS) is a 0-100 numerical activity index for Crohn's disease calculated from four Intestinal Ultrasound (IUS) parameters

Percentage of participants with Histologic remission at week 48 in group 1 and group 2week 48

Histologic remission is defined by Robarts Histopathology Index (RHI) score ≤3 (per segment) with subscores of 0 for lamina propria neutrophils and 0 for neutrophils in epithelium, as scored by central reader.

The RHI is a validated instrument that measures histologic disease activity and consists of 4 subscores (chronic inflammatory infiltrate, lamina propria neutrophils, neutrophils in epithelium, and erosion or ulceration). Each subscore ranges from 0-3, with higher subscores indicating greater histologic disease activity. The RHI score is calculated as: (1 x chronic inflammatory infiltrate) + (2 x lamina propria neutrophils) + (3 x neutrophils in epithelium) + (5 x erosion or ulceration). The RHI therefore ranges from 0-33, with higher scores indicating greater histologic disease activity.

Percentage of participants with Histologic response at week 48 in group 1 and group 2week 48

Histologic response is defined as ≥7-point reduction from baseline in RHI, as scored by a central reader.

The RHI is a validated instrument that measures histologic disease activity and consists of 4 subscores (chronic inflammatory infiltrate, lamina propria neutrophils, neutrophils in epithelium, and erosion or ulceration). Each subscore ranges from 0-3, with higher subscores indicating greater histologic disease activity. The RHI score is calculated as: (1 x chronic inflammatory infiltrate) + (2 x lamina propria neutrophils) + (3 x neutrophils in epithelium) + (5 x erosion or ulceration). The RHI therefore ranges from 0-33, with higher scores indicating greater histologic disease activity.

Percentage of patients with Biomarker remission at week 48, week 64, week 80 and week 96 in group 1 and group 2week 48, week 64, week 80, week 96

Biomarker remission is defined as Normalization of either C-reactive protein (CRP) \<5 mg/mL or fecal calprotectin (FCal) \<250 μg/g

Percentage of patients with Biomarker response at week 48, week 64, week 80 and week 96 in group 1 and group 2week 48, week 64, week 80, week 96

Biomarker response is defined as ≥50% reduction from baseline in either C-reactive protein (CRP) or fecal calprotectin (FCal)

Percentage of participants with C-reactive protein (CRP) response during follow-up (Week 6, week 14, week 22, week 30, week 38, week 48, week 64, week 80 and week 96) in group 1 and group 2week 6, week 14, week 22, week 30, week 38, week 48, week 64, week 80, week 96

C-reactive protein (CRP) response is defined by ≥50% reduction from baseline

Percentage of participants with fecal calprotectin (FCal) response during follow-up (Week 6, week 14, week 22, week 30, week 38, week 48, week 64, week 80 and week 96) in group 1 and group 2week 6, week 14, week 22, week 30, week 38, week 48, week 64, week 80, week 96

Fecal calprotectin (FCal) response is defined by ≥50% reduction from baseline

Changes in C-reactive protein (CRP) from baseline during follow-up (Week 6, week 14, week 22, week 30, week 38, week 48, week 64, week 80 and week 96) in group 1 and group 2week 6, week 14, week 22, week 30, week 38, week 48, week 64, week 80, week 96
Changes in fecal calprotectin (FCal) from baseline during follow-up (Week 6, week 14, week 22, week 30, week 38, week 48, week 64, week 80 and week 96) in group 1 and group 2week 6, week 14, week 22, week 30, week 38, week 48, week 64, week 80, week 96
2-item Patient-Reported Outcome (PRO-2) score and corresponding changes from baseline during follow-up (Weeks 6, week 14, week 22, week 30, week 38, week 48, week 64, week 80 and week 96) in group 1 and group 2week 6, week 14, week 22, week 30, week 38, week 48, week 64, week 80, week 96

The PRO-2 consists of the 2 CDAI component items: daily stool frequency and abdominal pain. Study participants record the number of liquid or very soft stools and rate abdominal pain (range, 0-3) daily in their participant diary for the 7 days prior to a clinic visit, excluding days of bowel preparation and ileocolonoscopy. The stool frequency and abdominal pain scores are calculated as the average scores over the 7-day period.

Symptoms and Impacts Questionnaire for CD (SIQ-CD) score and corresponding changes from baseline during follow-up (Weeks 6, week 14, week 22, week 30, week 38, week 48, week 64, week 80 and week 96) in group 1 and group 2week 6, week 14, week 22, week 30, week 38, week 48, week 64, week 80, week 96

SIQ-CD tool consists of a symptom domain, which includes Gastrointestinal (GI), pain and discomfort, nutrition-related, and fatigue-related symptoms; and an impact domain, which includes concepts related to daily activities, nutrition, emotional well-being, and productivity.

Urgency Numerical Rating Score (NRS) and corresponding changes from baseline during follow-up (Weeks 6, week 14, week 22, week 30, week 38, week 48, week 64, week 80 and week 96) in group 1 and group 2week 6, week 14, week 22, week 30, week 38, week 48, week 64, week 80, week 96

The Urgency NRS evaluates the participant's sense of urgency to have a bowel movement over the previous 24 hours and is rated on an 11-point Likert scale, from 0 for "no urgency" to 10 for "worst possible urgency"

Inflammatory Bowel Disease Questionnaire (IBDQ) score and corresponding changes from baseline during follow-up (Weeks 30, week 48 and week 96) in group 1 and group 2week 30, week 48, week 96

The IBDQ measures health related quality of life in subjects with inflammatory bowel disease. It consists of 32 questions each with a graded response of 1 (worst) to 7 (best). The score ranges from 32 to 224

Time to CD-related complication from randomization through Week 96 in group 1 and group 2from randomization through Week 96

CD-related complication will be defined as any of the following: (1) CD-related surgery; (2) CD-related hospitalization; (3) CD medication-related complication; (4) CD procedure-related complication; (5) Rescue therapy for a documented CD-related flare e.g., new initiation of an advanced therapy other than VDZ (approved biologic or small molecule), dose escalation of vedolizumab, or dose intensification beyond the dose used at randomization of a corticosteroid after Week 48 or; (6) Other CD-related complication

Time to each component of CD-related complication in group 1 and group 2from randomization through Week 96
Percentage of participants who switched to an alternate biologic (yes/no) by Week 48 and Week 96week 48, week 96
Exposure-adjusted incidence rates of serious adverse events (SAEs), all adverse events (AEs), and AEs of special interest (AESIs) in group 1 and group 2up to week 96

Defined as the number of participants experiencing the event per 100 person-years (PYs) of exposure.

Trial Locations

Locations (36)

Universitaetsklinikum Schleswig-Holstein (UKSH)- Campus Kiel

🇩🇪

Kiel, Schleswig-Holstein, Germany

South Metropolitan Health Service

🇦🇺

Murdoch, Western Australia, Australia

Toronto Immune and Digestive Health Institute Inc. (TIDHI)

🇨🇦

Toronto, Ontario, Canada

University College London Hospitals NHS Foundation Trust

🇬🇧

London, United Kingdom

Royal Adelaide Hospital

🇦🇺

Adelaide, South Australia, Australia

The Queen Elizabeth Hospital

🇦🇺

Woodville, Western Australia, Australia

Kings College Hospital NHS Foundation Trust

🇬🇧

London, United Kingdom

Medical Network Sp. Z O.O.

🇵🇱

Warsaw, Masovia, Poland

TLC Clinical Research Inc - Los Angeles

🇺🇸

Los Angeles, California, United States

The Alfred Hospital

🇦🇺

Melbourne, Victoria, Australia

Austin Health

🇦🇺

Heidelberg, Victoria, Australia

Royal Melbourne Hospital

🇦🇺

Melbourne, Victoria, Australia

GASTROMED - Kopon, Zmudzinski I Wspolnicy Sp.j.

🇵🇱

Torun, Kuyavian-Pomeranian, Poland

Radboud University Nijmegen Medical Centre

🇳🇱

Nijmegen, Gelderland, Netherlands

London North West University Healthcare NHS Trust - Northwick Park Hospital

🇬🇧

London, Harrow, United Kingdom

Amsterdam UMC - Academisch Medisch Centrum

🇳🇱

Amsterdam, North Holland, Netherlands

Barts Health NHS Trust - The Royal London Hospital

🇬🇧

London, United Kingdom

Nottingham University Hospitals NHS Trust - QMC

🇬🇧

Nottingham, East Midlands, United Kingdom

Sonomed Sp. z o.o. - Centrum Medyczne

🇵🇱

Szczecin, West Pomerianian, Poland

Bodyclinic Sp.z.o.o. Sp.K

🇵🇱

Warszawa, Masovia, Poland

Ospedale San Raffaele S.r.I.

🇮🇹

Milano, Milan, Italy

Policlinico Universitario Agostino Gemelli

🇮🇹

Roma, Rome, Italy

SOLUMED Centrum Medyczne

🇵🇱

Poznań, Greater Poland, Poland

Melita Medical Sp Zoo

🇵🇱

Wroclaw, Lower Silesian, Poland

Care Access EMC Szpital Wrocław

🇵🇱

Wrocław, Poland

VITAZ - AZ Nikolaas

🇧🇪

Sint-Niklaas, Antwerpen, Belgium

APHM

🇫🇷

Marseille, Provence-Alpes-Cote d'Azur, France

Ospedale Casa Sollievo della Sofferenza IRCCS

🇮🇹

San Giovanni Rotondo, Foggia, Italy

Ospedale Luigi Sacco

🇮🇹

Milano, Lombardia, Italy

Centrum Medyczne Medyk

🇵🇱

Rzeszów, Podkarpackie, Poland

University Hospital Ghent

🇧🇪

Ghent, East Flanders, Belgium

Vita Longa Sp. z o.o.

🇵🇱

Katowice, Silesian, Poland

University of Calgary

🇨🇦

Calgary, Alberta, Canada

Northern Hospital Epping

🇦🇺

Epping, Victoria, Australia

Oddzial Gastroenterologiczny SP ZOZ w Lecznej

🇵🇱

Leczna, Gmina Leczna, Poland

Mater Misericordiae Ltd

🇦🇺

South Brisbane, Queensland, Australia

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