A phase IIa, open label, Single-centre study to assess the initial antifibrotic efficacy, safety, tolerability, pharmacokinetic and pharmacodynamic profile of MBF-118 in Crohn’s disease patients with stenosis.
- Trial ID
- 2022-501464-18-00
- Protocol
- MBF-118CT-02
- Sponsor
- Medibiofarma S.L.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this phase IIa, open-label, single-centre study is to assess the **safety** and **tolerability** of MBF-118 in patients with **Crohn's disease** who have stenosis, in addition to their standard care, over a period of 28 days, with a follow-up extending to day 56. This is clinically relevant as it aims to ensure that MBF-118 can be safely administered to this patient population, potentially offering a new therapeutic option for managing stenosis in Crohn's disease.
Secondary objectives include:
- Assessing the effect of MBF-118 on stenosis as measured by intestinal ultrasound at Day -1, Day 28, and Day 56.
- Evaluating the pharmacokinetic profile and pharmacological effect of MBF-118 in plasma.
- Assessing the exposure of MBF-118 in the gastrointestinal local (ileal and/or colonic) tissue.
- Evaluating the exposure and pharmacological effect of MBF-118 in feces.
Participants
The clinical trial involves participants diagnosed with **Crohn's disease**, aiming to evaluate the safety and tolerability of MBF-118 in conjunction with standard care over a 28-day period, with follow-up extending to day 56. The study population comprises both male and female subjects, aged between 18 and 75 years. Participants are required to have a confirmed diagnosis of Crohn's disease, characterized by mild to severe ileocolonic involvement, established at least three months prior to screening. The trial includes individuals with no more than two naïve or anastomotic small bowel strictures, as defined by specific criteria. Participants must be on a stable dose of any current treatment for Crohn's disease, such as non-steroidal anti-inflammatory drugs or biologics, for at least three months before the study begins. The trial population was selected based on their ability to fully engage in all aspects of the clinical trial, with informed consent obtained and documented. The sponsor has not provided information regarding the total number of participants involved in the study.
Plans and Procedures
The clinical trial is a **phase IIa**, open-label, single-center study designed to evaluate the initial antifibrotic efficacy, safety, tolerability, pharmacokinetic, and pharmacodynamic profile of MBF-118 in patients with **Crohn's disease** who have stenosis. The primary objective is to assess the safety and tolerability of MBF-118 when administered alongside the standard of care over a 28-day period, with a follow-up extending to day 56. The trial is expected to conclude by April 30, 2024, with recruitment having commenced on December 1, 2022.
Participants will be involved in the study for a total of 56 days. The study includes several key visits: an initial screening visit to confirm eligibility based on inclusion criteria such as age, diagnosis, and disease severity, followed by baseline assessments. Participants will then undergo regular follow-up visits to monitor safety and efficacy endpoints, including changes in bowel wall thickness, fecal calprotectin, and plasma C-reactive protein levels. Pharmacokinetic parameters such as Cmax, Tmax, and AUC will also be evaluated at specified intervals. The end-of-study visit will occur on day 56, marking the completion of the follow-up period.
Inclusion criteria require participants to be male or nonpregnant, nonlactating females aged 18-75, with a confirmed diagnosis of Crohn's disease established at least three months prior to screening. Participants must have mild to severe ileocolonic Crohn's disease and no more than two naive or anastomotic small bowel strictures. Exclusion criteria are not specified in the provided data. Participants must be on a stable dose of any current treatment for Crohn's disease for at least three months before the study begins. Conditions that may lead to early termination from the study include the occurrence of severe adverse events or clinically significant changes in vital signs, physical examination, laboratory measurements, or ECGs.
Treatment
The clinical trial involves the administration of the experimental medication **MBF-118**, which is being evaluated for its antifibrotic efficacy, safety, tolerability, pharmacokinetic, and pharmacodynamic profile in patients with **Crohn's Disease**. MBF-118 is provided in the form of **hard capsules** and is administered orally. The active substance, MBF-118, is of chemical origin and is manufactured by MEDIBIOFARMA, S.L. The dosing regimen for MBF-118 involves a maximum daily dose of 80 mg, with a total maximum dose of 12,000 mg over a treatment period of up to 20 days. The study is designed to assess the effects of MBF-118 on top of standard-of-care therapy over a 28-day period, with follow-up extending to day 56.
In addition to the experimental treatment, participants will continue to receive standard-of-care therapy for **Crohn's Disease** as part of the study protocol. This standard-of-care therapy is not specified in the trial data but typically includes medications such as aminosalicylates, corticosteroids, immunomodulators, or biologics, depending on the individual patient's treatment plan. The study does not include a placebo or comparator treatment group, as it is an open-label trial. Participant compliance with the dosing schedule will be monitored throughout the study to ensure adherence to the treatment regimen.
Efficacy
Efficacy in this clinical trial will be assessed through several secondary endpoints. The primary focus will be on the change from baseline in specific parameters related to **Crohn's Disease**. These include the bowel wall thickness and color Doppler effect of stenosis, which will be measured at Day 28 and Day 56. Additionally, changes in fecal calprotectin levels will be evaluated at the same timepoints. Plasma C-reactive protein levels will also be assessed for changes from baseline at Day 28 and Day 56. These parameters will provide insights into the antifibrotic efficacy of MBF-118 in patients with Crohn's Disease.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Male or nonpregnant, nonlactating females, age 18-75.
- Diagnosis of CD based on clinical, endoscopic, and histologic evidence established at least 3 months prior to Screening.
- Has mild to severe ileocolonic CD.
- Participant has no more than 2 naïve or anastomotic small bowel strictures
- By MRE or IU in the terminal ileum at Screening. A stricture is defined as: a. localized luminal narrowing (luminal ≤ 50% relative to normal adjacent bowel); AND b. wall thickening (≥ 125% relative to adjacent bowel); AND c. length < 12 cm
- If participants are using a treatment for CD, they should be on a stable dose for at least 3 months prior to study commencement. Acceptable treatments include non-steroidal anti-inflammatory drugs (NSAIDs) and anti-inflammatory biologics.
- Ability to participate fully in all aspects of this clinical trial. Full comprehension of consent language and written informed consent must be obtained from the participant and documented.
Exclusion Criteria
- CD-related complications: • Previous ileorectal anastomosis, or a proctocolectomy. Patients who have received colonic resection are allowed in this study. • Short bowel syndrome • Ileostomy, colostomy, small bowel stoma, or ileoanal pouch • Fistulae in or adjacent to an ileal stenosis. Participants with perianal fistulae could be included if not septic. Participants with internally penetrating fistulae are excluded. • Suspected or diagnosed active intra-abdominal or perianal abscess that has not been appropriately treated • Toxic megacolon
- Use of corticosteroid treatment for symptoms of inflammatory bowel disease within the last 2 weeks. Corticosteroids should not be taken during the screening, treatment or follow-up periods of the trial.
- History or current diagnosis of ulcerative colitis, indeterminate colitis, ischemic colitis, nonsteroidal anti-inflammatory drug (NSAID)-induced colitis, idiopathic colitis (i.e., colitis not consistent with CD), radiation colitis, microscopic colitis, colonic mucosal dysplasia, or untreated bile acid malabsorption.
- Uncontrolled primary sclerosing cholangitis.
- Malignancies or history of malignancy within 5 years of the initial screening visit (V1), except for adequately treated or completely excised non-metastatic basal cell carcinoma, squamous cell carcinoma of the skin, or cervical carcinoma in situ.
- Has a severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration, or may interfere with the interpretation of study results, as determined by the investigator.
- New York Heart Association Class III or IV congestive heart failure.
- Clinically significant abnormal clinical laboratory values, vital signs, physical examination, or 12-lead electrocardiogram (ECG) at Screening or Baseline [PR ≥ 220 msec, QRS ≥120 msec and QTc ≥ 440 msec, bradycardia (<50 bpm) or clinically significant minor ST wave changes or any other abnormal changes on the screening ECG that would interfere with measurement of the QT interval].
- Systemic or opportunistic infections including: • Patients with active tuberculosis (TB) determined at Screening, defined as a positive QuantiFERON test, or a purified protein derivative (PPD) skin test. Patients who test positive and show symptoms of TB (abnormal chest x-ray, or positive sputum smear or culture, active TB bacteria in his/her body, usually feels sick and may have symptoms such as coughing, fever, and weight loss) will be excluded. Patients positive for TB who develop symptoms during the study period will be removed from the trial. An exception is made for subjects with a history of latent TB who are currently receiving treatment for latent TB, will initiate treatment for latent TB before the first dose of study treatment, or have documentation of completing appropriate treatment for latent TB within 3 years prior to the first dose of study treatment). Patients who test positive for TB during the study period but who do not show symptoms will be allowed to continue the study. • Active infection with HIV. • Evidence of positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb). NOTE: if a participant tests negative for HBsAg, but positive for HBcAb, the participant would be considered eligible if no presence of HBV DNA is confirmed by HBV DNA polymerase chain reaction reflex testing performed in the central laboratory. • Chronic hepatitis C (HCV) (positive HCVAb and HCV RNA). Note: Participants who are HCVAb positive without evidence of HCV RNA may be considered eligible (spontaneous viral clearance or previously treated and cured). • Evidence of Clostridioides difficile toxin or treatment for C. difficile infection, or other intestinal bacterial pathogen, within 30 days prior to Screening. • History of invasive fungal infections such as Candida or Aspergillus within 6 months prior to randomization. • History of herpes (simplex type 1, simplex type 2, or zoster) infection or reactivation within 12 weeks prior to randomization, or frequent recurrence of herpes (more than 2 times per year). • Evidence of active cytomegalovirus (CMV) infection at Screening. • Any other clinically significant extraintestinal infection or opportunistic, chronic, or recurring infection within 6 months before Screening. Examples include, but are not limited to, infections requiring intravenous (IV) antibiotics, hospitalization, or prolonged treatment.
- Concurrent or previous participation in another clinical trial and received investigational therapy within 4 weeks or 5 half-lives (whichever is longer) prior to Screening. Fecal microbiota transplant (includes human microbiota-based therapeutics) within 4 weeks prior to Screening are allowed.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Spain | Not Recruiting | 01 Dec 2022 | 10 |