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.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Medibiofarma S.L., Medibiofarma S.L.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

1 Mar 2023 → 10 Sep 2024

Decision date (initial)

2022-11-24

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Medibiofarma, S.L

External identifiers

EU CT number

2022-501464-18-00

ClinicalTrials.gov

NCT05940558

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Pharmacodynamic, Pharmacokinetic, Safety

To assess safety and tolerability of MBF-118 in participants with Crohn’s Disease (CD) on top of standard of care over 28 days, with follow-up to day 56

Secondary objectives 4

1. To assess the effect of MBF-118 on stenosis as measured by intestinal ultrasound at Day -1, Day 28 and Day 56.
2. To assess the pharmacokinetic profile and pharmacological effect of MBF-118 in plasma.
3. To assess exposure of MBF-118 in the GI local (ileal and/or colonic) tissue.
4. To assess exposure and pharmacological effect of MBF-118 in feces.

Conditions and MedDRA coding

Crohn’s disease

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. 1. Male or nonpregnant, nonlactating females, age 18-75.
2. 2. Diagnosis of CD based on clinical, endoscopic, and histologic evidence established at least 3 months prior to Screening.
3. 3. Has mild to severe ileocolonic CD.
4. 4. Participant has no more than 2 naïve or anastomotic small bowel strictures
5. 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
6. 6. 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.
7. 7. 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 10

1. 1. 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
2. 2. 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.
3. 3. 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.
4. 4. Uncontrolled primary sclerosing cholangitis.
5. 5. 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.
6. 6. 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.
7. 7. New York Heart Association Class III or IV congestive heart failure.
8. 8. 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].
9. 9. 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.
10. 10. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint of the study is safety and tolerability of MBF-118 administration for 28 days from baseline to end of the follow-up period at Day 56. Number and severity of AEs reported including Clinically Significant Changes in vital signs, physical examination, Laboratory Measurements, and ECGs.

Secondary endpoints 2

1. Efficacy endpoints • Change from baseline (Day -1) of bowel wall thickness and color Doppler effect of stenosis at Day 28 and Day 56. • Change from baseline (Day -1) of fecal calprotectin at Day 28 and Day 56. • Change from baseline (Day 1) of plasma C-reactive protein at Day 28 and Day 56.
2. Pharmacokinetics endpoints • Plasma: Cmax, Tmax, Area under curve (AUC) and Cmin in plasma at Day 1 and Day 28, and concentration on Day 56. • Feces: concentration of MBF-118 on Day 28 and Day 56, • GI tissue: Concentration of MBF-118 on Day 29.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Medibiofarma S.L.

Sponsor organisation

Medibiofarma S.L.

Address

Poligono Industrial Mocholi 2 B, Noain C Noain C

City

Noain (Valle De Elorz)

Postcode

31110

Country

Spain

Scientific contact point

Organisation

Medibiofarma S.L.

Contact name

Chief Scientific Officer

Public contact point

Organisation

Medibiofarma S.L.

Contact name

Chief Scientific Officer

Third parties 5

Medibiofarma S.L.

Sponsor organisation

Medibiofarma S.L.

Address

Poligono Industrial Mocholi 2 B, Noain C Noain C

City

Noain (Valle De Elorz)

Postcode

31110

Country

Spain

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 2 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications