Crohn Disease (CD)
Conditions
Keywords
Crohn's Disease, Inflammatory Bowel Disease, IBD, R-3750, Lactoccoccus lactis, Gut Microbiome
Brief summary
This is a multicenter, randomized, double-blind, placebo-controlled study evaluating the safety, tolerability, clinical activity, and pharmacodynamic effects of R-3750 in adults with active Crohn's disease. Approximately 40 participants will be randomized 1:1 to receive R-3750 or matching placebo orally once daily for 12 weeks. Participants will be followed for safety, clinical response, and durability of response through approximately Day 168. Assessments will include adverse events, Crohn's disease activity, endoscopic response, patient-reported outcomes, inflammatory biomarkers, microbiome composition, and pharmacodynamic measures.
Detailed description
This is a multicenter, randomized, double-blind, placebo-controlled Phase 1 study designed to evaluate the safety, tolerability, clinical activity, and pharmacodynamic effects of R-3750 in adults with active Crohn's disease. Approximately 40 participants will be randomized in a 1:1 ratio to receive either R-3750 at a dose of 9E10 colony-forming units (CFU) per day or matching placebo administered orally once daily for 12 weeks. Participants, investigators, study site personnel involved in outcome assessments, and Sponsor personnel involved in study conduct and assessment will remain blinded to treatment assignment. Eligible participants will be adults 18 to 80 years of age with active Crohn's disease, defined by a Harvey-Bradshaw Index (HBI) score of 5 to 15 and objective evidence of active inflammatory disease based on C-reactive protein (CRP), fecal calprotectin, biopsy-verified inflammation, and/or endoscopic assessment. The study consists of a screening period, a 12-week treatment period from Day 1 through Day 84, and a safety follow-up period through approximately Day 168. Safety and tolerability will be evaluated through the assessment of adverse events and serious adverse events, clinical laboratory parameters, vital signs, and physical examinations. Clinical activity will be evaluated using measures including the Crohn's Disease Activity Index (CDAI) and HBI. Additional assessments will evaluate clinical remission, endoscopic response, patient-reported outcomes, inflammatory biomarkers, microbiome composition, immune phenotypes, metabolomic profiles, and other pharmacodynamic measures. An independent Medical Monitor will review available safety data on an ongoing basis, and a Data Monitoring Committee (DMC) will review cumulative safety data during the study.
Interventions
DRUGR-3750
R-3750 DP is a live biotherapeutic product consisting of Lactococcus lactis engineered to express Surface Layer Protein A (SlpA), formulated in enteric-coated capsules for oral administration. Participants randomized to R-3750 will receive 9E10 colony-forming units (CFU) per day orally once daily from Day 1 through Day 84.
DRUGPlacebo
Matching placebo will be administered orally once daily from Day 1 through Day 84.
Sponsors
Rise Therapeutics LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Arm 1: R-3750, 9E10 CFU/day orally once daily for 12 weeks Arm 2: Matching placebo orally once daily for 12 weeks
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Age 18 to 80 years, inclusive, at the time of informed consent. * Able and willing to provide written informed consent and comply with study procedures and study visits. * Documented diagnosis of Crohn's disease with symptoms/onset of disease at least 3 months prior to Screening. * Active Crohn's disease defined by Harvey-Bradshaw Index (HBI) score between 5 and 15 at Screening. * Evidence of active inflammatory disease, defined by at least one of the following: CRP ≥5 mg/L, fecal calprotectin ≥50 µg/g, biopsy-verified inflammation, or endoscopic evidence of active inflammation. * Women of childbearing potential must have a negative pregnancy test at Screening and before dosing and agree to use highly effective contraception during the study and for at least 3 months after the last dose. * Men with partners of childbearing potential must agree to use contraception according to institutional requirements during the study and for at least 3 months after the last dose.
Exclusion criteria
* Crohn's disease in clinical remission, including HBI \<5 or CDAI \<150 at Screening. * Severe Crohn's disease requiring urgent escalation of therapy, hospitalization, or surgery in the opinion of the Investigator. * Imminent risk of scheduled intestinal surgery, including clinically significant stenosis, strictures, internal fistula, abscess, or obstructive complications. * History of partial or incomplete bowel obstruction within 6 months prior to Screening; current stoma, ileostomy, colostomy, or anticipated need for ostomy during the study; diagnosis of short bowel syndrome or clinically significant malabsorptive condition; uncontrolled chronic diarrhea due to a condition other than Crohn's disease; or bowel resection within 3 months prior to Screening. Subjects with prior bowel resection may be eligible if, in the opinion of the Investigator and Sponsor, the remaining bowel anatomy is adequate for study participation and interpretation of study endpoints. * History (past 6 months) or current Clostridioides difficile infection, clinically significant enteric infection, other active infection or chronic infection requiring ongoing antimicrobial treatment. * Treatment with antibiotics within 2 weeks prior to Day 1 or expected during the study period. * Use of biologic, targeted synthetic, or systemic immunomodulatory/immunosuppressive therapy for Crohn's disease within the 4 weeks washout period prior to Day 1, unless specifically permitted. Stable doses of aminosalicylates, budesonide, or low-dose systemic corticosteroids are permitted if stable for at least 2 weeks prior to Day 1 and expected to remain stable during the treatment period. Low-dose systemic corticosteroids are defined as prednisone ≤20 mg/day or equivalent. * Use of probiotics or live biotherapeutic products within 2 weeks prior to Day 1. * Severe comorbidities, including uncontrolled diabetes, clinically significant cardiopulmonary failure, severe liver disease, severe renal disease, or other clinically significant condition that would place the subject at risk or confound study interpretation. * Abnormal hepatic function, including ALT or ALP \>2.5 × ULN, liver cirrhosis, portal hypertension, or clinically significant active liver disease. * Abnormal renal function, including cystatin C \>ULN or other clinically significant renal abnormality. * Known active blood-borne infection, including HIV, active hepatitis A, B, or C infection, or tuberculosis. * History of malignancy within 5 years prior to Day 1, except adequately treated non-metastatic basal cell carcinoma, squamous cell carcinoma of the skin, or carcinoma in situ of the cervix. * Pregnant, breastfeeding, or planning to become pregnant during the study. Clinically significant mental disorder, substance use disorder, alcohol or drug addiction that may interfere with participation or compliance. * Participation in another interventional clinical trial within 30 days prior to Day 1 or simultaneous participation in another interventional clinical trial. * Any significant disease, disorder, laboratory abnormality, or circumstance that, in the opinion of the Investigator, may put the subject at risk, affect study results, or interfere with study participation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Adverse Events. | From first dose through Day 168 end of study | Number of participants experiencing one or more treatment-emergent adverse events following administration of R-3750 or placebo. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with serious adverse advents | From first dose through Day 168 end of study | Number of particpants experiencing one or more serious adverse events following administration of R-3750 or placebo. |
Contacts
CONTACTJanet L Stephens, PhD
CONTACTChristian F Freguia, PhD
Outcome results
None listed