Study to Evaluate Safety, Tolerability, and Early Efficacy of Oral E-B-FAHF-2 in Subjects with Mild-to-Moderate Crohn’s Disease
Primary Objective: Safety and Tolerability
Secondary Objective: Efficacy
- Male and female patients with Crohn’s disease (CD), 18-60 years of age and otherwise in good health as determined by medical history and physical examination
- Patients weighing 55lbs or more
- History of recently diagnosed (within 18 months) ileal or ileal-colonic CD that is mild-to-moderate in severity as determined by standard history, physical, endoscopy scoring results, CD Activity Index (CDAI)
- The patient is able to swallow the required capsules.
- The patient has been immunized according to the guidelines set forth by the CDC.
- The patient agrees to participate in the study.
- Females of childbearing potential must be sexually inactive or take effective birth control measures, as deemed appropriate by the investigator, for the duration of the study.
- Evidence of inflammation on colonoscopy with an SES-CD >3.
- Either an elevated fecal calprotectin or an elevated CRP.
- Willing and able to undergo upper endoscopy and colonoscopy with disease flares and after 6 months of treatment for the assessment of disease as per the standard of care for Crohn’s Disease.
- Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
- Patients with severe disease as determined by CDAI, or SES-CD scores at initial endoscopy > 16, or strictures or large ulcerations on endoscopy that exemplify severe disease.
- Acute respiratory illness with fever within 1 week before administration of study therapeutic formula.
- Any history of other systemic diseases that, in the investigator’s opinion, would preclude the patient from participating in this study, e.g. other autoimmune disease, neoplasm, HIV or hepatitis infection.
- Abnormal liver function (ALT, AST or bilirubin >2 x upper limit of normal).
- Abnormal bone marrow function (WBC <4 x 103/mm3; platelets <100 x 103/mm3).
- Abnormal kidney function (BUN and creatinine >1.5 x upper limit of normal for age or abnormal eGFR for age and race).
- Clinically significant abnormal electrocardiogram.
- Participation in another experimental therapy study within 30 days of this study.
- History of alcohol or drug abuse.
- Pregnant or lactating female patients: females of childbearing potential will need a negative pregnancy test at screening and at each visit to be considered and continued in this study. Lactating females will be excluded from the study.
- Previous use of intravenous or oral systemic steroids within the past six months or any use of immunomodulators (6-MP, azathioprine, methotrexate) or biologic medications, since these drugs have lasting effects and alter the patient’s inflammatory cell profile thus affecting the results of our study.
- Active perirectal disease including fistuli or abcesses.
- Use of any other Complementary and Alternative Medicine products.
- Known allergy to FAHF-2/E-B-FAHF-2 or any of its components.
- Concurrent use of any medications known to alter CYP3A function.
- Any other medical concerns not listed above that in the invistigator’s opinion may pose additional risks, interfere with adherance, or impact the quality or interpretation of the data.
Study description/explanation of participation:
Patients enrolled in the study will receive prescribed treatment with Entocort EC for 8 weeks to induce remission as determined by the CDAI scoring system. Those that respond will be allocated to the investigational treatment. For the initial 8-week safety and tolerability phase of the trial, patients will be randomly and blindly assigned to E-B-FAHF-2 or placebo (2 weeks low dose (2 capsules twice a day) followed by 6 week-long full dose (5 capsules twice a day). All participants who complete the Safety phase of the trial will be offered the option to continue into the open labeled Exploratory Efficacy Extension Trial, which will last 6 months. During this open-label phase, only E-B-FAHF-2 (no placebo) will be taken at the full dose of 5 capsules twice a day.
Description of treatment or intervention (mechanism of action):
E-B-FAHF-2 is an ethyl acetate butanol purified form of Food Allergy Herbal Formula-2 (FAHF-2) and is derived from the classical Therapeutic Chinese Medicine formula Wu Mei Wan, a well-known Chinese classical formula first documented by Zhang Zhong Jing in the classical Chinese medical text, the Shang Han Lun, compiled approximately 2,000 years ago. It consists of 9 Chinese herbal medicines. The full list of medicines will be provided by the study team. It is widely used to treat intermittent attacks of abdominal pain, a stifling sensation, irritability, pain accompanied by vomiting after eating and chronic dysentery.
Extensive pre-clinical data demonstrates that E-B-FAHF-2 suppresses multiple inflammatory cytokines (TNF-a, INF-g, IL-17, IL-6 and others) that are involved in the pathogenesis of Crohn’s disease. This was true both on assessment of blood and biopsies from patients with Crohn’s disease and in multiple mouse models of IBD. The suppression of inflammation was partly due to suppression of the NFkB inflammatory pathway.
Patient participation requirements:
Patients who choose to participate in the trial will be asked to:
- Participate in 11 study visits over the course of 8 months, which includes:
- Biweekly visits for 2 months (5 visits)
- Monthly visits for 6 months (6 visits)
- Provide stool specimens collected prior to each visit
- Complete standard labs and study bloodwork
- Allow collection of biopsy specimens for research at routine (non-study) colonoscopies
- Follow instructions for study medications, which includes taking FDA-approved, standard of care medication Entocort EC (budesonide) for induction of remission, along with study-assigned drug/placebo
- Complete questionnaires or answer questions at each visit
Possible risks and side effects:
The risks attendant to participation in this study are minimal and are justified by the potential benefits derived by both the patient and society. Patients will derive two major benefits from the study: accurate assessment of their Crohn’s disease and close follow up to ensure that they are adequately treated and stable, and treatment with E-B-FAHF-2 which may result in general improvement of their Crohn’s related symptoms over the time of the study.
Reasonably Forseeable Risks and Discomforts include:
- Known risks associated with taking the FDA-approved drug for induction of remission in mild-to-moderate CD Entocort EC (budesonide). These risks will be discussed by the study doctor when reviewing the drug package insert.
- Risk of losing remission once taken off Entocort EC. If this happens, the patient will be allowed to receive any treatment the physician chooses, including non-FDA approved medications for mild-to-moderate disease.
- Risk of loss of private information; this risk always exists, but there are procedures in place to minimize the risk.
- The risks of a blood draw include pain, bruising, and the slight possibility of infection at the place where the needle goes in. Some people feel dizzy or may faint during or after a blood draw.
- The risks associated with biopsy collection at time of routine colonoscopy being done for diagnostic or treatment purposes include infection, additional blood loss from biopsy location, and on very rare occasion, perforation (a puncture or small hole) of the intestine. Typically at least 13 sets of biopsies are taken during endoscopy/colonoscopy but sometimes can be up to 30. The study will obtain approximately 6 additional sets.
- Risk of increased gastrointestinal discomfort; in a Phase 2 allergy study, this was the only reported adverse effect associated with E-B-FAHF-2 use, though this was notably a rare occurrence.
Progress to date:
FAHF-2, B-FAHF-2 and E-B-FAHF-2 have been shown to be immunomodulatory in animal models of food allergy and in humans with multiple food allergies. In ex-vivo (outside the body, in the lab) studies, we have shown that FAHF-2/B-FAHF-2 suppresses production of multiple inflammatory proteins in intestinal mucosa from children with Crohn’s Disease: