Study to Evaluate Safety, Tolerability and Efficacy of Oral E-B-FAHF-2 in Mild-to-Moderate Crohn's Disease

NCT03992469 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: GCO 19-01250266-3308
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

Crohn's disease (CD) is the major form of inflammatory bowel disease (IBD) affecting adults. It is a life-long disease characterized by chronic and relapsing inflammation of the gastrointestinal tract. CD has multiple clinical phenotypes and disease severities that determine which therapy the study team utilizes. Currently, there are numerous treatment options for subjects with moderate-severe CD, but few that are approved to treat and maintain remission for the one-third of patients who present with mild-to-moderate disease. The study team hypothesizes that Butanol Purified Food Allergy Herbal Formula-2 (B-FAHF-2) will be safe and effective for maintaining remission of mild-to-moderate CD and can fill this therapeutic void. CD affects 241 per 100,000 adults in the United States and the incidence in both adults and children has increased in the past 60 years. One such potential therapy is Food Allergy Herbal Formula-2 (FAHF-2) which was originally developed to treat food allergy and has received FDA investigational new drug approval under the botanical drug title for treating patients with multiple food allergies. A completed phase I study showed that FAHF-2 is safe and well tolerated. A Phase II trial revealed that a high pill burden with FAHF-2 caused poor compliance. A butanol purified form of FAHF-2 (B-FAHF-2) is a more concentrated form of FAHF-2 which has also received an IND (FDA IND#77,468) and reduces the pill burden and improves compliance. Interestingly, the herbal components in B-FAHF-2 have long been used in Traditional Chinese Medicine (TCM) to treat gastrointestinal disorders including colitis. The study team has shown that B-FAHF-2 non-toxically inhibits TNF-#, a major inflammatory cytokine involved in CD, as well as multiple other pro-inflammatory cytokines produced by human peripheral blood mononuclear cells (PBMCs) and intestinal mucosa from subjects with CD. In addition, the study team has shown that FAHF-2 prevents disease progression in a murine model of colitis. The study team hypothesizes that E-B-FAHF-2 will be safe and effective for treating mild-to-moderate CD and can fill this therapeutic void. The study team proposes to investigate the safety and tolerability of B-FAHF-2 in subjects with mild-to-moderate CD. The goal is to establish safety and tolerability and explore efficacy at maintaining remission in this select patient population. Importantly, the study team will also determine the immunotherapeutic effects of E-B-FAHF-2 on PBMCs and intestinal mucosa to determine if there are immunologic alterations that would indicate that controlled efficacy evaluations of E-B-FAHF-2 are warranted. The new IND number is 143453. The FDA has completed their safety review of this protocol and has concluded that the study team's clinical trial may proceed with the proposed clinical investigation for Crohn's disease.

Conditions

Crohn's Disease

Keywords

Entocort EC induction; double blind, controlled safety/tolerability trial; open label exploratory efficacy trial; mild-to-moderate crohn's disease; Chinese Herbal Therapy

Outcome Measures

Primary Outcomes (1)

• Number of grades of adverse events

  Safety and tolerance will be assessed by number of adverse events using a previously established grading system by the study team.

  8 months

Secondary Outcomes (5)

• Number of participants requiring an escalation in therapy.

  6 months

• Fecal Calprotectin

  6 months

• PROMIS Profile 29

  6 months

• Self Efficacy Scale: IBDSES

  6 months

• Immunologic Changes in PBMC cytokine levels

  6 months

Study Arms (2)

E-B-FAHF-2

EXPERIMENTAL

Low dose EBFAHF-2 (29 mg/kg/d divided two times a day) for 2 weeks followed by a full dose (71mg/kg/d divided two times a day) for 6 weeks

Drug: EBFAHF-2

Placebo

PLACEBO COMPARATOR

capsules are identical in appearance to EBFAHF-2 capsules

Drug: Placebo

Interventions

EBFAHF-2 DRUG

EBFAHF-2 is a 0.55g capsule that is easy to swallow. The quality, safety and consistency of EBFAHF-2 are established per FDA guidance under a botanical drug title. Low dose (maximum of 2 capsules bid) and full dose (maximum of 5 capsules bid). Weight based dosing will ensure an equivalent amount is given to each individual.

E-B-FAHF-2

Placebo DRUG

Placebo capsules made of cornstarch

Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Male and female subjects with Crohn's disease (CD), 18-60 years of age and otherwise in good health as determined by medical history and physical examination
• Subjects weighing 25kg or more
• History of 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); patients with severe disease, which can be rapidly progressive and result in gastrointestinal hemorrhage, intestinal fistulas, abscesses and other complications, will be excluded because their risk of requiring rescue medications including steroids and biologicals as well as hospitalization or surgery are high.
• The subject is able to swallow the required capsules and tablets.
• The subject has been immunized according to the guidelines set forth by the CDC.
• The subject 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 CD.
• Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

You may not qualify if:

• Subjects will be excluded from the study if any of the following apply:
• Patients with severe disease as determined by CDAI, or SES-CD scores at initial endoscopy of greater than 16, or strictures or large ulcerations on endoscopy that exemplify severe disease.
• Acute febrile illness within 1 week before administration of study therapeutic formula.
• Any history of other systemic diseases that, in the investigator's opinion, would preclude the subject from participating in this study, e.g. other autoimmune disease, neoplasm, HIV or hepatitis infection.
• Abnormal hepatic 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 renal 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 subjects: 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.
• Active perirectal disease including fistuli or abcesses.
• Use of any other CAM products.
• Known allergy to FAHF-2/B-FAHF-2 or any of its components.
• Concurrent use of any medications known to alter CYP3A function.

Sponsors & Collaborators

• Icahn School of Medicine at Mount Sinai: lead

Study Sites (1)

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

MeSH Terms

Conditions

Crohn Disease

Condition Hierarchy (Ancestors)

Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Study Officials

• David Dunkin, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Double blind placebo controlled safety trial with random assignment to groups.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor, Pediatrics

Model Details: Safety and Tolerability phase is a double blind randomized controlled trial to evaluate safety and tolerability over 8 weeks. This is followed by an open-labeled exploratory efficacy extension phase for 6 months.

Study Record Dates

• First Submitted: June 18, 2019
• First Posted: June 20, 2019
• Study Start: February 15, 2023
• Primary Completion: February 2, 2026
• Study Completion: February 2, 2026
• Last Updated: September 23, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Immediately following publication. No end date.
• Access Criteria: Researchers who provide a methodologically sound proposal.Any purpose.Data are available indefinitely at (Link to be included).

Locations

US (1)