Oral E-B-FAHF-2 for Crohn's Disease

Overseen By David Dunkin, MD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Icahn School of Medicine at Mount Sinai

Must not be taking: CAM products, CYP3A alterers

Disqualifiers: Severe disease, Autoimmune, Neoplasm, others

Compensation: Varies

Number of Visits: 15

28 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot use any complementary and alternative medicine (CAM) products or medications that alter CYP3A function.

What data supports the effectiveness of the treatment E-B-FAHF-2 for Crohn's Disease?

The treatment E-B-FAHF-2, derived from Food Allergy Herbal Formula-2 (FAHF-2), has shown effectiveness in reducing peanut-induced allergic reactions in animal studies and has been safe and well-tolerated in humans with food allergies. Although this data is related to food allergies, it suggests potential immune-modulating benefits that might be relevant for Crohn's Disease. ^{1 2 3 4 5}

What makes the treatment E-B-FAHF-2 unique for Crohn's Disease?

E-B-FAHF-2 is unique because it is based on traditional Chinese medicine and has been refined to reduce the pill-load, making it more suitable for clinical studies, especially in children. It contains berberine, a bioactive component that has shown immune-modulating effects in other conditions like food allergies. ^{1 2 3 5 6}

What is the purpose of this trial?

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.

Research Team

David Dunkin

Principal Investigator

Icahn School of Medicine at Mount Sinai

Eligibility Criteria

Adults aged 18-30 with recently diagnosed mild-to-moderate Crohn's disease, able to undergo endoscopy and colonoscopy. Participants must be in good health, able to swallow pills, immunized per CDC guidelines, and if female and of childbearing potential, using effective birth control. Exclusions include severe CD cases, abnormal organ function tests, concurrent strong medication interactions, other systemic diseases or experimental therapy within the last month.

Inclusion Criteria

I weigh at least 25kg.

Either an elevated fecal calprotectin or an elevated CRP.

Evidence of inflammation on colonoscopy with an SES-CD >3.

Exclusion Criteria

I haven't taken steroids, immunomodulators, or biologic medications in the last six months.

My liver tests are higher than normal.

Abnormal bone marrow function (WBC <4 x 103/mm3; platelets <100 x 103/mm3).

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Induction

Subjects are induced with Entocort EC for 8 weeks to assess response before enrollment in the trial

8 weeks

4 visits (in-person), phone contacts in between

Safety and Tolerability

Double blind, placebo controlled dose escalation trial of E-B-FAHF-2 in subjects who responded to induction therapy

8 weeks

4 visits (in-person), phone contacts in between

Open-label Extension

Exploratory extension trial of E-B-FAHF-2 monotherapy to ensure sub-chronic safety and assess efficacy

6 months

6 visits (in-person), 1 PK study visit for a subset of subjects

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• BFAHF-2
• EBFAHF-2
• Placebo

Trial Overview The trial is testing E-B-FAHF-2 (a concentrated herbal formula) against a placebo for safety and effectiveness in maintaining remission of mild-to-moderate Crohn's disease. The study will also examine the effects on immune cells and intestinal mucosa to assess whether further efficacy trials are warranted.

Participant Groups

Group I: E-B-FAHF-2 Experimental Treatment 1 Intervention

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

Group II: Placebo Placebo Group 1 Intervention

capsules are identical in appearance to EBFAHF-2 capsules

BFAHF-2 is already approved in United States for the following indications:

Approved in United States as B-FAHF-2 for:

• Investigational for Crohn's disease

Who Is Running the Clinical Trial?

Icahn School of Medicine at Mount Sinai

Lead Sponsor

Trials

933

Recruited

579,000+

Findings from Research

B-FAHF-2, a refined version of Food Allergy Herbal Formula-2, effectively protects against peanut anaphylaxis in a mouse model, demonstrating safety and efficacy at a lower dosage than the original formula.

Berberine, a key component of B-FAHF-2, has low bioavailability when administered alone, but its absorption is significantly enhanced by other herbal constituents in the formula, indicating that these components work together to improve its therapeutic potential.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Berberine as a chemical and pharmacokinetic marker of the butanol-extracted Food Allergy Herbal Formula-2. Yang, N., Srivastava, K., Song, Y., et al.[2017]

FAHF-2, a 9-herb formula, was found to be safe and well tolerated in a study involving 68 participants with food allergies, with no serious adverse events reported.

While FAHF-2 showed favorable immunomodulatory effects in vitro, it did not demonstrate significant efficacy in improving tolerance to food allergens compared to placebo after 6 months of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, clinical, and immunologic efficacy of a Chinese herbal medicine (Food Allergy Herbal Formula-2) for food allergy. Wang, J., Jones, SM., Pongracic, JA., et al.[2023]

FAHF-2, a novel herbal formula based on traditional Chinese medicine, has shown effectiveness and safety in treating food allergies in mouse models, demonstrating persistent immune modulation even after treatment ends.

Early clinical trials indicate that FAHF-2 is well tolerated in humans, and an ongoing Phase II trial aims to confirm its efficacy in preventing allergic reactions during oral food challenges.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of food anaphylaxis with traditional Chinese herbal remedies: from mouse model to human clinical trials. Wang, J.[2021]

In a phase 1 trial involving 19 food allergic participants, the herbal product FAHF-2 was found to be safe and well tolerated, with only mild gastrointestinal symptoms reported by one patient in each of the treatment and placebo groups.

The treatment with FAHF-2 led to a significant decrease in interleukin-5 levels, suggesting potential immunomodulatory effects that could benefit patients with food allergies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, tolerability, and immunologic effects of a food allergy herbal formula in food allergic individuals: a randomized, double-blinded, placebo-controlled, dose escalation, phase 1 study. Wang, J., Patil, SP., Yang, N., et al.[2021]

The butanol-purified extract of Food Allergy Herbal Formula-2 (B-FAHF-2) significantly reduced the pill-load while maintaining efficacy, providing long-lasting protection against peanut anaphylaxis in a murine model for up to 50 weeks after treatment.

B-FAHF-2 demonstrated a high safety margin and effectively suppressed key immune responses associated with peanut allergy, including Th2 cytokines and IgE levels, indicating its potential as a safe therapeutic option for peanut allergy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy, safety and immunological actions of butanol-extracted Food Allergy Herbal Formula-2 on peanut anaphylaxis. Srivastava, K., Yang, N., Chen, Y., et al.[2021]

In an extended phase I clinical trial involving 18 patients with food allergies, Food Allergy Herbal Formula-2 (FAHF-2) was found to be safe and well tolerated over a 6-month period, with no significant adverse effects on vital signs or laboratory parameters.

FAHF-2 treatment resulted in a significant reduction in basophil activation markers, indicating potential efficacy in modulating immune responses related to food allergies, and suggests further investigation in a controlled phase II study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical safety of Food Allergy Herbal Formula-2 (FAHF-2) and inhibitory effect on basophils from patients with food allergy: Extended phase I study. Patil, SP., Wang, J., Song, Y., et al.[2022]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Berberine as a chemical and pharmacokinetic marker of the butanol-extracted Food Allergy Herbal Formula-2. [2017]

2. United States pubmed.ncbi.nlm.nih.gov

Safety, clinical, and immunologic efficacy of a Chinese herbal medicine (Food Allergy Herbal Formula-2) for food allergy. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Treatment of food anaphylaxis with traditional Chinese herbal remedies: from mouse model to human clinical trials. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Safety, tolerability, and immunologic effects of a food allergy herbal formula in food allergic individuals: a randomized, double-blinded, placebo-controlled, dose escalation, phase 1 study. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Efficacy, safety and immunological actions of butanol-extracted Food Allergy Herbal Formula-2 on peanut anaphylaxis. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Clinical safety of Food Allergy Herbal Formula-2 (FAHF-2) and inhibitory effect on basophils from patients with food allergy: Extended phase I study. [2022]