- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03992469
Study to Evaluate Safety, Tolerability and Efficacy of Oral E-B-FAHF-2 in Mild-to-Moderate Crohn's Disease
Study to Evaluate Safety, Tolerability, and Early Efficacy of Oral E-B-FAHF-2 in Subjects With Mild-To-Moderate Crohn's Disease
Study Overview
Detailed Description
The study team's current proposed study uses the same investigational agent, E-B-FAHF-2, being studied for food allergy under an active IND, and seeks to determine if this formula is safe for the treatment of mild-to-moderate CD. The study team's major goal focuses on safety, tolerability, beneficial immunomodulatory effect, and preliminary clinical efficacy of B-FAHF-2 to maintain remission in subjects with mild-to-moderate CD. B-FAHF-2 is currently undergoing a phase II clinical trial for treatment of food allergy, thus increasing the ease of obtaining an FDA IND for B-FAHF-2 use in CD. Preliminary data were generated in the study team's ongoing FAHF-2 and B-FAHF-2 studies on food allergy and IBD. In developing a botanical drug from a traditional Chinese medicine (TCM) formula, standardization of product is key to ensure safety, consistency, and potency. An IND for B-FAHF-2 has been accepted by the FDA, and is documented that the product's quality, safety and standardized methodology have been demonstrated. To date, the study team has demonstrated the safety of B-FAHF-2 in animal models and the safety and tolerability of B-FAHF-2 in patients, including adults and children with food allergy. The most specific data relevant to this proposal are the suppression by FAHF-2/B-FAHF-2 of TNF-alpha production by PBMC's and intestinal specimens from children with CD and the abrogation of colitis in a murine model.
CD is a life-long chronic, relapsing, immune mediated inflammatory disease characterized by inflammation in the gastrointestinal tract. Treatment is aimed at controlling mucosal inflammation, and thus symptoms of the disease, by inducing and then maintaining remission. Since CD causes abdominal pain, decreased appetite, malabsorption and diarrhea, children are particularly vulnerable because inadequate nutrition can lead to potentially irreversible growth stunting and delayed maturity. There is a lack of maintenance therapies for children and adults with mild-to-moderate disease since many of the medications used to treat CD. including steroids, immunomodulators and biological therapies are geared towards treating moderate-to-severe disease. The most commonly used medications for treatment and maintenance of remission in mild-to-moderate CD are 5-ASA compounds and antibiotics but they are not FDA approved and the literature does not support their utility in CD. Based on the inhibition of TNF-alpha by B-FAHF-2 and FAHF-2 in vitro, the study team hypothesizes that E-B-FAHF-2 will be safe and effective therapy that will fill this therapeutic void. The study team proposes to test the safety and tolerability of E-B-FAHF-2 in subjects with recently diagnosed mild-to-moderate CD that responds to induction with Entocort EC. To minimize any potential risk by exposing a large number of subjects to treatment: the study team will conduct the study in subjects 18-30 years old to assess for safety, tolerability and determine immunological and/or efficacy signals (subjective and objective measures). Since E-B-FAHF-2 is likely to be slow to work, subjects will be induced with Entocort EC for 8 weeks. Responders will then be enrolled in the trial. The safety and tolerability trial is eight weeks long, double blind, placebo controlled dose escalation trial of E-B-FAHF-2 in subjects who responded to induction therapy with Entocort EC. This portion of the study will serve to ensure safety and tolerability of E-B-FAHF-2. Subjects will be seen every 2 weeks and contacted by phone in between study visits to assess for any adverse events (AEs). This will be followed by a 6 month long, open-label exploratory extension trial of E-B-FAHF-2 monotherapy to ensure the sub-chronic safety as well as determine of there is any efficacy or immunologic alteration to pursue in randomized efficacy trials. During this phase, subjects will have follow-up visits every 4 weeks to assess for AEs and efficacy outcomes. In addition, a subset of 4 subjects will participate in PK studies for one of the visits during this phase. The exploratory efficacy phase of the study will be conducted in a population of subjects naive to immunomodulators, systemic steroids and biologics. This study population will provide us with an opportunity to determine the safety and immunologic effects of E-B-FAHF-2 in CD without the interference of systemic immunomodulating medications.
Study Type
Enrollment (Estimated)
Phase
- Phase 1
Contacts and Locations
Study Contact
- Name: Alana Mercurio, BA
- Phone Number: (212) 824-7740
- Email: alana.mercurio@mssm.edu
Study Contact Backup
- Name: David Dunkin, MD
- Phone Number: (212) 824-7785
- Email: pedsgi@mssm.edu
Study Locations
-
-
New York
-
New York, New York, United States, 10029
- Recruiting
- Icahn School of Medicine at Mount Sinai
-
Principal Investigator:
- David Dunkin, MD
-
Contact:
- Alan Mercurio, BA
- Phone Number: 212-824-7740
- Email: alana.mercurio@mssm.edu
-
Contact:
- David Dunkin, MD
- Email: pedsgi@mssm.edu
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
Participants must fulfill all of the following criteria to be eligible for inclusion in the study:
- 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.
Exclusion Criteria:
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.
- Any other medical concerns not listed above that in the invistigator's opinion may pose additional risks, interfere with adherence, or impact the quality or interpretation of the data.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: E-B-FAHF-2
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
|
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.
|
Placebo Comparator: Placebo
capsules are identical in appearance to EBFAHF-2 capsules
|
Placebo capsules made of cornstarch
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of grades of adverse events
Time Frame: 8 months
|
Safety and tolerance will be assessed by number of adverse events using a previously established grading system by the study team.
|
8 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of participants requiring an escalation in therapy.
Time Frame: 6 months
|
Before enrollment and at each visit a CDAI will be assessed. The CDAI is a clinical score for adults that includes history items, physical examination items, and laboratory tests and is based on the past 7 days. A score of <150 is defined as remission, 151-219 as mild activity, 220-450 as moderate activity and >450 as severe activity. Clinical response is defined as a decrease in score of at least 70 points or >25% in subjects with baseline CDAI >220. Any escalations in therapy will be recorded and assessed as described above. |
6 months
|
Fecal Calprotectin
Time Frame: 6 months
|
The level of calprotectin in stool as a way to detect inflammation in the intestines.
|
6 months
|
PROMIS Profile 29
Time Frame: 6 months
|
PROMIS Profile-29 is a validated, self-report collection of 4-item short forms that uses a 5-point Likert scale to assess anxiety, depression, fatigue, pain interference, physical function, sleep disturbance, and ability to participate in social roles and activities.
PROMIS measures are scored on the T-score metric.
High scores mean more of the concept being measured.
Norm-based scores have been calculated for each domain on the PROMIS measures, so that a score of 50 represents the mean or average of the reference population.
A score of 60 means that the person is one standard deviation above the reference population(standard deviation=10).
|
6 months
|
Self Efficacy Scale: IBDSES
Time Frame: 6 months
|
This self-administered efficacy scale includes 13 items that assess how patients with IBD manage items related to their disease and everyday life.
The validated scale uses 5-point Likert scales for each item.
the total score ranges from 13 to 65 with a lower score indicating lower self-efficacy.
|
6 months
|
Immunologic Changes in PBMC cytokine levels
Time Frame: 6 months
|
PBMCs will be obtained along with routine labs at the start of the safety trial and after starting (week 8), during (week 12 and 20) and completing the exploratory extension trial (week 32).
|
6 months
|
Collaborators and Investigators
Investigators
- Principal Investigator: David Dunkin, MD, Icahn School of Medicine at Mount Sinai
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- GCO 19-0125
- 0266-3308 (Other Grant/Funding Number: The Helmsley Charitable Trust)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
Study Data/Documents
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Crohn's Disease
-
ProgenaBiomeRecruitingCrohn Disease | Crohn Colitis | Crohn's Ileocolitis | Crohn's Gastritis | Crohn's Jejunitis | Crohn's Duodenitis | Crohn's Esophagitis | Crohn's | Crohn Disease of Ileum | Crohn Ileitis | Crohn's Disease Relapse | Crohns Disease Aggravated | Crohn Disease in Remission | Crohn's Disease of PylorusUnited States
-
Massachusetts General HospitalAmerican College of GastroenterologyNot yet recruitingInflammatory Bowel Diseases | Crohn Disease | Crohn Colitis | Crohn's Ileocolitis | Crohn's Gastritis | Crohn's Jejunitis | Crohn's Duodenitis | Crohn's EsophagitisUnited States
-
Richard Burt, MDTerminatedCROHN'S DISEASEUnited States
-
Agomab Spain S.L.RecruitingFibrostenotic Crohn's DiseaseUnited States, Italy, Poland, Spain, Denmark, Austria, Canada, Germany
-
AbbVieActive, not recruitingCrohn's Disease (CD)United States, Belgium, Canada, Czechia, Denmark, France, Germany, Hungary, Israel, Italy, Netherlands, New Zealand, Norway, Poland, Romania, Slovakia, Spain, United Kingdom
-
AbbVieActive, not recruitingCrohn's Disease (CD)United States, Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Chile, China, Czechia, France, Germany, Greece, Hungary, Israel, Italy, Korea, Republic of, Mexico, Netherlands, Poland, Romania, Russian Federation, Slo... and more
-
University Hospital, LilleMinistry of Health, FranceTerminatedCrohn's Disease AggravatedFrance
-
TakedaRecruitingCrohn's Disease (CD)United States, Australia, Israel, Belgium, Hungary, Canada, China, Croatia, Czechia, Greece, Italy, Japan, Korea, Republic of, Poland, United Kingdom, Lithuania, Slovakia, Spain
-
Weill Medical College of Cornell UniversityThe Kenneth Rainin FoundationRecruitingCrohn's Disease (CD)United States
Clinical Trials on EBFAHF-2
-
University College, LondonMoorfields Eye Hospital NHS Foundation Trust; Targeted Genetics CorporationCompletedRetinal DegenerationUnited Kingdom
-
Yuhan CorporationCompletedRheumatic ArthritisKorea, Republic of
-
Medifast, Inc.Completed
-
University of South CarolinaTerminatedSedentary Lifestyle | Knee Osteoarthritis | Knee Injuries | Knee Pain ChronicUnited States
-
University of PennsylvaniaNational Cancer Institute (NCI); PfizerCompleted
-
Metabolic Technologies Inc.National Institute on Aging (NIA); Vanderbilt UniversityCompleted
-
University of Sao Paulo General HospitalCompletedOveractive Bladder SyndromeBrazil
-
Metabolic Technologies Inc.National Institute on Aging (NIA); Vanderbilt UniversityCompleted
-
Hanmi Pharmaceutical Company LimitedCompletedHypertensionKorea, Republic of
-
Sanofi Pasteur, a Sanofi CompanyImmune DesignTerminated