An Open-Label, Proof of Consent Study of Vorinostat for the Treatment of Mdoerate-to-Severe Crohn s Disease and Maintenance Therapy With Ustekinumab

• Register: ClinicalTrials.gov
• Last refreshed on: 8 January 2024
• Main ID: NCT03167437
• Date of registration: 24/05/2017
• Prospective Registration: Yes
• Primary sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Public title: An Open-Label, Proof of Consent Study of Vorinostat for the Treatment of Mdoerate-to-Severe Crohn s Disease and Maintenance Therapy With Ustekinumab
• Scientific title: An Open-Label, Proof of Concept Study of Vorinostat for the Treatment of Moderate-to-Severe Crohn's Disease and Maintenance Therapy With Ustekinumab
• Date of first enrolment: October 30, 2017
• Target sample size: 35
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT03167437
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1/Phase 2

Countries of recruitment

United States

Contacts

• Name: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)

• Name: Ivan J Fuss, M.D.
• Affiliation: National Institute of Allergy and Infectious Diseases (NIAID)

• Name: Ivan J Fuss, M.D.

Key inclusion & exclusion criteria

- INCLUSION CRITERIA:

1. Are 18 to 65 years of age, inclusive, at enrollment date.

2. Have a diagnosis of CD that has been endoscopically or radiographically
confirmed. A colonoscopy will be required at baseline to document mucosal disease
activity. SES-CD will be obtained with minimum score of 7.

3. Have active CD symptoms as defined by a CDAI score between 220 and 350 and
demonstrate active symptoms as defined by continued weight loss, abdominal pain
and/or diarrhea not controlled by standard therapy.

4. The participant must have active CD symptoms and therefore have had an inadequate
response to, loss of response to, or intolerance to at least 1 of the following
agent groups in control of their disease (as defined below for each individual
agent group: Corticosteroids or Immunomodulators or TNF-alpha sign antagonists or
Anti-integrin antibodies)

a. Corticosteroids

i. Signs and symptoms of persistently active disease despite a history of at
least one 4-week induction regimen that included a dose

equivalent to prednisone greater than or equal to 30 mg PO once daily (QD) for 2
weeks or intravenously (IV) for 1 week OR

ii. One failed attempt to taper corticosteroids to below a dose equivalent to
prednisone 10 mg PO QD or to taper to below a dose

of 9 mg of budesonide OR

iii. History of intolerance of corticosteroids at the discretion of the principal
investigator (PI) (including but not limited to Cushing s

syndrome, osteopenia/osteoporosis, hyperglycemia, insomnia, or infection)

b. Immunomodulators

i. Signs and symptoms of persistently active disease despite a history of at
least one 12-week regimen of oral azathioprine (AZA) (greater than or equal to
2.5 mg/kg/Day) or 6-MP (greater than or equal to 1.5 mg/kg/Day) OR

ii. Signs and symptoms of persistently active disease despite a history of at
least one 12-week regimen of MTX (greater than or equal to 25 mg/week) OR

iii. History of intolerance of at least one immunomodulator (including but not
limited to nausea/vomiting leading to discontinuation,

abdominal pain, pancreatitis, liver function test abnormalities, lymphopenia,
thiopurine methyltransferase genetic mutation, or

serious infection)

c. TNF-alpha sign antagonists with signs and symptoms of persistently active
disease despite a history of receiving infliximab, adalimumab, or certolizumab at
a dose approved for the treatment of CD and:

i. Patient had an inadequate response after completing the full induction
regimen, per approved product labeling

ii. Responded initially but then lost response with continued therapy

iii. Patient had a significant adverse event response which precluded further use
including but not exclusion of infusion reaction, serum

sickness and/or lupus-like rash.

d. Anti-integrin antibodies: with signs and symptoms of persistently active
disease despite a history of receiving an anti-integrin antibody agent
(natalizumab or vedolizumab) at a dose approved for the treatment of CD and:

i. Patient had an inadequate response after completing the full induction
regimen, per approved product labeling

ii. Responded initially but then lost response with continued therapy

iii. Patient had a significant adverse event response which precluded further use
including but not exclusion of infusion reaction, serum

sickness and/or lupus-like reaction.

5. At the discretion of the PI, concomitant medications will be permitted if the
following conditions are met prior to baseline assessment (Day-1):

a. 5-aminosalicylic acid (ASA)-based compounds are permissible if:

i. Oral 5-ASA-based compounds must be at a stable dose for at least 3 weeks prior
to baseline or

ii. Recently discontinued oral 5-ASA-based compounds must have been discontinued
at least 3 weeks prior to baseline or

iii. Rectal 5-ASA-based compounds are not permissible during the study and must
have been discontinued at least 3 weeks prior to baseline.

b. Corticosteroids (e.g., prednisone, budesonide) are permissible if:

i. Oral corticosteroids must be at a prednisone-equivalent dose of less than or
equal to 40 mg/day, or 9 mg/day of budesonide, and have been at a stable dose for
at least 3 weeks prior to baseline or

ii. Discontinuation of oral corticosteroids must have been completed at least 3
weeks prior to baseline or

iii. Parenteral (subcutaneous, intramuscular, or IV) or rectal corticosteroids
are not permitted during the study and must not have been used within a 3-week
period prior to baseline

c. CD-specific antibiotics are permissible if using an antibiotic for treatment
of CD ( a CD-specific antibiotic i.e., metronidazole, ciprofloxacin, rifaximin,
ampicillin, sulfonamide and tetracycline)

i. Participants must have been using the antibiotic for at least 3 weeks before
baseline at a stable dose or

ii. If not currently using a CD-specific antibiotic, the stop date must have been
at least 3 weeks prior to baseline.

d. Immunomodulators are permissible if:

i. Participants receiving chronic (i.e., greater than or equal to 12 weeks)
treatment with AZA, 6-MP, or MTX prior to baseline must be on a stable dose for
at least 6- 8 weeks prior to baseline and must continue on this same dose during
the study. OR

ii. Participants who have discontinued therapy with AZA, 6-MP, or MTX must have
stopped the medication at least 4 weeks prior to baseline. OR

iii. Participants must not have received therapy with other known
immunomodulators (e.g., cyclosporine, tacrolimus, sirolimus, pentoxifylline, or
mycophenolate mofetil) or experimental agents (e.g., granulocyte- or macrophage
colony stimulating factor) for at least

8 weeks or 5 half-lives of agent from baseline, whichever is longer.

e. The use of Anti-TNF and Anti-integrin therapy or other biological therapy listed
below will not be permitted and the following washout peri


Age minimum: 18 Years
Age maximum: 65 Years
Gender: All

Health Condition(s) or Problem(s) studied

Crohn's Disease

Intervention(s)

Drug: Ustekinumab

Drug: Vorinostat

Primary Outcome(s)

To evaluate the safety and tolerability of vorinostat in patients with moderate to severe CD as measured by the rate, frequency, and severity of adverse events (AEs) after 12 weeks of treatment. [Time Frame: Days 28, 56 and 12 and 24 weeks after start of treatment]

Secondary Outcome(s)

170 or greater score on IBDQ [Time Frame: end of Phase III]

Determine safety and tolerability of ustekinumab maintenance [Time Frame: end of study]

Mucosal healing after ustekinumab maintenance [Time Frame: end of study]

Achieve continued remission with ustekinumab [Time Frame: end of study]

Acheive clinical remission [Time Frame: weeks 12 and 24]

Changes in CDAI score equal to or greater than 70 [Time Frame: weeks 12 and 24]

Mucosal healing from use of Vorinostat [Time Frame: end of Phase III]

Secondary ID(s)

170101

17-I-0101

Source(s) of Monetary Support

Please refer to primary and secondary sponsors