Vorinostat + Ustekinumab for Crohn's Disease
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Must not be taking: Anticoagulants, Anti-seizure, NSAIDs
Disqualifiers: Infections, Cancer, Diabetes, others
No Placebo Group
Approved in 2 Jurisdictions
Trial Summary
What is the purpose of this trial?Background:
Crohn s disease (CD) is an inflammatory bowel disease. It causes inflammation of the gut. Symptoms may include diarrhea, abdominal pain, fatigue, weight loss and malnutrition. CD has no cure, but symptoms can sometimes be controlled with medicine. Researchers want to see if it is safe to treat CD with the medicine vorinostat. It is thought that vorinostat may reduce the inflammation process of CD. This may then help to relieve symptoms of CD. Participants who respond to Vorinostat will be invited to an extension phase of treatment with Vorinostat and possibly a maintenance treatment using Ustekinumab.
Objectives:
To see if vorinostat is safe for people with moderate-to-severe CD. To see if it is safe for people with moderate-to-sever CD to receive maintenance therapy using Ustekinumab after successful treatment of Vorinostat.
Eligibility:
Adults 18-65 with moderate-to-severe CD that medicine is not controlling.
Design:
Phase I is screening. It may last 120 days. Participants will have:
Physical exam
Medical history
Tests of blood, urine, and stool samples
Heart test
Questionnaires
Tuberculosis skin test
They may have a colonoscopy and lymphapheresis collection. These will be explained in a separate consent.
They will keep a diary of symptoms.
Phase II is treatment using Vorinostat. It will take 12-13 weeks. Participants will take the study drug by mouth twice daily for 12 weeks. They will get a weekly phone call to talk about how the drug makes them feel. They will have blood taken regularly. Every 4 weeks, they will have a check-up that will repeat some screening tests.
Phase III extension treatment of Vorinostat for an additional 6 months for those who respond to vorinostat and it is safe for them to continue treatment. Participants will continue to receive weekly calls to talk about how the drug makes them feel. They will have blood taken regularly. Every 3 months, they will have a check-up that will repeat some screening tests.
Phase IV: is maintenance therapy for 2 years with Ustekinumab. Participants will receive a one time loading dose of ustekinumab, and then will receive the approved maintenance dose once every 8 weeks, at which time they will return to the NIH Clinical Center for evaluation. The participant will get a phone call 3 days after each dose and again 2 weeks later to see how the drug makes them feel. After two years of receiving treatment with ustekinumab the participant will have an end of study visit, where some of the screening tests, including a colonoscopy, will be repeated.
Will I have to stop taking my current medications?
The trial protocol allows some medications to be continued if they meet specific conditions. For example, certain medications like 5-aminosalicylic acid compounds, corticosteroids, and CD-specific antibiotics can be continued if they have been stable for a specified period before the trial. However, some medications, like anti-TNF and anti-integrin therapies, require a washout period (time without taking the medication) before starting the trial.
What data supports the effectiveness of the drug Ustekinumab for treating Crohn's Disease?
Research shows that Ustekinumab is effective and relatively safe for treating moderate to severe Crohn's Disease, as demonstrated in clinical trials and real-life studies. It is approved for patients who have not responded to other biologic treatments.
12345How is the drug Vorinostat + Ustekinumab unique for treating Crohn's disease?
Vorinostat + Ustekinumab is unique because it combines Vorinostat, a drug that modifies gene expression, with Ustekinumab, a monoclonal antibody targeting specific proteins involved in inflammation, offering a novel approach by potentially addressing Crohn's disease through different mechanisms than standard treatments.
16789Eligibility Criteria
Adults aged 18-65 with moderate-to-severe Crohn's Disease not well-controlled by standard treatments, including corticosteroids or immunomodulators. Participants must have a confirmed diagnosis of CD and active symptoms. Women of childbearing age must use birth control and not be pregnant or breastfeeding; men are also required to use contraception post-treatment.Inclusion Criteria
I have Crohn's disease confirmed by tests and need a colonoscopy to show my current condition.
I have Crohn's disease with moderate symptoms not managed by standard treatments.
I have tried treatments like steroids or biologics without success.
+2 more
Exclusion Criteria
I have a history of getting infections often.
I have a history of tuberculosis, hepatitis B or C, HIV, or serious infections.
Positive for tuberculosis via QuantiFERON-Gold (QFT-G)
+18 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
17 weeks
Multiple visits for exams and tests
Treatment
Participants receive Vorinostat 100mg PO BID for 12 weeks
12 weeks
Weekly phone calls, blood tests, and check-ups every 4 weeks
Extension Treatment
Participants who respond to Vorinostat continue treatment for an additional 6 months
24 weeks
Weekly phone calls, blood tests, and check-ups every 3 months
Maintenance Therapy
Participants receive Ustekinumab for 2 years with a loading dose followed by maintenance doses every 8 weeks
24 months
Phone calls 3 days and 2 weeks after each dose, end of study visit
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
The trial is testing Vorinostat for treating Crohn's Disease over a period of up to six months for responders, followed by maintenance therapy with Ustekinumab for two years. The study includes initial screening, treatment phases where participants take Vorinostat orally and receive Ustekinumab injections at intervals, along with regular check-ups and tests.
3Treatment groups
Experimental Treatment
Active Control
Group I: 2Experimental Treatment1 Intervention
participants will receive Vorinostat 100mg PO BID for 6months
Group II: 1Experimental Treatment1 Intervention
participants will receive Vorinostat 100mg PO BID for 12 weeks
Group III: 3Active Control1 Intervention
participants will receive ustekinumab (weight base induction dose followed by 90mg SC every 8 weeks for 24 months)
Vorinostat is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Zolinza for:
- Cutaneous T-cell lymphoma
🇪🇺 Approved in European Union as Zolinza for:
- Cutaneous T-cell lymphoma
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
National Institutes of Health Clinical CenterBethesda, MD
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Who Is Running the Clinical Trial?
National Institute of Allergy and Infectious Diseases (NIAID)Lead Sponsor
References
Ustekinumab in Crohn's Disease: New Data for Positioning in Treatment Algorithm. [2022]The treatment of patients with moderate to severe Crohn's disease [CD] is still challenging. Therapeutic options include steroids, immunosuppressants, anti-TNFα agents, vedolizumab, and ustekinumab. Ustekinumab is a monoclonal antibody blocking the p40 subunit of IL-12 and IL-23. It showed to be effective and safe in randomised clinical trials and real-life studies and is currently approved for the management of CD patients who are naive to biologics and those who have already been treated with such medications. However, to date, a detailed and approved therapeutic algorithm is not available. The aim of this review is to report the most recent and updated data on the efficacy and safety of ustekinumab for the treatment of patients with moderate to severe CD and to define the optimal management of these patients.
Ustekinumab in Crohn's disease: evidence to date and place in therapy. [2020]Crohn's disease (CD) is an inflammatory bowel disease (IBD) with uncertain etiology. Biologic agents have revolutionized the treatment of CD but nonresponders remain a challenge. Ustekinumab is an interleukin 12/23p40 inhibitor that was recently found effective in treating CD. We reviewed the current literature regarding the efficacy of ustekinumab in treating CD and concluded that ustekinumab is a novel, promising and relatively safe agent for the treatment of moderate to severe CD. Additional data from randomized controlled studies and real-life cohorts are pending.
Ustekinumab for Crohn's Disease: Results of the ICC Registry, a Nationwide Prospective Observational Cohort Study. [2020]Ustekinumab is approved for the treatment of Crohn's disease [CD]. Systematically registered prospective real-world data are scarce. We therefore aimed to study the effectiveness, safety and usage of ustekinumab for CD in everyday practice.
Matching-Adjusted Indirect Comparison Between Risankizumab and Ustekinumab for Induction and Maintenance Treatment of Moderately to Severely Active Crohn's Disease. [2023]Risankizumab (RZB) and ustekinumab (UST), interleukin (IL)-23 and IL-12/23 inhibitors, respectively, are approved treatments for moderately to severely active Crohn's disease (CD); direct comparison between the two is ongoing. We indirectly compared efficacy of RZB versus UST using data from phase 3 trials (RZB: NCT03104413; NCT03105128; NCT03105102; UST: NCT01369329; NCT01369342; NCT01369355).
Evolution of Symptoms After Ustekinumab Induction Therapy in Patients With Crohn's Disease. [2023]Ustekinumab is an effective treatment of Crohn's disease (CD). Of interest to patients is knowing how soon symptoms may improve. We analyzed ustekinumab response dynamics from the ustekinumab CD trials.
Ustekinumab Exposure-outcome Analysis in Crohn's Disease Only in Part Explains Limited Endoscopic Remission Rates. [2020]Ustekinumab, an anti-IL12/23p40 monoclonal antibody, has been approved for Crohn's disease [CD]. Real-life data in CD patients receiving ustekinumab intravenously [IV] during induction, followed by subcutaneous [SC] maintenance, are lacking. We assessed efficacy of ustekinumab and studied exposure-response correlations.
Real-world effectiveness and safety of ustekinumab for the treatment of Crohn's disease: the Scottish ustekinumab cohort. [2021]Ustekinumab is a monoclonal antibody that targets interleukin-12/23. In Scotland, it was approved for the treatment of moderate to severe Crohn's disease in 2017. The objective of this study was to establish the real-world effectiveness and safety of ustekinumab in the treatment of Crohn's disease.
Real World Experience With Ustekinumab in Children and Young Adults at a Tertiary Care Pediatric Inflammatory Bowel Disease Center. [2023]Ustekinumab is an effective therapy for Crohn disease currently approved for adults. Off-label use in the pediatric population is increasing, but its effectiveness in this age group has not been reported.
P066 Real-World Experience of Ustekinumab in Crohn's Disease Patients With Prior Anti-TNF Therapy at a Tertiary Care Hospital. [2023]Ustekinumab (UST) is a monoclonal antibody against the p40 subunit of IL-12/23. It is approved for the treatment of moderate to severe Crohn's disease (CD) and Ulcerative Colitis. We performed a retrospective study to demonstrate the efficacy and outcomes of UST in CD patients who received prior anti-TNF therapies.