Clinical Trial: Study of Safety, Tolerability, and Efficacy of Ustekinumab for Symptomatic Gastrointestinal Inflammation Associated With Common Variable Immunodeficiency

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: An Open-Label Phase I/II Pilot Study to Assess the Safety/Tolerability and Efficacy of Ustekinumab for Symptomatic Gastrointestinal Inflammation Associated With Common Variable I

Brief Summary:

Background:

- Some people with Common Variable Immunodeficiency Disease (CVID) have gastrointestinal inflammation. This can cause diarrhea, weight loss, and not being able to absorb nutrition from food. Researchers want to see if the drug ustekinumab can help these problems. This drug blocks some proteins that cause inflammation.

Objective:

- To test the safety and efficacy of the drug ustekinumab for people with CVID with gastrointestinal inflammation.

Eligibility:

- Adults ages 18-75 with CVID. They must have chronic diarrhea, have unintentionally lost weight in the last year, and/or need to use nutritional supplements to maintain their weight.

Design:

Participants will undergo the following screening studies to make sure that this study is a good fit for your medical situation, and to make sure it is safe for you to receive the study medications tests, including tests for HIV and hepatitis . This will be done as an inpatient at the NIH Clinical Center and takes about 5-6 days:

  • Participants will be screened with:
  • Medical history
  • Physical exam
  • Blood tests, including tests for HIV and hepatitis.
  • Stool tests, including a timed 48 hour collection for fat malabsorption and a 24 hour collection for protein malabsorption
  • Urine tests, including a pregnancy test for any women with the ability to have a child
  • The purpose of this study is to assess the safety/tolerability and efficacy of using ustekinumab in subjects with common variable immunodeficiency CVID or selective IgG subclass deficiency (functional agammaglobulinemia) who have associated symptomatic gastrointestinal inflammation (CVID enteropathy). Ustekinumab (a Food and Drug Administration [FDA] approved drug) is a monoclonal antibody to interleukin (IL)-12/23p40. CVID is a clinically heterogeneous disorder characterized by decreased serum immunoglobulin IgG and IgA levels. In addition to chronic or recurrent pyogenic sino-pulmonary infections, many patients develop non-infectious gastrointestinal manifestations that can be disabling or fatal. Currently there is no standard therapy for the associated gastrointestinal disease outside of empiric nutritional intervention for weight loss, anti-diarrheal agents, and non-specific anti-inflammatory agents.

    Recently, gut inflammation complicating functional hypogammaglobulinemia due to CVID and selective IgG subclass deficiency has been characterized as a T helper type 1 (Th1) inflammatory response, with excess IL-12 cytokine production associated with diarrhea and weight loss as well as reduced D-xylose absorption and steatorrhea. This protocol aims to test specific anti-IL-12 therapy in this patient group. It has been previously shown that therapy targeted to IL-12 successfully treated the Th1 gut inflammation of Crohn s disease (CD). Ustekinumab, a monoclonal antibody to the p40 subunit of IL-12 and IL-23, is FDA approved for the treatment of moderate to severe plaque psoriasis, active psoriatic arthritis, and more recently, moderately to severely active CD. This protocol is designed to measure the safety of ustekinumab in patients with functional hypogammaglobulinemia and CVID enteropathy, as well as measure effects on symptoms, gut function, expression of immune cell su
    Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

    Current Primary Outcome: The primary endpoint of the study is whether treatment with ustekinumab is safe and tolerated in CVID enteropathy patients and does not cause a significant increase in infection or result in any serious adverse events (SAEs) that are determined... [ Time Frame: From the date of study agent administration through the end of the study at 48 weeks. ]

    Original Primary Outcome: The primary endpoint of the study is whether treatment with ustekinumab is safe and tolerated in the CVID patients and does not cause a significant increase in infection or result in any SAEs that are determined to be definitely, probably or pos... [ Time Frame: From the date of study agent administration through the end of the study at 6 months ]

    Current Secondary Outcome: The secondary endpoint of the study is whether patients respond to the treatment with ustekinumab. Response will be defined as <1% decrease in weight or a decrease in the number of stools at the Week 8, Week 16, Week 24, Week 32 and Week 40 v... [ Time Frame: From the date of study agent administration through the end of the study at 48 weeks. ]

    Original Secondary Outcome: The secondary endpoint of the study is whether patients respond to the treatment with ustekinumab. Response will be defined as less than 1% decrease in weight from baseline or formed stools at the 6 week Endpoint Visit. We will also evaluate the... [ Time Frame: Through the 6 week endpoint ]

    Information By: National Institutes of Health Clinical Center (CC)

    Dates:
    Date Received: July 23, 2014
    Date Started: July 16, 2014
    Date Completion: April 30, 2019
    Last Updated: May 12, 2017
    Last Verified: February 6, 2017