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

Conditions

• CVID Enteropathy
• Gastrointestinal Inflammation Associated With CVID

Eligibility Criteria

Sex

ALL

Age

18 Years - 75 Years

Healthy Volunteers

Not accepted

Interventions

• Stelara (ustekinumab) — BIOLOGICAL
  * In the single-phase part of the study, subjects receive a single dose of Stelara (ustekinumab) 270 mg subcutaneously on Day 0 study visit. * In the multi-phase part of the study, subjects receive single dose of Stelara (ustekinumab) 270 mg subcutaneously on Day 0 study visit with follow up dose of Stelara (ustekinumab) 90 mg subcutaneously at Week 8, Week 16, Week 24, Week 32 and Week 40

Study Details

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 * Chest CT scan to look for infection * D-xylose testing, which involves drinking a sugary solution and then having a blood sample drawn to test carbohydrate (sugar) malabsorption * Hydrogen breath testing for test for small intestinal bacterial overgrowth (SIBO) this test also involves drinking a sugary solution and then collecting breath samples * Upper endoscopy (EGD) and/or colonoscopy to look at the lining of the GI tract and take biopsies for testing. This will be done under sedation by a qualified gastroenterologist. Participants who complete screening and meet all criteria will then return to the NIH Clinical Center for the following visits: * First Treatment Visit (1 clinic day): Medical history, physical exam, measurement of vital signs and weight, review of medications, and an assessment of number and consistency of stools each day. A pregnancy test for women of childbearing potential. A nurse will give you three shots of 90 mg ustekinumab (270 mg total dose) by very small needles injected under the skin, and then observe you for 1 hour. * Week 8 Treatment Visit (1 clinic day): Medical history, physical exam, measurement of vital signs and weight, review of medications, and an assessment of number and consistency of stools each day. Blood, urine and stool samples will be collected. A pregnancy test for women of childbearing potential. A nurse will give you one 90 mg dose of ustekinumab by a very small needle injected under the skin, and then observe you for 1 hour. * Week 16 Treatment Visit (1 clinic day): Medical history, physical exam, measurement of vital signs and weight, review of medications, and an assessment of number and consistency of stools each day. Blood, urine and stool samples will be collected. A pregnancy test for women of childbearing potential. A nurse will give you one 90 mg dose of ustekinumab by a very small needle injected under the skin, and then observe you for 1 hour. * Week 24 Treatment and Mid-point Evaluation Visit (4-6 inpatient days): Medical history, physical exam, measurement of vital signs and weight, review of medications, and an assessment of number and consistency of stools each day. Blood, urine and stool samples will be collected, including repeating the d-xylose carbohydrate malabsorption testing, the 24 hour stool collection for protein malabsorption and the 48 hour stool collection for fat malabsorption. A pregnancy test for women of childbearing potential. A nurse will give you one 90 mg dose of ustekinumab by a very small needle injected under the skin, and then observe you for 1 hour. * Week 32 Treatment Visit: Medical history, physical exam, measurement of vital signs and weight, review of medications, and an assessment of number and consistency of stools each day. Blood, urine and stool samples will be collected. A pregnancy test for women of childbearing potential. A nurse will give you one 90 mg dose of ustekinumab by a very small needle injected under the skin, and then observe you for 1 hour. * Week 40 Treatment Visit: Medical history, physical exam, measurement of vital signs and weight, review of medications, and an assessment of number and consistency of stools each day. Blood, urine and stool samples will be collected. A pregnancy test for women of childbearing potential. A nurse will give you one 90 mg dose of ustekinumab by a very small needle injected under the skin, and then observe you for 1 hour. * Week 48 ...

Key Dates

Start date

Oct 19, 2015

Status verified

Jul 2020

Primary completion

Aug 16, 2019

Completion

Jul 10, 2020

Study Design

Enrollment

5 participants (actual)

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: Cohort 1: Ustekinumab-Single-dose Phase 1, Multi-dose Phase 2
  Subjects given an induction dose of 270 mg Stelara (ustekinumab) subcutaneously then re-enrolled into the multi-dose phase. In multi-dose phase, subjects given an induction dose of 270 mg Stelara (ustekinumab) subcutaneously followed by every 8 week maintenance doses of 90 mg Stelara (ustekinumab) subcutaneously at week 8, week 16, week 24, week 32, and week 40
• Experimental: Cohort 2: Ustekinumab-Multi-dose Phase 2
  Subjects given an induction dose of 270 mg Stelara (ustekinumab) subcutaneously followed by every 8 week maintenance doses of 90 mg Stelara (ustekinumab) subcutaneously at week 8, week 16, week 24, week 32, and week 40

Primary Outcome Measure

Number of Participants With Increase in Infection or Serious Adverse Events (SAEs) Related to Single Dose Administration of Ustekinumab [ Time Frame: 6 months ]

Locations (1)

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