A Phase 1/2 interventional study of Stelara (ustekinumab) in Gastrointestinal Inflammation Associated With CVID and CVID Enteropathy, sponsored by National Institute of Allergy and Infectious Diseases (NIAID). Completed at 1 site in United States. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2020-08-24.
Sponsored by National Institute of Allergy and Infectious Diseases (NIAID) · Phase 1/2, Interventional, and Treatment
Background:
Objective:
Eligibility:
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 who complete screening and meet all criteria will then return to the NIH Clinical Center for the following visits:
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 surface markers, production of cytokines and global gene expression from blood and gut mucosal mononuclear cells, and the gut microbiota.
Patients with CVID and selective IgG subclass deficiency with gastrointestinal symptoms of malabsorption, maldigestion, and chronic diarrhea will be enrolled into this study. Subjects (up to a total of 10 individuals) will receive a treatment dose of 270 mg (3 doses of 90 mg either single-use prefilled syringe or single-use vial, depending on availability) will be injected subcutaneously in subjects by qualified nursing staff on the Day 0 study visit. Subjects will then receive a follow up treatment dose of 90 mg at Week 8, Week 16, Week 24, Week 32 and Week 40 and be followed for a total of 48 weeks.
Subjects will have study procedures prior to treatment and 48 weeks post-treatment, these include upper and/or lower endoscopies, to measure changes in immune responses and studies to evaluate physiologic measures of gut function at 48 weeks, as well as routine safety monitoring throughout the study. Gut absorption tests will be performed at the Week 24 visit. Variables will include safety (adverse event rate), clinical (weight, stool frequency, results of gut absorption tests), and laboratory (lymphocyte and cytokine assays) parameters for descriptive summary statistical analysis (n, mean, median, standard deviation, minimum and maximum range).
54 studies on the registry are indexed under Malabsorption Syndromes; 12 are open to participants now.
This study's enrollment of 5 is below the median of 38 across 44 interventional studies indexed under Malabsorption Syndromes.
Browse Malabsorption Syndromes studies →National Institute of Allergy and Infectious Diseases (NIAID) is the lead sponsor of 2,446 studies on the registry; 179 are open to participants now.
Of its 405 completed or terminated interventional studies of FDA-regulated products, 302 (75%) have results posted.
Counted across the registry records on this site, refreshed daily.
A subject is eligible for the study if all of the following criteria are met:
avoidance measures. Patient handout on pregnancy avoidance will be provided to patients at the time of consent and discussion regarding pregnancy avoidance during the study.
-Subjects who have previously been treated with a single 270 mg dose of ustekinumab on this study must be greater than 6 months from their treatment dose and have had recurrence of enteropathy symptoms.
CRITERIA FOR EXCLUSION:
A subject is excluded from the study if any of the following criteria are met:
GENERAL CRITERIA:
Has any of the following clinical chemistry values:
Has the following cell counts (cells/microL):
GASTROINTESTINAL CRITERIA
-Has a stool sample determined positive for acute gastrointestinal infection with impact of occurrence on gastrointestinal inflammation as determined by principal investigator during screening. In addition, stool samples positive for GI pathogens will be discussed with an infectious disease physician to determine impact of occurrence on gastrointestinal inflammation. If organism thought to be pathogenic, the subject will be treated with appropriate therapy. This will be documented in the subject s medical record.
PRIOR MEDICATION CRITERIA
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.
Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
INR, PT and aPTT (clotting tests)
Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.
Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Absolute neutrophil count (ANC)
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis C tests
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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
Biological: Stelara (ustekinumab)
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
Biological: Stelara (ustekinumab)
* 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
Number of Participants With Increase in Infection or Serious Adverse Events (SAEs) Related to Single Dose Administration of Ustekinumab
Whether treatment with ustekinumab is safe and tolerated in patients with common variable immunodeficiency (CVID) enteropathy as determined by no significant increase in infection or serious adverse events
Time frame: 6 months
Number of Participants With Increase in Infection or Serious Adverse Events (SAEs) Related to Multi-dose Administration of Ustekinumab (Cohort 1)
Whether treatment with ustekinumab is safe and tolerated in patients with common variable immunodeficiency (CVID) enteropathy as determined by no significant increase in infection or serious adverse events
Time frame: 48 weeks
Number of Participants With Increase in Infection or Serious Adverse Events (SAEs) Related to Multi-dose Administration of Ustekinumab (Cohort 2)
Whether treatment with ustekinumab is safe and tolerated in patients with common variable immunodeficiency (CVID) enteropathy as determined by no significant increase in infection or serious adverse events
Time frame: 48 weeks
| Milestone | Cohort 1: Single-dose Phase 1, Multi-dose Phase 2 | Cohort 2: Multi-Dose Ustekinumab Phase 2 |
|---|---|---|
| Started | 3 | 0 |
| Completed | 3 | 0 |
| Not completed | 0 | 0 |
| Milestone | Cohort 1: Single-dose Phase 1, Multi-dose Phase 2 | Cohort 2: Multi-Dose Ustekinumab Phase 2 |
|---|---|---|
| Started | 3 | 2 |
| Completed | 3 | 2 |
| Not completed | 0 | 0 |
Whether treatment with ustekinumab is safe and tolerated in patients with common variable immunodeficiency (CVID) enteropathy as determined by no significant increase in infection or serious adverse events
| participants | Cohort 1: Ustekinumab-Single Dose Phase 1 |
|---|---|
| Number of Participants With Increase in Infection or Serious Adverse Events (SAEs) Related to Single Dose Administration of Ustekinumab | 0 |
Whether treatment with ustekinumab is safe and tolerated in patients with common variable immunodeficiency (CVID) enteropathy as determined by no significant increase in infection or serious adverse events
| participants | Cohort 1: Ustekinumab-Multi-dose Phase 2 |
|---|---|
| Number of Participants With Increase in Infection or Serious Adverse Events (SAEs) Related to Multi-dose Administration of Ustekinumab (Cohort 1) | 0 |
Whether treatment with ustekinumab is safe and tolerated in patients with common variable immunodeficiency (CVID) enteropathy as determined by no significant increase in infection or serious adverse events
| participants | Cohort 2: Ustekinumab-Multi-dose Phase 2 |
|---|---|
| Number of Participants With Increase in Infection or Serious Adverse Events (SAEs) Related to Multi-dose Administration of Ustekinumab (Cohort 2) | 0 |
Collected over 6 months for Phase 1 and 48 Weeks for Phase 2. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Cohort 1: Ustekinumab-Single Dose Phase 1 | 0/3 (0%) | 0/3 (0%) | 3/3 (100%) |
| Cohort 1: Ustekinumab-Multi-dose Phase 2 | 0/3 (0%) | 1/3 (33.3%) | 3/3 (100%) |
| Cohort 2: Ustekinumab-Multi-dose Phase 2 | 0/2 (0%) | 2/2 (100%) | 2/2 (100%) |
| Event | Cohort 1: Ustekinumab-Single Dose Phase 1 | Cohort 1: Ustekinumab-Multi-dose Phase 2 | Cohort 2: Ustekinumab-Multi-dose Phase 2 |
|---|---|---|---|
| GastritisGastrointestinal disorders | 0/3 | 0/3 | 1/2 |
| Respiratory syncytial virus infectionInfections and infestations | 0/3 | 0/3 | 1/2 |
| Neuropathy peripheralNervous system disorders | 0/3 | 1/3 | 0/2 |
| Event | Cohort 1: Ustekinumab-Single Dose Phase 1 | Cohort 1: Ustekinumab-Multi-dose Phase 2 | Cohort 2: Ustekinumab-Multi-dose Phase 2 |
|---|---|---|---|
| DiarrhoeaGastrointestinal disorders | 0/3 | 3/3 | 2/2 |
| TendernessGeneral disorders | 0/3 | 0/3 | 2/2 |
| Gastroenteritis Escherichia coliInfections and infestations | 0/3 | 3/3 | 0/2 |
| Blood glucose increasedInvestigations | 0/3 | 0/3 | 2/2 |
| White blood cell count decreasedInvestigations | 2/3 | 3/3 | 0/2 |
| HypoproteinaemiaMetabolism and nutrition disorders | 1/3 | 3/3 | 0/2 |
| AnaemiaBlood and lymphatic system disorders | 0/3 | 2/3 | 1/2 |
| Abdominal distensionGastrointestinal disorders | 0/3 | 2/3 | 1/2 |
| Abdominal painGastrointestinal disorders | 0/3 | 2/3 | 0/2 |
| FatigueGeneral disorders | 1/3 | 2/3 | 0/2 |
| Age, Categorical(Participants) | Cohort 1: Ustekinumab-Single-dose Phase 1, Multi-dose Phase 2 | Cohort 2: Ustekinumab-Multi-dose Phase 2 | Total |
|---|---|---|---|
| <=18 years | 0 | 0 | 0 |
| Between 18 and 65 years | 3 | 2 | 5 |
| >=65 years | 0 | 0 | 0 |
| Sex: Female, Male(Participants) | Cohort 1: Ustekinumab-Single-dose Phase 1, Multi-dose Phase 2 | Cohort 2: Ustekinumab-Multi-dose Phase 2 | Total |
|---|---|---|---|
| Female | 1 | 0 | 1 |
| Male | 2 | 2 | 4 |
| Ethnicity (NIH/OMB)(Participants) | Cohort 1: Ustekinumab-Single-dose Phase 1, Multi-dose Phase 2 | Cohort 2: Ustekinumab-Multi-dose Phase 2 | Total |
|---|---|---|---|
| Hispanic or Latino | 0 | 0 | 0 |
| Not Hispanic or Latino | 3 | 2 | 5 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | Cohort 1: Ustekinumab-Single-dose Phase 1, Multi-dose Phase 2 | Cohort 2: Ustekinumab-Multi-dose Phase 2 | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 0 | 0 | 0 |
| White | 3 | 2 | 5 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 |
PDFs hosted by the registry, ClinicalTrials.gov.
Ran from Oct 2015 to primary completion in Aug 2019, 45 months.
Results were first posted in Aug 2020, 1 year after primary completion.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Jul 2020. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Ustekinumab
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