A Phase 1 interventional study of STA-5326 in Common Variable Immunodeficiency, 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 2017-07-02.
Sponsored by National Institute of Allergy and Infectious Diseases (NIAID) · Phase 1, Interventional, and Treatment
This study will determine whether an experimental medicine, STA-5326 mesylate, is safe to use in patients with common variable immunodeficiency (CVID) who have inflammation of the gut. It will also determine if patients who take this drug show improvement in their symptoms, decrease in inflammatory chemicals in the gut, changes in their immune cells, and improvement in how their gut is functioning to absorb food.
Patients between 18 and 75 years of age with CVID and chronic diarrhea or involuntary weight loss of more than 5 percent of their past body weight over the past 12 months may be eligible for this study. Candidates are screened with a review of their medical records, a medical history and physical examination, blood, urine and stool tests, chest x-rays and skin test for exposure to tuberculosis, and a hydrogen breath test. For the latter, breath samples are collected before and every 20 minutes (for 2 hours) after the subject drinks a sugar solution. This test determines the digestive effects of bacteria in the upper intestine. Samples are collected by having the subject blow into a balloon.
Participants undergo the following tests and procedures:
Immune System and Gastrointestinal Evaluation
Treatment Period (Study days 1 to 57)
Follow-up period (Day 85 and day 113)
-Physical examination, blood tests, medication history, questions about pain, discomfort and well being
The purpose of this study is to assess the toxicity of the oral IL-12/23 inhibitor STA-5326 mesylate in subjects with common variable immunodeficiency (CVID) and associated symptomatic gastrointestinal inflammation. Common variable immunodeficiency 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 and non-specific anti-diarrheal agents.
Recently gut inflammation complicating CVID has been characterized as a Th1 inflammatory response, with excess cytokine production associated with diarrhea and weight loss as well as reduced D-xylose absorption and steatorrhea. This protocol represents the first attempt to test specific anti-IL-12 therapy in this patient group; it has been previously shown that therapy targeted to IL-12/23 successfully treated the Th1 gut inflammation of Crohn's disease. While this protocol is designed to measure the safety of STA-5326 mesylate in CVID patients, it will also measure effects on symptoms, gut function, expression of immune cell surface markers and production of cytokines from blood and gut mucosal mononuclear cells.
CVID patients 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 STA-5326 mesylate 100 mg per os (PO) once daily (QD) (equivalent to 70 mg STA-5326 free base) for 8 weeks. Subjects will have pretreatment and end-of-study procedures, including upper and lower endoscopies, to measure changes in immune responses and physiologic measures of gut function, as well as routine safety monitoring throughout the treatment period. 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 Common Variable Immunodeficiency; 13 are open to participants now.
This study's enrollment of 10 is below the median of 40 across 39 interventional studies indexed under Common Variable Immunodeficiency.
Browse Common Variable Immunodeficiency 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.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
A subject is eligible for the study if all of the following criteria are met:
Has given written prior to screening.
Is male or female aged 18 through 75 years.
Has CVID diagnosed definitively prior to screening (based on the IUIS criteria).
Has a documented, unintended loss of greater than 5% of their body weight over the last year or requires nutritional supplements to maintain his/her body weight OR has chronic diarrhea defined as a complaint of liquid stools for at least 4 consecutive weeks (and an output of greater than 200 g stool/24hr on a diet of at least 1600 calories with 60 g fat.)
If taking oral antibiotics chronically, must have used a stable dose of the antibiotic continuously for at least 2 weeks prior to start of screening period.
Not taking any potential inhibitors/inducers (e.g., macrolide antibiotics, protease inhibitors, antifungals, grapefruit juice, St. John's Wort).
EXCLUSION CRITERIA:
A subject is excluded from the study if any of the following criteria are met:
General Criteria:
Has any disease (e.g., renal, hepatic, neurological, cardiovascular, pulmonary, endocrinologic, psychiatric, hematologic, urologic, or other acute or chronic illness) that in the opinion of the investigator would make the subject an unsuitable candidate for this trial.
Is a woman who has a positive serum pregnancy test or who is breast-feeding.
Is a woman of or a man who does not agree to use two forms of during the course of the study and follow-up period.
Has to any of the components of STA 5326 mesylate drug product.
Has any of the following clinical chemistry values:
greater than 2.5 x (ULN).
ALT greater than 2.5 x ULN.
Serum greater than 1.5 x ULN.
Serum creatinine greater than 1.5 x ULN.
Alkaline phosphatase greater than 2.5 x ULN.
Has a level less than 9 g/dL or hematocrit less than 30%.
Has a Prothromin Time greater than 1.3 or a Partial Thromboplastin Time greater than 3 sec compared to control value.
Has the following cell counts (cells/microliter):
count less than 90,000 or greater than 800,000.
White blood cell count less than 1,500.
less than 900.
Has a current infection requiring intravenous antibiotics, a serious local infection (e.g., cellulitis, abscess) or systemic infection (e.g., pneumonia, septicemia).
Has a history of cancer within the past 5 years, with the exception of excised basal cell carcinoma, squamous cell carcinoma of the skin, or cervical carcinoma in situ.
Had a dependency for any illicit drug, chemical, or alcohol within the past 5 years.
Has a history of active tuberculosis (or a CXR with findings suggestive of old TB infection including calcified nodular lesions, apical fibrosis, or pleural scarring), acute or chronic , , or (HIV).
Gastrointestinal Criteria:
Has a stool sample positive for gastrointestinal infection during screening.
Has a positive hydrogen breath test
Prior Medication Criteria:
Received parenteral within 1 month prior to receiving study drug. The use of short-term or single-dose corticosteroids as a pretreatment regimen for IVIG is acceptable.
Received any drug within 3 months prior to receiving study drug.
Received cyclosporine, tacrolimus, sirolimus, or mycophenolate mofetil within 2 months prior to receiving study drug.
Received any biological product (e.g., infliximab, adalimumab, natalizumab, etc.) within 3 months prior to receiving study drug.
Ever received treatment with STA-5326 mesylate, anti-IL 12 antibodies, or other specific IL 12 inhibitors.
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.
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
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.
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.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
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.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
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.
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.
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.
CYP3A (CYP3A4) inhibitors and inducers
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
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.
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.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
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.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
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.
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.
This study is completed, as verified in Jul 2008. You cannot join it, but the record below documents what was studied.
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Common Variable Immunodeficiency →
National Institute of Allergy and Infectious Diseases (NIAID) →