Ustekinumab (Anti-IL-12/23p40 Monoclonal Antibody) in Patients With Leukocyte Adhesion Deficiency Type 1 (LAD1) Who Have Inflammatory Pathology
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03366142|
Recruitment Status : Recruiting
First Posted : December 8, 2017
Last Update Posted : October 8, 2020
The disease leukocyte adhesion deficiency type 1 (LAD1) affects white blood cells. Those are immune system cells. In people with LAD1, white blood cells do not properly communicate with the rest of the body. This causes uncontrolled inflammation, particularly in the gums. People with LAD1 can get frequent infections and tend to lose their teeth before adulthood. Researchers want to see if a drug called ustekinumab helps people with LAD1.
To study the safety and tolerability of ustekinumab in treating gum inflammation in people with LAD1.
People ages 12 65 with LAD1
Participants will be screened with:
- Medical history
- Physical exam
- Oral exam
- A scan of the chest, abdomen, and pelvis for possible infection
- Blood and urine tests
The baseline visit will take 2 days. Participants will:
- Repeat most screening tests
- Have a skin exam
- Have small pieces of their gums removed (biopsy)
- Have mouth fluids collected
- Get the study drug injected under the skin of the abdomen, thigh, or elsewhere on the body. They will be watched for at least 2 hours.
Participants will be instructed on tracking how they are feeling and any side effects.
Participants will have 4 more visits over 40 weeks. They will get the study drug and repeat the baseline tests.
Participants may have up to 5 more tissue biopsies.
Participants will be called between visits to discuss how they are feeling and side effects.
Participants will have a final visit 52 weeks after the baseline. They will repeat most of the baseline tests.
Participants will answer questions about their oral ulcers.
|Condition or disease||Intervention/treatment||Phase|
|LAD1||Drug: Ustekinumab||Phase 1 Phase 2|
Lymphocyte adhesion deficiency type 1 (LAD1) is an autosomal recessive disorder of leukocyte function. Decreased expression of the <=2 subunit of leukocyte integrins results in abnormal cell-cell and cell extracellular matrix adhesion. This disease is characterized by recurrent bacterial infections, impaired wound formation, and other aberrations of adhesion-dependent functions. The severe phenotype can be fatal, but patients with even moderate phenotypes are prone to infection and lose their teeth despite treatment.
Ustekinumab is a monoclonal antibody directed against the p40 subunit of human interleukins IL-12 and IL-23. It is approved for treatment of moderate-to-severe plaque psoriasis, active psoriatic arthritis, and moderate-to-severe Crohn s disease. By binding the shared p40 subunit of IL-12 and IL-23, ustekinumab exerts clinical effects through interruption of the TH1 and TH17 cytokine pathways. Previous work at the NIH suggests that blockade of IL-17, which is highly expressed in the gingiva of people with LAD1, can reduce bacterial load and resolve inflammatory gingival disease. We have treated one patient with ustekinumab for 1 year; during this time, he had no serious infections and there was a dramatic resolution of his inflammatory lesions. Our goal is to explore the potential of ustekinumab as treatment for LAD1 inflammatory disease.
The objective of this open-label, proof-of-concept study is to evaluate the safety and tolerability of ustekinumab in 10 patients with LAD1. Participants will receive 5 doses of ustekinumab via subcutaneous injection over the course of 1 year. They will be evaluated for adverse events, as well as the effect of the drug on inflammatory lesions and biomarker expression.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Use of Ustekinumab (Anti-IL-12/23p40 Monoclonal Antibody) in Patients With Leukocyte Adhesion Deficiency Type 1 (LAD1) Who Have Inflammatory Pathology|
|Actual Study Start Date :||July 2, 2018|
|Estimated Primary Completion Date :||October 31, 2023|
|Estimated Study Completion Date :||October 31, 2023|
Experimental: Single Arm
treatment with ustekinumab based on weight
0.75 mg/kg or 45 or 90 mg via subcutaneous injection for 5 doses (second dose 4 weeks after first, subsequent doses every 12 weeks thereafter).
- Evaluate the safety and tolerability of ustekinumab in treating LAD1 affected patients who have inflammation, such as gingival, skin or gut. [ Time Frame: 13 months ]alteration of local gingival cytokine expression and peripheral blood cytokine expression, assessment of oral inflammation via gingival bleeding on probing measurements and changes to oral ulcer, lesions or gastro-intestinal inflammation.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03366142
|Contact: Dawn Shaw, R.N.||(301) firstname.lastname@example.org|
|United States, Maryland|
|National Institutes of Health Clinical Center||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR) 800-411-1222 ext TTY8664111010 email@example.com|
|Principal Investigator:||Beatriz E Marciano, M.D.||National Institute of Allergy and Infectious Diseases (NIAID)|