Ignite Creation Date:
2024-05-06 @ 10:51 AM
Last Modification Date:
2024-10-26 @ 12:36 PM
Study NCT ID:
NCT03366142
Status:
COMPLETED
Last Update Posted:
2024-05-24
First Post:
2017-12-07
Brief Title:
Ustekinumab Anti-IL-1223p40 Monoclonal Antibody in Patients With Leukocyte Adhesion Deficiency Type 1 LAD1 Who Have Inflammatory Pathology
Sponsor:
National Institute of Allergy and Infectious Diseases NIAID
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Use of Ustekinumab Anti-IL-1223p40 Monoclonal Antibody in Patients With Leukocyte Adhesion Deficiency Type 1 LAD1 Who Have Inflammatory Pathology
Status:
COMPLETED
Status Verified Date:
2024-10-18
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Background
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
Objective
To study the safety and tolerability of ustekinumab in treating gum inflammation in people with LAD1
Eligibility
People ages 12 65 with LAD1
Design
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
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
Objective
To study the safety and tolerability of ustekinumab in treating gum inflammation in people with LAD1
Eligibility
People ages 12 65 with LAD1
Design
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
Detailed Description:
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
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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 18-I-0022 | None | None | None |