LAD1Phase 1/2NCT03366142
Ustekinumab (Anti-IL-12/23p40 Monoclonal Antibody) in Patients With Leukocyte Adhesion Deficiency Type 1 (LAD1) Who Have Inflammatory Pathology
A Phase 1/2 study testing Ustekinumab in people with LAD1, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 12 to 65 years
- Conditions the study is for
- LAD1
- What is being tested?
- Ustekinumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Jul 2018to 17 Oct 2024
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Age 12-65 years.
- Molecularly and cellularly confirmed LAD1 with inflammatory lesions.
- Willing to allow storage of biological samples for future research.
- Willing to allow genetic testing of blood samples.
- Able to provide informed consent.
- Participants who can get pregnant or impregnate a partner must agree to use adequate contraception when engaging in sexual activities that can result in pregnancy. Adequate contraception must be used consistently starting at screening and lasting through the final study visit. Appropriate forms of contraception include the following:
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- Intrauterine device or equivalent.
- Hormonal contraceptive (eg, consistent, timely, and continuous use of contraceptive pill, patch, ring, implant, or injection) that has reached full efficacy before dosing.
- A double barrier method (eg, male/female condom, cap, or diaphragm plus spermicide).
- Be in a stable, long-term monogamous relationship, per assessment of the principal investigator (PI), with a partner who does not pose any potential pregnancy risk, eg, has undergone a vasectomy at least 6 months before the first dose of study agent or is of the same sex as the participant.
- Have had a hysterectomy and/or a bilateral tubal ligation or both ovaries removed.
Who cannot join
- History of malignancy (except for basal cell carcinoma) within the previous 5 years.
- Infected with HIV.
- Active uncontrolled bacterial, viral, or fungal infection.
- Active or chronic viral hepatitis.
- Active or latent untreated tuberculosis.
- Received Bacillus Calmette-Guerin vaccine within the last year.
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- Received live attenuated vaccines within 15 weeks before the first dose.
- Allergy to any component of the ustekinumab formulation.
- Pregnant or breastfeeding.
- Any condition that, in the opinion of the investigator, contraindicates participation in this study.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: Use of Ustekinumab (Anti-IL-12/23p40 Monoclonal Antibody) in Patients With Leukocyte Adhesion Deficiency Type 1 (LAD1) Who Have Inflammatory Pathology
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.
Read more
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.
Read the 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.
- Conditions
- LAD1
- Being tested
- Ustekinumab
- Keywords
- Autosomal Recessive Disorder, Immune, Gingival, Oral Ulcer, Cytokine Expression
- Medical subject headings
- Oral Ulcer
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
UstekinumabDrug
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).
| Study group | Role | What they receive |
|---|---|---|
| Single Arm | Experimental | treatment with ustekinumab based on weight Receives: Drug: Ustekinumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluate the safety and tolerability of ustekinumab in treating LAD1 affected patients who have inflammation, such as gingival, skin or gut.
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.
Measured: 13 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Dec 2017
- Study start2 Jul 2018
- Primary completion16 Oct 2024
- Study completion17 Oct 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for LAD1Studies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Beatriz E Marciano, M.D., Principal investigator, National Institute of Allergy and Infectious Diseases (NIAID)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03366142
- Sponsor's protocol ID
- 180022
- Other IDs
- 18-I-0022
- Status last verified
- 18 Oct 2024
- First submitted
- 7 Dec 2017
- Last updated
- 22 Oct 2024
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: We will share human data generated in this study for future research as follows:@@@-Identified data in the Biomedical Translational Research Information System (BTRIS, automatic for activities in the NIH CC).@@@-De-identified or identified data with approved outside collaborators under appropriate agreements.@@@-Data sharing may be complicated or limited in certain cases by contractual obligations or agreements with outside collaborators, such as cooperative research and development agreements, clinical trial agreements, other restraints, etc.
Study at a glance
From the registry record, last updated by the sponsor on 22 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Use of Ustekinumab (Anti-IL-12/23p40 Monoclonal Antibody) in Patients With Leukocyte Adhesion Deficiency Type 1 (LAD1) Who Have Inflammatory Pathology
- ClinicalTrials.gov ID
- NCT03366142
- Acronym / sponsor ID
- 180022
- Conditions
- LAD1
- Keywords
- Autosomal Recessive Disorder, Immune, Gingival, Oral Ulcer, Cytokine Expression
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 2 Jul 2018 (actual)
- Primary completion
- 16 Oct 2024 (actual)
- Study completion
- 17 Oct 2024 (actual)
- First posted
- 8 Dec 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single Arm | Experimental | Drug: Ustekinumabtreatment with ustekinumab based on weight |
Who may qualify
- Ages
- 12 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (11 listed)
- Age 12-65 years.
- Molecularly and cellularly confirmed LAD1 with inflammatory lesions.
- Willing to allow storage of biological samples for future research.
- Willing to allow genetic testing of blood samples.
- Able to provide informed consent.
Key exclusion criteria (10 listed)
- History of malignancy (except for basal cell carcinoma) within the previous 5 years.
- Infected with HIV.
- Active uncontrolled bacterial, viral, or fungal infection.
- Active or chronic viral hepatitis.
- Active or latent untreated tuberculosis.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ustekinumab0.75 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). | Drug | Single Arm |
Primary outcome
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Oct 2024.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. We will share human data generated in this study for future research as follows:@@@-Identified data in the Biomedical Translational Research Information System (BTRIS, automatic for activities in the NIH CC).@@@-De-identified or identified data with approved outside collaborators under appropriate agreements.@@@-Data sharing may be complicated or limited in certain cases by contractual obligations or agreements with outside collaborators, such as cooperative research and development agreements, clinical trial agreements, other restraints, etc.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Beatriz E Marciano, M.D. principal investigator
National Institute of Allergy and Infectious Diseases (NIAID)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Ustekinumab in people with LAD1, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Oct 2024.