Ustekinumab (Anti-IL-12/23p40 Monoclonal Antibody) in Patients With Leukocyte Adhesion Deficiency Type 1 (LAD1) Who Have Inflammatory Pathology

  • End date
    Oct 31, 2023
  • participants needed
  • sponsor
    National Institute of Allergy and Infectious Diseases (NIAID)
Updated on 25 January 2021



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.


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.

Condition LAD-1, Leukocyte Adhesion Deficiency Type 1, LAD1
Treatment ustekinumab
Clinical Study IdentifierNCT03366142
SponsorNational Institute of Allergy and Infectious Diseases (NIAID)
Last Modified on25 January 2021


Yes No Not Sure

Inclusion Criteria

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
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

Exclusion Criteria

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
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
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Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

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If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

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