Try the modernized beta website. Learn more about the modernization effort.
Working… Menu

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. Identifier: NCT03366142
Recruitment Status : Recruiting
First Posted : December 8, 2017
Last Update Posted : May 20, 2022
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )

Brief Summary:


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

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Arm Intervention/treatment
Experimental: Single Arm
treatment with ustekinumab based on weight
Drug: Ustekinumab
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).

Primary Outcome Measures :
  1. 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.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   12 Years to 65 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
  • 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:

    1. Intrauterine device or equivalent.
    2. Hormonal contraceptive (eg, consistent, timely, and continuous use of contraceptive pill, patch, ring, implant, or injection) that has reached full efficacy before dosing.
    3. A double barrier method (eg, male/female condom, cap, or diaphragm plus spermicide).
    4. 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.
    5. Have had a hysterectomy and/or a bilateral tubal ligation or both ovaries removed.


  • 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.

Information from the National Library of Medicine

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 identifier (NCT number): NCT03366142

Layout table for location contacts
Contact: Dawn Shaw, R.N. (301) 401-4740
Contact: Beatriz E Marciano, M.D. (301) 443-8332

Layout table for location information
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   
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Layout table for investigator information
Principal Investigator: Beatriz E Marciano, M.D. National Institute of Allergy and Infectious Diseases (NIAID)
Additional Information:
Layout table for additonal information
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID) Identifier: NCT03366142    
Other Study ID Numbers: 180022
First Posted: December 8, 2017    Key Record Dates
Last Update Posted: May 20, 2022
Last Verified: May 13, 2022

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) ):
Autosomal Recessive Disorder
Oral Ulcer
Cytokine Expression
Additional relevant MeSH terms:
Layout table for MeSH terms
Dermatologic Agents