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

NCT03366142 | Completed Phase 1 FDA Drug

• 2 other identifiers: 18002218-I-0022
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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.

Conditions

LAD1

Keywords

Autosomal Recessive Disorder; Immune; Gingival; Oral Ulcer; Cytokine Expression

Outcome Measures

Primary Outcomes (1)

• 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.

  13 months

Study Arms (1)

Single Arm

EXPERIMENTAL

treatment with ustekinumab based on weight

Drug: Ustekinumab

Interventions

Ustekinumab DRUG

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).

Single Arm

Eligibility Criteria

• Age: 12 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Oral Ulcer

Interventions

Ustekinumab

Condition Hierarchy (Ancestors)

Mouth Diseases; Stomatognathic Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Beatriz E Marciano, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 7, 2017
• First Posted: December 8, 2017
• Study Start: July 2, 2018
• Primary Completion: October 16, 2024
• Study Completion: October 17, 2024
• Last Updated: October 22, 2024

Record last verified: 2024-10-18

Data Sharing

• IPD Sharing: Will share
• Shared Documents: SAP
• Time Frame: @@@@@@IPD will become available after completion of the study@@@@@@Since LAD1 is a rare immune deficiency, we may reevaluate when IPD and associated sharing plan will be available as we approach the sample size.
• Access Criteria: Data will be shared through:@@@-BTRIS (automatic for activities in the NIH CC).@@@-Approved outside collaborators under appropriate individual agreements.@@@-Publication and/or public presentations.@@@Data might be shared before publication.@@@The PI and MAI will review and approve requests.

Locations

US (1)