A Study to Evaluate Efficacy and Safety of AVTX-803 in Patients With Leukocyte Adhesion Deficiency Type II

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate the efficacy and safety of AVTX-803 compared to withdrawal in patients with Leukocyte Adhesion Deficiency, Type II (LAD II).

Official Title
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A Phase 3, Randomized, Double-blind, Two-period, Crossover, Withdrawal Study to Assess the Efficacy and Safety of AVTX-803 in Subjects With Leukocyte Adhesion Deficiency Type II (LAD II)

Conditions
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Leukocyte Adhesion Deficiency

Intervention / Treatment
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* Drug: AVTX-803 (L-Fucose)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject must be between 6 months and 75 years old Subject has biochemically and genetically proven LAD II (SLC35C1-CDG) Subject has a documented history of Lewis antigen deficiency Subject has a history of recurrent infections, opportunistic infections or infections that did not respond well to standard of care treatment Subject or parent (for subjects under legal age for consent) has provided written informed consent for this study. Additionally, written informed assent has been provided, as appropriate, for minors of older age, per local institutional review board (IRB)/ethics committee (EC) policy and requirements Subject is willing and able to comply with the protocol Women of childbearing potential (WOCBP) meeting the criteria below: Non-lactating and has a negative pregnancy test at screening -AND- Uses an acceptable double-barrier method of contraception as determined by the investigator or sub-investigator for the duration of the study and 30 days following the last dose of study drug. Male subjects must agree to use an acceptable double-barrier method of contraception with their partner as determined by the investigator or sub-investigator for the duration of the study and 30 days following the last dose of study drug. Exclusion Criteria: Subject has severe anemia defined as hemoglobin <8.0 g/dL (<4.9 mmol/L) Subject has impaired renal function as defined by an eGFR <90 mL/min Subject has a total absence of fucosylation on red blood cells and the presence of anti-H antigen Subject has known or suspected intolerance or hypersensitivity to fucose or any ingredients of the investigational product In the investigator's opinion, subject has a history of failure to respond to fucose at adequate dosing In the investigator's opinion, subject is not able or not willing to comply with the study requirements. Subject is pregnant

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AVTX-803<br>Approximately 4 subjects will receive AVTX-803 at a dose specified by the investigator up to 5 times a day not to exceed 1700 mg/kg/day for 8 weeks. | Drug: AVTX-803 (L-Fucose)<br>* L-fucose crystalline powder<br>|
| No Intervention: Withdrawal<br>Subject will be in withdrawal for 8 weeks. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of AVTX-803 on the percent of leukocytes expressing Sialyl-Lewis X antigen | To assess the effect of AVTX-803 in subjects with leukocyte adhesion deficiency Type II (LAD II) by evaluating Sialyl-Lewis X on leukocytes as a percentage present at the end of each 8 week treatment period. | Change from Baseline at Day 56, Change from Baseline at Day 112 |