Evaluate Optimal Dosing and Long-term Safety of D-galactose in PGM1-CDG

Study Overview
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Brief Summary
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You have been asked to take part in this research study because you have been diagnosed with PGM1-CDG and are currently taking D-galactose.

Detailed Description
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Upon randomization, subjects will be randomly assigned to either AVTX-801 1.5 g/kg/day (not to exceed 50 g/day) or blinded withdrawal for 16 weeks. Efficacy will be assessed from the Baseline Visit (Day 1) to the End of Double-blind Period Visit (Day 112). Subjects who are D-galactose treatment-naïve may enter the randomized, double blind portion of the study after completing at least 6 weeks of stable doses of AVTX-801 at 1.5 g/kg/day. Dosing with AVTX-801 will begin with 0.25 g/kg/day for at least 14 days. Doses may be increased every 14 days at the following schedule: 0.5 g/kg/day, 1.0 g/kg/day, and 1.5 g/kg/day. Dose escalation will be based on the Investigator's assessment of individual subject tolerability and improvement in the key clinical laboratory parameters (ATIII, creatine kinase [CK], ALT, AST, and fasting blood glucose). Maximum daily dose should not exceed 50 g/kg/day. Once the Investigator has determined a safe, effective, and well tolerated dose, a 6-week run in period will begin with the selected dose. Upon completion of the 6-week run-in period, subject will be randomized and proceed into the study. During the randomized portion of the study, subjects will be closely monitored for clinical signs and symptoms related to or suspected to be related to withdrawal of D galactose therapy; specifically, recurrent or prolonged hypoglycemia, prolonged elevation of ALT, and decreases in ATIII.

Official Title
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A Phase 2b, Multicenter, Randomized, Double-blind, Placebo-Controlled, Crossover, Trial Assessing the Efficacy, Safety, and Tolerability of AVTX-801 in Subjects With Phosphoglucomutase 1 Deficiency Related Congenital Disorders of Glycosylation (PGM1-CDG)

Conditions
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PGM1-CDG - Phosphoglucomutase 1-Related Congenital Disorder of Glycosylation

Intervention / Treatment
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* Drug: AVTX-801


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Subject is aged 18 to 60 years. Subject has biologically and genetically proven PGM1-CDG. Subject is currently on a stable dose of D-galactose therapy. Non-pregnant, non-lactating female subjects of childbearing potential who are heterosexually active and non-sterile male subjects with female sexual partners of childbearing potential agree to use a highly effective method of contraception for the duration of the study, including the long-term safety follow-up period. A highly effective method of birth control is defined as one that results in a low failure rate (i.e., <1% per year) when used consistently and correctly, such as oral/injectable/inserted/implanted/transdermal contraceptives, condom with diaphragm, condom with spermicide, diaphragm with spermicide, intrauterine hormone- releasing system, or intrauterine device (IUD), or sexual abstinence. Contraception is not required where at least 6 weeks have passed since sterilization, defined as females having undergone one of the following surgeries: hysterectomy, bilateral tubal ligation or occlusion, bilateral oophorectomy, or bilateral salpingectomy; and males who are vasectomized. Contraception is not required where females are postmenopausal (defined as 12 consecutive months of spontaneous amenorrhea and age ≥51 years). Subject/legally authorized representative (LAR) is able to understand and provide written informed consent, and assent (as applicable) to participate in this study. Exclusion Criteria Subject has aldolase B deficiency, galactosemia, hemolytic uremic syndrome, or severe anemia. In the site Principal Investigator's opinion, subject has a history of galactose intolerance that precludes the subject from participation in this study. In the site Principal Investigator's opinion, subject has previously experienced any of the following severe AEs from oral galactose: Severe diarrhea Severe, recurrent vomiting Constipation Galactosuria Increased liver glycogen storage. Subject has any of the following: Liver failure ALT level >8x ULN AST level >8x ULN Use of investigational compounds within the previous 6 months or current enrollment in another trial involving investigational compounds. Subject is pregnant. Subject has hepatic impairment that would require a dose adjustment, defined by the site Principal Investigator. In the site Principal Investigator's opinion, subject is not able or willing to comply with the trial requirements.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AVTX-801<br>1.5g/kg/day AVTX-801 | Drug: AVTX-801<br>* D-Galactose medical grade supplement<br>* Other names: D-Galactose;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time (days) to rescue treatment from randomization | Length of time it takes for a patient on withdrawal arm to need rescue medication | 16 weeks |