Evaluating the Efficacy and Safety of D-galactose in PGM1-CDG (AVTX-801)

Participants who sign consent will be screened for enrollment, and if they meet all eligibility criteria, they will enter a 4-week Run-In period. During the Run-In period, participants will continue to take D-galactose therapy, and will be monitored for hypoglycemic events, to establish a baseline rate. Following completion of the Run-In period participants will complete Baseline Day 1 procedures for treatment period 1 and be randomized in a 1:1 fashion to one of two treatment sequences: 1) AVTX-801 (plus applesauce) 1.5 g/kg/day (not to exceed 50 g/day) (treatment period 1) followed by placebo (plus applesauce ) (treatment period 2) or 2) Placebo (plus applesauce) (treatment period 1) followed by AVTX-801 (plus applesauce) 1.5 g/kg/day (not to exceed 50 g/day) (treatment period 2).

Each treatment period will end upon completion of 18 weeks of treatment or upon occurrence of a PGM1-CDG related event. There will be an open label recovery period of 18 weeks separating the two treatment periods, during which time the subject will receive commercially available D-galactose.

During the double-blind period of the study, participants 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, elevation of ALT and decreases in ATIII.

Upon completion of the double-blind portion of the study (i.e., either completion of both 18-week double-blind periods or occurrence of a PGM1-CDG related event during treatment period 2), participants will be permitted to enter a long-term, open-label, safety follow-up period of 12 months with AVTX-801.

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.