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)
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 8
- 试验地点
- 1
- 主要终点
- Proportion of participants with at least one PGM1-CDG related event
研究概览
简要总结
This is a clinical trial to evaluate the efficacy of AVTX-801 (D-galactose) on the clinical manifestations of PGM1-CDG in participants currently taking D-galactose.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
AVTX-801, then Placebo
Participants receive AVTX-801 1.5g/kg/day (in applesauce) during Treatment Period 1 and then placebo (in applesauce) during Treatment Period 2.
干预措施: Placebo (Drug)
AVTX-801, then Placebo
Participants receive AVTX-801 1.5g/kg/day (in applesauce) during Treatment Period 1 and then placebo (in applesauce) during Treatment Period 2.
干预措施: AVTX-801 (Drug)
Placebo, then AVTX-801
Participants receive placebo (in applesauce) during Treatment Period 1 and then AVTX-801 1.5g/kg/day (in applesauce) during Treatment Period 2.
干预措施: AVTX-801 (Drug)
Placebo, then AVTX-801
Participants receive placebo (in applesauce) during Treatment Period 1 and then AVTX-801 1.5g/kg/day (in applesauce) during Treatment Period 2.
干预措施: Placebo (Drug)
结局指标
主要结局
Proportion of participants with at least one PGM1-CDG related event
时间窗: after each treatment period (treatment periods are 18 weeks)
Proportion of participants in each treatment group who experience at least one PGM1-CDG related event (recurrent or prolonged hypoglycemia, elevation of ALT and/or decrease in ATIII) during each treatment period.
次要结局
未报告次要终点
研究者
Eva Morava-Kozicz
Principal Investigator
Icahn School of Medicine at Mount Sinai