A Phase II, Randomized, Double-blind, Placebo-controlled, Parallel-group Proof-of-concept Study to Evaluate Efficacy and Safety of Distal Jejunal-release Dextrose (Aphaia Technology, AT) in Obese Subjects
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 150
- 试验地点
- 9
- 主要终点
- Changes from Baseline in Percent Weight Change Compared with Placebo
研究概览
简要总结
The primary purpose of the study is to evaluate the efficacy and safety of APHD-012 (distal jejunal-release dextrose [Aphaia technology, AT]) in obese participants.
详细描述
This is a randomized, double-blind, placebo-controlled, parallel-group, phase II proof-of-concept study to be conducted in 150 adult obese male and female participants who are 18 to 70 years of age with or without one or more endocrine and/or metabolic conditions. The study aims to evaluate the efficacy and safety of distal jejunal-release dextrose (Aphaia technology, AT) in obese participants.
Participants will be randomly assigned to receive either APHD-012 (distal jejunal-release dextrose or APH-012P (a matching placebo). There will be two cohorts in the study. Participants from Cohort 1 will receive study medication once daily for 12 months (360 days), and participants from Cohort 2 will receive study medication once daily for 6 months (180 days).
Overall, 150 participants will be enrolled in the study:
- Cohort 1 (60 participants) - 6-month treatment period + 6-month maintenance treatment period
- Cohort 2 (90 participants) - 6-month treatment period
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Body mass index 30.0-39.9 kg/m^2 and/or waist circumference: men >102 cm, women >88 cm
- •Stable body weight: gain or loss in body weight ≤5 kg over last 3 months
- •Obese participants with or without one or more of the following conditions:
- •NAFLD - simple steatosis based on a FibroScan CAP™ test result at screening (CAP Score ≥238 decibel-milliwatts (dB/m) (Steatosis Grades 1-3) with no or mild fibrosis (F0-F1 fibrosis Score)
- •NASH - steatohepatitis based on FibroScan fibrosis Score at screening (≥7.5 kPa and <14 kPa (Stage F2-F3)
- •Confirmed medical history of metabolic syndrome
- •Homeostatic Model Assessment of Insulin Resistance (HOMA IR) Score ≥2
- •Confirmed medical history of type 2 diabetes mellitus (T2DM) diagnosis or HbA1c ≥7.0 and <11 (based on screening values)
- •High total cholesterol ≥240 mg/dL (based on screening values)
- •Hypertension (participants with Stage 1 hypertension (systolic blood pressure [SBP] ≥130 mmHg <180 mmHg, diastolic blood pressure [DBP] ≥80 mmHg <110 mmHg) (based on screening values)
- •If on medication to manage endocrine/metabolic conditions, must be on stable doses of medication ≥3 months prior to screening:
- •Participants with T2DM may be treated with either diet and exercise alone, metformin, sulphonylurea, thiazolidinediones, sodium-glucose cotransporter-2 (SGLT-2) inhibitors, and bromocriptine quick-release (QR) as single agents or combination therapy.
- •As lipid-lowering medication participants may be treated with statins and fibrates, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, ezetimibe, or supplements like omega-3-fatty acids.
- •As antihypertensive medication participants may be treated with beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin-II-inhibitors, diuretics, or calcium channel blockers.
- •Normal GI function, or abnormalities which the clinical investigator does not consider a disqualification for participation in the study
排除标准
- •Incomplete Coronavirus Disease of 2019 (COVID-19) vaccination
- •Treatment with weight loss medications in the past 3 months
- •Proven history of bulimia or anorexia nervosa
- •Treatment with injectable antidiabetic medications in the last 3 months (e.g. Glucagon-like peptide-1 [GLP-1] receptor agonists, insulin)
- •Treatment with dipeptidyl peptidase-4 inhibitors in the last 3 months
- •NASH with cirrhosis (fibrosis Score=F4 (≥14 kPa) as determined by screening FibroScan
- •Confirmed medical history of liver cirrhosis, cholestatic disease, alcohol-related liver disease
- •Type 1 diabetes mellitus, HbA1c ≥11, fasting plasma glucose levels ≥270 mg/dL
- •Proliferative retinopathy or maculopathy
- •Abnormal liver function tests:
- •Transaminases:
- •Alanine transaminase (ALT)/aspartate aminotransferase (AST) ≥5 x upper limit of normal (ULN) for participants with NAFLD or NASH (as determined by screening FibroScan)
- •ALT/AST ≥2.5 x ULN for participants without NAFLD or NASH (as determined by screening FibroScan)
- •Alkaline phosphatase (ALK) ≥2.5 x ULN
- •Total bilirubin ≥2 x ULN
- •Stage 4 hypertension (SBP ≥180, DBP ≥110)
- •History or presence of any uncontrolled cardiovascular, pulmonary, hepatobiliary, renal, hematologic, gastrointestinal, endocrinologic, immunologic, dermatologic, neurological, psychiatric, metabolic, musculoskeletal, or malignant disease (except conditions accepted for inclusion) which the clinical investigator does not consider a disqualification for participation in the study
研究组 & 干预措施
APHD-012
Participants will receive a single dose of APHD-012 12 g daily, under fasting conditions prior to main daily meals for 180 days (6 months) for Cohort 2 and for 360 days (12 months) for Cohort 1.
干预措施: APHD-012 (Drug)
APHD-012P
Participants will receive a single dose of APHD-012P daily, under fasting conditions prior to main daily meals for 180 days (6 months) for Cohort 2 and for 360 days (12 months) for Cohort 1.
干预措施: APHD-012P (Drug)
结局指标
主要结局
Changes from Baseline in Percent Weight Change Compared with Placebo
时间窗: At Baseline and at each visit until Day 180 for Cohort 2 and Day 360 for Cohort 1
Bodyweight measurements will be done using standard personal balance referring to kilogram-Scale. Weighing will be done without shoes and with just underwear on. It is important that weighing is always done in the same way, preferably in the morning, before eating or drinking.
次要结局
- Mean Absolute Change and Percent Change of Heart Rate(At Baseline and at each visit until Day 180 for Cohort 2 and Day 360 for Cohort 1)
- Mean Absolute Change and Percent Change of Triglycerides and Cholesterol(At Baseline and at each visit until Day 180 for Cohort 2 and Day 360 for Cohort 1)
- Mean Absolute Change and Percent Change of Fatty Liver Controlled Attenuation Parameter Score and Liver Fibrosis Score(At Baseline and at Day 90, at Day 180 for Cohort 2 and at Day 360 for Cohort 1)
- Percentage of Participants with ≥5% Baseline Body Weight Loss at 6 Months Compared with Placebo (Weight Loss Responders)(At Baseline and at each visit until Day 180 for Cohort 2 and Day 360 for Cohort 1)
- Mean Absolute Change and Percent Change of Systolic Blood Pressure and Diastolic Blood Pressure(At Baseline and at each visit until Day 180 for Cohort 2 and Day 360 for Cohort 1)
- Mean Absolute Change and Percent Change of Fasting Plasma Glucose, Fasting Plasma Insulin and Glycated Hemoglobin(At Baseline and at each visit until Day 180 for Cohort 2 and Day 360 for Cohort 1)
- Percentage of Participants with ≥2.5% Baseline Body Weight Loss at 6 Months Compared with Placebo (Weight Loss Responders)(At Baseline and at each visit until Day 180 for Cohort 2 and Day 360 for Cohort 1)
- The Difference in Mean Absolute Weight Loss Compared with Placebo at 6 Months(At Baseline and at each visit until Day 180 for Cohort 2 and Day 360 for Cohort 1)
- Mean Absolute Change and Percent Change of Alanine Transaminase, Aspartate Transaminase and Gamma Glutamyl Transpeptidase(At Baseline and at Day 90, at Day 180 for Cohort 2 and at Day 360 for Cohort 1)
- Advance Understanding of Dose/Exposure - Response Relationships(At Baseline, at Day 90, Day 180 and at Day 360 for Cohort 1)
- Mean Absolute Change and Percent Change of Waist Circumference(At Baseline and at each visit until Day 180 for Cohort 2 and Day 360 for Cohort 1)
- Mean Absolute Change and Percent Change of Homeostatic Model Assessment of Insulin Resistance(At Baseline and at each visit until Day 180 for Cohort 2 and Day 360 for Cohort 1)
- Number of Participants Reported with At least One Treatment Emergent Adverse Event (TEAE)(At each visit until Day 180 for Cohort 2 and until Day 360 for Cohort 1)