A Study of Distal Jejunal-release Dextrose in Obese Participants

Sponsor

Aphaia Pharma US LLC (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05385978

Collaborator

(none)

150

Enrollment

Arms

12.9

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Obese	Drug: APHD-012 Drug: APHD-012P	Phase 2

Detailed Description

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

Study Design

Study Type:

Interventional

Anticipated Enrollment :

150 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Parallel Assignment Randomized, double-blind, placebo-controlled, parallel-group proof-of-concept efficacy and safety studyParallel Assignment Randomized, double-blind, placebo-controlled, parallel-group proof-of-concept efficacy and safety study

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Jul 1, 2022

Anticipated Primary Completion Date :

Jul 30, 2023

Anticipated Study Completion Date :

Jul 30, 2023

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 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.	Drug: APHD-012 Distal jejunal-release dextrose beads (Aphaia technology, AT) Other Names: Distal jejunal-release dextrose beads
Placebo Comparator: 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.	Drug: APHD-012P Distal jejunal-release placebo beads Other Names: Placebo

Arm

Intervention/Treatment

Active Comparator: 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.

Drug: APHD-012

Distal jejunal-release dextrose beads (Aphaia technology, AT)

Other Names:

Distal jejunal-release dextrose beads

Placebo Comparator: 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.

Drug: APHD-012P

Distal jejunal-release placebo beads

Other Names:

Placebo

Outcome Measures

Primary Outcome Measures

Changes from Baseline in Percent Weight Change Compared with Placebo [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.

Secondary Outcome Measures

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]
Body weight 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.
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]
Body weight 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.
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]
Body weight 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.
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]
Waist circumference measurements will be done using a standard measuring tape referring to centimeter Scale.
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]
Systolic blood pressure (SBP) and diastolic blood pressure (DBP) will be measured using a standard sphygmomanometer with the Riva-Rocci cuff and a stethoscope; alternatively, an automatic device with upper arm cuff can be used. Measurements are done in sitting position after 5 minutes of rest.
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]
Heart rate measurement will be obtained along with the blood pressure measurement.
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]
Triglycerides and cholesterol (including total cholesterol, low-density lipoprotein [LDL], and high-density lipoprotein [HDL]) will be measured using standard clinical laboratory methods at the site laboratories.
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]
Homeostasis model assessment-estimated insulin resistance (HOMA-IR) will be determined with standard clinical laboratory methods.
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]
Fasting plasma glucose will be determined using a standard blood glucometer. Fasting plasma insulin will be determined with standard clinical laboratory methods. Glycated hemoglobin (HbA1c) will be measured using a standard enzyme-linked immunoassay (ELISA) method. HbA1c will be measured in participants with type two diabetes (T2DM).
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]
Liver enzymes (ALT, AST, GGT) will be measured using standard clinical laboratory methods.
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]
Fatty liver Controlled Attenuation Parameter (CAP) Score will be measured in: Participants with Non-alcoholic fatty liver disease (NAFLD): Steatosis grade and; Participants with Non-alcoholic steatohepatitis (NASH): fibrosis Score category Fatty liver CAP Score and liver fibrosis Score will be measured using FibroScan™ equipment or equivalent.
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]
A treatment-emergent adverse event is defined as any event not present prior to the initiation of the drug treatment or any event already present that worsens in either intensity or frequency following exposure to the drug treatment
Advance Understanding of Dose/Exposure - Response Relationships [At Baseline, at Day 90, Day 180 and at Day 360 for Cohort 1]
Dose/Exposure - Response Relationships will be evaluated.

Other Outcome Measures

Glucagon-like Peptide-1 Level Determination [At Baseline, at Day 90, Day 180 and at Day 360 for Cohort 1]
Blood samples of 2 mL will be taken at pre-dose (-0.5 h [within 5 minutes]) and 1.0, 2.0, 3.0, 4.0, 5.0, 6.0 and 8.0 hours after investigational medicinal product administration. The blood samples for the determination of Glucagon-like peptide-1 (GLP-1) and circulating biomarkers and micro Ribonucleic acid (miRNA)1983 will be collected in BD P800 tubes.
Area Under the Plasma Concentration-time Curve from Time 0 to 8 Hours (AUC0-8) [At Baseline, at Day 90, Day 180 and at Day 360 for Cohort 1]
Maximum Plasma Concentration (Cmax) [At Baseline, at Day 90, Day 180 and at Day 360 for Cohort 1]
Time to Reach the Maximum Plasma Concentration (Tmax) [At Baseline, at Day 90, Day 180 and at Day 360 for Cohort 1]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Exclusion Criteria:

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