Back to resultsA Study of Distal Jejunal-release Dextrose in Obese Participants
Primary Purpose
Obese
Status
Recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
APHD-012
APHD-012P
Sponsored by
About this trial
This is an interventional treatment trial for Obese focused on measuring Obese, Dextrose, Hypertension, NASH, 034B20, Distal jejunal-release dextrose, Endocrine disorders, Metabolic conditions, NAFLD
Eligibility Criteria
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
Sites / Locations
- Universitätsklinikum Schleswig-HolsteinRecruiting
- Universitätsklinikum Ruppin-BrandenburgRecruiting
- FDI Clinical ResearchRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
APHD-012
APHD-012P
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
Changes from Baseline in Percent Weight Change Compared with Placebo
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)
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)
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
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
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
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
Heart rate measurement will be obtained along with the blood pressure measurement.
Mean Absolute Change and Percent Change of Triglycerides and Cholesterol
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
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
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
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
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)
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
Dose/Exposure - Response Relationships will be evaluated.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05385978
Brief Title
A Study of Distal Jejunal-release Dextrose in Obese Participants
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
Study Type
Interventional
2. Study Status
Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 1, 2022 (Actual)
Primary Completion Date
March 30, 2024 (Anticipated)
Study Completion Date
March 30, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Aphaia Pharma US LLC
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. 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.
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Obese
Keywords
Obese, Dextrose, Hypertension, NASH, 034B20, Distal jejunal-release dextrose, Endocrine disorders, Metabolic conditions, NAFLD
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Parallel Assignment Randomized, double-blind, placebo-controlled, parallel-group proof-of-concept efficacy and safety study
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Allocation
Randomized
Enrollment
150 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
APHD-012
Arm Type
Active Comparator
Arm Description
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.
Arm Title
APHD-012P
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
APHD-012
Other Intervention Name(s)
Distal jejunal-release dextrose beads
Intervention Description
Distal jejunal-release dextrose beads (Aphaia technology, AT)
Intervention Type
Drug
Intervention Name(s)
APHD-012P
Other Intervention Name(s)
Placebo
Intervention Description
Distal jejunal-release placebo beads
Primary Outcome Measure Information:
Title
Changes from Baseline in Percent Weight Change Compared with Placebo
Description
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.
Time Frame
At Baseline and at each visit until Day 180 for Cohort 2 and Day 360 for Cohort 1
Secondary Outcome Measure Information:
Title
Percentage of Participants with ≥2.5% Baseline Body Weight Loss at 6 Months Compared with Placebo (Weight Loss Responders)
Description
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.
Time Frame
At Baseline and at each visit until Day 180 for Cohort 2 and Day 360 for Cohort 1
Title
Percentage of Participants with ≥5% Baseline Body Weight Loss at 6 Months Compared with Placebo (Weight Loss Responders)
Description
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.
Time Frame
At Baseline and at each visit until Day 180 for Cohort 2 and Day 360 for Cohort 1
Title
The Difference in Mean Absolute Weight Loss Compared with Placebo at 6 Months
Description
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.
Time Frame
At Baseline and at each visit until Day 180 for Cohort 2 and Day 360 for Cohort 1
Title
Mean Absolute Change and Percent Change of Waist Circumference
Description
Waist circumference measurements will be done using a standard measuring tape referring to centimeter Scale.
Time Frame
At Baseline and at each visit until Day 180 for Cohort 2 and Day 360 for Cohort 1
Title
Mean Absolute Change and Percent Change of Systolic Blood Pressure and Diastolic Blood Pressure
Description
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.
Time Frame
At Baseline and at each visit until Day 180 for Cohort 2 and Day 360 for Cohort 1
Title
Mean Absolute Change and Percent Change of Heart Rate
Description
Heart rate measurement will be obtained along with the blood pressure measurement.
Time Frame
At Baseline and at each visit until Day 180 for Cohort 2 and Day 360 for Cohort 1
Title
Mean Absolute Change and Percent Change of Triglycerides and Cholesterol
Description
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.
Time Frame
At Baseline and at each visit until Day 180 for Cohort 2 and Day 360 for Cohort 1
Title
Mean Absolute Change and Percent Change of Homeostatic Model Assessment of Insulin Resistance
Description
Homeostasis model assessment-estimated insulin resistance (HOMA-IR) will be determined with standard clinical laboratory methods.
Time Frame
At Baseline and at each visit until Day 180 for Cohort 2 and Day 360 for Cohort 1
Title
Mean Absolute Change and Percent Change of Fasting Plasma Glucose, Fasting Plasma Insulin and Glycated Hemoglobin
Description
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).
Time Frame
At Baseline and at each visit until Day 180 for Cohort 2 and Day 360 for Cohort 1
Title
Mean Absolute Change and Percent Change of Alanine Transaminase, Aspartate Transaminase and Gamma Glutamyl Transpeptidase
Description
Liver enzymes (ALT, AST, GGT) will be measured using standard clinical laboratory methods.
Time Frame
At Baseline and at Day 90, at Day 180 for Cohort 2 and at Day 360 for Cohort 1
Title
Mean Absolute Change and Percent Change of Fatty Liver Controlled Attenuation Parameter Score and Liver Fibrosis Score
Description
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.
Time Frame
At Baseline and at Day 90, at Day 180 for Cohort 2 and at Day 360 for Cohort 1
Title
Number of Participants Reported with At least One Treatment Emergent Adverse Event (TEAE)
Description
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
Time Frame
At each visit until Day 180 for Cohort 2 and until Day 360 for Cohort 1
Title
Advance Understanding of Dose/Exposure - Response Relationships
Description
Dose/Exposure - Response Relationships will be evaluated.
Time Frame
At Baseline, at Day 90, Day 180 and at Day 360 for Cohort 1
Other Pre-specified Outcome Measures:
Title
Glucagon-like Peptide-1 Level Determination
Description
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.
Time Frame
At Baseline, at Day 90, Day 180 and at Day 360 for Cohort 1
Title
Area Under the Plasma Concentration-time Curve from Time 0 to 8 Hours (AUC0-8)
Time Frame
At Baseline, at Day 90, Day 180 and at Day 360 for Cohort 1
Title
Maximum Plasma Concentration (Cmax)
Time Frame
At Baseline, at Day 90, Day 180 and at Day 360 for Cohort 1
Title
Time to Reach the Maximum Plasma Concentration (Tmax)
Time Frame
At Baseline, at Day 90, Day 180 and at Day 360 for Cohort 1
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Kai Deusch, MD
Phone
+41 41 784 96 33
Email
deusch@aphaiapharma.com
First Name & Middle Initial & Last Name or Official Title & Degree
Abbie Liu, MSc
Phone
787-299-6563
Email
liu@aphaiapharma.com
Facility Information:
Facility Name
Universitätsklinikum Schleswig-Holstein
City
Lübeck
ZIP/Postal Code
23538
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Franziska Klingbiel
Email
franziska.klingbiel@uksh.de
Facility Name
Universitätsklinikum Ruppin-Brandenburg
City
Neuruppin
ZIP/Postal Code
16816
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Silke Görgens
Email
s.goergens@ruppiner-kliniken.de
Facility Name
FDI Clinical Research
City
San Juan
Country
Puerto Rico
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Michelle Echeandia
Email
mecheandia@fdipr.com
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Study of Distal Jejunal-release Dextrose in Obese Participants
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