A Study of Distal Jejunal-release Dextrose in Obese Participants

NCT05385978 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: 034B20
• Study Type: interventional
• Target: 150
• Locations: 3 countries
• Sites: 9

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.

Conditions

Obese

Keywords

Obese; Dextrose; Hypertension; NASH; 034B20; Distal jejunal-release dextrose; Endocrine disorders; Metabolic conditions; NAFLD

Outcome Measures

Primary Outcomes (1)

• 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.

  At Baseline and at each visit until Day 180 for Cohort 2 and Day 360 for Cohort 1

Secondary Outcomes (13)

• 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

• 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

• 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 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 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

Other Outcomes (4)

• Glucagon-like Peptide-1 Level Determination

  At Baseline, at Day 90, Day 180 and at Day 360 for Cohort 1

• 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

Study Arms (2)

APHD-012

ACTIVE COMPARATOR

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

APHD-012P

PLACEBO COMPARATOR

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

Interventions

APHD-012 DRUG

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

Also known as: Distal jejunal-release dextrose beads

APHD-012

APHD-012P DRUG

Distal jejunal-release placebo beads

Also known as: Placebo

APHD-012P

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Aphaia Pharma US LLC: lead

Study Sites (9)

LTD "Israeli-Georgian Medical Research Clinic Healthycore"

Tbilisi, 0112, Georgia

Location

LTD "Acad. G. Chapidze Emergency Cardiology Center"

Tbilisi, 0159, Georgia

Location

LTD "Diacor"

Tbilisi, 0159, Georgia

Location

LTD "National Institute of Endocrinology"

Tbilisi, 0159, Georgia

Location

LTD "Tbilisi Heart Center"

Tbilisi, 0186, Georgia

Location

Universitätsklinikum Schleswig-Holstein

Lübeck, 23538, Germany

Location

Universitätsklinikum Ruppin-Brandenburg

Neuruppin, 16816, Germany

Location

GCM Medilcal Group

San Juan, 00917-3104, Puerto Rico

Location

FDI Clinical Research

San Juan, Puerto Rico

Location

MeSH Terms

Conditions

Obesity; Hypertension; Endocrine System Diseases; Non-alcoholic Fatty Liver Disease

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Vascular Diseases; Cardiovascular Diseases; Fatty Liver; Liver Diseases; Digestive System Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

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

Study Record Dates

• First Submitted: May 13, 2022
• First Posted: May 23, 2022
• Study Start: November 1, 2022
• Primary Completion: November 11, 2024
• Study Completion: November 11, 2024
• Last Updated: October 16, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

DE (2); GE (5); PR (2)