Clinical trial NCT05385978: 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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Obese
Keywords: Obese
Dextrose
Hypertension
NASH
034B20
Distal jejunal-release dextrose
Endocrine disorders
Metabolic conditions
NAFLD
Lead sponsor: Aphaia Pharma US LLC
Sponsor class: INDUSTRY
First posted: 2022-05-23
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parallel Assignment Randomized, double-blind, placebo-controlled, parallel-group proof-of-concept efficacy and safety study
Primary purpose: TREATMENT

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

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:

  1. 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)
  2. NASH - steatohepatitis based on FibroScan fibrosis Score at screening (≥7.5 kPa and \<14 kPa (Stage F2-F3)
  3. Confirmed medical history of metabolic syndrome
  4. Homeostatic Model Assessment of Insulin Resistance (HOMA IR) Score ≥2
  5. Confirmed medical history of type 2 diabetes mellitus (T2DM) diagnosis or HbA1c ≥7.0 and \<11 (based on screening values)
  6. High total cholesterol ≥240 mg/dL (based on screening values)
  7. 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:

  1. 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.
  2. 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.
  3. 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:

  1. 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)
  2. Alkaline phosphatase (ALK) ≥2.5 x ULN
  3. 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

Primary outcomes:
measure: Changes from Baseline in Percent Weight Change Compared with Placebo
timeFrame: At Baseline and at each visit until Day 180 for Cohort 2 and Day 360 for Cohort 1
Secondary outcomes:
measure: Percentage of Participants with ≥2.5% Baseline Body Weight Loss at 6 Months Compared with Placebo (Weight Loss Responders)
timeFrame: At Baseline and at each visit until Day 180 for Cohort 2 and Day 360 for Cohort 1
measure: Percentage of Participants with ≥5% Baseline Body Weight Loss at 6 Months Compared with Placebo (Weight Loss Responders)
timeFrame: At Baseline and at each visit until Day 180 for Cohort 2 and Day 360 for Cohort 1
measure: The Difference in Mean Absolute Weight Loss Compared with Placebo at 6 Months
timeFrame: At Baseline and at each visit until Day 180 for Cohort 2 and Day 360 for Cohort 1
measure: Mean Absolute Change and Percent Change of Waist Circumference
timeFrame: At Baseline and at each visit until Day 180 for Cohort 2 and Day 360 for Cohort 1
measure: Mean Absolute Change and Percent Change of Systolic Blood Pressure and Diastolic Blood Pressure
timeFrame: At Baseline and at each visit until Day 180 for Cohort 2 and Day 360 for Cohort 1
measure: Mean Absolute Change and Percent Change of Heart Rate
timeFrame: At Baseline and at each visit until Day 180 for Cohort 2 and Day 360 for Cohort 1
measure: Mean Absolute Change and Percent Change of Triglycerides and Cholesterol
timeFrame: At Baseline and at each visit until Day 180 for Cohort 2 and Day 360 for Cohort 1
measure: Mean Absolute Change and Percent Change of Homeostatic Model Assessment of Insulin Resistance
timeFrame: At Baseline and at each visit until Day 180 for Cohort 2 and Day 360 for Cohort 1
measure: Mean Absolute Change and Percent Change of Fasting Plasma Glucose, Fasting Plasma Insulin and Glycated Hemoglobin
timeFrame: At Baseline and at each visit until Day 180 for Cohort 2 and Day 360 for Cohort 1
measure: Mean Absolute Change and Percent Change of Alanine Transaminase, Aspartate Transaminase and Gamma Glutamyl Transpeptidase
timeFrame: At Baseline and at Day 90, at Day 180 for Cohort 2 and at Day 360 for Cohort 1
measure: Mean Absolute Change and Percent Change of Fatty Liver Controlled Attenuation Parameter Score and Liver Fibrosis Score
timeFrame: At Baseline and at Day 90, at Day 180 for Cohort 2 and at Day 360 for Cohort 1
measure: Number of Participants Reported with At least One Treatment Emergent Adverse Event (TEAE)
timeFrame: At each visit until Day 180 for Cohort 2 and until Day 360 for Cohort 1
measure: Advance Understanding of Dose/Exposure - Response Relationships
timeFrame: At Baseline, at Day 90, Day 180 and at Day 360 for Cohort 1
Other outcomes:
measure: Glucagon-like Peptide-1 Level Determination
timeFrame: At Baseline, at Day 90, Day 180 and at Day 360 for Cohort 1
measure: Area Under the Plasma Concentration-time Curve from Time 0 to 8 Hours (AUC0-8)
timeFrame: At Baseline, at Day 90, Day 180 and at Day 360 for Cohort 1
measure: Maximum Plasma Concentration (Cmax)
timeFrame: At Baseline, at Day 90, Day 180 and at Day 360 for Cohort 1
measure: Time to Reach the Maximum Plasma Concentration (Tmax)
timeFrame: At Baseline, at Day 90, Day 180 and at Day 360 for Cohort 1
Locations:
city: Tbilisi
country: Georgia
facility: LTD "Israeli-Georgian Medical Research Clinic Healthycore"
city: Tbilisi
country: Georgia
facility: LTD "Acad. G. Chapidze Emergency Cardiology Center"
city: Tbilisi
country: Georgia
facility: LTD "Diacor"
city: Tbilisi
country: Georgia
facility: LTD "National Institute of Endocrinology"
city: Tbilisi
country: Georgia
facility: LTD "Tbilisi Heart Center"
city: Lübeck
country: Germany
facility: Universitätsklinikum Schleswig-Holstein
city: Neuruppin
country: Germany
facility: Universitätsklinikum Ruppin-Brandenburg
city: San Juan
country: Puerto Rico
facility: GCM Medilcal Group
city: San Juan
country: Puerto Rico
facility: FDI Clinical Research
Study officials:
References: