Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of (PEG)-BHD1028

NCT06563115 | Completed Phase 1 FDA Drug

• 1 other identifier: ECN1028-101
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief Summary

Adiponectin has been known to play critical roles in various physio-regulatory processes, and adiponectin deficiency may contribute to insulin resistance. (PEG)-BHD1028 was developed as an agonist of adiponectin receptors. This first-in-human study evaluates the safety, tolerability, pharmacokinetics, and pharmacodynamics of (PEG)-BHD1028 in healthy overweight/obese subjects with insulin resistance.

Conditions

Insulin Resistance

Outcome Measures

Primary Outcomes (2)

• Safety and tolerability of (PEG)-BHD1028 -Single ascending dose as measured by TEAEs

  Treatment emergent adverse events (including clinical AEs and Lab AEs) after a single dose of (PEG)-BHD1028 (including clinical AEs and Lab AEs) of (PEG)-BHD1028

  Baseline to Day 3

• Safety and tolerability of (PEG)-BHD1028 -Multiple ascending dose as measured by TEAEs

  Treatment emergent adverse events (including clinical AEs and Lab AEs) after multiple doses of (PEG)-BHD1028

  Baseline to Day 29

Secondary Outcomes (19)

• Pharmacokinetics of (PEG)-BHD1028 after a single dose, Cmax

  pre-dose, and at 30 min, 1 hr, 2 hr, 4 hr, 8 hr, 12 hr, and 24 hr after the single dose

• Pharmacokinetics of (PEG)-BHD1028 after a single dose, Tmax

  pre-dose, and at 30 min, 1 hr, 2 hr, 4 hr, 8 hr, 12 hr, and 24 hr after the single dose

• Pharmacokinetics of (PEG)-BHD1028 after a single dose, t1/2

  pre-dose, and at 30 min, 1 hr, 2 hr, 4 hr, 8 hr, 12 hr, and 24 hr after the single dose

• Pharmacokinetics of (PEG)-BHD1028 after a single dose, AUClast

  pre-dose, and at 30 min, 1 hr, 2 hr, 4 hr, 8 hr, 12 hr, and 24 hr after the single dose

• Pharmacokinetics of (PEG)-BHD1028 after a single dose, AUCinf

  pre-dose, and at 30 min, 1 hr, 2 hr, 4 hr, 8 hr, 12 hr, and 24 hr after the single dose

Study Arms (4)

Placebo_Single Ascending Dose

PLACEBO COMPARATOR

Participants received a single SC dose of placebo on Day 1

Other: Placebo

Experimental (PEG)-BHD1028_Single Ascending Dose

EXPERIMENTAL

Participants received a single escalated SC dose of (PEG)-BHD1028 on Day 1

Drug: (PEG)-BHD1028 Single Ascending Dose

Placebo_Multiple Ascending Dose

PLACEBO COMPARATOR

Participants received SC doses of placebo once a day for 28 days

Other: Placebo

Experimental (PEG)-BHD1028_Multiple Ascending Dose

EXPERIMENTAL

Participants received SC doses of (PEG)-BHD1028 once a day for 28 days

Drug: (PEG)-BHD1028 Multiple Ascending Dose

Interventions

(PEG)-BHD1028 Single Ascending Dose DRUG

4, 8, 16, 32, and 64 μg/Kg

Also known as: adiponectin receptor agonist

Experimental (PEG)-BHD1028_Single Ascending Dose

(PEG)-BHD1028 Multiple Ascending Dose DRUG

8, 16, and 32 μg/Kg

Also known as: adiponectin receptor agonist

Experimental (PEG)-BHD1028_Multiple Ascending Dose

Placebo OTHER

Diluent

Placebo_Multiple Ascending Dose; Placebo_Single Ascending Dose

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• HbA1c \< 6.5 % by local laboratory analysis (one retest is permitted)
• Body Mass Index (BMI) ≥ 27 kg/m2
• HOMA-IR ≥ 1.8
• Female subjects must be non-pregnant and non-lactating, and females of childbearing potential must have used a stable regimen of highly effective contraceptive methods (for at least 2 months prior to the Screening) that they were willing to continue for at least 30 days after the last dose of the study drug.
• Male subjects must be surgically sterile, abstinent or, if engaged in sexual relations with a woman of childbearing potential, the subject and his partner must use an acceptable method of contraception for at least 90 days after the last dose of the study drug.
• Ability and willingness to comply with all protocol procedures
• Ability to provide written informed consent

You may not qualify if:

• History of type 1 or 2 diabetes mellitus (T1DM, T2DM)
• Systolic blood pressure \> 159 mm Hg or diastolic blood pressure \> 99 mmHg at ----Screening (reading may be repeated on a different day)
• Treatment with antihypertensive medication or statins if the medication was not stable during the 2 months prior to Screening
• Treatment with thyroid hormones was not stable during the 3 months prior to Screening
• History of any weight control treatment, including over-the-counter and herbal medication and supplements, or any medication with a labeled indication for weight loss or weight gain within 30 days prior to Screening
• History of gastrointestinal surgery for obesity that may induce malabsorption, or any malabsorption disorder, or clinically significant (C.S.) ongoing gastrointestinal disorders (including gastroparesis, peptic ulcers, and severe gastrointestinal reflux disease)
• History of symptomatic heart failure (New York Heart Association class II, III, or IV), myocardial infarction, unstable angina, transient ischemic attack, cerebral infarct, cerebral hemorrhage, or invasive cardiovascular procedure (including coronary artery bypass grafting \[CABG\] and percutaneous coronary intervention \[PCI\]) within 6 months of Screening
• Presence of CS ECG findings (including corrected Q.T. interval using Fridericia's formula \[QTcF\] \> 450 msec for males, QTcF \> 470 msec for females, left bundle branch block \[LBBB\]) at Screening, or cardiac arrhythmia requiring medical or surgical treatment within 6 months prior to Screening
• Presence of any C.S. physical, laboratory, ECG finding, or medical condition (including moderate to severe osteoarthritis or other C.S. rheumatological disease), that (in the opinion of an Investigator) may interfere with any aspect of the study conduct or interpretation of results
• Estimated glomerular filtration rate \[eGFR\] \< 60 mL/min/1.73 m2 at Screening (using the Modification of Diet in Renal Disease \[MDRD\] equation)
• Clinically significant disease (within the last five years) of the gastrointestinal, cardiovascular, hepatic, neurological, renal, pancreatic, immunological, dermatological, endocrine, genitourinary or hematological system
• Chronic liver disease, HIV, HBV- or active HCV infection, or a positive test at Screening
• History of mental handicap, major depression, suicidal behavior or attempts, or other psychiatric disorders requiring medical treatment (within 2 years of Screening), including selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), antipsychotics, lithium, or other psychiatric disorders including eating disorders and seizures
• Fasting triglycerides \> 500 mg/dL or alanine aminotransferase (ALT) and/or (aspartate aminotransferase ) AST d\> 2 x upper limit of normal (ULN) (a single retest of triglycerides, ALT, or AST was allowed)
• Use of any drugs that were known to interfere with glucose or insulin metabolism, including oral corticosteroids, glucagon-like peptide-1 (GLP-1) receptor agonists, monoamine oxidase (MAO) inhibitors, and growth hormone, or use of non-prescription drugs within 7 days of first dosing

Sponsors & Collaborators

• EncuraGen, Inc: lead

Study Sites (1)

Altasciences Clinical

Overland Park, Kansas, 66212, United States

Location

MeSH Terms

Conditions

Insulin Resistance

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Martin Kankam, MD

  Altasciences Clinical

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Double: participant, investigator
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized, Double-Blinded, Placebo-Controlled, Single and Multiple Ascending Dose Study

Study Record Dates

• First Submitted: July 26, 2024
• First Posted: August 20, 2024
• Study Start: April 18, 2022
• Primary Completion: April 23, 2024
• Study Completion: June 23, 2024
• Last Updated: August 20, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)