Avexitide for Treatment of Post-Bariatric Hypoglycemia

NCT06747468 | Active Not Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: AVX-001
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 21

Brief Summary

AVX-001 (LUCIDITY) is a Phase 3 study to evaluate avexitide compared to placebo in participants with post bariatric hypoglycemia (PBH) related to Roux-en-Y gastric bypass (RYGB). The study will assess avexitide compared to placebo for safety and efficacy, measured by reduction of hypoglycemic events. The study includes a Screening period with a Run-in period (of up to 6- and 3-weeks, respectively); a randomized, double-blind, placebo-controlled study treatment period of 16 weeks; and a two-part open-label extension (OLE) period with a duration of approximately 32 weeks.

Conditions

Post Bariatric Hypoglycemia

Keywords

avexitide; post bariatric hypoglycemia; PBH; hypoglycemia; hypoglycemia post bariatric surgery; Roux-en-Y gastric bypass (RYGB); RYGB; AVX; LUCIDITY; exendin 9-39; exendin; exendin 939; Roux-en-Y; gastric bypass; low blood sugar; Roux-en-Y gastric bypass

Outcome Measures

Primary Outcomes (3)

• Composite rate of Level 2 and Level 3 hypoglycemic events

  Composite rate of Level 2 hypoglycemia (as measured by self-monitoring of blood glucose \[SMBG\]) and Level 3 hypoglycemia (per American Diabetes Association \[ADA\], European Association for the Study of Diabetes \[EASD\]; adjudicated by independent Event Adjudication Committee \[EAC\]), assessed during the Double-Blind study treatment period

  During the double-blind treatment period (approximately 16 weeks)

• Safety and Tolerability of avexitide

  Incidence of adverse events (AEs)-e.g., incidence of treatment-emergent AEs (TEAEs), serious AEs (SAEs), AEs of special interest (AESIs), and TEAEs leading to discontinuation-and other safety assessments (e.g., clinical laboratory results and vital sign measurements), assessed during the Double-Blind study treatment period

  During the double-blind treatment period (approximately 16 weeks)

• Incidence of anti-drug antibodies (ADAb)

  Incidence of ADAb, assessed during the Double-Blind study treatment period

  During the double-blind treatment period (approximately 16 weeks)

Secondary Outcomes (1)

• Further evaluate the efficacy of avexitide compared to placebo for reduction of hypoglycemia

  During the double-blind treatment period (approximately 16 weeks)

Study Arms (2)

AVEXITIDE

EXPERIMENTAL

Avexitide (90 mg via subcutaneous \[SC\] injection) will be taken once per day, in the morning at least 60 minutes before the morning meal, through the duration of the treatment and OLE periods.

Drug: Avexitide

PLACEBO

PLACEBO COMPARATOR

Placebo will be taken once per day, via subcutaneous \[SC\] injection, in the morning at least 60 minutes before the morning meal, through the duration of the treatment period. Participants receiving Placebo in the double-blind treatment period will transition to Avexitide 90 mg (via subcutaneous \[SC\] injection) in the open-label extension (OLE) period.

Other: Placebo

Interventions

Avexitide DRUG

Avexitide (also known as exendin 9-39), a first-in-class glucagon-like peptide-1 (GLP-1) receptor antagonist, is a 31-amino acid peptide with a free amino group at the N-terminus and an amidated C-terminus. By binding to the GLP-1 receptor, avexitide inhibits GLP-1 receptor signaling, thereby reducing GLP-1 receptor-mediated insulin secretion

Also known as: exendin 9-39

AVEXITIDE

Placebo OTHER

Matching placebo comparator

PLACEBO

Eligibility Criteria

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

You may qualify if:

• Able to provide written informed consent and understand the purpose and risks of the study
• Willing and able to adhere to study requirements, including the use of the study-provided CGM device, SMBG device, and eDiary device as well as the other study evaluations and procedures.
• Is male or female, at least 18 years of age (inclusive) at the time of consent.
• Body mass index (BMI) of up to 40 kg/m2 and has stable body weight-i.e., not varying by \>5% for at least 2 months prior to Screening
• Has undergone documented RYGB performed ≥12 months prior to Screening.
• Has clinical diagnosis of PBH-defined as history of recurrent hypoglycemia with onset after surgery and having ruled out other causes of hypoglycemia as per Investigator judgment.
• Has recurrent hypoglycemia, as demonstrated by experiencing at least 3 discrete hypoglycemic episodes during the 3-week study Run-in period.
• Must agree to consistently follow the dietary management guidance and to maintain consistent exercise and/or physical activity level throughout the Screening period (including the Run-in period), the Double-Blind study treatment period, and Part A of the OLE period.
• If female, must meet all of the following:
• Is not breastfeeding or lactating;
• If of childbearing potential, has negative serum pregnancy test result at Screening and on Day 1 ahead of dosing
• If of childbearing potential, must also agree to use a highly effective method of birth control-and agree not to participate in egg (ova) donation or storage, throughout the duration of study participation and for at least 1 month after the last dose of study drug.
• If male and engaging in heterosexual intercourse with a female partner of childbearing potential, must utilize a highly effective method of contraception, and agree not to donate sperm, from the time of providing written informed consent until at least 3 months after the last dose of study drug.

You may not qualify if:

• Has received avexitide (exendin 9-39) at any time prior to Screening Visit 1.
• Has received another investigational drug, for any indication, within 5 half-lives of that drug prior to Screening Visit 1.
• Has participated in another interventional clinical study within 30 days prior to Screening Visit 1.
• Presence of gastrostomy tube (G-tube).
• Any known or suspected allergy to one of the investigational medicinal products (avexitide or placebo) or any related product (e.g., exenatide).
• History or presence of insulinoma or other cause of endogenous hyperinsulinism other than PBH.
• Active psychiatric disease or active eating disorder (e.g., uncontrolled major depressive disorder, schizophrenia, bipolar disorder, or other severe mood, anxiety, or eating disorder). Note: prospective participants with stable conditions, per Investigator judgement, may be considered, provided they are not on an excluded medication.
• History of major surgery within 6 months prior to Screening.
• History of upper GI surgery, other than RYGB. Note that history of vertical sleeve gastrectomy (VSG) with subsequent RYGB conversion may be considered on a case-by-case basis upon discussion with the Medical Monitor.
• Current or prior use of agent(s) that may alter glucose metabolism, or promote weight loss, within 5 medication half-lives of Screening Visit 1. Such agents include, but are not limited to, the following: acarbose; calcium channel blockers; diazoxide; dipeptidyl-peptidase-4 (DPP-4) inhibitors; GLP-1 agonists; glucocorticoids; glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 dual agonists; insulin; lithium; meglitinides; metformin; pentamide; sodium-glucose-linked transporter (SGLT)-1 inhibitors; SGLT-2 inhibitors; somatostatin analogs; sulfonylureas; and thiazolidinediones (TZDs).
• Use of drugs that interfere with the Dexcom G7 sensor within 5 half-lives of Screening Visit 1. Such drugs include acetaminophen administered at a dosage greater than 1000 mg every 6 hours, and hydroxyurea.

Sponsors & Collaborators

• Amylyx Pharmaceuticals Inc.: lead

Study Sites (21)

Stanford Health Care - Endocrinology Clinic

Stanford, California, 94304, United States

Location

University of Colorado Health Anschutz Medical Campus

Aurora, Colorado, 80045-2541, United States

Location

East Coast Institute for Research

Jacksonville, Florida, 32216, United States

Location

Hanson Diabetes Center

Port Charlotte, Florida, 33952-6722, United States

Location

Georgia Clincal Research

Lawrenceville, Georgia, 30044, United States

Location

Cotton-O'Neil Diabetes and Endocrinology Center

Topeka, Kansas, 66606-2806, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Joslin Diabetes Center

Boston, Massachusetts, 02215-5306, United States

Location

NYC Health + Hospitals/Queens - BRANY

New Hyde Park, New York, 11042-1214, United States

Location

Duke Center for Metabolic and Weight Loss Surgery

Durham, North Carolina, 27704-2726, United States

Location

Centricity Research Morehead City Multispecialty

Morehead City, North Carolina, 28557-3126, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195-0001, United States

Location

Penn Medicine University City

Philadelphia, Pennsylvania, 19104, United States

Location

Vanderbilt Weight Loss Center

Nashville, Tennessee, 37212-3609, United States

Location

Endocrine and Psychiatry Center

Houston, Texas, 77095-2856, United States

Location

Southern Endocrinology & Diabetes Associates

Mesquite, Texas, 75149, United States

Location

UT Health San Antonio

San Antonio, Texas, 78229-3931, United States

Location

Diabetes and Gandular Disease Clinic

San Antonio, Texas, 78229-4801, United States

Location

Consano Clinical Research

Shavano Park, Texas, 78231-1281, United States

Location

Texas Valley Clinical Research, LLC

Weslaco, Texas, 78596-7288, United States

Location

UWHealth - Junction Rd Medical Center Endocrinology Clinic

Madison, Wisconsin, 53717-2656, United States

Location

MeSH Terms

Conditions

Hypoglycemia

Interventions

exendin (9-39)

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Amylyx Medical Director

  Amylyx Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Sponsor, Participant and Investigator are all masked to treatment assignment
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Upon entering the Double-Blind period, approximately 75 participants will be randomized and assigned in a 3:2 ratio to either the avexitide treatment group or the placebo group, respectively.

Study Record Dates

• First Submitted: December 18, 2024
• First Posted: December 24, 2024
• Study Start: April 29, 2025
• Primary Completion: March 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: March 4, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: TBD: proposals for access to IPD will be reviewed after data is used in regulatory approval in all major countries or regions where filing is planned or after publication, whichever is latest. Exact timing is not currently known.
• Access Criteria: Access to IPD will be granted to qualified investigators whose proposed use of the data has been approved by an independent review committee to achieve the aims in their proposal.

Locations

US (21)