Avexitide for Treatment of Post-Bariatric Hypoglycemia (LUCIDITY)

A Phase 3 Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Avexitide in Participants With Post-Bariatric Hypoglycemia

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Post Bariatric Hypoglycemia
• Intervention / Treatment: Drug: Avexitide; Other: Placebo

Detailed Description

AVX-001 (LUCIDITY) is a Phase 3 multicenter study to evaluate avexitide compared to placebo in participants with post bariatric hypoglycemia (PBH) related to Roux-en-Y gastric bypass (RYGB).

Eligible participants must have a confirmed diagnosis of PBH related to RYGB, must be a minimum of 1-year post-surgery, and must have experienced at least 3 discrete hypoglycemic events during the 3-week study Run-in period while adhering to consistent dietary management.

The study includes a Screening period of up to 6 weeks in duration, inclusive of a 3-week Run-in period; a randomized, double-blind, placebo-controlled study treatment period of 16 weeks in duration; and a two-part open-label extension (OLE) period with a duration of 32 weeks.

The Double-Blind period is designed to evaluate the efficacy and safety of 90 mg per day of avexitide (given by subcutaneous injection) compared to placebo in participants with PBH after Roux-en-Y gastric bypass (RYGB), who are not adequately controlled on dietary management for reduction of hypoglycemic events.

The subsequent 32-week Open Label Extension (OLE) period is intended to further evaluate the safety and efficacy of avexitide (90 mg per day, given by subcutaneous injection) in participants who have completed the Double-Blind period. The OLE period consists of an 8-week initial Part A and a subsequent 24-week Part B.

Participants will use a continuous glucose monitor (CGM) in blinded mode, a self-monitoring of blood glucose (SMBG) device (glucose meter), and an electronic diary (eDiary) on a smartphone to record hypoglycemic events and study drug administration during the screening period, 16-week double-blind period, and 8-week OLE Part A. While the CGM is in blinded mode, participants will not see their specific blood glucose values on their CGM, but they will receive an alert when their blood glucose is low; they may check their blood glucose via the SMBG glucose meter device at any time. During the 24-week OLE Part B, participants will use a CGM in unblinded mode (blood glucose values are visible to the participant) and the SMBG and eDiary devices will not be assessed.

• Study Type: Interventional
• Enrollment (Estimated): 75
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94304
      • Stanford Health Care - Endocrinology Clinic
  • Colorado
    • Aurora, Colorado, United States, 80045-2541
      • University of Colorado Health Anschutz Medical Campus
  • Florida
    • Jacksonville, Florida, United States, 32216
      • East Coast Institute for Research
    • Port Charlotte, Florida, United States, 33952-6722
      • Hanson Diabetes Center
  • Georgia
    • Lawrenceville, Georgia, United States, 30044
      • Georgia Clincal Research
  • Kansas
    • Topeka, Kansas, United States, 66606-2806
      • Cotton-O'Neil Diabetes and Endocrinology Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
    • Boston, Massachusetts, United States, 02215-5306
      • Joslin Diabetes Center
  • New York
    • New Hyde Park, New York, United States, 11042-1214
      • NYC Health + Hospitals/Queens - BRANY
  • North Carolina
    • Durham, North Carolina, United States, 27704-2726
      • Duke Center for Metabolic and Weight Loss Surgery
    • Morehead City, North Carolina, United States, 28557-3126
      • Centricity Research Morehead City Multispecialty
  • Ohio
    • Cleveland, Ohio, United States, 44195-0001
      • Cleveland Clinic
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Penn Medicine University City
  • Tennessee
    • Nashville, Tennessee, United States, 37212-3609
      • Vanderbilt Weight Loss Center
  • Texas
    • Houston, Texas, United States, 77095-2856
      • Endocrine and Psychiatry Center
    • Mesquite, Texas, United States, 75149
      • Southern Endocrinology & Diabetes Associates
    • San Antonio, Texas, United States, 78229-3931
      • UT Health San Antonio
    • San Antonio, Texas, United States, 78229-4801
      • Diabetes and Gandular Disease Clinic
    • Shavano Park, Texas, United States, 78231-1281
      • Consano Clinical Research
    • Weslaco, Texas, United States, 78596-7288
      • Texas Valley Clinical Research, LLC
  • Wisconsin
    • Madison, Wisconsin, United States, 53717-2656
      • UWHealth - Junction Rd Medical Center Endocrinology Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.
• Investigator-assessed evidence of alcohol or drug abuse within 12 months prior to Screening. Unwillingness to restrict alcohol use to no more than 1 drink per day is also exclusionary.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AVEXITIDE; 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; 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; Other Names: exendin 9-39
Placebo Comparator: PLACEBO; 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; Matching placebo comparator

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Further evaluate the efficacy of avexitide compared to placebo for reduction of hypoglycemia	Rates of the following, assessed during the Double-Blind study treatment period: Level 2 hypoglycemia as measured by SMBG; Level 3 hypoglycemia, adjudicated by EAC; Level 2 hypoglycemia as measured by CGM	During the double-blind treatment period (approximately 16 weeks)

Collaborators and Investigators

• Sponsor: Amylyx Pharmaceuticals Inc.
• Investigators: Study Director: Amylyx Medical Director, Amylyx Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): April 29, 2025
• Primary Completion (Estimated): March 1, 2026
• Study Completion (Estimated): October 1, 2026

Study Registration Dates

• First Submitted: December 18, 2024
• First Submitted That Met QC Criteria: December 18, 2024
• First Posted (Actual): December 24, 2024

Study Record Updates

• Last Update Posted (Actual): March 4, 2026
• Last Update Submitted That Met QC Criteria: March 3, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: hypoglycemia; Roux-en-Y; avexitide; Roux-en-Y gastric bypass; gastric bypass; Roux-en-Y gastric bypass (RYGB); RYGB; low blood sugar; exendin; PBH; post bariatric hypoglycemia; hypoglycemia post bariatric surgery; AVX; LUCIDITY; exendin 9-39; exendin 939
• Additional Relevant MeSH Terms: Metabolic Diseases; Glucose Metabolism Disorders; Nutritional and Metabolic Diseases; Hypoglycemia; Substandard Drugs; Pharmaceutical Preparations; exendin (9-39)
• Other Study ID Numbers: AVX-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Proposals for access to IPD by qualified investigators will be reviewed by an independent review committee. Only the de-identified data elements needed to achieve the specific scientific aims of a proposal as outlined in a pre-specified analysis plan will be provided. Study documents such as protocol, SAP, ICF, and CSR, may be provided, if requested and if needed, to conduct the specified analyses.
• IPD Sharing 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.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No