Active, not recruiting
Phase 3
Avexitide for Treatment of Post-Bariatric Hypoglycemia
Condition(s) studied
Post Bariatric Hypoglycemia
Investigational drug(s) / intervention(s)
AvexitidePlacebo
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
Placebo: Matching placebo comparator
Study 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.
Eligibility
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.
Primary outcome measure(s)
- Composite rate of Level 2 and Level 3 hypoglycemic events — During the double-blind treatment period (approximately 16 weeks)
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
- Safety and Tolerability of avexitide — During the double-blind treatment period (approximately 16 weeks)
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
- Incidence of anti-drug antibodies (ADAb) — During the double-blind treatment period (approximately 16 weeks)
Incidence of ADAb, assessed during the Double-Blind study treatment period
Trial sites (21)
| Facility | City | Region | Status |
| Stanford Health Care - Endocrinology Clinic |
Stanford |
California |
|
| University of Colorado Health Anschutz Medical Campus |
Aurora |
Colorado |
|
| East Coast Institute for Research |
Jacksonville |
Florida |
|
| Hanson Diabetes Center |
Port Charlotte |
Florida |
|
| Georgia Clincal Research |
Lawrenceville |
Georgia |
|
| Cotton-O'Neil Diabetes and Endocrinology Center |
Topeka |
Kansas |
|
| Brigham and Women's Hospital |
Boston |
Massachusetts |
|
| Joslin Diabetes Center |
Boston |
Massachusetts |
|
| NYC Health + Hospitals/Queens - BRANY |
New Hyde Park |
New York |
|
| Duke Center for Metabolic and Weight Loss Surgery |
Durham |
North Carolina |
|
| Centricity Research Morehead City Multispecialty |
Morehead City |
North Carolina |
|
| Cleveland Clinic |
Cleveland |
Ohio |
|
| Penn Medicine University City |
Philadelphia |
Pennsylvania |
|
| Vanderbilt Weight Loss Center |
Nashville |
Tennessee |
|
| Endocrine and Psychiatry Center |
Houston |
Texas |
|
| Southern Endocrinology & Diabetes Associates |
Mesquite |
Texas |
|
| UT Health San Antonio |
San Antonio |
Texas |
|
| Diabetes and Gandular Disease Clinic |
San Antonio |
Texas |
|
| Consano Clinical Research |
Shavano Park |
Texas |
|
| Texas Valley Clinical Research, LLC |
Weslaco |
Texas |
|
| UWHealth - Junction Rd Medical Center Endocrinology Clinic |
Madison |
Wisconsin |
|
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