Overview

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.