Avexitide for Hypoglycemia

(LUCIDITY Trial)

Recruiting at 22 trial locations

Overseen By Amylyx Clinical Trials Team

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Amylyx Pharmaceuticals Inc.

Must not be taking: Insulin, GLP-1 agonists, Metformin, others

Disqualifiers: Insulinoma, Active psychiatric disease, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: 16 weeks

75 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop taking any medications that alter glucose metabolism or promote weight loss before starting, such as insulin, metformin, and GLP-1 agonists. You also need to avoid drugs that interfere with the study's sensor, like high doses of acetaminophen.

What data supports the effectiveness of the drug Avexitide for treating hypoglycemia?

Research shows that Avexitide, also known as exendin 9-39, is effective in treating post-bariatric hypoglycemia, a condition where blood sugar drops too low after weight-loss surgery. This suggests it may help manage hypoglycemia by stabilizing blood sugar levels. ^{1 2 3 4 5}

How does the drug Avexitide differ from other treatments for hypoglycemia?

Avexitide is unique because it is a subcutaneous (under the skin) injection that specifically targets post-bariatric hypoglycemia by blocking the effects of a hormone called GLP-1, which helps regulate insulin. This mechanism is different from other treatments like glucagon, which directly raises blood sugar levels, or somatostatin analogues, which inhibit insulin secretion. ^{1 6 7 8 9}

What is the purpose of this trial?

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.

Research Team

Amylyx Medical Director

Principal Investigator

Amylyx Pharmaceuticals

Eligibility Criteria

This trial is for adults over 18 with a BMI up to 40 who've had Roux-en-Y gastric bypass at least a year ago and are experiencing low blood sugar episodes after the surgery. They must not be pregnant, breastfeeding, or have weight fluctuations greater than 5% in the past two months.

Inclusion Criteria

I can sign and understand the consent form for this study.

I am willing and able to follow the study's requirements and use the provided devices.

My BMI is 40 or less and my weight has been stable for the last 2 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

6 weeks

Includes a 3-week Run-in period

Treatment

Randomized, double-blind, placebo-controlled study treatment period with avexitide or placebo

16 weeks

Participants receive daily subcutaneous injections

Open-label extension (Part A)

Participants receive avexitide in an open-label setting to further evaluate safety and efficacy

8 weeks

Participants continue daily subcutaneous injections

Open-label extension (Part B)

Continuation of open-label treatment with avexitide, with unblinded CGM monitoring

24 weeks

Participants continue daily subcutaneous injections

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Avexitide

Trial Overview The study tests Avexitide against a placebo in managing low blood sugar in post-bariatric patients. It includes initial screening, a controlled treatment period of 16 weeks, and an extension phase where everyone gets Avexitide for about 32 weeks.

Participant Groups

Group I: AVEXITIDE Experimental Treatment 1 Intervention

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.

Group II: PLACEBO Placebo Group 1 Intervention

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.

Who Is Running the Clinical Trial?

Amylyx Pharmaceuticals Inc.

Lead Sponsor

Trials

12

Recruited

1,600+

Findings from Research

In a phase 2 study involving 19 women with post-bariatric hypoglycaemia, subcutaneous avexitide significantly reduced symptoms of hypoglycaemia and improved glucose levels, with both formulations (lyophilized and liquid) showing effectiveness without requiring glycaemic rescue in higher doses.

The liquid formulation of avexitide at 30 mg twice daily resulted in greater and more sustained plasma concentrations compared to the lyophilized version, leading to a 47% increase in glucose nadir and a 67% reduction in peak insulin, indicating its potential as a viable treatment for post-bariatric hypoglycaemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, efficacy and pharmacokinetics of repeat subcutaneous dosing of avexitide (exendin 9-39) for treatment of post-bariatric hypoglycaemia. Tan, M., Lamendola, C., Luong, R., et al.[2021]

In a study involving 10 patients with type 1 diabetes and impaired awareness of hypoglycemia (IAH), treatment with exenatide did not improve awareness of hypoglycemia compared to placebo, despite a decrease in body weight.

Exenatide treatment did not significantly change glucose levels or the frequency of hypoglycemic events, indicating that while it may aid in weight loss, it does not enhance hypoglycemia awareness in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of the GLP-1 Receptor Agonist Exenatide on Impaired Awareness of Hypoglycemia in Type 1 Diabetes: A Randomized Controlled Trial. van Meijel, LA., Rooijackers, HM., Tack, CJ., et al.[2023]

A single 50-mg dose of albiglutide was well tolerated in 44 subjects with type 2 diabetes and did not impair the body's natural counter-regulatory responses to hypoglycemia, indicating its safety during low blood sugar events.

Albiglutide increased pancreatic β-cell secretion of C-peptide in a glucose-dependent manner when blood sugar levels were above 5.0 mmol/l, suggesting it enhances insulin secretion without increasing the risk of hypoglycemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Albiglutide does not impair the counter-regulatory hormone response to hypoglycaemia: a randomized, double-blind, placebo-controlled, stepped glucose clamp study in subjects with type 2 diabetes mellitus. Hompesch, M., Jones-Leone, A., Carr, MC., et al.[2018]

In a case series of 6 patients with sulfonylurea-induced hypoglycemia, octreotide was successfully used to manage prolonged hypoglycemia, especially in patients with renal or heart failure where traditional treatments were ineffective.

Octreotide administration (50 microg subcutaneously every 8 hours) led to a prompt and sustained resolution of hypoglycemia, confirming its efficacy in this context, as evidenced by insulin and C-peptide measurements in 3 of the patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful treatment of sulfonylurea-induced prolonged hypoglycemia with use of octreotide. Fleseriu, M., Skugor, M., Chinnappa, P., et al.[2021]

Octreotide has been shown to effectively reduce the frequency of sulfonylurea-induced hypoglycemic episodes, as demonstrated in both animal models and human case reports.

In clinical trials, octreotide combined with supplemental dextrose not only increased blood glucose levels but also resulted in fewer hypoglycemic events, supporting its use as a treatment for sulfonylurea overdose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Octreotide's role in the management of sulfonylurea-induced hypoglycemia. Dougherty, PP., Klein-Schwartz, W.[2021]

Exenatide, a GLP-1 mimetic, improves glycemic control in type 2 diabetes through multiple mechanisms, including stimulating insulin secretion and reducing appetite, while significantly lowering HbA1c levels and body weight.

The risk of hypoglycemia is minimized with exenatide since it only stimulates insulin release when blood glucose levels are elevated, making it a safer option for managing diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exenatide. Barnett, AH.[2018]

Dasiglucagon is an effective treatment for severe hypoglycemia, showing significantly faster plasma glucose recovery compared to placebo in clinical trials involving both children and adults.

It is the first glucagon analogue that is stable in aqueous solution, eliminating the need for reconstitution before use, which enhances its practicality for emergency treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dasiglucagon: A Novel Ready-to-Use Treatment for Severe Hypoglycemia. Goodhart, AL.[2023]

Pasireotide, a multireceptor-targeted somatostatin analogue, effectively prevented glyburide-induced hypoglycemia in rats for up to 6 hours in a dose-dependent manner, showing stronger effects in non-fasted conditions.

In contrast, octreotide did not prevent hypoglycemia in fasted and non-fasted rats at lower doses, indicating that pasireotide may be a more potent option for managing severe hypoglycemia caused by sulfonylurea treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pasireotide (SOM230) prevents sulfonylurea-induced hypoglycemia in rats. Schmid, HA.[2015]

Effective glycemic control is crucial for preventing complications in type 1 diabetes, but it increases the risk of severe hypoglycemia, which can significantly impact patients' quality of life.

There is a pressing need for better glucagon treatments, particularly stable liquid formulations, to simplify emergency treatment for hypoglycemia and potentially expand its use in other conditions like congenital hyperinsulinism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stable Liquid Glucagon: Beyond Emergency Hypoglycemia Rescue. Wilson, LM., Castle, JR.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Safety, efficacy and pharmacokinetics of repeat subcutaneous dosing of avexitide (exendin 9-39) for treatment of post-bariatric hypoglycaemia. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Effect of the GLP-1 Receptor Agonist Exenatide on Impaired Awareness of Hypoglycemia in Type 1 Diabetes: A Randomized Controlled Trial. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Albiglutide does not impair the counter-regulatory hormone response to hypoglycaemia: a randomized, double-blind, placebo-controlled, stepped glucose clamp study in subjects with type 2 diabetes mellitus. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

Successful treatment of sulfonylurea-induced prolonged hypoglycemia with use of octreotide. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Octreotide's role in the management of sulfonylurea-induced hypoglycemia. [2021]

6. Spain pubmed.ncbi.nlm.nih.gov

Exenatide. [2018]

7. United States pubmed.ncbi.nlm.nih.gov

Dasiglucagon: A Novel Ready-to-Use Treatment for Severe Hypoglycemia. [2023]

8. Germany pubmed.ncbi.nlm.nih.gov

Pasireotide (SOM230) prevents sulfonylurea-induced hypoglycemia in rats. [2015]

9. United States pubmed.ncbi.nlm.nih.gov

Stable Liquid Glucagon: Beyond Emergency Hypoglycemia Rescue. [2023]