Phase 2 Trial of Oral ARD-101 in Controlling Hunger Enrolling in US

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by Steve Bryson, PhD |

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A Phase 2 study evaluating ARD-101, an investigational, gut-targeting Prader-Willi syndrome (PWS) oral therapy, is now enrolling up to 12 patients, ages 17 to 65.

The open-label study, sponsored by Aardvark Therapeutics, the treatment’s developer, will be held at two sites: Children’s Hospital in Colorado, which is now screening potential participants, and Stanford Children’s Health in California, expected to start enrollment in a few weeks, according to an announcement than includes a video trial presentation.

Hyperphagia is a hallmark of PWS, characterized by an intense, persistent sensation of hunger.

ARD-101 is a small molecule designed to target bitter taste receptors in the digestive tract, triggering the production of gut hormones that regulate appetite, metabolism, and inflammation.

Shawn McCandless, MD, a trial investigator at the Colorado hospital, gave the video presentation on the ARD-101 trial, hosted by the Foundation for Prader-Willi Research.

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Animal studies by Aardvark showed the therapy significantly reduced food intake and body weight, lowered glucose and insulin levels, as well as decreased low-density lipoprotein (LDL), the fat-like molecule associated with heart disease and stroke, McCandless said. Over two months, animals treated with ARD-101 continued to lose body weight without reaching a plateau.

These data supported the launch of a now-completed Phase 1 safety trial in 42 healthy volunteers, ages 19–55. Three dose levels of ARD-101 were tested (40, 100, 240 mg), given twice daily for two weeks after determining safety.

The therapy was found to be safe and well-tolerated at all doses, with no serious adverse events observed. Side effects associated with ARD-101 were mild and self-resolving, mostly digestive tract issues. There were also no clinically significant findings in lab tests, vital signs, heart assessments, and physical examinations.

Notably, more than 99% of the compound remained in the digestive tract and was not absorbed into the bloodstream, which may contribute to its good safety profile, McCandless said. Tests also showed an increased release of hormones in the gut.

The Phase 2 study (NCT05153434) will evaluate ARD-101 at 200 mg given twice daily for 28 days in 12 eligible patients. Five in-person site visits will be required.

Its primary goal is safety, with secondary outcomes assessing body weight and hyperphagia. Exploratory analyses will include body composition, waist circumference, body fat, fat and fat-like molecules in the bloodstream, insulin resistance (a sign of diabetes), psychiatric status, and changes in metabolic markers.

Both male and female patients, ranging in age from 17 to 65 with a confirmed PWS diagnosis, are eligible. Participants must also have stable blood pressure and vital signs, fasting glucose levels below 140 mg/deciliter (mg/dL) indicting no diabetes, be overweight or obese but have stable body weight for about the past two months, and a normal heartbeat and lab test results.

Patients on stable medication doses for at least three months prior to study entry — excepting diabetic treatments — will be allowed.

The Foundation for Prader-Willi Research also recently announced an investment in Aardvark to support for the therapy’s development. In addition, the company raised $29 million in financing to help support three planned Phase 2 studies of ARD-101.