A Study of ATR-101 for the Treatment of Endogenous Cushing's Syndrome

A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study of ATR-101 for the Treatment of Cushing's Syndrome

This is a Phase 2 multicenter, randomized, double-blind, placebo controlled study of ATR-101 to evaluate the efficacy and safety of orally-administered ATR-101 in adults with endogenous Cushing's syndrome. Following wash-out (if needed), all eligible subjects will enter an open-label intra-subject dose-escalation period of 8 weeks' duration, followed either by a double-blind randomized withdrawal period of 4 weeks' duration (if the subject meets randomization criteria) or by an additional open label dosing period of 4 weeks' duration (if the subject does not meet randomization criteria).It is anticipated that the overall duration of the study per subject will range from approximately 16-22 weeks.

Study Overview

• Status: Terminated
• Conditions: Cushing Syndrome
• Intervention / Treatment: Drug: ATR-101; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • Middlesbrough, United Kingdom, TS4 3 BW
    • The James Cook University Hospital
• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • The Cleveland Clinic Foundation
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53051
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Confirmed diagnosis of endogenous Cushing's syndrome
• Baseline UFC 1.3 to 10 × upper limit of normal (ULN)
• If previous pituitary surgery, participants must be at least 3 months since surgery at the time of screening
• BMI between 18 and 60 kg/m2, inclusive

Exclusion Criteria:

• Pseudo-Cushing's syndrome, cyclic Cushing's syndrome or current iatrogenic Cushing's syndrome
• Candidates for surgical treatment of Cushing's syndrome, unless surgery is not anticipated to occur during the study
• Normal late night salivary cortisol or 24-hr urine free cortisol
• Radiotherapy of the pituitary within 6 months

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: ATR-101; During the 4-week randomized withdrawal period, eligible subjects will receive ATR-101 at the same dose level being used at the completion of the open-label dose-escalation period.	Drug: ATR-101; During the 4-week randomized withdrawal period, subjects will be dosed for 4 weeks at the same dose level being used at the completion of the open-label dose-escalation period.; Other Names: nevanimibe HCl
Placebo Comparator: Placebo; During the 4-week randomized withdrawal period, eligible subjects will receive a placebo that matches the same ATR-101 dose level being used at the completion of the open-label dose-escalation period.	Drug: Placebo; During the 4-week randomized withdrawal period, subjects will be dosed for 4 weeks with placebo that matches the same ATR-101 dose level being used at the completion of the open-label dose-escalation period.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Proportion of Subjects With Either a Normal 24-hr Urinary Free Cortisol (UFC) or a Reduction in 24-hr UFC of ≥ 50% Relative to Their Baseline Value	The number of subjects meeting the criterion was divided by the total number of subjects.	Through Day 85

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Proportion of Subjects With a Normal 24-hr UFC	The number of subjects meeting the criterion was divided by the total number of subjects.	Through Day 85
The Proportion of Subjects With a Reduction in 24-hr UFC of ≥ 50% Relative to Their Baseline Value	The number of subjects meeting the criterion was divided by the total number of subjects.	Through Day 85
The Proportion of Subjects With a Normal 24-hr UFC	The number of subjects meeting the criterion was divided by the total number of subjects.	Through Day 57 and Day 85
The Proportion of Subjects With a Reduction in 24-hr UFC of ≥ 50% Relative to Their Baseline Value	The number of subjects meeting the criterion was divided by the total number of subjects.	Through Day 57 and Day 85

Collaborators and Investigators

• Sponsor: Millendo Therapeutics US, Inc.
• Investigators: Principal Investigator: James Findling, MD, Medical College of Wisconsin

Study record dates

Study Major Dates

• Study Start (Actual): April 13, 2017
• Primary Completion (Actual): June 17, 2019
• Study Completion (Actual): August 12, 2019

Study Registration Dates

• First Submitted: February 6, 2017
• First Submitted That Met QC Criteria: February 10, 2017
• First Posted (Actual): February 15, 2017

Study Record Updates

• Last Update Posted (Actual): March 2, 2021
• Last Update Submitted That Met QC Criteria: February 10, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: Endogenous Cushing's Syndrome; ATR-101; CS
• Additional Relevant MeSH Terms: Pathologic Processes; Endocrine System Diseases; Disease; Adrenocortical Hyperfunction; Adrenal Gland Diseases; Syndrome; Cushing Syndrome
• Other Study ID Numbers: ATR-101-301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

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