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

• ClinicalTrials.gov Identifier: NCT03053271
• Recruitment Status: Terminated
• First Posted: February 15, 2017
• Results First Posted: March 2, 2021
• Last Update Posted: March 2, 2021
• Sponsor: Millendo Therapeutics US, Inc.
• Information provided by (Responsible Party): Millendo Therapeutics, Inc. ( Millendo Therapeutics US, Inc. )

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Cushing Syndrome	Drug: ATR-101; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 4 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study of ATR-101 for the Treatment of Cushing's Syndrome
• Actual Study Start Date: April 13, 2017
• Actual Primary Completion Date: June 17, 2019
• Actual Study Completion Date: August 12, 2019

Arms and Interventions

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 Name: 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.

Outcome Measures

Primary Outcome Measures :

1. 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 [ Time Frame: Through Day 85 ]
   The number of subjects meeting the criterion was divided by the total number of subjects.

Secondary Outcome Measures :

1. The Proportion of Subjects With a Normal 24-hr UFC [ Time Frame: Through Day 85 ]
   The number of subjects meeting the criterion was divided by the total number of subjects.
2. The Proportion of Subjects With a Reduction in 24-hr UFC of ≥ 50% Relative to Their Baseline Value [ Time Frame: Through Day 85 ]
   The number of subjects meeting the criterion was divided by the total number of subjects.
3. The Proportion of Subjects With a Normal 24-hr UFC [ Time Frame: Through Day 57 and Day 85 ]
   The number of subjects meeting the criterion was divided by the total number of subjects.
4. The Proportion of Subjects With a Reduction in 24-hr UFC of ≥ 50% Relative to Their Baseline Value [ Time Frame: Through Day 57 and Day 85 ]
   The number of subjects meeting the criterion was divided by the total number of subjects.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, Massachusetts

Massachusetts General Hospital

Boston, Massachusetts, United States, 02114

United States, Ohio

The Cleveland Clinic Foundation

Cleveland, Ohio, United States, 44195

United States, Wisconsin

Medical College of Wisconsin

Milwaukee, Wisconsin, United States, 53051

United Kingdom

The James Cook University Hospital

Middlesbrough, United Kingdom, TS4 3 BW

Sponsors and Collaborators

Millendo Therapeutics US, Inc.

Investigators

• Principal Investigator: James Findling, MD; Medical College of Wisconsin

  Study Documents (Full-Text)

Documents provided by Millendo Therapeutics, Inc. ( Millendo Therapeutics US, Inc. ):

Study Protocol  [PDF] March 14, 2018

Statistical Analysis Plan  [PDF] September 18, 2019

More Information

• Responsible Party: Millendo Therapeutics US, Inc.
• ClinicalTrials.gov Identifier: NCT03053271
• Other Study ID Numbers: ATR-101-301
• First Posted: February 15, 2017
• Results First Posted: March 2, 2021
• Last Update Posted: March 2, 2021
• Last Verified: February 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Millendo Therapeutics, Inc. ( Millendo Therapeutics US, Inc. ):

Endogenous Cushing's Syndrome; ATR-101; CS

Additional relevant MeSH terms:

Cushing Syndrome; Syndrome; Disease; Pathologic Processes; Adrenocortical Hyperfunction; Adrenal Gland Diseases; Endocrine System Diseases