A Study of ATR-101 for the Treatment of Congenital Adrenal Hyperplasia

• Sponsor: Millendo Therapeutics, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02804178
• Collaborator: (none)
• Enrollment: 10
• Locations: 6
• Arm: 1
• Actual Duration (Months): 15
• Patients Per Site: 1.7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is a Phase 2 multicenter, single-blind, multiple dose study to evaluate the safety and efficacy of orally administered ATR-101 in subjects with classic congenital adrenal hyperplasia (CAH). Treatment duration will range from a minimum of approximately 2 months to 6 months per subject. A subject may receive a minimum of one dose level or up to a maximum of 5 dose levels, in sequentially increasing dose strengths. Each dose level will last 28 days.

Condition or Disease	Intervention/Treatment	Phase
Congenital Adrenal Hyperplasia	Drug: ATR-101	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Single treatment arm with up to 5 planned dosing periods with escalating doses. Subjects were dosed with each dose level for 2 weeks, followed by 2 weeks of matching placebo (subjects blinded).Single treatment arm with up to 5 planned dosing periods with escalating doses. Subjects were dosed with each dose level for 2 weeks, followed by 2 weeks of matching placebo (subjects blinded).
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Multicenter Study of ATR-101 for the Treatment of Congenital Adrenal Hyperplasia
• Actual Study Start Date: May 18, 2016
• Actual Primary Completion Date: Aug 17, 2017
• Actual Study Completion Date: Aug 17, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ATR-101 Ascending dose levels of ATR-101 beginning with 125 mg by mouth twice per day up to 1000 mg twice per day.	Drug: ATR-101; 125-1000 mg twice per week; Other Names: Nevanimibe hydrochloride

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Reduction of 17-hydroxyprogesterone to </= 2 Times the Upper Limit of Normal at Any Time Following 2 Weeks of Dosing With ATR-101 [Evaluated at baseline and day 15 of each dose level. Each subject will have up to 5 dose levels.]

   17-hydroxyprogesterone was measured predose in the morning at the beginning and end of each dose level.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Documented historical diagnosis of classic CAH due to 21-hydroxylase deficiency based on: Documented genetic mutation in the CYP21A2 enzyme consistent with a diagnosis of classic CAH, or historical documentation of elevated 17-hydroxyprogesterone

• Biochemical marker of disease status of 17-hydroxyprogesterone ≥ 4 times the upper limit of normal

• Chronic glucocorticoid replacement therapy for at least 6 consecutive months

• Stable glucocorticoid and mineralocorticoid regimen for at least 1 month

Exclusion Criteria:

• Non-classic CAH

• Other causes of adrenal insufficiency

• Surgery within the previous 3 months prior to screening or planned surgery during study participation

• History of active cancer requiring medical or surgical therapy within the past 6 months

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Johns Hopkins University	Baltimore	Maryland	United States	21287
2	National Institutes of Health Clinical Center	Bethesda	Maryland	United States	20892
3	University of Michigan	Ann Arbor	Michigan	United States	48109
4	Mayo Clinic - Rochester	Rochester	Minnesota	United States	55905
5	The University of Oklahoma - Tulsa Schusterman Center	Tulsa	Oklahoma	United States	74135
6	The Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	10021

Sponsors and Collaborators

• Millendo Therapeutics, Inc.

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Jan 14, 2016
• Statistical Analysis Plan - Sep 6, 2017

More Information

Publications

None provided.

• Responsible Party: Millendo Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT02804178
• Other Study ID Numbers: ATR-101-201
• First Posted: Jun 17, 2016
• Last Update Posted: Mar 10, 2021
• Last Verified: Feb 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Millendo Therapeutics, Inc.: ATR-101; classic congenital adrenal hyperplasia; 21-hydroxylase deficiency; CAH
• Additional relevant MeSH terms: Adrenal Hyperplasia, Congenital; Adrenogenital Syndrome; Adrenocortical Hyperfunction; Hyperplasia

Study Results

Participant Flow

Arm/Group Title	ATR-101
Arm/Group Description	Ascending dose levels of ATR-101 beginning with 125 mg by mouth twice per day up to 1000 mg twice per day.
Period Title: Overall Study
STARTED	10
COMPLETED	9
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	ATR-101
Arm/Group Description	Ascending dose levels of ATR-101 beginning with 125 mg by mouth twice per day up to 1000 mg twice per day.
Overall Participants	10
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	30.3 (13.76)
Sex: Female, Male (Count of Participants)
Female	5 50%
Male	5 50%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 10%
Not Hispanic or Latino	9 90%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 10%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	9 90%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	10 100%
17-hydroxyprogesterone (ng/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [ng/dL]	6591.0 (5371.80)

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Reduction of 17-hydroxyprogesterone to </= 2 Times the Upper Limit of Normal at Any Time Following 2 Weeks of Dosing With ATR-101
Description	17-hydroxyprogesterone was measured predose in the morning at the beginning and end of each dose level.
Time Frame	Evaluated at baseline and day 15 of each dose level. Each subject will have up to 5 dose levels.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ATR-101
Arm/Group Description	Ascending dose levels of ATR-101 beginning with 125 mg by mouth twice per day up to 1000 mg twice per day.
Measure Participants	10
Count of Participants [Participants]	2 20%

Adverse Events

Time Frame	Adverse events were collected from the time the patient signed informed consent until 4 weeks after the last dose of active drug.
Arm/Group Title	ATR-101
Arm/Group Description	Ascending dose levels of ATR-101 beginning with 125 mg by mouth twice per day up to 1000 mg twice per day.
All Cause Mortality
	ATR-101
	Affected / at Risk (%)	# Events
Total	0/10 (0%)
Serious Adverse Events
	ATR-101
	Affected / at Risk (%)	# Events
Total	1/10 (10%)
Gastrointestinal disorders
Enteritis	1/10 (10%)	1
Other (Not Including Serious) Adverse Events
	ATR-101
	Affected / at Risk (%)	# Events
Total	9/10 (90%)
Cardiac disorders
Atrioventricular block first degree	1/10 (10%)	1
Gastrointestinal disorders
Abdominal pain upper	3/10 (30%)	3
Diarrhoea	3/10 (30%)	3
Vomiting	2/10 (20%)	2
Dyspepsia	1/10 (10%)	1
Gingival recession	1/10 (10%)	1
General disorders
Fatigue	1/10 (10%)	1
Oedema peripheral	1/10 (10%)	1
Infections and infestations
Nasopharyngitis	4/10 (40%)	4
Gastroenteritis viral	1/10 (10%)	1
Tooth infection	1/10 (10%)	1
Upper respiratory tract infection	1/10 (10%)	2
Urinary tract infection	1/10 (10%)	1
Viral infection	1/10 (10%)	1
Injury, poisoning and procedural complications
Muscle strain	1/10 (10%)	1
Investigations
Weight decreased	1/10 (10%)	1
Metabolism and nutrition disorders
Decreased appetite	1/10 (10%)	1
Hypokalemia	1/10 (10%)	1
Hyponatremia	1/10 (10%)	1
Musculoskeletal and connective tissue disorders
Back pain	1/10 (10%)	1
Musculoskeletal pain	1/10 (10%)	1
Nervous system disorders
Headache	4/10 (40%)	5
Migraine	3/10 (30%)	3
Dizziness	1/10 (10%)	1
Somnolence	1/10 (10%)	1
Psychiatric disorders
Depression	1/10 (10%)	1
Insomnia	1/10 (10%)	1
Respiratory, thoracic and mediastinal disorders
Nasal congestion	2/10 (20%)	2
Dysphonia	1/10 (10%)	1
Oropharyngeal pain	1/10 (10%)	1
Skin and subcutaneous tissue disorders
Acne	2/10 (20%)	2
Pruritis generalised	1/10 (10%)	1
Rash	1/10 (10%)	2

Limitations/Caveats

The small number of subjects analyzed as a result of the rarity of the disease (congenital adrenal hyperplasia).and the stage of the study (phase 2a)

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.