Congenital Adrenal Hyperplasia
Conditions
Keywords
CAH, nevanimibe
Brief summary
This is a multicenter, intra-subject dose-titration open-label study of nevanimibe hydrochloride (HCl) for the treatment of classic congenital adrenal hyperplasia (CAH). Following a Screening Period of approximately 2-14 weeks, eligible subjects will enter a Baseline Period of approximately 2-8 weeks and then a 16-week Treatment Period. It is anticipated that the overall duration of the study per subject will range from 24-42 weeks.
Interventions
DRUGNevanimibe hydrochloride
During the 16-week treatment period, all subjects will begin dosing with nevanimibe HCl 500 mg BID and be dose titrated to 1000 mg BID, 1500 mg BID, and 2000 mg BID as needed based on serum 17-OHP assessments every 4 weeks.
Sponsors
Millendo Therapeutics US, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Documented historical diagnosis of classic CAH due to 21-hydroxylase deficiency and/or historical documentation of elevated 17-OHP * Chronic glucocorticoid replacement therapy for at least 6 consecutive months prior to screening * Stable glucocorticoid and mineralocorticoid regimen for at least 4 weeks prior to screening and throughout the treatment period of the study
Exclusion criteria
* Nonclassic CAH * Other causes of adrenal insufficiency * HIV, hepatitis B, or hepatitis C * AST or ALT \>2x ULN, bilirubin or serum creatinine \>1.5x ULN
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects Achieving Serum 17-OHP Targets | Through Day 113 | The primary efficacy endpoint was the overall response rate within each cohort, defined as the percentage of patients achieving serum 17-OHP targets as follows: * Men and postmenopausal women: 17-OHP ≤ 2x ULN * Premenopausal women: * Follicular phase: 17-OHP ≤ 2x follicular phase ULN * Luteal phase: 17-OHP ≤ (2x follicular phase ULN + (luteal phase ULN - follicular phase ULN)) |
Countries
Brazil, Czechia, France, Israel, Spain
Participant flow
Recruitment details
Global Amendment 1: Approximately 20-24 adults with a documented history of classic CAH will be enrolled Global Amendment 2: Approximately 20-24 evaluable adults with a documented history of classic CAH will be enrolled 20-24 patients planned, 15 patients analyzed
Pre-assignment details
Screening Period of 2-14 weeks After signing informed consent, patients with classic CAH entered the Screening Period to assess preliminary eligibility for the study based on the inclusion and exclusion criteria. In addition, pertinent information was collected such as past medical history, demographic data, and prior and current medications.
Participants by arm
| Arm | Count |
|---|---|
| Nevanimibe HCl Ascending dose level of oral nevanimibe hydrochloride beginning with 500 mg BID up to 2000 mg BID
Nevanimibe hydrochloride: During the 16-week treatment period, all subjects will begin dosing with nevanimibe HCl 500 mg BID and be dose titrated to 1000 mg BID, 1500 mg BID, and 2000 mg BID as needed based on serum 17-OHP assessments every 4 weeks. | 15 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 4 |
| Overall Study | Study terminated by the Sponsor | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Nevanimibe HCl |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants |
| Age, Continuous | 29.3 years STANDARD_DEVIATION 11 |
| Baseline serum 17-hydroxyprogesterone | 10644.1 ng/dL STANDARD_DEVIATION 10618.3 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 15 Participants |
| Region of Enrollment Brazil | 1 participants |
| Region of Enrollment Czechia | 2 participants |
| Region of Enrollment France | 2 participants |
| Region of Enrollment Israel | 4 participants |
| Region of Enrollment Spain | 6 participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 0 / 5 | 0 / 14 | 0 / 9 | 0 / 9 |
| other Total, other adverse events | 3 / 14 | 5 / 5 | 8 / 14 | 7 / 9 | 5 / 9 |
| serious Total, serious adverse events | 0 / 14 | 0 / 5 | 1 / 14 | 0 / 9 | 0 / 9 |
Outcome results
Primary
Percentage of Subjects Achieving Serum 17-OHP Targets
The primary efficacy endpoint was the overall response rate within each cohort, defined as the percentage of patients achieving serum 17-OHP targets as follows: * Men and postmenopausal women: 17-OHP ≤ 2x ULN * Premenopausal women: * Follicular phase: 17-OHP ≤ 2x follicular phase ULN * Luteal phase: 17-OHP ≤ (2x follicular phase ULN + (luteal phase ULN - follicular phase ULN))
Time frame: Through Day 113
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nevanimibe HCl | Percentage of Subjects Achieving Serum 17-OHP Targets | 7.1 percent |