Trial Outcomes & Findings for Nevanimibe HCl for the Treatment of Classic CAH (NCT NCT03669549)
NCT ID: NCT03669549
Last Updated: 2021-03-04
Results Overview
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))
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
15 participants
Primary outcome timeframe
Through Day 113
Results posted on
2021-03-04
Participant Flow
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
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.
Participant milestones
| Measure |
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.
|
|---|---|
|
Overall Study
STARTED
|
15
|
|
Overall Study
COMPLETED
|
9
|
|
Overall Study
NOT COMPLETED
|
6
|
Reasons for withdrawal
| Measure |
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.
|
|---|---|
|
Overall Study
Adverse Event
|
4
|
|
Overall Study
Withdrawal by Subject
|
1
|
|
Overall Study
Study terminated by the Sponsor
|
1
|
Baseline Characteristics
Nevanimibe HCl for the Treatment of Classic CAH
Baseline characteristics by cohort
| Measure |
Nevanimibe HCl
n=15 Participants
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.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
15 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
29.3 years
STANDARD_DEVIATION 11.0 • n=5 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
15 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
Czechia
|
2 participants
n=5 Participants
|
|
Region of Enrollment
Brazil
|
1 participants
n=5 Participants
|
|
Region of Enrollment
Israel
|
4 participants
n=5 Participants
|
|
Region of Enrollment
France
|
2 participants
n=5 Participants
|
|
Region of Enrollment
Spain
|
6 participants
n=5 Participants
|
|
Baseline serum 17-hydroxyprogesterone
|
10644.1 ng/dL
STANDARD_DEVIATION 10618.3 • n=5 Participants
|
PRIMARY outcome
Timeframe: Through Day 113The 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))
Outcome measures
| Measure |
Nevanimibe HCl
n=15 Participants
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.
|
|---|---|
|
Percentage of Subjects Achieving Serum 17-OHP Targets
|
7.1 percent
|
Adverse Events
Nevanimibe HCl Dose Level: <500 mg BID
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Nevanimibe HCl Dose Level:500 to <1000 mg BID
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Nevanimibe HCl Dose Level: 1000 to <1500 mg BID
Serious events: 1 serious events
Other events: 8 other events
Deaths: 0 deaths
Nevanimibe HCl Dose Level: 1500 to <2000 mg BID
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Nevanimibe HCl Dose Level:2000 mg BID
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Nevanimibe HCl Dose Level: <500 mg BID
n=14 participants at risk
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.
|
Nevanimibe HCl Dose Level:500 to <1000 mg BID
n=5 participants at risk
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.
|
Nevanimibe HCl Dose Level: 1000 to <1500 mg BID
n=14 participants at risk
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.
|
Nevanimibe HCl Dose Level: 1500 to <2000 mg BID
n=9 participants at risk
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.
|
Nevanimibe HCl Dose Level:2000 mg BID
n=9 participants at risk
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.
|
|---|---|---|---|---|---|
|
Infections and infestations
Uroinfection
|
0.00%
0/14 • From the time of informed consent through treatment period and until 30 days after the last dose of study drug
|
0.00%
0/5 • From the time of informed consent through treatment period and until 30 days after the last dose of study drug
|
7.1%
1/14 • Number of events 1 • From the time of informed consent through treatment period and until 30 days after the last dose of study drug
|
0.00%
0/9 • From the time of informed consent through treatment period and until 30 days after the last dose of study drug
|
0.00%
0/9 • From the time of informed consent through treatment period and until 30 days after the last dose of study drug
|
Other adverse events
| Measure |
Nevanimibe HCl Dose Level: <500 mg BID
n=14 participants at risk
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.
|
Nevanimibe HCl Dose Level:500 to <1000 mg BID
n=5 participants at risk
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.
|
Nevanimibe HCl Dose Level: 1000 to <1500 mg BID
n=14 participants at risk
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.
|
Nevanimibe HCl Dose Level: 1500 to <2000 mg BID
n=9 participants at risk
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.
|
Nevanimibe HCl Dose Level:2000 mg BID
n=9 participants at risk
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.
|
|---|---|---|---|---|---|
|
Immune system disorders
Drug hypersensitivity
|
7.1%
1/14 • Number of events 1 • From the time of informed consent through treatment period and until 30 days after the last dose of study drug
|
0.00%
0/5 • From the time of informed consent through treatment period and until 30 days after the last dose of study drug
|
0.00%
0/14 • From the time of informed consent through treatment period and until 30 days after the last dose of study drug
|
0.00%
0/9 • From the time of informed consent through treatment period and until 30 days after the last dose of study drug
|
0.00%
0/9 • From the time of informed consent through treatment period and until 30 days after the last dose of study drug
|
|
General disorders
Asthenia, Chest pain, Fatigue, Noncardiac chest pain, Pyrexia
|
0.00%
0/14 • From the time of informed consent through treatment period and until 30 days after the last dose of study drug
|
40.0%
2/5 • Number of events 2 • From the time of informed consent through treatment period and until 30 days after the last dose of study drug
|
7.1%
1/14 • Number of events 1 • From the time of informed consent through treatment period and until 30 days after the last dose of study drug
|
0.00%
0/9 • From the time of informed consent through treatment period and until 30 days after the last dose of study drug
|
22.2%
2/9 • Number of events 2 • From the time of informed consent through treatment period and until 30 days after the last dose of study drug
|
|
Psychiatric disorders
Insomnia, Panic attack
|
0.00%
0/14 • From the time of informed consent through treatment period and until 30 days after the last dose of study drug
|
0.00%
0/5 • From the time of informed consent through treatment period and until 30 days after the last dose of study drug
|
0.00%
0/14 • From the time of informed consent through treatment period and until 30 days after the last dose of study drug
|
22.2%
2/9 • Number of events 2 • From the time of informed consent through treatment period and until 30 days after the last dose of study drug
|
0.00%
0/9 • From the time of informed consent through treatment period and until 30 days after the last dose of study drug
|
|
Reproductive system and breast disorders
Vaginal hemorrhage
|
0.00%
0/14 • From the time of informed consent through treatment period and until 30 days after the last dose of study drug
|
0.00%
0/5 • From the time of informed consent through treatment period and until 30 days after the last dose of study drug
|
0.00%
0/14 • From the time of informed consent through treatment period and until 30 days after the last dose of study drug
|
0.00%
0/9 • From the time of informed consent through treatment period and until 30 days after the last dose of study drug
|
11.1%
1/9 • Number of events 1 • From the time of informed consent through treatment period and until 30 days after the last dose of study drug
|
|
Injury, poisoning and procedural complications
Toxicity to various agents
|
0.00%
0/14 • From the time of informed consent through treatment period and until 30 days after the last dose of study drug
|
0.00%
0/5 • From the time of informed consent through treatment period and until 30 days after the last dose of study drug
|
0.00%
0/14 • From the time of informed consent through treatment period and until 30 days after the last dose of study drug
|
11.1%
1/9 • Number of events 1 • From the time of informed consent through treatment period and until 30 days after the last dose of study drug
|
0.00%
0/9 • From the time of informed consent through treatment period and until 30 days after the last dose of study drug
|
|
Investigations
Blood glucose increased
|
0.00%
0/14 • From the time of informed consent through treatment period and until 30 days after the last dose of study drug
|
0.00%
0/5 • From the time of informed consent through treatment period and until 30 days after the last dose of study drug
|
0.00%
0/14 • From the time of informed consent through treatment period and until 30 days after the last dose of study drug
|
0.00%
0/9 • From the time of informed consent through treatment period and until 30 days after the last dose of study drug
|
11.1%
1/9 • Number of events 1 • From the time of informed consent through treatment period and until 30 days after the last dose of study drug
|
|
Respiratory, thoracic and mediastinal disorders
Cough, Oropharyngeal pain
|
0.00%
0/14 • From the time of informed consent through treatment period and until 30 days after the last dose of study drug
|
40.0%
2/5 • Number of events 2 • From the time of informed consent through treatment period and until 30 days after the last dose of study drug
|
0.00%
0/14 • From the time of informed consent through treatment period and until 30 days after the last dose of study drug
|
0.00%
0/9 • From the time of informed consent through treatment period and until 30 days after the last dose of study drug
|
0.00%
0/9 • From the time of informed consent through treatment period and until 30 days after the last dose of study drug
|
|
Nervous system disorders
Disturbance in attention, Headache, Syncope
|
0.00%
0/14 • From the time of informed consent through treatment period and until 30 days after the last dose of study drug
|
0.00%
0/5 • From the time of informed consent through treatment period and until 30 days after the last dose of study drug
|
14.3%
2/14 • Number of events 2 • From the time of informed consent through treatment period and until 30 days after the last dose of study drug
|
11.1%
1/9 • Number of events 1 • From the time of informed consent through treatment period and until 30 days after the last dose of study drug
|
0.00%
0/9 • From the time of informed consent through treatment period and until 30 days after the last dose of study drug
|
|
Eye disorders
Dry eye
|
0.00%
0/14 • From the time of informed consent through treatment period and until 30 days after the last dose of study drug
|
40.0%
2/5 • Number of events 2 • From the time of informed consent through treatment period and until 30 days after the last dose of study drug
|
0.00%
0/14 • From the time of informed consent through treatment period and until 30 days after the last dose of study drug
|
0.00%
0/9 • From the time of informed consent through treatment period and until 30 days after the last dose of study drug
|
0.00%
0/9 • From the time of informed consent through treatment period and until 30 days after the last dose of study drug
|
|
Gastrointestinal disorders
Abdominal discomfort, Diarrhoea, Dyspepsia, Flatulence, Gingival bleeding, Nausea
|
0.00%
0/14 • From the time of informed consent through treatment period and until 30 days after the last dose of study drug
|
40.0%
2/5 • Number of events 2 • From the time of informed consent through treatment period and until 30 days after the last dose of study drug
|
14.3%
2/14 • Number of events 2 • From the time of informed consent through treatment period and until 30 days after the last dose of study drug
|
44.4%
4/9 • Number of events 4 • From the time of informed consent through treatment period and until 30 days after the last dose of study drug
|
22.2%
2/9 • Number of events 2 • From the time of informed consent through treatment period and until 30 days after the last dose of study drug
|
|
Renal and urinary disorders
Dysuria, Hypertonic bladder, Micturition urgency, Pollakiuria
|
0.00%
0/14 • From the time of informed consent through treatment period and until 30 days after the last dose of study drug
|
60.0%
3/5 • Number of events 3 • From the time of informed consent through treatment period and until 30 days after the last dose of study drug
|
21.4%
3/14 • Number of events 3 • From the time of informed consent through treatment period and until 30 days after the last dose of study drug
|
11.1%
1/9 • Number of events 1 • From the time of informed consent through treatment period and until 30 days after the last dose of study drug
|
0.00%
0/9 • From the time of informed consent through treatment period and until 30 days after the last dose of study drug
|
|
Skin and subcutaneous tissue disorders
Acne, Eczema, Pruritus, Rash, Urticaria
|
14.3%
2/14 • Number of events 2 • From the time of informed consent through treatment period and until 30 days after the last dose of study drug
|
60.0%
3/5 • Number of events 3 • From the time of informed consent through treatment period and until 30 days after the last dose of study drug
|
14.3%
2/14 • Number of events 2 • From the time of informed consent through treatment period and until 30 days after the last dose of study drug
|
0.00%
0/9 • From the time of informed consent through treatment period and until 30 days after the last dose of study drug
|
0.00%
0/9 • From the time of informed consent through treatment period and until 30 days after the last dose of study drug
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.00%
0/14 • From the time of informed consent through treatment period and until 30 days after the last dose of study drug
|
0.00%
0/5 • From the time of informed consent through treatment period and until 30 days after the last dose of study drug
|
7.1%
1/14 • Number of events 1 • From the time of informed consent through treatment period and until 30 days after the last dose of study drug
|
11.1%
1/9 • Number of events 1 • From the time of informed consent through treatment period and until 30 days after the last dose of study drug
|
0.00%
0/9 • From the time of informed consent through treatment period and until 30 days after the last dose of study drug
|
|
Infections and infestations
Cystitis, Nasopharyngitis, Urinary tract infection
|
0.00%
0/14 • From the time of informed consent through treatment period and until 30 days after the last dose of study drug
|
0.00%
0/5 • From the time of informed consent through treatment period and until 30 days after the last dose of study drug
|
14.3%
2/14 • Number of events 2 • From the time of informed consent through treatment period and until 30 days after the last dose of study drug
|
0.00%
0/9 • From the time of informed consent through treatment period and until 30 days after the last dose of study drug
|
11.1%
1/9 • Number of events 1 • From the time of informed consent through treatment period and until 30 days after the last dose of study drug
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place