Trial Outcomes & Findings for Phase 1/2 Study of Vorinostat Therapy in Niemann-Pick Disease, Type C1 (NCT NCT02124083)
NCT ID: NCT02124083
Last Updated: 2018-02-22
Results Overview
The number of Niemann-Pick Disease, type C1 patients completing 3 month 200 mg phase
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
12 participants
Primary outcome timeframe
3 months
Results posted on
2018-02-22
Participant Flow
Participant milestones
| Measure |
Vorinostat
Trial participants were treated with Vorinostat (3 days on/4 days off regimen) to limit toxicity. Subjects were initially dosed with 200 mg (two 100 mg capsules) by mouth daily for three months, followed by dose escalation to 400 mg (four 100 mg capsules) by mouth daily for three months.
|
|---|---|
|
Overall Study
STARTED
|
12
|
|
Overall Study
COMPLETED
|
11
|
|
Overall Study
NOT COMPLETED
|
1
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Phase 1/2 Study of Vorinostat Therapy in Niemann-Pick Disease, Type C1
Baseline characteristics by cohort
| Measure |
Vorinostat
n=12 Participants
Trial participants were treated with Vorinostat (3 days on/4 days off regimen) to limit toxicity. Subjects were initially dosed with 200 mg (two 100 mg capsules) by mouth daily for three months, followed by dose escalation to 400 mg (four 100 mg capsules) by mouth daily for three months.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
12 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
11 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 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
|
11 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 3 monthsPopulation: All participants who started study
The number of Niemann-Pick Disease, type C1 patients completing 3 month 200 mg phase
Outcome measures
| Measure |
Vorinostat
n=12 Participants
Trial participants were treated with Vorinostat (3 days on/4 days off regimen) to limit toxicity. Subjects were initially dosed with 200 mg (two 100 mg capsules) by mouth daily for three months, followed by dose escalation to 400 mg (four 100 mg capsules) by mouth daily for three months.
|
|---|---|
|
Number of Participants With Tolerabilty of 200 mg Vorinostat in Niemann-Pick Disease, Type C1
|
12 Participants
|
PRIMARY outcome
Timeframe: 3 monthsPopulation: All participants completing 200 mg phase and starting 400 mg phase
The number of Niemann-Pick Disease, type C1 patients completing 3 month 400 mg phase
Outcome measures
| Measure |
Vorinostat
n=11 Participants
Trial participants were treated with Vorinostat (3 days on/4 days off regimen) to limit toxicity. Subjects were initially dosed with 200 mg (two 100 mg capsules) by mouth daily for three months, followed by dose escalation to 400 mg (four 100 mg capsules) by mouth daily for three months.
|
|---|---|
|
Number of Participants With Tolerabilty of 400 mg Vorinostat in Niemann-Pick Disease, Type C1
|
11 Participants
|
SECONDARY outcome
Timeframe: 6 monthsPopulation: All participants completing both 200 and 400 mg phases
Serum concentration of Cathepsin D. Cathepsin D is an aspartyl protease involved in protein catabolism and tissue remodeling. Cathepsin D normal range = 220-515 ng/ml.
Outcome measures
| Measure |
Vorinostat
n=11 Participants
Trial participants were treated with Vorinostat (3 days on/4 days off regimen) to limit toxicity. Subjects were initially dosed with 200 mg (two 100 mg capsules) by mouth daily for three months, followed by dose escalation to 400 mg (four 100 mg capsules) by mouth daily for three months.
|
|---|---|
|
Biochemical Efficacy as Measured by Serum Cathepsin D
|
625.3 ng/mL
Standard Deviation 183.8
|
SECONDARY outcome
Timeframe: BaselinePopulation: All participants who started study
Serum concentration of Cathepsin D. Cathepsin D is an aspartyl protease involved in protein catabolism and tissue remodeling. Cathepsin D normal range = 220-515 ng/ml.
Outcome measures
| Measure |
Vorinostat
n=12 Participants
Trial participants were treated with Vorinostat (3 days on/4 days off regimen) to limit toxicity. Subjects were initially dosed with 200 mg (two 100 mg capsules) by mouth daily for three months, followed by dose escalation to 400 mg (four 100 mg capsules) by mouth daily for three months.
|
|---|---|
|
Biochemical Efficacy as Measured by Serum Cathepsin D
|
648.2 ng/mL
Standard Deviation 266
|
SECONDARY outcome
Timeframe: 6 monthsPopulation: All participants completing both 200 and 400 mg phases
Serum concentration of LGALS3 (galectin-3). Galectin-3 is a carbohydrate-binding lectin whose expression is associated with inflammatory cells including macrophages, neutrophils, and mast cells. LGALS3 normal range = 1.4-5.3 ng/ml.
Outcome measures
| Measure |
Vorinostat
n=11 Participants
Trial participants were treated with Vorinostat (3 days on/4 days off regimen) to limit toxicity. Subjects were initially dosed with 200 mg (two 100 mg capsules) by mouth daily for three months, followed by dose escalation to 400 mg (four 100 mg capsules) by mouth daily for three months.
|
|---|---|
|
Biochemical Efficacy as Measured by Serum LGALS3
|
6.565 ng/mL
Standard Deviation 4.775
|
SECONDARY outcome
Timeframe: BaselinePopulation: All participants who started study
Serum concentration of LGALS3 (galectin-3). Galectin-3 is a carbohydrate-binding lectin whose expression is associated with inflammatory cells including macrophages, neutrophils, and mast cells. LGALS3 normal range = 1.4-5.3 ng/ml.
Outcome measures
| Measure |
Vorinostat
n=12 Participants
Trial participants were treated with Vorinostat (3 days on/4 days off regimen) to limit toxicity. Subjects were initially dosed with 200 mg (two 100 mg capsules) by mouth daily for three months, followed by dose escalation to 400 mg (four 100 mg capsules) by mouth daily for three months.
|
|---|---|
|
Biochemical Efficacy as Measured by Serum LGALS3
|
6.667 ng/mL
Standard Deviation 2.303
|
Adverse Events
Vorinostat
Serious events: 5 serious events
Other events: 11 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Vorinostat
n=12 participants at risk
Trial participants were treated with Vorinostat (3 days on/4 days off regimen) to limit toxicity. Subjects were initially dosed with 200 mg (two 100 mg capsules) by mouth daily for three months, followed by dose escalation to 400 mg (four 100 mg capsules) by mouth daily for three months.
|
|---|---|
|
Gastrointestinal disorders
Vomiting
|
8.3%
1/12 • 6 months
|
|
Infections and infestations
Epstein-Barr viraemia
|
8.3%
1/12 • 6 months
|
|
Infections and infestations
Pyrexia
|
8.3%
1/12 • 6 months
|
|
Injury, poisoning and procedural complications
Cerebrospinal fluid leakage
|
16.7%
2/12 • 6 months
|
|
Investigations
Liver function test increased
|
8.3%
1/12 • 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia aspiration
|
8.3%
1/12 • 6 months
|
Other adverse events
| Measure |
Vorinostat
n=12 participants at risk
Trial participants were treated with Vorinostat (3 days on/4 days off regimen) to limit toxicity. Subjects were initially dosed with 200 mg (two 100 mg capsules) by mouth daily for three months, followed by dose escalation to 400 mg (four 100 mg capsules) by mouth daily for three months.
|
|---|---|
|
Ear and labyrinth disorders
Tympanic membrane perforation
|
8.3%
1/12 • 6 months
|
|
Gastrointestinal disorders
Constipation
|
8.3%
1/12 • 6 months
|
|
Gastrointestinal disorders
Dry mouth
|
16.7%
2/12 • 6 months
|
|
Gastrointestinal disorders
Dysphagia
|
8.3%
1/12 • 6 months
|
|
Gastrointestinal disorders
Gastrostomy tube site complication
|
8.3%
1/12 • 6 months
|
|
Gastrointestinal disorders
Reflux gastritis
|
8.3%
1/12 • 6 months
|
|
Gastrointestinal disorders
Salivary hypersecretion
|
8.3%
1/12 • 6 months
|
|
Gastrointestinal disorders
Vomiting
|
16.7%
2/12 • 6 months
|
|
General disorders
Fatigue
|
33.3%
4/12 • 6 months
|
|
General disorders
Irritability
|
8.3%
1/12 • 6 months
|
|
Infections and infestations
Bronchitis
|
8.3%
1/12 • 6 months
|
|
Infections and infestations
Lip infection
|
8.3%
1/12 • 6 months
|
|
Infections and infestations
Mouth ulceration
|
8.3%
1/12 • 6 months
|
|
Infections and infestations
Rhinitis
|
41.7%
5/12 • 6 months
|
|
Injury, poisoning and procedural complications
Contusion
|
8.3%
1/12 • 6 months
|
|
Injury, poisoning and procedural complications
Fall
|
25.0%
3/12 • 6 months
|
|
Investigations
Liver function test increased
|
8.3%
1/12 • 6 months
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
8.3%
1/12 • 6 months
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
8.3%
1/12 • 6 months
|
|
Musculoskeletal and connective tissue disorders
Pain
|
8.3%
1/12 • 6 months
|
|
Nervous system disorders
Ataxia
|
33.3%
4/12 • 6 months
|
|
Nervous system disorders
Cataplexy
|
8.3%
1/12 • 6 months
|
|
Nervous system disorders
Dysgeusia
|
16.7%
2/12 • 6 months
|
|
Nervous system disorders
Headache
|
16.7%
2/12 • 6 months
|
|
Nervous system disorders
Memory impairment
|
25.0%
3/12 • 6 months
|
|
Nervous system disorders
Seizure
|
8.3%
1/12 • 6 months
|
|
Nervous system disorders
Tremor
|
8.3%
1/12 • 6 months
|
|
Psychiatric disorders
Agitation
|
8.3%
1/12 • 6 months
|
|
Psychiatric disorders
Depression
|
16.7%
2/12 • 6 months
|
|
Psychiatric disorders
Insomnia
|
8.3%
1/12 • 6 months
|
|
Psychiatric disorders
Mania
|
8.3%
1/12 • 6 months
|
|
Psychiatric disorders
Personality change
|
16.7%
2/12 • 6 months
|
|
Psychiatric disorders
Psychotic disorder
|
16.7%
2/12 • 6 months
|
|
Reproductive system and breast disorders
Dysmenorrhoea
|
8.3%
1/12 • 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
8.3%
1/12 • 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Hiccups
|
8.3%
1/12 • 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Throat irritation
|
8.3%
1/12 • 6 months
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
8.3%
1/12 • 6 months
|
|
Skin and subcutaneous tissue disorders
Rash
|
8.3%
1/12 • 6 months
|
|
Surgical and medical procedures
Tracheostomy
|
8.3%
1/12 • 6 months
|
Additional Information
Porter, Forbes
National Institute of Child Health and Human Development
Phone: +1 301 435 4432
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place