Trial Outcomes & Findings for An Open Label Phase 2 Study of ManNAc in Subjects With GNE Myopathy (NCT NCT02346461)
NCT ID: NCT02346461
Last Updated: 2019-04-16
Results Overview
The mean area under the plasma ManNAc concentration-versus time curve from time 0 (dosing) to the time of last quantifiable concentration.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
12 participants
Primary outcome timeframe
Day 7
Results posted on
2019-04-16
Participant Flow
Participant milestones
| Measure |
ManNAc: Cohort A
Cohort A received oral ManNAc 3 g twice daily (6 g/day) for 7 days and, then were escalated to 6 g twice daily (12 g/day) for the remainder of the study.
|
ManNAc: Cohort B
Cohort B received oral ManNAc 6 g twice daily (12 g/day) for the duration of the study.
|
|---|---|---|
|
Overall Study
STARTED
|
6
|
6
|
|
Overall Study
COMPLETED
|
6
|
6
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
An Open Label Phase 2 Study of ManNAc in Subjects With GNE Myopathy
Baseline characteristics by cohort
| Measure |
ManNAc: Cohort A
n=6 Participants
Cohort A received oral ManNAc 3 g twice daily (6 g/day) for 7 days and, then were escalated to 6 g twice daily (12 g/day) for the remainder of the study.
|
ManNAc: Cohort B
n=6 Participants
Cohort B received oral ManNAc 6 g twice daily (12 g/day) for the duration of the study.
|
Total
n=12 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
6 Participants
n=99 Participants
|
6 Participants
n=107 Participants
|
12 Participants
n=206 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
6 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
6 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
6 Participants
n=99 Participants
|
6 Participants
n=107 Participants
|
12 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
4 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
White
|
4 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
8 Participants
n=206 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: Day 7Population: All subjects received ManNAc
The mean area under the plasma ManNAc concentration-versus time curve from time 0 (dosing) to the time of last quantifiable concentration.
Outcome measures
| Measure |
ManNAc: Cohort A
n=6 Participants
ManNAc 3 g twice daily (6 g/day) for 7 days
|
ManNAc: Cohort B
n=6 Participants
ManNAc 6 g twice daily (12 g/day)
|
|---|---|---|
|
Mean Area Under the Curve (AUClast) of Plasma ManNAc (Baseline-adjusted)
|
7461 hr*ng/mL
Standard Deviation 1776
|
9432 hr*ng/mL
Standard Deviation 2710
|
PRIMARY outcome
Timeframe: Day 7Population: All subjects received ManNAc
The maximum (or peak) plasma ManNAc concentration that the drug achieves in the body after the drug has been administrated.
Outcome measures
| Measure |
ManNAc: Cohort A
n=6 Participants
ManNAc 3 g twice daily (6 g/day) for 7 days
|
ManNAc: Cohort B
n=6 Participants
ManNAc 6 g twice daily (12 g/day)
|
|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) of ManNAc (Baseline-adjusted)
|
1588 ng/mL
Standard Deviation 28.9
|
1774 ng/mL
Standard Deviation 21.2
|
PRIMARY outcome
Timeframe: Day 7Population: All subjects received ManNAc
The time taken to achieve the maximum observed plasma concentration for ManNAc .
Outcome measures
| Measure |
ManNAc: Cohort A
n=6 Participants
ManNAc 3 g twice daily (6 g/day) for 7 days
|
ManNAc: Cohort B
n=6 Participants
ManNAc 6 g twice daily (12 g/day)
|
|---|---|---|
|
The Time to Cmax (Tmax) for ManNAc
|
2.0 hours
Standard Deviation 0.4
|
2.5 hours
Standard Deviation 0.8
|
PRIMARY outcome
Timeframe: Day 7Population: All subjects received ManNAc
The amount of time it takes for plasma ManNAc concentration to decline by half.
Outcome measures
| Measure |
ManNAc: Cohort A
n=6 Participants
ManNAc 3 g twice daily (6 g/day) for 7 days
|
ManNAc: Cohort B
n=6 Participants
ManNAc 6 g twice daily (12 g/day)
|
|---|---|---|
|
Half-life (t ½) for ManNAc
|
2.0 hours
Standard Deviation 0.3
|
2.1 hours
Standard Deviation 1.1
|
PRIMARY outcome
Timeframe: Day 7Population: All subjects received ManNAc
The mean area under the plasma Neu5Ac concentration-versus time curve from time 0 (dosing) to the time of last quantifiable concentration.
Outcome measures
| Measure |
ManNAc: Cohort A
n=6 Participants
ManNAc 3 g twice daily (6 g/day) for 7 days
|
ManNAc: Cohort B
n=6 Participants
ManNAc 6 g twice daily (12 g/day)
|
|---|---|---|
|
Mean Area Under the Curve (AUClast) of Plasma Neu5Ac (Baseline-adjusted)
|
4206 hr*ng/mL
Standard Deviation 1352
|
5175 hr*ng/mL
Standard Deviation 1421
|
PRIMARY outcome
Timeframe: Day 7Population: All subjects received ManNAc
The maximum (or peak) plasma Neu5Ac concentration that the drug achieves in the body after the drug has been administrated.
Outcome measures
| Measure |
ManNAc: Cohort A
n=6 Participants
ManNAc 3 g twice daily (6 g/day) for 7 days
|
ManNAc: Cohort B
n=6 Participants
ManNAc 6 g twice daily (12 g/day)
|
|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) of Neu5Ac (Baseline-adjusted)
|
469 ng/mL
Standard Deviation 35.1
|
620 ng/mL
Standard Deviation 25.5
|
PRIMARY outcome
Timeframe: Day 7Population: All subjects received ManNAc
The time taken to achieve the maximum observed plasma concentration for Neu5Ac.
Outcome measures
| Measure |
ManNAc: Cohort A
n=6 Participants
ManNAc 3 g twice daily (6 g/day) for 7 days
|
ManNAc: Cohort B
n=6 Participants
ManNAc 6 g twice daily (12 g/day)
|
|---|---|---|
|
The Time to Cmax (Tmax) for Neu5Ac
|
8.0 hours
Standard Deviation 4.1
|
6.0 hours
Standard Deviation 3.4
|
Adverse Events
ManNAc 3 g - 7 Days
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
ManNAc 6 g - 7 Days
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
ManNAc 6 g - Day 8 to 30 Months
Serious events: 0 serious events
Other events: 12 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
ManNAc 3 g - 7 Days
n=6 participants at risk
Subjects who received oral ManNAc 3 g twice daily (6 g/day) for the first 7 days.
|
ManNAc 6 g - 7 Days
n=6 participants at risk
Subjects who received oral ManNAc 6 g twice daily (12 g/day) for the first 7 days.
|
ManNAc 6 g - Day 8 to 30 Months
n=12 participants at risk
All subjects received oral ManNAc 6 g twice daily (12 g/day) from day 8 to the end of the study at 30 months.
|
|---|---|---|---|
|
Gastrointestinal disorders
Abdominal distension
|
33.3%
2/6 • 30 months
|
16.7%
1/6 • 30 months
|
16.7%
2/12 • 30 months
|
|
Gastrointestinal disorders
Abdominal pain
|
16.7%
1/6 • 30 months
|
0.00%
0/6 • 30 months
|
0.00%
0/12 • 30 months
|
|
Investigations
Activated partial thromboplastin time prolonged
|
0.00%
0/6 • 30 months
|
33.3%
2/6 • 30 months
|
58.3%
7/12 • 30 months
|
|
Investigations
Alanine aminotransferase increased
|
33.3%
2/6 • 30 months
|
50.0%
3/6 • 30 months
|
50.0%
6/12 • 30 months
|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/6 • 30 months
|
33.3%
2/6 • 30 months
|
25.0%
3/12 • 30 months
|
|
Investigations
Aspartate aminotransferase increased
|
16.7%
1/6 • 30 months
|
66.7%
4/6 • 30 months
|
16.7%
2/12 • 30 months
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/6 • 30 months
|
0.00%
0/6 • 30 months
|
8.3%
1/12 • 30 months
|
|
Skin and subcutaneous tissue disorders
Basal cell carcinoma
|
0.00%
0/6 • 30 months
|
0.00%
0/6 • 30 months
|
8.3%
1/12 • 30 months
|
|
Investigations
Blood bilirubin increased
|
0.00%
0/6 • 30 months
|
16.7%
1/6 • 30 months
|
8.3%
1/12 • 30 months
|
|
Investigations
Blood cholesterol increased
|
0.00%
0/6 • 30 months
|
0.00%
0/6 • 30 months
|
25.0%
3/12 • 30 months
|
|
Investigations
Blood creatine phosphokinase increased
|
33.3%
2/6 • 30 months
|
66.7%
4/6 • 30 months
|
66.7%
8/12 • 30 months
|
|
Infections and infestations
Bronchitis
|
0.00%
0/6 • 30 months
|
0.00%
0/6 • 30 months
|
8.3%
1/12 • 30 months
|
|
Gastrointestinal disorders
Constipation
|
16.7%
1/6 • 30 months
|
0.00%
0/6 • 30 months
|
0.00%
0/12 • 30 months
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/6 • 30 months
|
0.00%
0/6 • 30 months
|
25.0%
3/12 • 30 months
|
|
Skin and subcutaneous tissue disorders
Dyshidrotic eczema
|
0.00%
0/6 • 30 months
|
0.00%
0/6 • 30 months
|
8.3%
1/12 • 30 months
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/6 • 30 months
|
0.00%
0/6 • 30 months
|
16.7%
2/12 • 30 months
|
|
Investigations
Electrocardiogram QT prolonged
|
0.00%
0/6 • 30 months
|
0.00%
0/6 • 30 months
|
8.3%
1/12 • 30 months
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/6 • 30 months
|
0.00%
0/6 • 30 months
|
41.7%
5/12 • 30 months
|
|
Gastrointestinal disorders
Flatulence
|
33.3%
2/6 • 30 months
|
33.3%
2/6 • 30 months
|
33.3%
4/12 • 30 months
|
|
Investigations
Gamma-glutamyltransferase increased
|
0.00%
0/6 • 30 months
|
16.7%
1/6 • 30 months
|
16.7%
2/12 • 30 months
|
|
Renal and urinary disorders
Haematuria
|
0.00%
0/6 • 30 months
|
0.00%
0/6 • 30 months
|
8.3%
1/12 • 30 months
|
|
Nervous system disorders
Headache
|
16.7%
1/6 • 30 months
|
0.00%
0/6 • 30 months
|
16.7%
2/12 • 30 months
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
16.7%
1/6 • 30 months
|
0.00%
0/6 • 30 months
|
41.7%
5/12 • 30 months
|
|
Metabolism and nutrition disorders
Hypertriglyceridaemia
|
33.3%
2/6 • 30 months
|
0.00%
0/6 • 30 months
|
25.0%
3/12 • 30 months
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
0.00%
0/6 • 30 months
|
16.7%
1/6 • 30 months
|
8.3%
1/12 • 30 months
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
0.00%
0/6 • 30 months
|
0.00%
0/6 • 30 months
|
8.3%
1/12 • 30 months
|
|
Investigations
Lymphocyte count decreased
|
0.00%
0/6 • 30 months
|
33.3%
2/6 • 30 months
|
0.00%
0/12 • 30 months
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/6 • 30 months
|
0.00%
0/6 • 30 months
|
8.3%
1/12 • 30 months
|
|
Musculoskeletal and connective tissue disorders
Myositis
|
0.00%
0/6 • 30 months
|
0.00%
0/6 • 30 months
|
8.3%
1/12 • 30 months
|
|
Metabolism and nutrition disorders
Obesity
|
33.3%
2/6 • 30 months
|
0.00%
0/6 • 30 months
|
50.0%
6/12 • 30 months
|
|
General disorders
Oedema peripheral
|
16.7%
1/6 • 30 months
|
0.00%
0/6 • 30 months
|
0.00%
0/12 • 30 months
|
|
General disorders
Pain
|
16.7%
1/6 • 30 months
|
0.00%
0/6 • 30 months
|
8.3%
1/12 • 30 months
|
|
Investigations
Platelet count decreased
|
0.00%
0/6 • 30 months
|
0.00%
0/6 • 30 months
|
8.3%
1/12 • 30 months
|
|
Nervous system disorders
Presyncope
|
0.00%
0/6 • 30 months
|
0.00%
0/6 • 30 months
|
8.3%
1/12 • 30 months
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/6 • 30 months
|
0.00%
0/6 • 30 months
|
8.3%
1/12 • 30 months
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
16.7%
1/6 • 30 months
|
0.00%
0/6 • 30 months
|
16.7%
2/12 • 30 months
|
|
Infections and infestations
Sinusitis
|
0.00%
0/6 • 30 months
|
0.00%
0/6 • 30 months
|
8.3%
1/12 • 30 months
|
|
Skin and subcutaneous tissue disorders
Skin induration
|
16.7%
1/6 • 30 months
|
0.00%
0/6 • 30 months
|
0.00%
0/12 • 30 months
|
|
Infections and infestations
Skin infection
|
0.00%
0/6 • 30 months
|
0.00%
0/6 • 30 months
|
16.7%
2/12 • 30 months
|
|
Nervous system disorders
syncope
|
0.00%
0/6 • 30 months
|
0.00%
0/6 • 30 months
|
8.3%
1/12 • 30 months
|
|
Metabolism and nutrition disorders
Vitamin D deficiency
|
0.00%
0/6 • 30 months
|
0.00%
0/6 • 30 months
|
16.7%
2/12 • 30 months
|
|
Investigations
Weight decreased
|
0.00%
0/6 • 30 months
|
0.00%
0/6 • 30 months
|
8.3%
1/12 • 30 months
|
|
Investigations
Weight increased
|
0.00%
0/6 • 30 months
|
0.00%
0/6 • 30 months
|
41.7%
5/12 • 30 months
|
|
Investigations
White blood cell count decreased
|
0.00%
0/6 • 30 months
|
0.00%
0/6 • 30 months
|
8.3%
1/12 • 30 months
|
Additional Information
Carrillo, Nuria
National Human Genome Research Institute
Phone: +1 301 402 2324
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place