Trial Outcomes & Findings for Open-Label, Dose-Escalating Study Assessing Safety, Tolerability, Efficacy, of RP103 in Mitochondrial Disease (NCT NCT02023866)
NCT ID: NCT02023866
Last Updated: 2024-12-27
Results Overview
The NPMDS evaluates the progression of mitochondrial disease in pediatric patients in 4 domains: I - Current Function (vision, hearing, communication, feeding, and mobility) with scores ranging from 0 to 21; II -System Specific Involvement (seizures, encephalopathy, bleeding diathesis or coagulation defects, gastrointestinal, endocrine, respiratory, cardiovascular, renal, liver, and blood) with scores ranging from 0 to 30. III - Current Clinical Assessment (growth and development over past 6 months, vision, strabismus and eye movement, myopathy, ataxia, pyramidal, extrapyramidal, and neuropathy) with scores ranging from 0 to 28; and IV - Quality of Life with scores ranging from 0 to 25. For sections I-III, higher scores reflect more severe disease. For Section IV, a higher score reflects a lower quality of life.
COMPLETED
PHASE2
36 participants
Baseline through Week 24
2024-12-27
Participant Flow
Participant milestones
| Measure |
Cysteamine Bitartrate Delayed-release
Cysteamine bitartrate delayed-release capsules were administered twice daily following a dose-escalation design with a progressive weekly dose increase over the first 6 weeks. The starting dose was 0.2 g/m²/day, up to a maximum dose of 1.3 g/m²/day. Participants remained on their highest tolerated dose until Week 24.
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|---|---|
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Overall Study
STARTED
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36
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Overall Study
COMPLETED
|
30
|
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Overall Study
NOT COMPLETED
|
6
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Reasons for withdrawal
| Measure |
Cysteamine Bitartrate Delayed-release
Cysteamine bitartrate delayed-release capsules were administered twice daily following a dose-escalation design with a progressive weekly dose increase over the first 6 weeks. The starting dose was 0.2 g/m²/day, up to a maximum dose of 1.3 g/m²/day. Participants remained on their highest tolerated dose until Week 24.
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|---|---|
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Overall Study
Non-compliance
|
2
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Overall Study
Adverse Event
|
3
|
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Overall Study
Withdrawal by Subject
|
1
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Baseline Characteristics
Open-Label, Dose-Escalating Study Assessing Safety, Tolerability, Efficacy, of RP103 in Mitochondrial Disease
Baseline characteristics by cohort
| Measure |
Cysteamine Bitartrate Delayed-release
n=36 Participants
Cysteamine bitartrate delayed-release capsules were administered twice daily following a dose-escalation design with a progressive weekly dose increase over the first 6 weeks. The starting dose was 0.2 g/m²/day, up to a maximum dose of 1.3 g/m²/day. Participants remained on their highest tolerated dose until Week 24.
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|---|---|
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Age, Continuous
|
9.3 years
STANDARD_DEVIATION 4.8 • n=5 Participants
|
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Sex: Female, Male
Female
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17 Participants
n=5 Participants
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Sex: Female, Male
Male
|
19 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
5 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
31 Participants
n=5 Participants
|
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Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
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Race/Ethnicity, Customized
American Indian or Alaska Native
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3 Participants
n=5 Participants
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Race/Ethnicity, Customized
Asian
|
0 Participants
n=5 Participants
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Race/Ethnicity, Customized
Black of African American
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0 Participants
n=5 Participants
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|
Race/Ethnicity, Customized
Native Hawaiian or other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
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28 Participants
n=5 Participants
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Race/Ethnicity, Customized
Other
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2 Participants
n=5 Participants
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Race/Ethnicity, Customized
Multiple
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3 Participants
n=5 Participants
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Mitochondrial Disease Subtype
Leigh Syndrome
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9 Participants
n=5 Participants
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Mitochondrial Disease Subtype
POLG-related disorders
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7 Participants
n=5 Participants
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Mitochondrial Disease Subtype
MELAS
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6 Participants
n=5 Participants
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Mitochondrial Disease Subtype
MERFF
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4 Participants
n=5 Participants
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Mitochondrial Disease Subtype
Others
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4 Participants
n=5 Participants
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|
Mitochondrial Disease Subtype
LHON
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3 Participants
n=5 Participants
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|
Mitochondrial Disease Subtype
NUBPL Related Encephalopathy
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2 Participants
n=5 Participants
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|
Mitochondrial Disease Subtype
Kearns-Sayre syndrome
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1 Participants
n=5 Participants
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PRIMARY outcome
Timeframe: Baseline through Week 24Population: Completers Analysis Set included all participants who received at least one dose of study drug (RP103) with at least one post-baseline NPMDS assessment and an evaluable Week 24 NPMDS assessment within the protocol specified window.
The NPMDS evaluates the progression of mitochondrial disease in pediatric patients in 4 domains: I - Current Function (vision, hearing, communication, feeding, and mobility) with scores ranging from 0 to 21; II -System Specific Involvement (seizures, encephalopathy, bleeding diathesis or coagulation defects, gastrointestinal, endocrine, respiratory, cardiovascular, renal, liver, and blood) with scores ranging from 0 to 30. III - Current Clinical Assessment (growth and development over past 6 months, vision, strabismus and eye movement, myopathy, ataxia, pyramidal, extrapyramidal, and neuropathy) with scores ranging from 0 to 28; and IV - Quality of Life with scores ranging from 0 to 25. For sections I-III, higher scores reflect more severe disease. For Section IV, a higher score reflects a lower quality of life.
Outcome measures
| Measure |
Cysteamine Bitartrate Delayed-release
n=18 Participants
Cysteamine bitartrate delayed-release capsules were administered twice daily following a dose-escalation design with a progressive weekly dose increase over the first 6 weeks. The starting dose was 0.2 g/m²/day, up to a maximum dose of 1.3 g/m²/day. Participants remained on their highest tolerated dose until Week 24.
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|---|---|
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Change From Baseline in Newcastle Paediatric Mitochondrial Disease Scale (NPMDS) Sections I-IV
Section I
|
-0.3 units on a scale
Standard Deviation 0.7
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Change From Baseline in Newcastle Paediatric Mitochondrial Disease Scale (NPMDS) Sections I-IV
Section II
|
0.1 units on a scale
Standard Deviation 1.1
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Change From Baseline in Newcastle Paediatric Mitochondrial Disease Scale (NPMDS) Sections I-IV
Section III
|
-0.6 units on a scale
Standard Deviation 1.2
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|
Change From Baseline in Newcastle Paediatric Mitochondrial Disease Scale (NPMDS) Sections I-IV
Section IV
|
0.0 units on a scale
Standard Deviation 4.0
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SECONDARY outcome
Timeframe: Baseline and Weeks 4, 8, 12, 16, 20, 24Population: The pharmacodynamic (PD) analysis set included all participants who received at least one dose of study drug and had at least one post-baseline PD assessment. Participants with available data at each time point are included in the analysis.
Outcome measures
| Measure |
Cysteamine Bitartrate Delayed-release
n=26 Participants
Cysteamine bitartrate delayed-release capsules were administered twice daily following a dose-escalation design with a progressive weekly dose increase over the first 6 weeks. The starting dose was 0.2 g/m²/day, up to a maximum dose of 1.3 g/m²/day. Participants remained on their highest tolerated dose until Week 24.
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|---|---|
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Change From Baseline in Glutathione
Week 4
|
16.8 µmol/L
Standard Deviation 277.1
|
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Change From Baseline in Glutathione
Week 8
|
141.5 µmol/L
Standard Deviation 275.5
|
|
Change From Baseline in Glutathione
Week 12
|
10.2 µmol/L
Standard Deviation 419.4
|
|
Change From Baseline in Glutathione
Week 16
|
88.7 µmol/L
Standard Deviation 343.9
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|
Change From Baseline in Glutathione
Week 20
|
51.4 µmol/L
Standard Deviation 207.8
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Change From Baseline in Glutathione
Week 24
|
122.4 µmol/L
Standard Deviation 244.8
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SECONDARY outcome
Timeframe: Baseline and Weeks 4, 8, 12, 16, 20, 24Population: PD analysis set participants with available data at each time point.
Outcome measures
| Measure |
Cysteamine Bitartrate Delayed-release
n=26 Participants
Cysteamine bitartrate delayed-release capsules were administered twice daily following a dose-escalation design with a progressive weekly dose increase over the first 6 weeks. The starting dose was 0.2 g/m²/day, up to a maximum dose of 1.3 g/m²/day. Participants remained on their highest tolerated dose until Week 24.
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|---|---|
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Change From Baseline in Glutathione Disulfide
Week 4
|
29.4 µmol/L
Standard Deviation 96.8
|
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Change From Baseline in Glutathione Disulfide
Week 8
|
-9.8 µmol/L
Standard Deviation 43.9
|
|
Change From Baseline in Glutathione Disulfide
Week 12
|
18.8 µmol/L
Standard Deviation 105.3
|
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Change From Baseline in Glutathione Disulfide
Week 16
|
-11.2 µmol/L
Standard Deviation 46.2
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Change From Baseline in Glutathione Disulfide
Week 20
|
0.8 µmol/L
Standard Deviation 7.1
|
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Change From Baseline in Glutathione Disulfide
Week 24
|
-11.5 µmol/L
Standard Deviation 47.6
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SECONDARY outcome
Timeframe: Baseline and Weeks 4, 8, 12, 16, 20, 24Population: PD analysis set participants with available data at each time point.
Outcome measures
| Measure |
Cysteamine Bitartrate Delayed-release
n=31 Participants
Cysteamine bitartrate delayed-release capsules were administered twice daily following a dose-escalation design with a progressive weekly dose increase over the first 6 weeks. The starting dose was 0.2 g/m²/day, up to a maximum dose of 1.3 g/m²/day. Participants remained on their highest tolerated dose until Week 24.
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|---|---|
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Change From Baseline in Lactic Acid
Week 24
|
0.0 mmol/L
Standard Deviation 1.2
|
|
Change From Baseline in Lactic Acid
Week 4
|
0.2 mmol/L
Standard Deviation 1.0
|
|
Change From Baseline in Lactic Acid
Week 8
|
0.4 mmol/L
Standard Deviation 1.6
|
|
Change From Baseline in Lactic Acid
Week 12
|
0.3 mmol/L
Standard Deviation 2.4
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|
Change From Baseline in Lactic Acid
Week 16
|
0.1 mmol/L
Standard Deviation 1.2
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Change From Baseline in Lactic Acid
Week 20
|
0.1 mmol/L
Standard Deviation 1.1
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SECONDARY outcome
Timeframe: Baseline and Weeks 4, 8, 12, 16, 20, 24Population: Participants who received at least one dose of study drug (RP103) and had at least one post-baseline 6 minute walk test assessment and for whom myopathy was prespecified as a preeminent symptom and with available data at each time point.
The investigator selected the two most preeminent symptoms for each participant during the screening visit from the following: Myopathy, dystonia, ataxia, retarded motor development, reduced activities of daily living, and vision. The 2 symptoms selected for each participant were then assessed at each subsequent study visit. Myopathy was assessed using the 6 minute walk test, which measures the distance walked in a 6 minute walk test.
Outcome measures
| Measure |
Cysteamine Bitartrate Delayed-release
n=15 Participants
Cysteamine bitartrate delayed-release capsules were administered twice daily following a dose-escalation design with a progressive weekly dose increase over the first 6 weeks. The starting dose was 0.2 g/m²/day, up to a maximum dose of 1.3 g/m²/day. Participants remained on their highest tolerated dose until Week 24.
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|---|---|
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Change From Baseline in 6 Minute Walk Test
Week 20
|
21.3 meters
Standard Deviation 61.9
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Change From Baseline in 6 Minute Walk Test
Week 4
|
-23.5 meters
Standard Deviation 86.3
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Change From Baseline in 6 Minute Walk Test
Week 8
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-36.2 meters
Standard Deviation 73.3
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Change From Baseline in 6 Minute Walk Test
Week 12
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-14.5 meters
Standard Deviation 71.5
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Change From Baseline in 6 Minute Walk Test
Week 16
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-21.3 meters
Standard Deviation 90.6
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Change From Baseline in 6 Minute Walk Test
Week 24
|
-18.9 meters
Standard Deviation 123.9
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SECONDARY outcome
Timeframe: Baseline and Weeks 4, 8, 12, 16, 20, 24Population: Participants who received at least one dose of study drug (RP103) and had at least one post-baseline Jamar hand strength assessment and for whom myopathy was prespecified as a preeminent symptom and with available data at each time point.
The investigator selected the two most preeminent symptoms for each participant during the screening visit from the following: myopathy, dystonia, ataxia, retarded motor development, reduced activities of daily living, and vision. The 2 symptoms selected for each participant were then assessed at each subsequent study visit. Myopathy was assessed using standard grip strength evaluation, which measures hand strength in both hands using a Jamar dynamometer.
Outcome measures
| Measure |
Cysteamine Bitartrate Delayed-release
n=9 Participants
Cysteamine bitartrate delayed-release capsules were administered twice daily following a dose-escalation design with a progressive weekly dose increase over the first 6 weeks. The starting dose was 0.2 g/m²/day, up to a maximum dose of 1.3 g/m²/day. Participants remained on their highest tolerated dose until Week 24.
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|---|---|
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Change From Baseline in Jamar Dynamometer Hand Strength
Week 4 - Left hand
|
1.3 kg
Standard Deviation 2.4
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Change From Baseline in Jamar Dynamometer Hand Strength
Week 8 - Left hand
|
1.1 kg
Standard Deviation 2.3
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Change From Baseline in Jamar Dynamometer Hand Strength
Week 12 - Left hand
|
1.3 kg
Standard Deviation 2.6
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|
Change From Baseline in Jamar Dynamometer Hand Strength
Week 16 - Left hand
|
0.0 kg
Standard Deviation 3.3
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|
Change From Baseline in Jamar Dynamometer Hand Strength
Week 20 - Left hand
|
0.7 kg
Standard Deviation 3.1
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Change From Baseline in Jamar Dynamometer Hand Strength
Week 24 - Left hand
|
1.3 kg
Standard Deviation 2.2
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Change From Baseline in Jamar Dynamometer Hand Strength
Week 4 - Right hand
|
0.5 kg
Standard Deviation 3.0
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Change From Baseline in Jamar Dynamometer Hand Strength
Week 8 - Right hand
|
1.6 kg
Standard Deviation 2.1
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Change From Baseline in Jamar Dynamometer Hand Strength
Week 12 - Right hand
|
1.6 kg
Standard Deviation 2.6
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Change From Baseline in Jamar Dynamometer Hand Strength
Week 16 - Right hand
|
0.7 kg
Standard Deviation 2.9
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Change From Baseline in Jamar Dynamometer Hand Strength
Week 20 - Right hand
|
0.9 kg
Standard Deviation 2.4
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Change From Baseline in Jamar Dynamometer Hand Strength
Week 24 - Right hand
|
1.2 kg
Standard Deviation 2.1
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SECONDARY outcome
Timeframe: Baseline and Weeks 4, 8, 12, 16, 20, 24Population: Participants who received at least one dose of study drug (RP103) and had at least one post-baseline dystonia assessment and for whom dystonia was prespecified as a preeminent symptom and with available data at each time point.
The investigator selected the two most preeminent symptoms for each participant during the screening visit from the following: myopathy, dystonia, ataxia, retarded motor development, reduced activities of daily living, and vision. The 2 symptoms selected for each participant were then assessed at each subsequent study visit. Dystonia symptoms were assessed using the Barry-Albright Dystonia Scale for Dystonia. Participants were assessed for dystonia in each of the following regions: eyes, mouth, neck, trunk, and each upper and lower extremity (8 body regions) on a scale from 0 (absent) to 4 (severe symptoms). The individual scores were summed to calculate the total score which ranges from 0 (dystonia absent) to 32 (severe dystonia).
Outcome measures
| Measure |
Cysteamine Bitartrate Delayed-release
n=4 Participants
Cysteamine bitartrate delayed-release capsules were administered twice daily following a dose-escalation design with a progressive weekly dose increase over the first 6 weeks. The starting dose was 0.2 g/m²/day, up to a maximum dose of 1.3 g/m²/day. Participants remained on their highest tolerated dose until Week 24.
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|---|---|
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Change From Baseline in Barry-Albright Dystonia Scale Total Score
Week 16
|
0.3 units on a scale
Standard Deviation 3.1
|
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Change From Baseline in Barry-Albright Dystonia Scale Total Score
Week 4
|
1.3 units on a scale
Standard Deviation 1.0
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Change From Baseline in Barry-Albright Dystonia Scale Total Score
Week 8
|
0.7 units on a scale
Standard Deviation 0.6
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Change From Baseline in Barry-Albright Dystonia Scale Total Score
Week 12
|
0.3 units on a scale
Standard Deviation 3.1
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Change From Baseline in Barry-Albright Dystonia Scale Total Score
Week 20
|
-0.7 units on a scale
Standard Deviation 4.7
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Change From Baseline in Barry-Albright Dystonia Scale Total Score
Week 24
|
0.7 units on a scale
Standard Deviation 3.5
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SECONDARY outcome
Timeframe: Baseline and Weeks 4, 8, 12, 16, 20, 24Population: Participants who received at least one dose of study drug (RP103) and had at least one post-baseline ataxia assessment and for whom ataxia was prespecified as a preeminent symptom and with available data at each time point.
The investigator selected the two most preeminent symptoms for each participant during the screening visit from the following: myopathy, dystonia, ataxia, retarded motor development, reduced activities of daily living, and vision. The 2 symptoms selected for each participant were then assessed at each subsequent study visit. Ataxia was assessed using the Friedreich Ataxia Rating Scale (FARS). FARS comprises a functional ataxia staging score of overall mobility (score 0 to 6), an assessment of the activities of daily living (ADL) (score 0 to 36) and a neurological assessment (score from 0 to 117) which is composed of bulbar (score 0-11), upper limb (score 0- 36) and lower limb (score 0-16), peripheral nerve (score 0-26) and upright stability/gait (score 0-28). The scores were summed to calculate the total score which ranges from 0 to 159. A higher score indicates a greater level of disability.
Outcome measures
| Measure |
Cysteamine Bitartrate Delayed-release
n=4 Participants
Cysteamine bitartrate delayed-release capsules were administered twice daily following a dose-escalation design with a progressive weekly dose increase over the first 6 weeks. The starting dose was 0.2 g/m²/day, up to a maximum dose of 1.3 g/m²/day. Participants remained on their highest tolerated dose until Week 24.
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|---|---|
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Change From Baseline in Friedreich Ataxia Rating Scale
Week 4
|
16.9 units on a scale
Standard Deviation 27.2
|
|
Change From Baseline in Friedreich Ataxia Rating Scale
Week 8
|
13.9 units on a scale
Standard Deviation 25.6
|
|
Change From Baseline in Friedreich Ataxia Rating Scale
Week 12
|
15.9 units on a scale
Standard Deviation 23.1
|
|
Change From Baseline in Friedreich Ataxia Rating Scale
Week 16
|
19.4 units on a scale
Standard Deviation 23.0
|
|
Change From Baseline in Friedreich Ataxia Rating Scale
Week 20
|
16.5 units on a scale
Standard Deviation 21.5
|
|
Change From Baseline in Friedreich Ataxia Rating Scale
Week 24
|
20.5 units on a scale
Standard Deviation 18.5
|
SECONDARY outcome
Timeframe: Baseline and Weeks 4, 8, 12, 16, 20, 24Population: Participants who received at least one dose of study drug (RP103) and had at least one post-baseline gross motor function assessment and for whom retarded motor development was prespecified as a preeminent symptom and with available data at each time point.
The investigator selected the two most preeminent symptoms for each participant during the screening visit from the following: myopathy, dystonia, ataxia, retarded motor development, reduced activities of daily living, and vision. The 2 symptoms selected for each participant were then assessed at each subsequent study visit. Retarded motor development was assessed using the Gross Motor Function Measure (GMFM)-88 which consists of 88 items scored on a scale of 0 to 3: 0: Does not initiate the task; 1. Initiates the task (completes \< 10%); 2. Partially completes the task (10 to 99%); 3. Completes the task (100%). The 88 items are grouped into five dimensions: 1) lying and rolling, 2) sitting, 3) crawling and kneeling, 4) standing, and 5) walking, running and jumping. Scores are expressed as a percentage of the maximum score for that dimension. The total score is the average of the 5 the percentage scores where higher scores indicate better performance.
Outcome measures
| Measure |
Cysteamine Bitartrate Delayed-release
n=12 Participants
Cysteamine bitartrate delayed-release capsules were administered twice daily following a dose-escalation design with a progressive weekly dose increase over the first 6 weeks. The starting dose was 0.2 g/m²/day, up to a maximum dose of 1.3 g/m²/day. Participants remained on their highest tolerated dose until Week 24.
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|---|---|
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Change From Baseline in Gross Motor Function
Week 20
|
4.0 units on a scale
Standard Deviation 8.2
|
|
Change From Baseline in Gross Motor Function
Week 24
|
2.2 units on a scale
Standard Deviation 8.2
|
|
Change From Baseline in Gross Motor Function
Week 4
|
0.4 units on a scale
Standard Deviation 4.3
|
|
Change From Baseline in Gross Motor Function
Week 8
|
0.9 units on a scale
Standard Deviation 7.9
|
|
Change From Baseline in Gross Motor Function
Week 12
|
0.5 units on a scale
Standard Deviation 3.6
|
|
Change From Baseline in Gross Motor Function
Week 16
|
4.4 units on a scale
Standard Deviation 5.6
|
SECONDARY outcome
Timeframe: Baseline and Weeks 4, 8, 12, 16, 20, 24Population: Participants who received at least one dose of study drug (RP103) and had at least one post-baseline Lansky play performance scale assessment and for whom reduced activities of daily living was prespecified as a preeminent symptom and with available data at each time point.
The investigator selected the 2 most preeminent symptoms for each participant during the screening visit from the following: myopathy, dystonia, ataxia, retarded motor development, reduced activities of daily living, and vision. The 2 symptoms were assessed at each subsequent study visit. Reduced activities of daily living was assessed using the modified Lansky Play Performance Scale, completed by parents based on their child's activity in the past week, where 100=fully active; 90=minor restrictions in strenuous physical activity; 80=active, gets tired more quickly; 70=greater restriction of play, less time spent in play activity; 60=up and around, active play minimal; quieter activities; 50=lying around much of the day; no active playing, all quiet play and activities; 40=mainly in bed; quiet activities; 30=bedbound; needs assistance even for quiet play; 20=sleeps often; play limited to very passive activities; 10=doesn't play or get out of bed; 5=unresponsive 0=dead
Outcome measures
| Measure |
Cysteamine Bitartrate Delayed-release
n=6 Participants
Cysteamine bitartrate delayed-release capsules were administered twice daily following a dose-escalation design with a progressive weekly dose increase over the first 6 weeks. The starting dose was 0.2 g/m²/day, up to a maximum dose of 1.3 g/m²/day. Participants remained on their highest tolerated dose until Week 24.
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|---|---|
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Change From Baseline in Modified Lansky Play Performance Scale
Week 4
|
-2.0 units on a scale
Standard Deviation 4.5
|
|
Change From Baseline in Modified Lansky Play Performance Scale
Week 8
|
-6.0 units on a scale
Standard Deviation 8.9
|
|
Change From Baseline in Modified Lansky Play Performance Scale
Week 12
|
-2.0 units on a scale
Standard Deviation 4.5
|
|
Change From Baseline in Modified Lansky Play Performance Scale
Week 20
|
-4.0 units on a scale
Standard Deviation 11.4
|
|
Change From Baseline in Modified Lansky Play Performance Scale
Week 24
|
-6.0 units on a scale
Standard Deviation 8.9
|
|
Change From Baseline in Modified Lansky Play Performance Scale
Week 16
|
2.0 units on a scale
Standard Deviation 11.0
|
Adverse Events
Cysteamine Bitartrate Delayed-release
Serious adverse events
| Measure |
Cysteamine Bitartrate Delayed-release
n=36 participants at risk
Cysteamine bitartrate delayed-release capsules were administered twice daily following a dose-escalation design with a progressive weekly dose increase over the first 6 weeks. The starting dose was 0.2 g/m²/day, up to a maximum dose of 1.3 g/m²/day. Participants remained on their highest tolerated dose until Week 24.
|
|---|---|
|
Cardiac disorders
Atrioventricular block complete
|
2.8%
1/36 • 24 weeks
|
|
Cardiac disorders
Atrioventricular block second degree
|
2.8%
1/36 • 24 weeks
|
|
Cardiac disorders
Cardiomyopathy
|
2.8%
1/36 • 24 weeks
|
|
Gastrointestinal disorders
Vomiting
|
8.3%
3/36 • 24 weeks
|
|
Gastrointestinal disorders
Constipation
|
2.8%
1/36 • 24 weeks
|
|
General disorders
Pyrexia
|
2.8%
1/36 • 24 weeks
|
|
Infections and infestations
Adenovirus infection
|
2.8%
1/36 • 24 weeks
|
|
Infections and infestations
Ear infection
|
2.8%
1/36 • 24 weeks
|
|
Infections and infestations
Urinary tract infection
|
2.8%
1/36 • 24 weeks
|
|
Metabolism and nutrition disorders
Dehydration
|
5.6%
2/36 • 24 weeks
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
2.8%
1/36 • 24 weeks
|
|
Nervous system disorders
Convulsion
|
5.6%
2/36 • 24 weeks
|
|
Nervous system disorders
Lethargy
|
2.8%
1/36 • 24 weeks
|
|
Nervous system disorders
Status epilepticus
|
2.8%
1/36 • 24 weeks
|
|
Psychiatric disorders
Mental status changes
|
2.8%
1/36 • 24 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory arrest
|
2.8%
1/36 • 24 weeks
|
|
Surgical and medical procedures
Cardiac pacemaker insertion
|
2.8%
1/36 • 24 weeks
|
Other adverse events
| Measure |
Cysteamine Bitartrate Delayed-release
n=36 participants at risk
Cysteamine bitartrate delayed-release capsules were administered twice daily following a dose-escalation design with a progressive weekly dose increase over the first 6 weeks. The starting dose was 0.2 g/m²/day, up to a maximum dose of 1.3 g/m²/day. Participants remained on their highest tolerated dose until Week 24.
|
|---|---|
|
Cardiac disorders
Sinus tachycardia
|
2.8%
1/36 • 24 weeks
|
|
Ear and labyrinth disorders
Motion sickness
|
2.8%
1/36 • 24 weeks
|
|
Eye disorders
Eye movement disorder
|
2.8%
1/36 • 24 weeks
|
|
Eye disorders
Eye pain
|
2.8%
1/36 • 24 weeks
|
|
Eye disorders
Eyelid oedema
|
2.8%
1/36 • 24 weeks
|
|
Eye disorders
Eyelid ptosis
|
5.6%
2/36 • 24 weeks
|
|
Eye disorders
Mydriasis
|
2.8%
1/36 • 24 weeks
|
|
Eye disorders
Ocular hyperaemia
|
2.8%
1/36 • 24 weeks
|
|
Gastrointestinal disorders
Abdominal discomfort
|
2.8%
1/36 • 24 weeks
|
|
Gastrointestinal disorders
Abdominal distension
|
2.8%
1/36 • 24 weeks
|
|
Gastrointestinal disorders
Abdominal pain
|
19.4%
7/36 • 24 weeks
|
|
Gastrointestinal disorders
Abdominal pain upper
|
11.1%
4/36 • 24 weeks
|
|
Gastrointestinal disorders
Breath odour
|
33.3%
12/36 • 24 weeks
|
|
Gastrointestinal disorders
Constipation
|
11.1%
4/36 • 24 weeks
|
|
Gastrointestinal disorders
Diarrhoea
|
41.7%
15/36 • 24 weeks
|
|
Gastrointestinal disorders
Eructation
|
2.8%
1/36 • 24 weeks
|
|
Gastrointestinal disorders
Faecal incontinence
|
2.8%
1/36 • 24 weeks
|
|
Gastrointestinal disorders
Flatulence
|
2.8%
1/36 • 24 weeks
|
|
Gastrointestinal disorders
Gastroesophageal reflux disease
|
2.8%
1/36 • 24 weeks
|
|
Gastrointestinal disorders
Haematemesis
|
2.8%
1/36 • 24 weeks
|
|
Gastrointestinal disorders
Nausea
|
33.3%
12/36 • 24 weeks
|
|
Gastrointestinal disorders
Retching
|
2.8%
1/36 • 24 weeks
|
|
Gastrointestinal disorders
Salivary hypersecretion
|
2.8%
1/36 • 24 weeks
|
|
Gastrointestinal disorders
Vomiting
|
58.3%
21/36 • 24 weeks
|
|
General disorders
Asthenia
|
2.8%
1/36 • 24 weeks
|
|
General disorders
Chest pain
|
5.6%
2/36 • 24 weeks
|
|
General disorders
Fatigue
|
30.6%
11/36 • 24 weeks
|
|
General disorders
Gait disturbance
|
5.6%
2/36 • 24 weeks
|
|
General disorders
Malaise
|
2.8%
1/36 • 24 weeks
|
|
General disorders
Pyrexia
|
33.3%
12/36 • 24 weeks
|
|
Infections and infestations
Bursitis infective
|
2.8%
1/36 • 24 weeks
|
|
Infections and infestations
Croup infectious
|
2.8%
1/36 • 24 weeks
|
|
Infections and infestations
Gastroenteritis viral
|
2.8%
1/36 • 24 weeks
|
|
Infections and infestations
Influenza
|
13.9%
5/36 • 24 weeks
|
|
Infections and infestations
Nasopharyngitis
|
11.1%
4/36 • 24 weeks
|
|
Infections and infestations
Oral herpes
|
2.8%
1/36 • 24 weeks
|
|
Infections and infestations
Otitis media
|
2.8%
1/36 • 24 weeks
|
|
Infections and infestations
Pharyngitis streptococcal
|
8.3%
3/36 • 24 weeks
|
|
Infections and infestations
Rhinovirus infection
|
2.8%
1/36 • 24 weeks
|
|
Infections and infestations
Tooth infection
|
2.8%
1/36 • 24 weeks
|
|
Infections and infestations
Upper respiratory tract infection
|
5.6%
2/36 • 24 weeks
|
|
Infections and infestations
Viral infection
|
2.8%
1/36 • 24 weeks
|
|
Injury, poisoning and procedural complications
Contusion
|
5.6%
2/36 • 24 weeks
|
|
Injury, poisoning and procedural complications
Foot fracture
|
2.8%
1/36 • 24 weeks
|
|
Injury, poisoning and procedural complications
Laceration
|
5.6%
2/36 • 24 weeks
|
|
Injury, poisoning and procedural complications
Radial head dislocation
|
2.8%
1/36 • 24 weeks
|
|
Investigations
Alanine aminotransferase increased
|
2.8%
1/36 • 24 weeks
|
|
Investigations
Amylase increased
|
2.8%
1/36 • 24 weeks
|
|
Investigations
Aspartate aminotransferase increased
|
2.8%
1/36 • 24 weeks
|
|
Investigations
Blood alkaline phosphatase increased
|
2.8%
1/36 • 24 weeks
|
|
Investigations
Blood bicarbonate decreased
|
2.8%
1/36 • 24 weeks
|
|
Investigations
Blood creatine phosphokinase increased
|
2.8%
1/36 • 24 weeks
|
|
Investigations
Blood creatinine increased
|
2.8%
1/36 • 24 weeks
|
|
Investigations
Blood glucose increased
|
2.8%
1/36 • 24 weeks
|
|
Investigations
Blood urea increased
|
2.8%
1/36 • 24 weeks
|
|
Investigations
Clostridium test positive
|
2.8%
1/36 • 24 weeks
|
|
Investigations
Ejection fraction decreased
|
2.8%
1/36 • 24 weeks
|
|
Investigations
Electrocardiogram abnormal
|
2.8%
1/36 • 24 weeks
|
|
Investigations
Gamma-glutamyltransferase increased
|
2.8%
1/36 • 24 weeks
|
|
Investigations
Respiratory rate decreased
|
2.8%
1/36 • 24 weeks
|
|
Investigations
Weight decreased
|
5.6%
2/36 • 24 weeks
|
|
Metabolism and nutrition disorders
Acidosis
|
2.8%
1/36 • 24 weeks
|
|
Metabolism and nutrition disorders
Decreased appetite
|
38.9%
14/36 • 24 weeks
|
|
Metabolism and nutrition disorders
Dehydration
|
2.8%
1/36 • 24 weeks
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
2.8%
1/36 • 24 weeks
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
2.8%
1/36 • 24 weeks
|
|
Musculoskeletal and connective tissue disorders
Muscle atrophy
|
2.8%
1/36 • 24 weeks
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
2.8%
1/36 • 24 weeks
|
|
Musculoskeletal and connective tissue disorders
Muscle tightness
|
5.6%
2/36 • 24 weeks
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
2.8%
1/36 • 24 weeks
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
5.6%
2/36 • 24 weeks
|
|
Musculoskeletal and connective tissue disorders
Posture abnormal
|
2.8%
1/36 • 24 weeks
|
|
Nervous system disorders
Akathisia
|
2.8%
1/36 • 24 weeks
|
|
Nervous system disorders
Ataxia
|
2.8%
1/36 • 24 weeks
|
|
Nervous system disorders
Balance disorder
|
2.8%
1/36 • 24 weeks
|
|
Nervous system disorders
Convulsion
|
11.1%
4/36 • 24 weeks
|
|
Nervous system disorders
Disturbance in attention
|
2.8%
1/36 • 24 weeks
|
|
Nervous system disorders
Dizziness
|
2.8%
1/36 • 24 weeks
|
|
Nervous system disorders
Dysgeusia
|
2.8%
1/36 • 24 weeks
|
|
Nervous system disorders
Dystonia
|
8.3%
3/36 • 24 weeks
|
|
Nervous system disorders
Encephalopathy
|
2.8%
1/36 • 24 weeks
|
|
Nervous system disorders
Headache
|
19.4%
7/36 • 24 weeks
|
|
Nervous system disorders
Lethargy
|
22.2%
8/36 • 24 weeks
|
|
Nervous system disorders
Migraine
|
2.8%
1/36 • 24 weeks
|
|
Nervous system disorders
Parkinsonian rest tremor
|
2.8%
1/36 • 24 weeks
|
|
Nervous system disorders
Peroneal nerve palsy
|
2.8%
1/36 • 24 weeks
|
|
Nervous system disorders
Somnolence
|
5.6%
2/36 • 24 weeks
|
|
Nervous system disorders
Speech disorder
|
2.8%
1/36 • 24 weeks
|
|
Nervous system disorders
Tremor
|
8.3%
3/36 • 24 weeks
|
|
Psychiatric disorders
Abnormal behaviour
|
2.8%
1/36 • 24 weeks
|
|
Psychiatric disorders
Agitation
|
5.6%
2/36 • 24 weeks
|
|
Psychiatric disorders
Anxiety
|
2.8%
1/36 • 24 weeks
|
|
Psychiatric disorders
Depression
|
2.8%
1/36 • 24 weeks
|
|
Psychiatric disorders
Insomnia
|
2.8%
1/36 • 24 weeks
|
|
Psychiatric disorders
Irritability
|
5.6%
2/36 • 24 weeks
|
|
Psychiatric disorders
Mental status changes
|
2.8%
1/36 • 24 weeks
|
|
Psychiatric disorders
Mood swings
|
5.6%
2/36 • 24 weeks
|
|
Psychiatric disorders
Restlessness
|
2.8%
1/36 • 24 weeks
|
|
Psychiatric disorders
Sleep disorder
|
2.8%
1/36 • 24 weeks
|
|
Psychiatric disorders
Tic
|
2.8%
1/36 • 24 weeks
|
|
Renal and urinary disorders
Pollakiuria
|
5.6%
2/36 • 24 weeks
|
|
Renal and urinary disorders
Urinary retention
|
2.8%
1/36 • 24 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Bronchospasm
|
2.8%
1/36 • 24 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
8.3%
3/36 • 24 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
2.8%
1/36 • 24 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
2.8%
1/36 • 24 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
2.8%
1/36 • 24 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
2.8%
1/36 • 24 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Rhonchi
|
2.8%
1/36 • 24 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
2.8%
1/36 • 24 weeks
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
2.8%
1/36 • 24 weeks
|
|
Skin and subcutaneous tissue disorders
Eczema
|
2.8%
1/36 • 24 weeks
|
|
Skin and subcutaneous tissue disorders
Hair colour changes
|
16.7%
6/36 • 24 weeks
|
|
Skin and subcutaneous tissue disorders
Rash
|
2.8%
1/36 • 24 weeks
|
|
Skin and subcutaneous tissue disorders
Skin depigmentation
|
2.8%
1/36 • 24 weeks
|
|
Skin and subcutaneous tissue disorders
Skin disorder
|
2.8%
1/36 • 24 weeks
|
|
Skin and subcutaneous tissue disorders
Skin odour abnormal
|
19.4%
7/36 • 24 weeks
|
|
Vascular disorders
Pallor
|
2.8%
1/36 • 24 weeks
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Horizon requests that any Investigator/institution that plans on presenting or publishing results provide written notification of their request a minimum of 60 days prior to presentation or publication. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsors' Intellectual Property rights .
- Publication restrictions are in place
Restriction type: OTHER