Trial Outcomes & Findings for Ataluren for Nonsense Mutation in CDKL5 and Dravet Syndrome (NCT NCT02758626)
NCT ID: NCT02758626
Last Updated: 2023-02-16
Results Overview
Convulsive seizure frequency per 28 days is defined as total number of convulsive seizures reported during the period divided by number of days during the period seizures were assessed, multiplied by 28. Percent change from Baseline will be defined as the frequency of seizures per 28 days during the Ataluren Treatment Period minus frequency of seizures per 28 days at Baseline, divided by the frequency of seizures per 28 days at Baseline, multiplied by 100. Negative percent change from Baseline indicates improvement.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
15 participants
Primary outcome timeframe
Baseline, Week 12 of Ataluren Treatment (Up to Week 28)
Results posted on
2023-02-16
Participant Flow
Participant milestones
| Measure |
Ataluren Followed By Placebo
Cross Over Design: Treatment Period 1 with Ataluren (Week 0/Day 1 to Week 12), Washout Period (Week 12 to Week 16), crossover to Placebo Treatment Period 2 (Week 16 to Week 28), and Follow-up (Week 28 to Week 32). Participants have option to enroll in open-label extension (OLE) at Week 28. During the OLE, all participants receive open-label Ataluren.
ataluren: Powder formulation. Dose: 3 times per day (TID; 10 mg/kg, 10 mg/kg, and 20 mg/kg at morning, midday, and evening, respectively)
Placebo: Powder formulation. Dose: 3 times per day (TID; 10 mg/kg, 10 mg/kg, and 20 mg/kg morning, midday, and evening, respectively)
|
Placebo Followed by Ataluren
Cross Over Design: Treatment Period 1 with Placebo (Week 0/Day 1 to Week 12), Washout Period (Week 12 to Week 16), crossover to Treatment Period 2 with Ataluren(Week 16 to Week 28). Participants have option to enroll in open-label extension (OLE) at Week 28. During the OLE, all participants receive open-label Ataluren.
ataluren: Powder formulation. Dose: 3 times per day (TID; 10 mg/kg, 10 mg/kg, and 20 mg/kg at morning, midday, and evening, respectively)
Placebo: Powder formulation. Dose: 3 times per day (TID; 10 mg/kg, 10 mg/kg, and 20 mg/kg morning, midday, and evening, respectively)
|
|---|---|---|
|
Double-Blind Phase (Week 0 - Week 28)
STARTED
|
9
|
6
|
|
Double-Blind Phase (Week 0 - Week 28)
COMPLETED
|
8
|
6
|
|
Double-Blind Phase (Week 0 - Week 28)
NOT COMPLETED
|
1
|
0
|
|
Open-Label Extension (Week 28-Week 124)
STARTED
|
8
|
6
|
|
Open-Label Extension (Week 28-Week 124)
COMPLETED
|
6
|
3
|
|
Open-Label Extension (Week 28-Week 124)
NOT COMPLETED
|
2
|
3
|
Reasons for withdrawal
| Measure |
Ataluren Followed By Placebo
Cross Over Design: Treatment Period 1 with Ataluren (Week 0/Day 1 to Week 12), Washout Period (Week 12 to Week 16), crossover to Placebo Treatment Period 2 (Week 16 to Week 28), and Follow-up (Week 28 to Week 32). Participants have option to enroll in open-label extension (OLE) at Week 28. During the OLE, all participants receive open-label Ataluren.
ataluren: Powder formulation. Dose: 3 times per day (TID; 10 mg/kg, 10 mg/kg, and 20 mg/kg at morning, midday, and evening, respectively)
Placebo: Powder formulation. Dose: 3 times per day (TID; 10 mg/kg, 10 mg/kg, and 20 mg/kg morning, midday, and evening, respectively)
|
Placebo Followed by Ataluren
Cross Over Design: Treatment Period 1 with Placebo (Week 0/Day 1 to Week 12), Washout Period (Week 12 to Week 16), crossover to Treatment Period 2 with Ataluren(Week 16 to Week 28). Participants have option to enroll in open-label extension (OLE) at Week 28. During the OLE, all participants receive open-label Ataluren.
ataluren: Powder formulation. Dose: 3 times per day (TID; 10 mg/kg, 10 mg/kg, and 20 mg/kg at morning, midday, and evening, respectively)
Placebo: Powder formulation. Dose: 3 times per day (TID; 10 mg/kg, 10 mg/kg, and 20 mg/kg morning, midday, and evening, respectively)
|
|---|---|---|
|
Double-Blind Phase (Week 0 - Week 28)
Adverse Event
|
1
|
0
|
|
Open-Label Extension (Week 28-Week 124)
Adverse Event
|
1
|
1
|
|
Open-Label Extension (Week 28-Week 124)
Parental/Legal Guardian withdrawal of consent
|
1
|
1
|
|
Open-Label Extension (Week 28-Week 124)
Lost to Follow-up
|
0
|
1
|
Baseline Characteristics
Ataluren for Nonsense Mutation in CDKL5 and Dravet Syndrome
Baseline characteristics by cohort
| Measure |
Ataluren Followed By Placebo
n=9 Participants
Cross Over Design: Treatment Period 1 with Ataluren (Week 0/Day 1 to Week 12), Washout Period (Week 12 to Week 16), crossover to Placebo Treatment Period 2 (Week 16 to Week 28), and Follow-up (Week 28 to Week 32).
ataluren: Powder formulation
Placebo: Powder formulation
|
Placebo Followed by Ataluren
n=6 Participants
Treatment Period 1 with Placebo (Week 0/Day 1 to Week 12), Washout Period (Week 12 to Week 16), crossover to Treatment Period 2 with Ataluren(Week 16 to Week 28).
ataluren: Powder formulation
Placebo: Powder formulation
|
Total
n=15 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
9.3 years
STANDARD_DEVIATION 4.7 • n=5 Participants
|
12.0 years
STANDARD_DEVIATION 0.0 • n=7 Participants
|
10.4 years
STANDARD_DEVIATION 5.1 • n=5 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
8 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
6 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
9 participants
n=5 Participants
|
6 participants
n=7 Participants
|
15 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, Week 12 of Ataluren Treatment (Up to Week 28)Convulsive seizure frequency per 28 days is defined as total number of convulsive seizures reported during the period divided by number of days during the period seizures were assessed, multiplied by 28. Percent change from Baseline will be defined as the frequency of seizures per 28 days during the Ataluren Treatment Period minus frequency of seizures per 28 days at Baseline, divided by the frequency of seizures per 28 days at Baseline, multiplied by 100. Negative percent change from Baseline indicates improvement.
Outcome measures
| Measure |
Ataluren
n=14 Participants
12-week treatment regimen.
|
|---|---|
|
Percent Change From Baseline in 28-Day Convulsive Seizure Frequency During Ataluren Treatment Period
|
723.17 percent change
Standard Deviation 279.912
|
PRIMARY outcome
Timeframe: Baseline, Week 12 of Placebo Treatment (Up to Week 28)Convulsive seizure frequency per 28 days is defined as total number of convulsive seizures reported during the period divided by number of days during the period seizures were assessed, multiplied by 28. Percent change from Baseline will be defined as the frequency of seizures per 28 days during the Placebo Treatment Period minus frequency of seizures per 28 days at Baseline, divided by the frequency of seizures per 28 days at Baseline, multiplied by 100. Negative percent change from Baseline indicates improvement.
Outcome measures
| Measure |
Ataluren
n=14 Participants
12-week treatment regimen.
|
|---|---|
|
Percent Change From Baseline in 28-Day Convulsive Seizure Frequency During Placebo Treatment Period
|
0.72 percent change
Standard Deviation 222.82
|
Adverse Events
Ataluren
Serious events: 7 serious events
Other events: 13 other events
Deaths: 0 deaths
Placebo
Serious events: 1 serious events
Other events: 5 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Ataluren
n=15 participants at risk
ataluren: Powder formulation
|
Placebo
n=14 participants at risk
Placebo: Powder formulation
|
|---|---|---|
|
Infections and infestations
Influenza
|
13.3%
2/15 • up to Year 1
|
7.1%
1/14 • up to Year 1
|
|
Infections and infestations
Croup Infections
|
6.7%
1/15 • up to Year 1
|
0.00%
0/14 • up to Year 1
|
|
Infections and infestations
Ear infection
|
6.7%
1/15 • up to Year 1
|
0.00%
0/14 • up to Year 1
|
|
Infections and infestations
Tooth infection
|
6.7%
1/15 • up to Year 1
|
0.00%
0/14 • up to Year 1
|
|
Infections and infestations
Pneumonia Mycoplasmal
|
6.7%
1/15 • up to Year 1
|
0.00%
0/14 • up to Year 1
|
|
Infections and infestations
Respiratory syncytial virus infection
|
6.7%
1/15 • up to Year 1
|
0.00%
0/14 • up to Year 1
|
|
Investigations
Drug Level Decreased
|
20.0%
3/15 • up to Year 1
|
0.00%
0/14 • up to Year 1
|
|
Investigations
Hepatic enzyme increased
|
6.7%
1/15 • up to Year 1
|
0.00%
0/14 • up to Year 1
|
|
Nervous system disorders
Seizures
|
6.7%
1/15 • up to Year 1
|
0.00%
0/14 • up to Year 1
|
Other adverse events
| Measure |
Ataluren
n=15 participants at risk
ataluren: Powder formulation
|
Placebo
n=14 participants at risk
Placebo: Powder formulation
|
|---|---|---|
|
Infections and infestations
Viral upper respiratory tract infection
|
60.0%
9/15 • up to Year 1
|
14.3%
2/14 • up to Year 1
|
|
Infections and infestations
Camphylobacter gastroenteritis
|
6.7%
1/15 • up to Year 1
|
0.00%
0/14 • up to Year 1
|
|
Infections and infestations
Gastroenteriritis viral
|
13.3%
2/15 • up to Year 1
|
0.00%
0/14 • up to Year 1
|
|
Infections and infestations
Influenza
|
33.3%
5/15 • up to Year 1
|
14.3%
2/14 • up to Year 1
|
|
Infections and infestations
Viral infection
|
6.7%
1/15 • up to Year 1
|
7.1%
1/14 • up to Year 1
|
|
Infections and infestations
Croup infection
|
6.7%
1/15 • up to Year 1
|
7.1%
1/14 • up to Year 1
|
|
Infections and infestations
Sinusitis
|
6.7%
1/15 • up to Year 1
|
0.00%
0/14 • up to Year 1
|
|
Infections and infestations
Pnuemonia mycoplasmal
|
0.00%
0/15 • up to Year 1
|
7.1%
1/14 • up to Year 1
|
|
Infections and infestations
Urinary tract infection
|
13.3%
2/15 • up to Year 1
|
0.00%
0/14 • up to Year 1
|
|
Infections and infestations
Ear infection
|
6.7%
1/15 • up to Year 1
|
0.00%
0/14 • up to Year 1
|
|
Infections and infestations
Tooth infection
|
6.7%
1/15 • up to Year 1
|
0.00%
0/14 • up to Year 1
|
|
Infections and infestations
Respiratory tract infection
|
6.7%
1/15 • up to Year 1
|
0.00%
0/14 • up to Year 1
|
|
Infections and infestations
Respiratory syncytial virus infection
|
6.7%
1/15 • up to Year 1
|
0.00%
0/14 • up to Year 1
|
|
Infections and infestations
Cellulitis
|
6.7%
1/15 • up to Year 1
|
0.00%
0/14 • up to Year 1
|
|
Gastrointestinal disorders
Diarrhea
|
40.0%
6/15 • up to Year 1
|
28.6%
4/14 • up to Year 1
|
|
Gastrointestinal disorders
Flatulence
|
26.7%
4/15 • up to Year 1
|
7.1%
1/14 • up to Year 1
|
|
Gastrointestinal disorders
Abdominal Discomfort
|
6.7%
1/15 • up to Year 1
|
0.00%
0/14 • up to Year 1
|
|
Gastrointestinal disorders
Vomiting
|
40.0%
6/15 • up to Year 1
|
7.1%
1/14 • up to Year 1
|
|
Gastrointestinal disorders
Constipation
|
13.3%
2/15 • up to Year 1
|
7.1%
1/14 • up to Year 1
|
|
Gastrointestinal disorders
Eructation
|
6.7%
1/15 • up to Year 1
|
0.00%
0/14 • up to Year 1
|
|
Gastrointestinal disorders
Retching
|
6.7%
1/15 • up to Year 1
|
0.00%
0/14 • up to Year 1
|
|
Gastrointestinal disorders
Gastroesophagael reflux disease
|
6.7%
1/15 • up to Year 1
|
0.00%
0/14 • up to Year 1
|
|
General disorders
Pyrexia
|
80.0%
12/15 • up to Year 1
|
14.3%
2/14 • up to Year 1
|
|
General disorders
Fatigue
|
6.7%
1/15 • up to Year 1
|
7.1%
1/14 • up to Year 1
|
|
Investigations
Increased Drug level
|
13.3%
2/15 • up to Year 1
|
0.00%
0/14 • up to Year 1
|
|
Investigations
Body temperature increased
|
6.7%
1/15 • up to Year 1
|
7.1%
1/14 • up to Year 1
|
|
Investigations
Hepatic enzyme increased
|
6.7%
1/15 • up to Year 1
|
0.00%
0/14 • up to Year 1
|
|
Metabolism and nutrition disorders
Polydipsia
|
6.7%
1/15 • up to Year 1
|
0.00%
0/14 • up to Year 1
|
|
Metabolism and nutrition disorders
Decreased appetite
|
13.3%
2/15 • up to Year 1
|
7.1%
1/14 • up to Year 1
|
|
Nervous system disorders
Increased seizures
|
6.7%
1/15 • up to Year 1
|
7.1%
1/14 • up to Year 1
|
|
Nervous system disorders
Lethargy
|
26.7%
4/15 • up to Year 1
|
0.00%
0/14 • up to Year 1
|
|
Nervous system disorders
Focal dyscognitive seizures
|
6.7%
1/15 • up to Year 1
|
0.00%
0/14 • up to Year 1
|
|
Nervous system disorders
Drooling
|
6.7%
1/15 • up to Year 1
|
7.1%
1/14 • up to Year 1
|
|
Nervous system disorders
Seizures
|
33.3%
5/15 • up to Year 1
|
0.00%
0/14 • up to Year 1
|
|
Nervous system disorders
Balance disorder
|
6.7%
1/15 • up to Year 1
|
0.00%
0/14 • up to Year 1
|
|
Nervous system disorders
Movement disorder
|
6.7%
1/15 • up to Year 1
|
0.00%
0/14 • up to Year 1
|
|
Nervous system disorders
Hypersomnia
|
6.7%
1/15 • up to Year 1
|
0.00%
0/14 • up to Year 1
|
|
Nervous system disorders
Tremor
|
6.7%
1/15 • up to Year 1
|
0.00%
0/14 • up to Year 1
|
|
Psychiatric disorders
Insomnia
|
13.3%
2/15 • up to Year 1
|
0.00%
0/14 • up to Year 1
|
|
Psychiatric disorders
Tics
|
6.7%
1/15 • up to Year 1
|
0.00%
0/14 • up to Year 1
|
|
Psychiatric disorders
Screaming
|
6.7%
1/15 • up to Year 1
|
0.00%
0/14 • up to Year 1
|
|
Injury, poisoning and procedural complications
Fall
|
13.3%
2/15 • up to Year 1
|
0.00%
0/14 • up to Year 1
|
|
Injury, poisoning and procedural complications
Laceration
|
6.7%
1/15 • up to Year 1
|
0.00%
0/14 • up to Year 1
|
|
Renal and urinary disorders
Pollakuria
|
13.3%
2/15 • up to Year 1
|
0.00%
0/14 • up to Year 1
|
|
Skin and subcutaneous tissue disorders
Rash
|
13.3%
2/15 • up to Year 1
|
0.00%
0/14 • up to Year 1
|
|
Skin and subcutaneous tissue disorders
Skin warm to touch
|
6.7%
1/15 • up to Year 1
|
0.00%
0/14 • up to Year 1
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
6.7%
1/15 • up to Year 1
|
0.00%
0/14 • up to Year 1
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
6.7%
1/15 • up to Year 1
|
0.00%
0/14 • up to Year 1
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhea
|
26.7%
4/15 • up to Year 1
|
7.1%
1/14 • up to Year 1
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
20.0%
3/15 • up to Year 1
|
7.1%
1/14 • up to Year 1
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
6.7%
1/15 • up to Year 1
|
0.00%
0/14 • up to Year 1
|
|
Respiratory, thoracic and mediastinal disorders
Sneezing
|
6.7%
1/15 • up to Year 1
|
0.00%
0/14 • up to Year 1
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory tract congestion
|
0.00%
0/15 • up to Year 1
|
7.1%
1/14 • up to Year 1
|
|
Immune system disorders
Multiple allergies
|
6.7%
1/15 • up to Year 1
|
0.00%
0/14 • up to Year 1
|
|
Vascular disorders
Pallor
|
6.7%
1/15 • up to Year 1
|
0.00%
0/14 • up to Year 1
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
6.7%
1/15 • up to Year 1
|
0.00%
0/14 • up to Year 1
|
Additional Information
Orrin Devinsky, MD
NYU Langone Health, Comprehensive Epilepsy Center
Phone: 6465580803
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place