Trial Outcomes & Findings for Study of Ataluren (PTC124) in Hemophilia A and B (NCT NCT00947193)
NCT ID: NCT00947193
Last Updated: 2020-06-16
Results Overview
A plasma FVIII/FIX activity response was defined as an end-of-treatment (Day 14) activity of ≥1%.
TERMINATED
PHASE2
13 participants
Baseline up to Day 14
2020-06-16
Participant Flow
In this study, participants with HA or HB due to a nonsense mutation were recruited for the study.
Participants requiring treatment with Factor 8 (FVIII)/Factor 9 (FIX) concentrate during 14-day ataluren treatment could continue ataluren treatment for at least 14 days following discontinuing FVIII concentrate treatment for hemophilia type A (HA) and for at least 18 days following discontinuing FIX concentrate treatment for hemophilia type B (HB)
Participant milestones
| Measure |
5 mg/kg, 5 mg/kg, and 10 mg/kg Ataluren
Ataluren was provided as a vanilla-flavored powder to be mixed with water or milk. Ataluren was taken 3 times per day, with dosing based on the participant's body weight. The dose level for ataluren was 5 milligrams/kilograms (mg/kg) in the morning, 5 mg/kg at midday, and 10 mg/kg in the evening for 14 days, followed by an interval of 14 days without treatment.
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10 mg/kg, 10 mg/kg, and 20 mg/kg Ataluren
Ataluren was provided as a vanilla-flavored powder to be mixed with water or milk. Ataluren was taken 3 times per day, with dosing based on the participant's body weight. The dose level for ataluren was 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 14 days, followed by an interval of 14 days without treatment.
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|---|---|---|
|
Overall Study
STARTED
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3
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10
|
|
Overall Study
Received at Least 1 Dose of Study Drug
|
3
|
10
|
|
Overall Study
COMPLETED
|
0
|
10
|
|
Overall Study
NOT COMPLETED
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3
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0
|
Reasons for withdrawal
| Measure |
5 mg/kg, 5 mg/kg, and 10 mg/kg Ataluren
Ataluren was provided as a vanilla-flavored powder to be mixed with water or milk. Ataluren was taken 3 times per day, with dosing based on the participant's body weight. The dose level for ataluren was 5 milligrams/kilograms (mg/kg) in the morning, 5 mg/kg at midday, and 10 mg/kg in the evening for 14 days, followed by an interval of 14 days without treatment.
|
10 mg/kg, 10 mg/kg, and 20 mg/kg Ataluren
Ataluren was provided as a vanilla-flavored powder to be mixed with water or milk. Ataluren was taken 3 times per day, with dosing based on the participant's body weight. The dose level for ataluren was 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 14 days, followed by an interval of 14 days without treatment.
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|---|---|---|
|
Overall Study
Lost to Follow-up
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1
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0
|
|
Overall Study
Withdrawal by Subject
|
1
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0
|
|
Overall Study
Factor VIII >1%
|
1
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0
|
Baseline Characteristics
Study of Ataluren (PTC124) in Hemophilia A and B
Baseline characteristics by cohort
| Measure |
Ataluren Overall Study
n=13 Participants
Ataluren was provided as a vanilla-flavored powder to be mixed with water or milk. Ataluren was taken 3 times per day, with dosing based on the participant's body weight. The dose level for ataluren was 5 mg/kg in the morning, 5 mg/kg at midday, and 10 mg/kg in the evening or 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 14 days, followed by an interval of 14 days without treatment.
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|---|---|
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Age, Continuous
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42 years
STANDARD_DEVIATION 17.3 • n=99 Participants
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Sex: Female, Male
Female
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0 Participants
n=99 Participants
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Sex: Female, Male
Male
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13 Participants
n=99 Participants
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PRIMARY outcome
Timeframe: Baseline up to Day 14Population: All enrolled participants who received at least 1 dose of study drug and completed the study.
A plasma FVIII/FIX activity response was defined as an end-of-treatment (Day 14) activity of ≥1%.
Outcome measures
| Measure |
10 mg/kg, 10 mg/kg, and 20 mg/kg Ataluren
n=10 Participants
Ataluren was provided as a vanilla-flavored powder to be mixed with water or milk. Ataluren was taken 3 times per day, with dosing based on the participant's body weight. The dose level for ataluren was 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 14 days, followed by an interval of 14 days without treatment.
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|---|---|
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Number of Participants With a Plasma FVIII/FIX Activity Response at Day 14
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0 Participants
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SECONDARY outcome
Timeframe: Baseline and Day 14Population: All enrolled participants who received at least 1 dose of study drug and completed the study.
To assess the change from Baseline in plasma anti-FVIII/FIX inhibitor titers, it was determined if any potential antibodies were neutralizing using the Bethesda assay. The Bethesda assay demonstrates antibodies that are neutralizing by quantifying residual FVIII/FIX activity in normal plasma after serial dilutions with participant plasma. For this assay, the neutralizing antibody threshold value was 0.6 Bethesda units (BU).
Outcome measures
| Measure |
10 mg/kg, 10 mg/kg, and 20 mg/kg Ataluren
n=10 Participants
Ataluren was provided as a vanilla-flavored powder to be mixed with water or milk. Ataluren was taken 3 times per day, with dosing based on the participant's body weight. The dose level for ataluren was 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 14 days, followed by an interval of 14 days without treatment.
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|---|---|
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Number of Participants With a Change From Baseline in Plasma Anti-FVIII/FIX Inhibitor Titers at Day 14
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1 Participants
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SECONDARY outcome
Timeframe: Baseline up to Day 28Population: All enrolled participants who received at least 1 dose of study drug.
The relationship of TEAEs and SAEs to the study drugs was assessed as: probable related, possible related, unlikely related, and unrelated. The severity of TEAEs were graded using the Common Terminology Criteria for Adverse Events, Version 3.0, as: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (life-threatening), or Grade 5 (fatal). A summary of other non-serious adverse events (AEs) and all serious AEs, regardless of causality is located in Reported AE section.
Outcome measures
| Measure |
10 mg/kg, 10 mg/kg, and 20 mg/kg Ataluren
n=13 Participants
Ataluren was provided as a vanilla-flavored powder to be mixed with water or milk. Ataluren was taken 3 times per day, with dosing based on the participant's body weight. The dose level for ataluren was 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 14 days, followed by an interval of 14 days without treatment.
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|---|---|
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Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs) by Severity and Relationship to Study Drug
TEAEs
|
8 Participants
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs) by Severity and Relationship to Study Drug
TEAEs Related to Study Drug
|
2 Participants
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs) by Severity and Relationship to Study Drug
Severe TEAEs
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0 Participants
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs) by Severity and Relationship to Study Drug
SAEs
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0 Participants
|
SECONDARY outcome
Timeframe: Baseline up to Day 28Population: All enrolled participants who received at least 1 dose of study drug and had evaluable clinical laboratory data.
The Investigator used his/her judgment in determining whether an abnormality was clinically significant, diagnostic evaluation was warranted, and potential interruption of ataluren was appropriate. Life-threatening (Grade 4) or severe (Grade 3) laboratory abnormalities were considered dose-limiting, although recurrent or persistent moderate (Grade 2) events were also considered dose-limiting in certain circumstances. Values considered abnormal included -Hematology: Serum total bilirubin Grade 2 (\>1.5-3.0\*upper limit of normal \[ULN\]) and Serum alanine aminotransferase, Serum aspartate aminotransferase, and Serum gamma glutamyl transferase Grade 2 (\>2.5-3.0\*ULN); -Adrenal: Plasma adrenocorticotropic hormone \>ULN (and cortisol within normal limits); and -Renal: serum creatinine Grade 1 (\>ULN-1.5\*ULN) and Serum blood urea nitrogen ≥1.5-3.0\*ULN. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Outcome measures
| Measure |
10 mg/kg, 10 mg/kg, and 20 mg/kg Ataluren
n=13 Participants
Ataluren was provided as a vanilla-flavored powder to be mixed with water or milk. Ataluren was taken 3 times per day, with dosing based on the participant's body weight. The dose level for ataluren was 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 14 days, followed by an interval of 14 days without treatment.
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|---|---|
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Number of Participants With a Clinically Meaningful Abnormal Clinical Laboratory (Hematology, Adrenal Assays, Biochemistry, and Urinalysis) Parameters
Hematology Assays
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0 Participants
|
|
Number of Participants With a Clinically Meaningful Abnormal Clinical Laboratory (Hematology, Adrenal Assays, Biochemistry, and Urinalysis) Parameters
Biochemistry Assays
|
0 Participants
|
|
Number of Participants With a Clinically Meaningful Abnormal Clinical Laboratory (Hematology, Adrenal Assays, Biochemistry, and Urinalysis) Parameters
Adrenal Assays
|
0 Participants
|
|
Number of Participants With a Clinically Meaningful Abnormal Clinical Laboratory (Hematology, Adrenal Assays, Biochemistry, and Urinalysis) Parameters
Urinalysis
|
1 Participants
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SECONDARY outcome
Timeframe: Baseline up to Day 28Population: All enrolled participants who received at least 1 dose of study drug, completed the study, and had evaluable compliance with ataluren administration data.
Ataluren compliance as assessed by quantification of used and unused drug. Data were not collected or analyzed for this measure because participants were terminated early from the study.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Day 10 (pre-dose) and Day 14 (post-dose)Population: All enrolled participants who received at least 1 dose of study drug, completed the study, and had evaluable plasma data.
The ataluren plasma concentrations before and 2 hours after the first morning dose at end of treatment was measured.
Outcome measures
| Measure |
10 mg/kg, 10 mg/kg, and 20 mg/kg Ataluren
n=10 Participants
Ataluren was provided as a vanilla-flavored powder to be mixed with water or milk. Ataluren was taken 3 times per day, with dosing based on the participant's body weight. The dose level for ataluren was 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 14 days, followed by an interval of 14 days without treatment.
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|---|---|
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Ataluren Plasma Exposure
Pre-Dose
|
14.7 microgram/milliliters (μg/mL)
Interval 5.94 to 28.7
|
|
Ataluren Plasma Exposure
Post-Dose
|
6.66 microgram/milliliters (μg/mL)
Interval 1.04 to 28.3
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SECONDARY outcome
Timeframe: Baseline up to Day 28Population: All enrolled participants who received at least 1 dose of study drug.
Frequency, timing, anatomic location, and severity of any bleeding episodes were recorded. A summary of serious and all other non-serious adverse events, regardless of causality, is located in the Reported Adverse Events module.
Outcome measures
| Measure |
10 mg/kg, 10 mg/kg, and 20 mg/kg Ataluren
n=13 Participants
Ataluren was provided as a vanilla-flavored powder to be mixed with water or milk. Ataluren was taken 3 times per day, with dosing based on the participant's body weight. The dose level for ataluren was 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 14 days, followed by an interval of 14 days without treatment.
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|---|---|
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Occurrence of Bleeding Episodes
Participants Who Experienced a Bleeding Episode
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3 Participants
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Occurrence of Bleeding Episodes
Spontaneous Right Hip Bleed
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1 Participants
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Occurrence of Bleeding Episodes
Soft Tissue Bleed
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1 Participants
|
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Occurrence of Bleeding Episodes
Right Knee Bleed
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1 Participants
|
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Occurrence of Bleeding Episodes
Upper Shoulder Bleed
|
1 Participants
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Adverse Events
Ataluren Overall Study
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Ataluren Overall Study
n=13 participants at risk
Ataluren was provided as a vanilla-flavored powder to be mixed with water or milk. Ataluren was taken 3 times per day, with dosing based on the participant's body weight. The dose level for ataluren was 5 mg/kg in the morning, 5 mg/kg at midday, and 10 mg/kg in the evening or 10 mg/kg in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening for 14 days, followed by an interval of 14 days without treatment.
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|---|---|
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Gastrointestinal disorders
Diarrhoea
|
7.7%
1/13 • Baseline up to Day 28
Adverse event data were collected from all enrolled participants who received at least 1 dose of study drug.
|
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Gastrointestinal disorders
Constipation
|
7.7%
1/13 • Baseline up to Day 28
Adverse event data were collected from all enrolled participants who received at least 1 dose of study drug.
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|
Gastrointestinal disorders
Dyspepsia
|
7.7%
1/13 • Baseline up to Day 28
Adverse event data were collected from all enrolled participants who received at least 1 dose of study drug.
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Gastrointestinal disorders
Nausea
|
7.7%
1/13 • Baseline up to Day 28
Adverse event data were collected from all enrolled participants who received at least 1 dose of study drug.
|
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Cardiac disorders
Conduction disorder
|
7.7%
1/13 • Baseline up to Day 28
Adverse event data were collected from all enrolled participants who received at least 1 dose of study drug.
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General disorders
Asthenia
|
7.7%
1/13 • Baseline up to Day 28
Adverse event data were collected from all enrolled participants who received at least 1 dose of study drug.
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Renal and urinary disorders
Haematuria
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7.7%
1/13 • Baseline up to Day 28
Adverse event data were collected from all enrolled participants who received at least 1 dose of study drug.
|
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Renal and urinary disorders
Dysuria
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7.7%
1/13 • Baseline up to Day 28
Adverse event data were collected from all enrolled participants who received at least 1 dose of study drug.
|
|
Vascular disorders
Haemorrhage
|
23.1%
3/13 • Baseline up to Day 28
Adverse event data were collected from all enrolled participants who received at least 1 dose of study drug.
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Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The Sponsor can review results and/or communications prior to public release and can embargo communications regarding trial results for a period that is up to 180 days from the time submitted to the sponsor for review. The sponsor may consult with the PI to require changes to the communication or extend the embargo.
- Publication restrictions are in place
Restriction type: OTHER