Clinical Trial Results:
An Open-Label Exploratory Study of UCB5857 in Subjects with Activated Phosphoinositide 3 Kinase (PI3K) Delta Syndrome (APDS)
Summary
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EudraCT number |
2015-002900-10 |
Trial protocol |
IT DE ES FR |
Global end of trial date |
23 Jan 2018
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Results information
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Results version number |
v1(current) |
This version publication date |
05 Aug 2018
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First version publication date |
05 Aug 2018
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
APD001
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
UCB Celltech, UK Registered Branch of UCB Pharma SA
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Sponsor organisation address |
208 Bath Road, Slough, United Kingdom, SL1 3WE
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Public contact |
Clin Trial Reg & Results Disclosure, UCB BIOSCIENCES GmbH, clinicaltrials@ucb.com
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Scientific contact |
Clin Trial Reg & Results Disclosure, UCB BIOSCIENCES GmbH, clinicaltrials@ucb.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
20 Feb 2018
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
23 Jan 2018
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To evaluate the safety and tolerability of UCB5857 in subjects with Activated PI3K delta syndrome (APDS).
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Protection of trial subjects |
During the conduct of the study all subjects were closely monitored, including a Safety Monitoring Committee review of ongoing safety and efficacy data.
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Background therapy |
Background therapy as permitted in the protocol. | ||
Evidence for comparator |
Not applicable. | ||
Actual start date of recruitment |
23 May 2016
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Safety | ||
Long term follow-up duration |
5 Years | ||
Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
France: 2
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Country: Number of subjects enrolled |
Germany: 1
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Country: Number of subjects enrolled |
Italy: 2
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Country: Number of subjects enrolled |
Spain: 2
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Worldwide total number of subjects |
7
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EEA total number of subjects |
7
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
6
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Adults (18-64 years) |
1
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
The study started to enroll subjects in May 2016 and concluded in Jan 2018. | ||||||||||
Pre-assignment
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Screening details |
The study included 8 subjects in the Enrollment Set. 1 subject represented a screen failure due to being underweight, leaving 7 subjects that formed the Safety Set (SS) and the Pharmacokinetic Set (PKS). | ||||||||||
Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||
Arms
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Arm title
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UCB5857 | ||||||||||
Arm description |
UCB5857 capsules were supplied at doses of 5 mg, 15 mg, and 30 mg, depending on body weight, to allow a flexible dosing regimen by combining the capsule strengths. The study investigational medicinal product (IMP) was administered orally, once per day, in the morning, during a 12-week Treatment Period. | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
Seletalisib
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Investigational medicinal product code |
UCB5857
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
Capsules of UCB5857 5 mg,15 mg or 30 mg, administered daily, by oral intake for 12 weeks.
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Baseline characteristics reporting groups
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Reporting group title |
UCB5857
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Reporting group description |
UCB5857 capsules were supplied at doses of 5 mg, 15 mg, and 30 mg, depending on body weight, to allow a flexible dosing regimen by combining the capsule strengths. The study investigational medicinal product (IMP) was administered orally, once per day, in the morning, during a 12-week Treatment Period. | ||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
UCB5857
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Reporting group description |
UCB5857 capsules were supplied at doses of 5 mg, 15 mg, and 30 mg, depending on body weight, to allow a flexible dosing regimen by combining the capsule strengths. The study investigational medicinal product (IMP) was administered orally, once per day, in the morning, during a 12-week Treatment Period. | ||
Subject analysis set title |
UCB5857 (SS)
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
At least one dose of UCB5857 capsules was administered orally to all subjects forming the Safety Set (SS), once per day during a 12-week Treatment Period, supplied at doses of 5 mg, 15 mg, and 30 mg, depending on body weight, to allow a flexible dosing regimen by combining the capsule strengths.
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Subject analysis set title |
UCB5857 (PKS)
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
At least one dose of UCB5857 capsules was administered orally to all subjects forming the Pharmacokinetic Set (PKS), once per day during a 12-week Treatment Period, supplied at doses of 5 mg, 15 mg, and 30 mg, depending on body weight, to allow a flexible dosing regimen by combining the capsule strengths. Subjects had at least 1 measurable plasma concentration available of the UCB5857 investigational medicinal product.
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End point title |
The total number of subjects experiencing at least one Treatment Emergent Adverse Event during the study [1] | ||||||||
End point description |
Treatment-Emergent Adverse Events (TEAEs) are any untoward medical incidence in a subject during administered study treatment, whether or not these events are related to study treatment.
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End point type |
Primary
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End point timeframe |
Baseline to week 16
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No formal statistical hypothesis testing was planned for this study. Results were summarized as descriptive statistics only. |
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No statistical analyses for this end point |
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End point title |
The total number of subjects experiencing at least one Serious Adverse Event during the study [2] | ||||||||
End point description |
A Serious Adverse Event (SAE) is any untoward medical incidence that occurs at any dose.
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End point type |
Primary
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End point timeframe |
Baseline to week 16
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Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No formal statistical hypothesis testing was planned for this study. Results were summarized as descriptive statistics only. |
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No statistical analyses for this end point |
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End point title |
Plasma Concentration of UCB5857 at Baseline Visit, 15-30 minutes post-dose | ||||||||||
End point description |
UCB5857 concentration in plasma was expressed in nanograms per milliliter (ng/mL) as measured by a validated high-performance liquid chromatography method with tandem mass spectrometry (HPLC-MS). Summary statistics (except for n, Min, and Max) were only performed if at least 2/3 of the concentrations were quantified at the respective time-point.
*Note: -9999 is a placeholder value that replaced missing or bellow limit of quantification values
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End point type |
Secondary
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End point timeframe |
Baseline Visit, 15-30 minutes post-dose
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No statistical analyses for this end point |
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End point title |
Plasma Concentration of UCB5857 at Baseline Visit, 2-4 hours post-dose | ||||||||||
End point description |
UCB5857 concentration in plasma was expressed in nanograms per milliliter (ng/mL) as measured by a validated high-performance liquid chromatography method with tandem mass spectrometry (HPLC-MS). Summary statistics (except for n, Min, and Max) were only performed if at least 2/3 of the concentrations were quantified at the respective time-point.
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End point type |
Secondary
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End point timeframe |
Baseline Visit, 2-4 hours post-dose
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No statistical analyses for this end point |
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End point title |
Plasma Concentration of UCB5857 at Baseline Visit, 24 hours post-dose | ||||||||||
End point description |
UCB5857 concentration in plasma was expressed in nanograms per milliliter (ng/mL) as measured by a validated high-performance liquid chromatography method with tandem mass spectrometry (HPLC-MS). Summary statistics (except for n, Min, and Max) were only performed if at least 2/3 of the concentrations were quantified at the respective time-point.
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End point type |
Secondary
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End point timeframe |
Baseline Visit, 24 hours post-dose
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No statistical analyses for this end point |
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End point title |
Plasma Concentration of UCB5857 at Week 2, pre-dose | ||||||||||
End point description |
UCB5857 concentration in plasma was expressed in nanograms per milliliter (ng/mL) as measured by a validated high-performance liquid chromatography method with tandem mass spectrometry (HPLC-MS). Summary statistics (except for n, Min, and Max) were only performed if at least 2/3 of the concentrations were quantified at the respective time-point.
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End point type |
Secondary
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End point timeframe |
Week 2, pre-dose
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No statistical analyses for this end point |
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End point title |
Plasma Concentration of UCB5857 at Week 2, 2-4 hours post-dose | ||||||||||
End point description |
UCB5857 concentration in plasma was expressed in nanograms per milliliter (ng/mL) as measured by a validated high-performance liquid chromatography method with tandem mass spectrometry (HPLC-MS). Summary statistics (except for n, Min, and Max) were only performed if at least 2/3 of the concentrations were quantified at the respective time-point.
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End point type |
Secondary
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End point timeframe |
Week 2, 2-4 hours post-dose
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No statistical analyses for this end point |
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End point title |
Plasma Concentration of UCB5857 at Week 6, pre-dose | ||||||||||
End point description |
UCB5857 concentration in plasma was expressed in nanograms per milliliter (ng/mL) as measured by a validated high-performance liquid chromatography method with tandem mass spectrometry (HPLC-MS). Summary statistics (except for n, Min, and Max) were only performed if at least 2/3 of the concentrations were quantified at the respective time-point.
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End point type |
Secondary
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End point timeframe |
Week 6, pre-dose
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No statistical analyses for this end point |
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End point title |
Plasma Concentration of UCB5857 at Week 6, 2-4 hours post-dose | ||||||||||
End point description |
UCB5857 concentration in plasma was expressed in nanograms per milliliter (ng/mL) as measured by a validated high-performance liquid chromatography method with tandem mass spectrometry (HPLC-MS). Summary statistics (except for n, Min, and Max) were only performed if at least 2/3 of the concentrations were quantified at the respective time-point.
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End point type |
Secondary
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End point timeframe |
Week 6, 2-4 hours post-dose
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No statistical analyses for this end point |
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End point title |
Plasma Concentration of UCB5857 at Week 12, pre-dose | ||||||||||
End point description |
UCB5857 concentration in plasma was expressed in nanograms per milliliter (ng/mL) as measured by a validated high-performance liquid chromatography method with tandem mass spectrometry (HPLC-MS). Summary statistics (except for n, Min, and Max) were only performed if at least 2/3 of the concentrations were quantified at the respective time-point.
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End point type |
Secondary
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End point timeframe |
Week 12, pre-dose
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No statistical analyses for this end point |
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End point title |
Plasma Concentration of UCB5857 at Week 12, 15-30 minutes post-dose | ||||||||||
End point description |
UCB5857 concentration in plasma was expressed in nanograms per milliliter (ng/mL) as measured by a validated high-performance liquid chromatography method with tandem mass spectrometry (HPLC-MS). Summary statistics (except for n, Min, and Max) were only performed if at least 2/3 of the concentrations were quantified at the respective time-point.
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End point type |
Secondary
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End point timeframe |
Week 12, 15-30 minutes post-dose
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No statistical analyses for this end point |
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End point title |
Plasma Concentration of UCB5857 at Week 12, 2-4 hours post-dose | ||||||||||
End point description |
UCB5857 concentration in plasma was expressed in nanograms per milliliter (ng/mL) as measured by a validated high-performance liquid chromatography method with tandem mass spectrometry (HPLC-MS). Summary statistics (except for n, Min, and Max) were only performed if at least 2/3 of the concentrations were quantified at the respective time-point.
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End point type |
Secondary
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End point timeframe |
Week 12, 2-4 hours post-dose
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No statistical analyses for this end point |
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End point title |
Plasma Concentration of UCB5857 at Week 12, 24 hours post-dose | ||||||||||
End point description |
UCB5857 concentration in plasma was expressed in nanograms per milliliter (ng/mL) as measured by a validated high-performance liquid chromatography method with tandem mass spectrometry (HPLC-MS). Summary statistics (except for n, Min, and Max) were only performed if at least 2/3 of the concentrations were quantified at the respective time-point.
*Note: 999 is a placeholder value, as mean concentration was not calculated.
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End point type |
Secondary
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End point timeframe |
Week 12, 24 hours post-dose
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
Baseline to week 24
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
20.0
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Reporting groups
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Reporting group title |
UCB5857 (SS)
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Reporting group description |
At least one dose of UCB5857 capsules was administered orally to all subjects forming the Safety Set (SS), once per day during a 12-week Treatment Period, supplied at doses of 5 mg, 15 mg, and 30 mg, depending on body weight, to allow a flexible dosing regimen by combining the capsule strengths. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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04 Mar 2016 |
Protocol Amendment 2 was implemented to prohibit the co-administration of known P-glycoprotein (PGP) inhibitors with UCB5857. Since UCB5857 is likely (although not yet confirmed) to be a substrate of PGP, the possibility exists that UCB5857 might be susceptible to Pharmacokinetic (PK) interactions as a victim drug when co administered with a PGP inhibitor.
In addition, subjects were required to remain at the site for 24 hours after their first dose of Investigational Medicinal Product (IMP) at Baseline (Visit 2). Subjects were observed as a safety precaution, and had vital signs and electrocardiogram (ECG) recordings taken, in addition to obtaining 24 hour blood samples for PK and phospho-S6 ribosomal protein (p-S6) measurements. |
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05 Apr 2017 |
Protocol Amendment 4, provided the following key changes:
•Modified the restriction regarding PGP inhibitors and removed the table of PGP inhibitors from the protocol based on newly available nonclinical data
•Added procedures for assessment and management of Tuberculosis (TB) in order to comply with the UCB policy applied to all UCB-sponsored studies (excluding noninterventional studies) that include subjects with immunological diseases, who are at increased risk of TB infection either associated with the IMP, underlying disease, concomitant treatments, or other medical or sociological factors
•Aligned local versions of the protocol into a single global version
•Added guidance on Adverse Events Of Interest (AEOI), management of AEOI, and immediate reporting of Adverse Events (AEs) |
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Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |