SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT02593539

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

An Open-label, Single Arm Study to Investigate the Safety, Pharmacokinetics and Pharmacodynamics of Repeat Doses of Inhaled GSK2269557 in Patients With APDS/PASLI

This is a multi-center, non-randomised, open-label, uncontrolled, single group study to investigate the safety and pharmacokinetics (PK) during 84 days repeat dosing treatment with 1000 micrograms (mcg) of inhaled GSK2269557 in addition to standard of care, in subjects with activated phosphoinositide 3-kinase (PI3K) delta syndrome /p110delta-activating mutation causing senescent T Cells, lymphadenopathy and immunodeficiency (APDS/PASLI). To date GSK2269557 has been administered to healthy subjects (smokers and non smokers), subjects with: stable Chronic Obstructive Pulmonary Disease (COPD); subjects experiencing a COPD exacerbation; and subjects with persistent, uncontrolled asthma. As this study is the first administration of GSK2269557 to subjects with APDS, this study will provide safety, tolerability, efficacy and pharmacokinetic data in this patient population. Up to 20 subjects will be enrolled into the study. The total duration of the study is approximately 30 weeks, including pre-screening/screening and follow-up.

NCT02593539 Activated PI3K-delta Syndrome
MeSH: Immunologic Deficiency Syndromes
HPO: Immunodeficiency

1 Interventions

Name: GSK2269557 DPI 500 mcg

Description: Subjects will receive 2 inhalations of GSK2269557 500 mcg in DPI (total dose: 1000 mcg) to be taken every day before breakfast (with the exception of days when the subjects have a planned visit to the study clinic. On those days, they will be dosed at the clinic). The subject should hold their breath for 10 seconds before exhaling. Inhalations should be taken approximately 30 seconds apart.

Type: Drug

GSK2269557 DPI 1000 mcg


Primary Outcomes

Description: An AE is any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.

Measure: Number of subjects with any adverse events (AE)

Time: Up to 6 months

Description: Systolic and diastolic blood pressure will be measured in semi-supine position after 5 minutes rest.

Measure: Systolic and diastolic blood pressure as a measure of safety

Time: Up to 7.5 months

Description: Temperature will be measured in semi-supine position after 5 minutes rest.

Measure: Temperature as a measure of safety

Time: Up to 7.5 months

Description: Pulse rate will be measured in semi-supine position after 5 minutes rest.

Measure: Pulse rate as a measure of safety

Time: Up to 7.5 months

Description: Respiratory rate will be measured in semi-supine position after 5 minutes rest.

Measure: Respiratory rate as a measure of safety

Time: Up to 7.5 months

Description: Single (triplicate at screening) 12-lead ECGs will be obtained at each time point during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals.

Measure: 12-lead electrocardiogram (ECG) as a measure of safety

Time: Up to 7.5 months

Description: The following hematology parameters will be measured: Platelet Count, red blood cell (RBC) Count, Hemoglobin, Hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), white blood cells (WBC) count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, and Basophils

Measure: Composite of hematology parameters as a measure of safety

Time: Up to 7.5 months

Description: The following clinical chemistry parameters will be measured: blood urea nitrogen (BUN)/Urea, Creatinine, Glucose, C-reactive protein (CRP), Potassium, Sodium, Calcium, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, Total and direct bilirubin, Total Protein, and Albumin

Measure: Composite of clinical chemistry parameters as a measure of safety

Time: Up to 7.5 months

Description: Specific gravity, power of hydrogen (pH), glucose, protein, blood and ketones measured by dipstick; and microscopic examination (if blood or protein is abnormal)

Measure: Composite of urinalysis parameters as a measure of safety

Time: Up to 7.5 months

Description: FEV1 is the maximal amount of air that can be forcefully exhaled in one second.

Measure: Spirometry: Forced expiratory volume in one second (FEV1)

Time: Up to 7.5 months

Secondary Outcomes

Measure: GSK2269557 trough plasma concentration following single and repeated treatment

Time: Pre-dose, 5 minutes, 3 hours and 24 hours post-dose on Day 1 and pre-dose on Days 2, 14, and 83 and early withdrawal

Purpose: Treatment

Single Group Assignment


There are 4 SNPs

SNPs


1 C416R

E1021K, N334K, E525K and C416R). --- E1021K --- --- N334K --- --- E525K --- --- C416R ---


2 E1021K

E1021K, N334K, E525K and C416R). --- E1021K ---


3 E525K

E1021K, N334K, E525K and C416R). --- E1021K --- --- N334K --- --- E525K ---


4 N334K

E1021K, N334K, E525K and C416R). --- E1021K --- --- N334K ---



HPO Nodes


HPO:
Immunodeficiency
Genes 196
CYBB MYC MYD88 IL12B IRF2BP2 IL12RB1 RNF168 ACD ATRX AICDA TNFSF12 RTEL1 ACP5 CFTR NCF1 ACTB GATA1 CPLX1 GATA2 BLNK CDH23 FGFRL1 IKZF1 NCF2 CHD1 IRF7 SLC46A1 MAGT1 RREB1 PTEN ADA BCR ADA2 LYST ZBTB24 MEIS2 STAT1 PGM3 HIRA TNFRSF4 TYK2 STIM1 STK4 JAK3 MALT1 STX1A ICOS ANTXR2 PTPRC MBTPS2 TINF2 FCGR3A COG6 PIK3CA CARD9 CCDC47 NFE2L2 PIK3CD PIK3R1 AGL NFKB1 BTK NFKB2 UFD1 IL21 BUB1B PKP1 DKC1 AK2 UNG AKT1 NOP10 BCL10 UROS AP3D1 RAB27A SEC23B TBX1 SDHB SDHC RAC2 SDHD TBCE GP1BB DNMT3B CUL4B DOCK2 FOXN1 RAG1 RAG2 FRAS1 TCF3 CLCA4 LAMTOR2 WAS COMT WIPF1 USB1 CTC1 WHCR NSD2 FOS POLE SMARCAL1 AGPAT2 IRF8 IKBKG XIAP CHD7 SIN3A LMNB2 CAV1 SIK3 LCK PPARG XRCC4 WRAP53 FCN3 NHP2 SKIV2L CR2 TERC SP110 TERT JMJD1C SHANK3 LETM1 CRKL RBCK1 EPG5 TFRC TGFB1 TTC7A IFNGR1 IFNGR2 UNC119 RMRP USP8 ORAI1 LIG4 CORO1A CD3D CD3E KLLN CD3G CD247 BCL11B SEC24C LAT CD19 MS4A1 ISG15 ARVCF DCLRE1C CDCA7 MTHFD1 CD28 IGHM IL21R CD40 CD40LG IRAK4 TNFRSF13C LRRC8A TNFRSF13B PRKCD CD79A CD79B CD81 CTBP1 CARD11 PARN CAVIN1 BSCL2 CTLA4 IGLL1 PRKDC ATM MAPK1 LRBA DCTN4 TNFRSF1B CTPS1 IKBKB NHEJ1 HBB SH2D1A CDC42 IL2RA SPATA5 IL2RG MMUT IL7R HELLS CYBA PRPS1