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Nemiralisib

Phase 2

Activated PI3K-delta Syndrome | Small molecule | Rare Disease |GSK plc|Last Updated: Jun 18, 2021

Success Probability

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Trial Design

UNCONTROLLED
Total Trials1
Total Enrollment5

FDA Designations

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Clinical trial landscape

Nemiralisib · 2 trials · 2 indications

Phase 2 1Phase 1 1
NCT02593539Safety, Pharmacokinetic (PK) and Pharmacodynamic (PD) Study of Repeat Doses of Inhaled Nemiralisib in Patients With APDS/PASLIActivated PI3K-delta Syndrome
COMPLETED5 Analytics
PHASE2COMPLETED
Safety, Pharmacokinetic (PK) and Pharmacodynamic (PD) Study of Repeat Doses of Inhaled Nemiralisib in Patients With APDS/PASLI
Activated PI3K-delta SyndromeUnlock trial analytics

Study Endpoints

Primary Endpoints

Number of Participants With Any Serious Adverse Events (SAEs) and Any Non-serious Adverse Events (Non-SAEs)
Upto 7.5 months

An adverse event is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that; results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, other situations as judged by physician. Number of participants with any SAE and non-SAEs are presented.

Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
Baseline (Day 1 pre-dose) and at Days 14, 28, 56, 83 and 84

SBP and DBP were measured in participants in a semi-supine position after 5 minutes rest. Baseline value is defined as latest pre-dose (Day 1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value. Not applicable (NA) indicates that standard deviation could not be calculated as a single participant was analyzed.

Change From Baseline in Pulse Rate
Baseline (Day 1 pre-dose) and at Days 14, 28, 56, 83 and 84

Pulse rate was measured in participants in a semi-supine position after 5 minutes rest. Baseline value is defined as latest pre-dose (Day 1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value. NA indicates that standard deviation could not be calculated as a single participant was analyzed.

Change From Baseline in Respiratory Rate
Baseline (Day 1 pre-dose) and at Days 14, 28, 56, 83 and 84

Respiratory rate was measured in participants in a semi-supine position after 5 minutes rest. . Baseline value is defined as latest pre-dose (Day 1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value. NA indicates that standard deviation could not be calculated as a single participant was analyzed.

Change From Baseline in Body Temperature
Baseline (Day 1 pre-dose) and at Days 14, 28, 56, 83 and 84

Temperature was measured in participants in a semi-supine position after 5 minutes rest. Baseline value is defined as latest pre-dose (Day 1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value. NA indicates that standard deviation could not be calculated as a single participant was analyzed.

Change From Baseline in Electrocardiogram (ECG) Mean Heart Rate
Baseline (Day 1 pre-dose) and at Days 14, 28, 56 and 83

Single 12-lead ECGs were recorded at indicated timepoints using an ECG machine that automatically calculated the heart rate. Baseline value is defined as latest pre-dose (Day 1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value.

Change From Baseline in PR Interval, QRS Duration, Uncorrected QT Interval, QT Corrected Interval-Fredericia Interval (QTcF) and QTc Corrected by Bazett's Formula (QTcB)
Baseline (Day 1 pre-dose) and at Days 14, 28, 56 and 83

Twelve lead ECGs were recorded at indicated timepoints. At each time point, ECG machine automatically measured QRS duration, uncorrected QT interval, QTcF interval and QTcB. Baseline value is defined as latest pre-dose (Day 1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value.

Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP) and Aspartate Aminotransferase (AST)
Baseline (Day -1) and at Days 14, 28, 56 and 83

Blood samples were collected for the analysis of clinical parameters including ALT, ALP and AST. Baseline value is defined as latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value.

Change From Baseline in Clinical Chemistry Parameters : Albumin and Total Protein
Baseline (Day -1) and at Days 14, 28, 56 and 83

Blood samples were collected for the analysis of clinical chemistry parameter-albumin and total protein. Baseline value is defined as latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value.

Change From Baseline Values in Clinical Chemistry Parameters: Sodium, Potassium, Calcium, Glucose and Urea
Baseline (Day -1) and at Days 14, 28, 56 and 83

Blood samples were collected for the analysis of clinical parameters including sodium, potassium, calcium, glucose and urea. Baseline value is defined as latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value.

Change From Baseline Values in Clinical Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine
Baseline (Day -1) and at Days 14, 28, 56 and 83

Blood samples were collected for the analysis of clinical chemistry parameters: direct bilirubin, total bilirubin and creatinine. Baseline value is defined as latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value.

Change From Baseline Values in Clinical Chemistry Parameter: C-Reactive Protein
Baseline (Day 1 pre-dose) and at Days 14, 28, 56 and 83

Blood samples were collected for the analysis of clinical chemistry parameter:C-Reactive Protein. Baseline value is defined as latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value.

Change From Baseline for Hematology Parameters: Basophil, Eosinophils, White Blood Cells (WBC), Lymphocytes, Neutrophils, Monocytes and Platelets
Baseline (Day -1) and at Days 14, 28, 56 and 83

Blood samples were collected for the analysis of hematology parameters including basophils, eosinophils, WBC, lymphocytes, neutrophils, monocytes and platelets at indicated timepoints. Baseline value is defined as latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value.

Change From Baseline for Hematology Parameter: Hemoglobin
Baseline (Day 1 pre-dose) and at Days 14, 28, 56 and 83

Blood samples were collected for the analysis of hematology parameter: hemoglobin at indicated timepoints. Baseline value is defined as latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value.

Change From Baseline for Hematology Parameter: Hematocrit
Baseline (Day 1 pre-dose) and at Days 14, 28, 56 and 83

Blood samples were collected for the analysis of hematology parameter: hematocrit at indicated timepoints. Baseline value is defined as latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value.

Change From Baseline in Hematology Parameter: Mean Corpuscular Volume (MCV)
Baseline (Day 1 pre-dose) and at Days 14, 28, 56 and 83

Blood samples were collected for the analysis of hematology parameter: MCV at indicated timepoints. Baseline value is defined as latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value.

Change From Baseline in Hematology Parameter: Mean Corpuscular Hemoglobin (MCH)
Baseline (Day 1 pre-dose) and at Days 14, 28, 56 and 83

Blood samples were collected for the analysis of hematology parameters including MCH at indicated timepoints. Baseline value is defined as latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value.

Change From Baseline for Hematology Parameter: Red Blood Cell Count
Baseline (Day 1 pre-dose) and at Days 14, 28, 56 and 83

Blood samples were collected for the analysis of hematology parameter: Blood Cell Count at indicated timepoints. Baseline value is defined as latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value.

Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1)
Baseline (Day 1: pre-dose) and at Day 1: 1 Hour post-dose; Day 2: 1 Hour post-dose; Day 14: Pre-dose; Day 14: 1 Hour post-dose and Day 83: Pre-dose

FEV1 is used to assess pulmonary function using a spirometer at indicated timepoints. Baseline value is defined as the maximum measurement of the planned pre-dose measurements on Day 1, predose. Change from Baseline is defined as post-dose visit value minus Baseline value. Spirometry assessments were performed in accordance with American Thoracic Society (ATS)/European Respiratory Society (ERS) guidelines

Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-inf]) of Nemiralisib in Plasma
Period 1: Pre-dose, and 5, 30 minutes, 2, 6, 12, 24, 48, 72, 96 and 120 hours post-dose on Day 1. Period 2: Pre-dose, and 5 min, 30 min, 2, 6, 12, 24, 48, 72, 96, 120 and 144 hours post-dose on Day 5

Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate pharmacokinetic parameters of nemiralisib in both treatment period 1 and 2. Pharmacokinetic analysis was conducted using standard non-compartmental methods. Pharmacokinetic population comprised of all participants enrolled in the study who took at least 1 dose of nemiralisib and for whom a nemiralisib pharmacokinetic sample was obtained and analyzed.

Area Under the Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC [0-t]) of Nemiralisib in Plasma
Period 1: Pre-dose, and 5, 30 minutes, 2, 6, 12, 24, 48, 72, 96 and 120 hours post-dose on Day 1. Period 2: Pre-dose, and 5 min, 30 min, 2, 6, 12, 24, 48, 72, 96, 120 and 144 hours post-dose on Day 5

Blood samples were collected from participants at indicated time frames after the administration of study treatment to investigate pharmacokinetic parameters of Nemiralisib in both treatment period 1 and 2. Pharmacokinetic analysis was conducted using standard non-compartmental methods.

Maximum Observed Plasma Concentration (Cmax) of Nemiralisib in Plasma
Period 1: Pre-dose, and 5, 30 minutes, 2, 6, 12, 24, 48, 72, 96 and 120 hours post-dose on Day 1. Period 2: Pre-dose, and 5 min, 30 min, 2, 6, 12, 24, 48, 72, 96, 120 and 144 hours post-dose on Day 5

Blood samples were collected from participants at indicated time frames after the administration of study treatment to investigate pharmacokinetic parameters of Nemiralisib in both treatment period 1 and 2. Pharmacokinetic analysis was conducted using standard non-compartmental methods.

Apparent Terminal Half-life (t1/2) of Nemiralisib in Plasma
Period 1: Pre-dose, and 5, 30 minutes, 2, 6, 12, 24, 48, 72, 96 and 120 hours post-dose on Day 1. Period 2: Pre-dose, and 5 min, 30 min, 2, 6, 12, 24, 48, 72, 96, 120 and 144 hours post-dose on Day 5

Blood samples were collected from participants at indicated time frames after the administration of study treatment to investigate pharmacokinetic parameters of Nemiralisib in both treatment period 1 and 2. Pharmacokinetic analysis was conducted using standard non-compartmental methods.

Time to Maximum Observed Plasma Concentration (Tmax) of Nemiralisib in Plasma
Period 1: Pre-dose, and 5, 30 minutes, 2, 6, 12, 24, 48, 72, 96 and 120 hours post-dose on Day 1. Period 2: Pre-dose, and 5 min, 30 min, 2, 6, 12, 24, 48, 72, 96, 120 and 144 hours post-dose on Day 5

Blood samples were collected at indicated time points after administration of repeated doses of itraconazole along with Nemiralisib. Pharmacokinetic analysis was conducted using standard non-compartmental methods.

Secondary Endpoints

Plasma Concentration Following Administration of NEMI
Day 1: Pre-dose, 5 minutes, 3 hours and 24 hours post-dose; Days 14 and 83: pre-dose
AUC(0-inf) of Itraconazole and Hydroxy Itraconazole When Co-administered With Nemiralisib in Treatment Period 2
Pre-dose, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post-dose (itraconazole) on Day 1; Pre-dose, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose (itraconazole) on Day 5
AUC(0-t) of Itraconazole and Hydroxy Itraconazole When Co-administered With Nemiralisib in Treatment Period 2
Pre-dose, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post-dose (itraconazole) on Day 1; Pre-dose, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours post-dose (itraconazole) on Day 5
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Study Design & Arms

AllocationNA
MaskingNONE
ModelSINGLE_GROUP
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
Participants recieving nemiralisibEXPERIMENTAL -
Subjects receiving nemiralisib and itraconazoleEXPERIMENTALEligible subjects will receive a single dose of 100 micrograms (mcg) nemiralisib on Day 1 in Period 1. Subjects will also receive a single dose of 200 milligrams (mg) itraconazole in the morning from Day 1 to Day 10 and single dose of 100 mcg nemiralisib on Day 5, one hour after the dose of itraconazole in Period 2. There will be a washout of at least 14 days between the administration of nemiralisib in Period 1 and Period 2.

Interventions

NameTypeDescription
NemiralisibDRUGParticipants will be administered nemiralisib
ItraconazoleDRUGItraconazole will be given as 100 mg per capsule per day administered orally with water
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Eligibility Criteria

Age Range18 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites1

Inclusion Criteria: * Male and female subjects aged 18 or older at the time of signing the informed consent. * Patients with a clinical phenotype consistent with APDS, including a history of recurrent (frequency greater than would be expected in an immunocompetent individual) ear, sinus or pulmonar...

Countries:United KingdomUnited States
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Frequently asked questions about Nemiralisib

What is Nemiralisib used for?

Nemiralisib is an investigational small molecule being studied for Activated PI3K-delta Syndrome (APDS) and Chronic Obstructive Pulmonary Disease (COPD). It is developed by GSK plc (GSK) and has been evaluated in clinical trials for these conditions.

How does Nemiralisib work?

Nemiralisib targets the PI3K-delta enzyme, which plays a role in immune cell signaling. By inhibiting this target, it aims to modulate the overactive immune response associated with Activated PI3K-delta Syndrome and related pulmonary conditions.

Who makes Nemiralisib?

Nemiralisib is developed by GSK plc, a global biopharma company listed on the stock exchange under the ticker GSK. GSK is conducting clinical research to evaluate the drug's safety and efficacy in relevant patient populations.

What phase is Nemiralisib in?

Nemiralisib has completed a Phase 2 clinical trial in patients with Activated PI3K-delta Syndrome. It remains an investigational drug, meaning it has not been approved by regulatory authorities and is still in clinical development.

What clinical trials is Nemiralisib in?

Nemiralisib has been studied in two completed trials: NCT02593539, a Phase 2 study in patients with Activated PI3K-delta Syndrome in the United Kingdom, and NCT03398421, a Phase 1 drug interaction study in healthy volunteers with COPD in the United States.

Is Nemiralisib the same as GSK2269557?

Nemiralisib is also known by the code name GSK2269557. This alternative name may appear in scientific literature and clinical trial registries, referring to the same investigational drug developed by GSK.