Activated PI3K-delta SyndromePhase 2NCT02593539

Safety, Pharmacokinetic (PK) and Pharmacodynamic (PD) Study of Repeat Doses of Inhaled Nemiralisib in Patients With APDS/PASLI

A Phase 2 study testing Nemiralisib in people with Activated PI3K-delta Syndrome, run by GlaxoSmithKline at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This is an open-label study conducted to investigate safety, pharmacokinetics and pharmacodynamics of repeat doses of inhaled nemiralisib (NEMI) in participants with activated phosphoinositide 3-kinase (PI3K) delta syndrome /p110 delta-activating mutation causing senescent T Cells, lymphadenopathy and immunodeficiency… Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Activated PI3K-delta Syndrome
What is being tested?: Nemiralisib
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 5 participants
Where: 1 siteUnited Kingdom
Study dates: 22 Jul 2016to 4 Jun 2020
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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 pulmonary infections, and who have a known type 1 APDS-associated genetic PI3K delta mutation (i.e. E1021K, N334K, E525K and C416R).
Body weight >=45 kilograms (kg) and body mass index (BMI) >=18 kg/square meter (m^2) (inclusive)
Male subject. Male subjects with female partners of child bearing potential must comply with the following contraception requirements from the time of first dose of study medication until completion of the follow-up telephone call at 1-2 weeks from last dose. Vasectomy with documentation of azoospermia. Male condom plus partner use of one of the following contraceptive options: 1. Contraceptive subdermal implant 2. Intrauterine device or intrauterine system 3. Combined estrogen and progestogen oral contraceptive, 4. Injectable progestogen 5. Contraceptive vaginal ring 6. Percutaneous contraceptive patches. This is an all inclusive list of those methods that meet the GSK definition of highly effective: having a failure rate of less than 1% per year when used consistently and, correctly and, when applicable, in accordance with the product label. For non-product methods (e.g. male sterility), the investigator determines what is consistent and correct use. The GlaxoSmithKline (GSK) definition is based on the definition provided by International Conference on Harmonisation (ICH).
Female subject. A female subject is eligible to participate if she is not pregnant (as confirmed by a negative urine human chorionic gonadotrophin [hCG] test), not lactating, and at least one of the following conditions applies: 1. Non-reproductive potential defined as: Pre-menopausal females with one of the following: Documented tubal ligation, Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion, Hysterectomy, Documented Bilateral Oophorectomy. Postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous follicle stimulating hormone [FSH] and estradiol levels consistent with menopause). Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment. 2. Reproductive potential and agrees to follow one of the options listed in the Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP) from 30 days prior to the first dose of study medication and until completion of the follow-up telephone call at 1-2 weeks from last dose.
Capable of giving signed informed consent as described in protocol which includes compliance with the requirements and restrictions listed in the consent form and in the protocol.

Who cannot join

Alanine aminotransferase (ALT) >2xupper limit normal (ULN) and bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
Current or chronic history of liver disease except where hepatomegaly is identified by their clinician to be secondary to APDS, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
Corrected QT interval (QTc) > 450 milliseconds (msec) or QTc > 480 msec in subjects with Bundle Branch Block
A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, outside the reference range for the population being studied may be included only if the investigator, in consultation with the Medical Monitor if required, agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
Regular or chronic treatment with strong inhibitors of Cytochrome P450 (CYP) 3A4 and/or CYP2D6 (this includes some anti-epileptic treatments, macrolide antibiotics, oral antifungal treatments and anti-tuberculosis therapy are prohibited from the screening visit until the end of treatment visit. Where clinically appropriate, an alternative drug in the same class (or unrelated class) that is not a strong CYP3A4 and/or CYP2D6 inhibitor can, after signing informed consent, be substituted for the original strong inhibitor of these enzymes
Use of unstable dosing regimen with intravenous (i.v.) immunoglobulin (Ig) /subcutaneous (s.c.) Ig in the last 6 months before screening. Stable maintenance immunoglobulin regimen, as per local practice, such as regular injections with a consistent dosing interval (e.g. monthly) is acceptable.

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Previous use of an mechanistic target of rapamycin (mTOR) antagonist (e.g. rapamycin, everolimus) or PI3K delta inhibitor (selective or non-selective PI3K inhibitors).
History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of >21 units for males or >14 units for females. One unit is equivalent to 8 grams (g) of alcohol: a half-pint (~240 milliliters [mL]) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
History of sensitivity to any of the study medications, or components thereof (including lactose) or a history of drug or other allergy (including a milk protein allergy) that, in the opinion of the investigator or Medical Monitor, contraindicates their participation.
History of previous intolerance of the induced sputum procedure.
Bronchoalveolar Lavage (BAL) sub study only: History of bronchospasm in response to the brochoscopy/BAL procedure
Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment.
Where participation in the study would result in donation of blood or blood products in excess of 500 mL within 56 days.
The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dose of study medication in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
A positive test for human immunodeficiency virus (HIV) antibody.
Exposure to more than 4 investigational medicinal products within 12 months prior to the first dose of study medication.

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

GSK Investigational Site
Cambridge, CB2 0GG

Other trials in United Kingdom

About this study

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

Conditions: Activated PI3K-delta Syndrome
Being tested: Nemiralisib
Keywords: APDS, Safety, Pharmacokinetics, GSK2269557, PASLI
Medical subject headings: Activated PI3K-delta Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

NemiralisibDrug
Participants will be administered nemiralisib

Study groups in NCT02593539
Study group	Role	What they receive
Participants recieving nemiralisib	Experimental	Not described Receives: Drug: Nemiralisib

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Participants With Any Serious Adverse Events (SAEs) and Any Non-serious Adverse Events (Non-SAEs)
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.
Measured: Upto 7.5 months
Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
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.
Measured: Baseline (Day 1 pre-dose) and at Days 14, 28, 56, 83 and 84
Change From Baseline in Pulse Rate
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.
Measured: Baseline (Day 1 pre-dose) and at Days 14, 28, 56, 83 and 84
Change From Baseline in Respiratory Rate
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.
Measured: Baseline (Day 1 pre-dose) and at Days 14, 28, 56, 83 and 84
Change From Baseline in Body Temperature
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.
Measured: Baseline (Day 1 pre-dose) and at Days 14, 28, 56, 83 and 84
Change From Baseline in Electrocardiogram (ECG) Mean Heart Rate
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.
Measured: Baseline (Day 1 pre-dose) and at Days 14, 28, 56 and 83
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)
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.
Measured: Baseline (Day 1 pre-dose) and at Days 14, 28, 56 and 83
Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP) and Aspartate Aminotransferase (AST)
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.
Measured: Baseline (Day -1) and at Days 14, 28, 56 and 83
Change From Baseline in Clinical Chemistry Parameters : Albumin and Total Protein
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.
Measured: Baseline (Day -1) and at Days 14, 28, 56 and 83
Change From Baseline Values in Clinical Chemistry Parameters: Sodium, Potassium, Calcium, Glucose and Urea
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.
Measured: Baseline (Day -1) and at Days 14, 28, 56 and 83
Change From Baseline Values in Clinical Chemistry Parameters: Direct Bilirubin, Total Bilirubin and Creatinine
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.
Measured: Baseline (Day -1) and at Days 14, 28, 56 and 83
Change From Baseline Values in Clinical Chemistry Parameter: C-Reactive Protein
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.
Measured: Baseline (Day 1 pre-dose) and at Days 14, 28, 56 and 83
Change From Baseline for Hematology Parameters: Basophil, Eosinophils, White Blood Cells (WBC), Lymphocytes, Neutrophils, Monocytes and Platelets
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.
Measured: Baseline (Day -1) and at Days 14, 28, 56 and 83
Change From Baseline for Hematology Parameter: Hemoglobin
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.
Measured: Baseline (Day 1 pre-dose) and at Days 14, 28, 56 and 83
Change From Baseline for Hematology Parameter: Hematocrit
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.
Measured: Baseline (Day 1 pre-dose) and at Days 14, 28, 56 and 83
Change From Baseline in Hematology Parameter: Mean Corpuscular Volume (MCV)
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.
Measured: Baseline (Day 1 pre-dose) and at Days 14, 28, 56 and 83
Change From Baseline in Hematology Parameter: Mean Corpuscular Hemoglobin (MCH)
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.
Measured: Baseline (Day 1 pre-dose) and at Days 14, 28, 56 and 83
Change From Baseline for Hematology Parameter: Red Blood Cell Count
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.
Measured: Baseline (Day 1 pre-dose) and at Days 14, 28, 56 and 83
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1)
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
Measured: 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

Secondary outcomes (1)

Plasma Concentration Following Administration of NEMI
Blood samples for pharmacokinetic analysis was collected at the indicated time points following administration of NEMI. NA indicates that standard deviation could not be calculated as a single participant was analyzed
Measured: Day 1: Pre-dose, 5 minutes, 3 hours and 24 hours post-dose; Days 14 and 83: pre-dose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

22 Jul 20164 Jun 2020

First posted2 Nov 2015 (estimated)
Study start22 Jul 2016
Primary completion4 Jun 2020
Study completion4 Jun 2020

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Activated PI3K-delta SyndromeStudies of the same condition, open and under way.
More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 5 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02593539
Sponsor's protocol ID: 204745
Other IDs: 2015-004876-31, 2015
Status last verified: May 2021
First submitted: 29 Oct 2015
Last updated: 18 Jun 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingObservational study
Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
Rare Disorders, Undiagnosed Disorders
Active, not recruitingPhase 3
Pediatric Patients Aged 1 to 6 Years With APDS
APDS
Active, not recruitingPhase 3
Pediatric Patients Aged 4 to 11 Years With APDS
APDS
RecruitingObservational study
New Biomarker-based Strategy to Screen and Monitor for Activated Phosphoinositide 3-kinase δ Syndrome
Activated PI3K Delta Syndrome

All Activated PI3K-delta Syndrome trials

Study at a glance

From the registry record, last updated by the sponsor on 18 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An Open-label, Single Arm Study to Investigate the Safety, Pharmacokinetics and Pharmacodynamics of Repeat Doses of Inhaled Nemiralisib in Patients With APDS/PASLI
ClinicalTrials.gov ID: NCT02593539
Acronym / sponsor ID: 204745
Conditions: Activated PI3K-delta Syndrome
Keywords: APDS, Safety, Pharmacokinetics, GSK2269557, PASLI
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 5 participants (actual)
Lead sponsor: GlaxoSmithKlineIndustry (pharma, biotech, devices)
Study start: 22 Jul 2016 (actual)
Primary completion: 4 Jun 2020 (actual)
Study completion: 4 Jun 2020 (actual)
First posted: 2 Nov 2015 (estimated)
Results: Posted 18 Jun 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Participants recieving nemiralisib	Experimental	Drug: Nemiralisib

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

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 pulmonary infections, and who have a known type 1 APDS-associated genetic PI3K delta mutation (i.e. E1021K, N334K, E525K and C416R).
Body weight >=45 kilograms (kg) and body mass index (BMI) >=18 kg/square meter (m^2) (inclusive)
Male subject. Male subjects with female partners of child bearing potential must comply with the following contraception requirements from the time of first dose of study medication until completion of the follow-up telephone call at 1-2 weeks from last dose. Vasectomy with documentation of azoospermia. Male condom plus partner use of one of the following contraceptive options: 1. Contraceptive subdermal implant 2. Intrauterine device or intrauterine system 3. Combined estrogen and progestogen oral contraceptive, 4. Injectable progestogen 5. Contraceptive vaginal ring 6. Percutaneous contraceptive patches. This is an all inclusive list of those methods that meet the GSK definition of highly effective: having a failure rate of less than 1% per year when used consistently and, correctly and, when applicable, in accordance with the product label. For non-product methods (e.g. male sterility), the investigator determines what is consistent and correct use. The GlaxoSmithKline (GSK) definition is based on the definition provided by International Conference on Harmonisation (ICH).
Female subject. A female subject is eligible to participate if she is not pregnant (as confirmed by a negative urine human chorionic gonadotrophin [hCG] test), not lactating, and at least one of the following conditions applies: 1. Non-reproductive potential defined as: Pre-menopausal females with one of the following: Documented tubal ligation, Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion, Hysterectomy, Documented Bilateral Oophorectomy. Postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous follicle stimulating hormone [FSH] and estradiol levels consistent with menopause). Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment. 2. Reproductive potential and agrees to follow one of the options listed in the Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP) from 30 days prior to the first dose of study medication and until completion of the follow-up telephone call at 1-2 weeks from last dose.

Key exclusion criteria (16 listed)

Alanine aminotransferase (ALT) >2xupper limit normal (ULN) and bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
Current or chronic history of liver disease except where hepatomegaly is identified by their clinician to be secondary to APDS, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
Corrected QT interval (QTc) > 450 milliseconds (msec) or QTc > 480 msec in subjects with Bundle Branch Block
A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, outside the reference range for the population being studied may be included only if the investigator, in consultation with the Medical Monitor if required, agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
Regular or chronic treatment with strong inhibitors of Cytochrome P450 (CYP) 3A4 and/or CYP2D6 (this includes some anti-epileptic treatments, macrolide antibiotics, oral antifungal treatments and anti-tuberculosis therapy are prohibited from the screening visit until the end of treatment visit. Where clinically appropriate, an alternative drug in the same class (or unrelated class) that is not a strong CYP3A4 and/or CYP2D6 inhibitor can, after signing informed consent, be substituted for the original strong inhibitor of these enzymes

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
NemiralisibParticipants will be administered nemiralisib	Drug	Participants recieving nemiralisib

Primary outcome

Number of Participants With Any Serious Adverse Events (SAEs) and Any Non-serious Adverse Events (Non-SAEs)
Time frame: 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)
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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)
Time frame: 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)
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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)
Time frame: 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)
Time frame: 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
Time frame: 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)
Time frame: 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

1 secondary outcome

Plasma Concentration Following Administration of NEMI
Time frame: Day 1: Pre-dose, 5 minutes, 3 hours and 24 hours post-dose; Days 14 and 83: pre-dose

Results and safety

Results posted to the registry on 18 Jun 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
All NEMI	5	4

Primary outcome: Number of Participants With Any Serious Adverse Events (SAEs) and Any Non-serious Adverse Events (Non-SAEs)

Time frame: Upto 7.5 months. Count of participants. Unit: Participants

Measure	All NEMI n = 5
Any non-SAE	5
Any SAE	0

Population analysed: All Subjects Population consisted of all participants who received at least one dose of the study treatment.

Primary outcome: Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)

Time frame: Baseline (Day 1 pre-dose) and at Days 14, 28, 56, 83 and 84. Mean (Standard Deviation). Unit: Millimeters of Mercury (mmHg)

Measure	All NEMI n = 5
DBP, Day 14, n= 5	1.0 (6.44)
DBP, Day 28, n= 4	4.0 (6.98)
DBP, Day 56, n= 4	8.5 (5.80)
DBP, Day 83, n= 4	2.0 (4.40)
DBP, Day 84 n= 1	17.0 (NA)
SBP, Day 14, n= 5	-1.0 (3.67)
SBP, Day 28, n= 4	5.3 (8.54)
SBP, Day 56, n= 4	10.0 (9.31)

Population analysed: All Subjects Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

Primary outcome: Change From Baseline in Pulse Rate

Time frame: Baseline (Day 1 pre-dose) and at Days 14, 28, 56, 83 and 84. Mean (Standard Deviation). Unit: Beats per minute

Measure	All NEMI n = 5
Day 14, n= 5	3.2 (7.73)
Day 28, n= 4	2.0 (10.86)
Day 56, n= 4	6.8 (9.43)
Day 83, n= 4	4.8 (7.76)
Day 84 n= 1	7.0 (NA)

Population analysed: All Subjects Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

Primary outcome: Change From Baseline in Respiratory Rate

Time frame: Baseline (Day 1 pre-dose) and at Days 14, 28, 56, 83 and 84. Mean (Standard Deviation). Unit: Breaths per minute

Measure	All NEMI n = 5
Day 14, n= 5	0.2 (2.28)
Day 28, n= 4	0.8 (4.57)
Day 56, n= 4	1.5 (5.26)
Day 83, n= 4	1.0 (2.45)
Day 84 n= 1	2.0 (NA)

Population analysed: All Subjects Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

1 secondary outcome is reported in the full results.

Adverse events

Time frame: Non-serious and serious adverse events were collected up to 7.5 months. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
All NEMI	0 of 5 (0%)	5 of 5 (100%)	0 of 5

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 18 Jun 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

GSK Clinical Trials study director

GlaxoSmithKline

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Nemiralisib in people with Activated PI3K-delta Syndrome, run by GlaxoSmithKline at 1 site in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 18 Jun 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Any Serious Adverse Events (SAEs) and Any Non-serious Adverse Events (Non-SAEs) (time frame: Upto 7.5 months). The study lists 19 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02593539.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jun 2021.