Last updated: 07/18/2020 12:13:43
A study to investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of single doses of inhaled GSK1995057
Clinicaltrials.gov ID
EudraCT ID
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Trial overview
Official title: A two-part, randomised, placebo-controlled study to investigatethe safety, tolerability, pharmacokinetics and pharmacodynamicsof single doses of inhaled GSK1995057 in healthy subjects
Trial description: GSK1995057 is a fully human, single domain antibody directed against the TNFR1 receptor. The purpose of this study is to investigate the safety, tolerability and pharmacokinetics of inhaled GSK1995057 in healthy subjects. The study will be in two parts. Part 1 is a single-dose escalating design of 5 sequential cohorts of healthy subjects. Part 2 is a single-dose, parallel group design comprising 2 groups of healthy subjects assessing the effect of GSK1995057 on lung inflammation following inhaled LPS challenge. Actual dose administered in Part 2 will be determined from emerging safety and PK data from Part 1 and Study TFR110951.
Primary purpose:
Other
Trial design:
Single Group Assignment
Masking:
Single (Participant)
Allocation:
Randomized
Primary outcomes:
Safety and tolerability of ascending single inhaled doses of GSK1995057
Timeframe: 56 Days
Levels and specificity of anti-GSK1995057 binding antibodies.
Timeframe: Up to 84 Days
Plasma pharmacokinetics of ascending single inhaled doses of GSK1995057
Timeframe: 3 days
Urine pharmacokinetics of single inhaled doses of GSK1995057
Timeframe: 3 Days
Concentration of GSK1995057 in lung epithelial lining fluid after inhalation of a single dose
Timeframe: 1 Day
Effect of single inhaled doses of GSK1995057 on biomarkers
Timeframe: 3 Days
Effect of single inhaled doses of GSK1995057 on biomarkers in BAL
Timeframe: 1 Day
To explore the GSK1995057 PK-PD relationship
Timeframe: 1 Day
Secondary outcomes:
Not applicable
Interventions:
Enrollment:
53
Primary completion date:
2012-19-11
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Proudfoot AG, O’Kane CM, Bayliffe A, Serone AP, Bareille P, Smith SP, Brown V, Wright TJ, Chen Y, Wilson R, Cordy JC, Morley PJ, Elborn S, Hind M, Chilvers ER, Griffiths MJ, Summers C, McAuley DF . A novel TNFR1-targeting domain antibody attenuates pulmonary inflammation in a human model of lung injury, via actions on the lung micro-vascular endothelium.. American Journal of Respiratory and Critical Care Medicine. 2014;189:A6589
A. G. Proudfoot, A. I. Bayliffe, C. M. O’Kane, , A.P. Serone, P. J. Bareille, V. G. Brown, U. I. Hamid, T. J. Wright, Y. Chen, R. Wilson, J.C. Cordy, P.J. Morley, J. S. Elborn, M. Hind, E. R. Chilvers, M.J.D. Griffiths, C. Summers, D. F. McAuley.A novel anti-tumour necrosis factor receptor-1 (TNFR1) domain antibody prevents pulmonary inflammation in experimental acute lung injury.Thorax.2018;73(8):723-730
DOI: 10.1136/thoraxjnl-2017-210305
PMID: 29382797
Medical condition
Respiratory Disorders
Product
GSK1995057
Collaborators
Not applicable
Study date(s)
March 2012 to November 2012
Type
Interventional
Phase
1
Participation criteria
Sex
Female & Male
Age
18 - 55 years
Accepts healthy volunteers
Yes
- Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests nd cardiac monitoring. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator considers that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. The investigator may discuss with GSK medical monitor as required.
- Male or female between 18 and 55 years of age inclusive: A female subject is eligible to participate if she is of non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhoea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) greater than 40 MlU/ml and oestradiol less than 40 pg/ml (less than 140 pmol/L) is confirmatory]. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method. Male subjects must agree to use one of the contraception methods listed in the protocol. This criterion must be followed from the time of the first dose of study medication until the last follow-up visit.
- A history of Hepatitis B, Hepatitis C or HIV infection and/or a positive pre-study HIV, Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities. (With the exception of known Gilbert's syndrome or asymptomatic gallstones).
Inclusion and exclusion criteria
Inclusion criteria:
- Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests nd cardiac monitoring. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator considers that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. The investigator may discuss with GSK medical monitor as required.
- Male or female between 18 and 55 years of age inclusive: A female subject is eligible to participate if she is of non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhoea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) greater than 40 MlU/ml and oestradiol less than 40 pg/ml (less than 140 pmol/L) is confirmatory]. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method. Male subjects must agree to use one of the contraception methods listed in the protocol. This criterion must be followed from the time of the first dose of study medication until the last follow-up visit.
- Normal creatinine clearance values at screening (calculated from serum creatinine by a predicting equation using Cockcroft-Gault formula), normal serum creatinine value as defined by the local reference laboratory, normal urine microscopy and no significant proteinuria on dipstick testing.
- Body weight greater than and equal to 50 kg and BMI within the range 19 – 29.9 kg/m2 (inclusive).
- No evidence of previous or active TB infection and a negative QuantiFERON TB Gold test taken within 7 days of dosing, and negative medical history with respect to active or latent mycobacterium tuberculosis complex infection.
- Normal spirometry (FEV1 greater than and equal to 85% of predicted, FEV1/FVC ratio greater than and equal to 70%) at screening. Predictions should be according to ECCS equations, and race corrections should be made for non-caucasians.
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
- Available to complete all study assessments.
- Subjects who are able to use the inhaler device correctly.
- Able to read, comprehend and write English at a sufficient level to complete study related materials.
Exclusion criteria:
- A history of Hepatitis B, Hepatitis C or HIV infection and/or a positive pre-study HIV, Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities. (With the exception of known Gilbert's syndrome or asymptomatic gallstones).
- A positive pre-study drug/alcohol screen.
- History of and/or a positive test for toxoplasmosis consistent with active toxoplasmosis infection at the time of enrollment.
- A positive RT-PCR test for influenza A/B.
- Current evidence or history of an influenza-like illness as defined by fever (greater than 380C) and two or more of the following symptoms within the last 7 days: cough, sore throat, runny nose, sneezing, limb/joint pain, headache, vomiting/diarrhoea in the absence of a known cause, other than influenza.
- Corrected QT interval (QTc) >450msec.
- History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of greater than 21 units for males or greater than 14 units for females. One unit is equivalent to 8 g of alcohol and the following can be used as a guide: a half-pint (approximately 240 ml) of beer, 1 glass (125 ml) of wine or 1 (25 ml) measure of spirits.
- The subject is unwilling to abstain from alcohol consumption from 24 hr prior to dosing until discharge from the clinic, and for 24 hr prior to all other out-patient clinic visits.
- Subjects with a smoking history of greater than 5 cigarettes per day in the last 3 months (Part 1); smokers are not eligible to take part in Part 2.
Trial location(s)
Study documents
Clinical study report
Available language(s): English
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Refer to study documents
Recruitment status
Study complete
Actual primary completion date
2012-19-11
Actual study completion date
2012-19-11
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
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Additional information
Results for study 116236 can be found on the GSK Clinical Study Register.
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