Towards an inhaled vaccine against pneumonia - trial of inhaled low-dose interleukin-12 as an immune potentiator to enhance natural responses against pneumococci colonising the nasopharynx

ISRCTN	ISRCTN82733574
DOI	https://doi.org/10.1186/ISRCTN82733574
Secondary identifying numbers	BAL0801

Submission date: 16/01/2008
Registration date: 04/03/2008
Last edited: 17/05/2017

Recruitment status: Stopped
Overall study status: Stopped
Condition category: Respiratory

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Stephen Gordon
Scientific

Liverpool School of Tropical Medicine
Pembroke Place
Liverpool
L3 5QA
United Kingdom

Phone	+44 (0)151 705 3169
Email	Stephen.Gordon@lstmed.ac.uk

Study information

Study design	SA1: Observational study lung effects subcut IL-12 SA2: Bayesian dual endpoint phase 1 dosing trial SA3: Open label RCT of inhaled IL-12 vs placebo and experimental pneumococcal carriage
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details below to request a patient information sheet
Scientific title	Interleukin-12 as an adjuvant for mucosal vaccination against pneumococcal disease
Study acronym	Mucosal IL-12 Pneumovac
Study objectives	1. Is IL-12 a safe and potentially effective adjuvant for human mucosal vaccination? 2. Will the adjuvant effect of IL-12 on mucosal defence against pneumococcus seen in animal models also be observed in studies with human experimental pneumococcal carriage?
Ethics approval(s)	Ethics approval pending as of 16/01/2008: 1. The Central Office for Research Ethics Committees (National Research Ethics Service, NHS, UK) 2. Liverpool School of Tropical Medicine Research Ethics Committee
Health condition(s) or problem(s) studied	Pneumococcal carriage, otitis media, pneumonia and invasive pneumococcal disease
Intervention	Specific aim 1 (SA1): 100 ng/kg subcutaneous IL-12 all participants (no control arm). IL-12 has been extensively phase 1 and 2 tested by this route and this is selected as a minimally toxic dose. All participants have bronchoscopy before and after to determine the pulmonary effect of subcutaneous IL-12 by paired comparison. The pulmonary measurements are the novel bit so SA1 is just an observational study of low-dose IL-12. Specific aim 2 (SA2): Starts at inhaled 0.25 ng/kg and proceeds in doubling measures to 2.5 ng/kg inhaled IL-12. The dual endpoints of toxicity (grade 1 symptoms only in 50% subjects) and efficacy (defined as equalling the pulmonary effect of 100 ng/kg IL-12 subcut from SA1) will be combined using a Bayesian dual endpoint trial design to obtain an optimal dose. Specific aim 3 (SA3 - the intervention study): Open label randomised controlled trial (RCT) comparing a single dose of inhaled IL-12 (dose defined in SA2) versus placebo. Endpoint is the effect on experimentally induced pneumococcal carriage.
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	Interleukin-12 (IL-12)
Primary outcome measure	Specific Aim 1: Pulmonary markers of adjuvant activity following subcutaneous IL-12 (determination of efficacy endpoint for Specific Aim 2) Specific Aim 2: Optimal mucosal dose of IL-12 (using dual endpoint [efficacy and toxicity] phase 1 design) Specific Aim 3: Mucosal humoral and cellular responses to experimental pneumococcal carriage
Secondary outcome measures	1. Duration of pneumococcal carriage following IL-12 challenge 2. Effect of IL-12 and experimental pneumococcal carriage on susceptibility to repeat pneumococcal carriage challenge
Overall study start date	01/10/2008
Completion date	30/09/2011
Reason abandoned (if study stopped)	Lack of funding/sponsorship

Eligibility

Participant type(s)	Healthy volunteer
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	100
Key inclusion criteria	1. Aged over 18, either sex 2. Healthy volunteers 3. Normal lung function 4. Non-smokers
Key exclusion criteria	1. Asthma 2. Any pre-existing chronic illness 3. Current ill-health 4. Pregnancy 5. Recent ex-smokers
Date of first enrolment	01/10/2008
Date of final enrolment	30/09/2011

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

Liverpool School of Tropical Medicine

Liverpool
L3 5QA
United Kingdom

Sponsor information

Liverpool School of Tropical Medicine (UK)
Hospital/treatment centre

Liverpool School of Tropical Medicine
Pembroke Place
Liverpool
L3 5QA
England
United Kingdom

Phone	+44 (0)151 705 3212
Email	s.roberts@liverpool.ac.uk
Website	http://www.liv.ac.uk/lstm/
"ROR"	https://ror.org/03svjbs84

Funders

Funder type

Charity

Wellcome Trust (UK) - funding applied for but pending, result due in mid July 2008

No information available

National Institute of Health Research (NIHR) Biomedical Research Centre Royal Liverpool University Hospital (UK) - partial funding obtained for staff costs for 3 years

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Editorial Notes

17/05/2017: This trial never received funding and so did not take place.
13/04/2017: No publications found in PubMed, verifying study status with principal investigator
24/06/2008: More details on the pending sources of funding have been added to this record (i.e., duration of funding and date of result for Wellcome Trust funding). They can be seen below in the sources of funding section.