Clinical Trial Results:
Randomized, prospective double-blind placebo controlled study for the evaluation of the number, duration and severity of Respiratory Tract Infections in adults with risk of recurrence after standard treatment with bacterial lysates Paspat 3 mg tablets, over an observation period of six months.
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Summary
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EudraCT number |
2016-000978-38 |
Trial protocol |
IT |
Global end of trial date |
02 Aug 2018
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Results information
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Results version number |
v1(current) |
This version publication date |
26 Jul 2021
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First version publication date |
26 Jul 2021
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Other versions |
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Summary report(s) |
Prot. DS IT-2015-01 SUMMARY of RESULTS |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
DSIT-2015-01
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Additional study identifiers
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ISRCTN number |
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US NCT number |
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WHO universal trial number (UTN) |
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Sponsors
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Sponsor organisation name |
Daiichi Sankyo Italia S.p.A
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Sponsor organisation address |
Via Paolo di Tono, 73, Roma, Italy,
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Public contact |
Dr.ssa Maria Strano-Medical Manage, Daiichi Sankyo Italia S.p.A, 0039 0685255264, Maria.Strano@daiichi-sankyo.it
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Scientific contact |
Dr.ssa Maria Strano-Medical Manage, Daiichi Sankyo Italia S.p.A, 0039 0685255264, Maria.Strano@daiichi-sankyo.it
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
05 Dec 2018
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
02 Aug 2018
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Global end of trial reached? |
Yes
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Global end of trial date |
02 Aug 2018
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To assess the clinical efficacy of Paspat 3 mg tablets in preventing, number and severity of recurring infections of the respiratory tract in adults at risk, testified by at least six recurrences in the previous 12 months
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Protection of trial subjects |
After the finalization of Vers. 1.0 of the protocol (18 Apr 2016), three substantial amendments were generated: Vers. 1.1 embedding substantial amendment 20 Sep 2016, Vers. 1.2 embedding
substantial amendment 27 Oct 2016 and Vers. 1.3 embedding substantial amendment 16 Nov2016.
Regulatory procedures including IEC/CA submission were carried out by the CRO through the on-line Regulatory Platform (OsSC) set by AIFA.
Having obtained the favourable opinion from the competent ECs, CEC (on 16June2016) and following the approval of the Competent Authority (CA) on 06Jul2016, sites were initiated
This study (Study identification: DS IT-2015-01; EudraCT Number: 2016-000978-38) was conducted in compliance with specific regulatory requirements of the Italian Ministry of Health, including D.lgs 24 June 2003 no. 211, DPR 21 September 2001 no. 439, DM 26 April 2002, DM 21 December2007, DM 13 September 2012, Determina AIFA 07 January 2013, Determina AIFA 809/2015.
This trial was conducted in compliance with the most recent version of the Declaration of Helsinki (Fortaleza, Brazil, October 2013), the most recent version of the Good Clinical Practice (GCP), and all
applicable regulatory requirements (European Directive 2001/20/EC, 04 April 2001), and Italian Laws(D.lgs no. 211, 24 June 2003 and all applicable regulations).
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
16 Sep 2016
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Italy: 211
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Worldwide total number of subjects |
211
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EEA total number of subjects |
211
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
206
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From 65 to 84 years |
5
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85 years and over |
0
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Recruitment
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Recruitment details |
The study was conducted in Italy, by involving 25 Italian General Practitioners geographically distributed in three Italian Districts for Health (ASL), ASL 3 Genovese, ASL1 Imperiese and USL Umbria2. The recruitment was fractionated in two consecutive campaigns, one from 17/09/2016 to 31/01/2017 and the other one from 05/09/2017 to 18/01/2018. | |||||||||||||||||||||
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Pre-assignment
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Screening details |
In total 211 patients were screened and randomized by 25 GPs who enrolled an average of 8.4 patients each. A pre-screening was conducted by each GP by querying its own patients’ database. All the patients accepted to sign the Informed Consent Form before to be recruited and therefore no screening failure occurred. | |||||||||||||||||||||
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Period 1
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Period 1 title |
overall trial (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst | |||||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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paspat | |||||||||||||||||||||
Arm description |
3 mg tablets a) First treatment period of 28 days b) Off-drug period of 28 days c) Second treatment period of 28 days | |||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||
Investigational medicinal product name |
PASPAT
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
3 mg/ daily- whole tablet, away from meals
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Arm title
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placebo | |||||||||||||||||||||
Arm description |
3mg tablet a) First treatment period of 28 days b) Off-drug period of 28 days c) Second treatment period of 28 days | |||||||||||||||||||||
Arm type |
Placebo | |||||||||||||||||||||
Investigational medicinal product name |
PLACEBO
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
3 mg/ daily- whole tablet, away from meals
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Baseline characteristics reporting groups
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Reporting group title |
overall trial
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
paspat
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Reporting group description |
3 mg tablets a) First treatment period of 28 days b) Off-drug period of 28 days c) Second treatment period of 28 days | ||
Reporting group title |
placebo
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Reporting group description |
3mg tablet a) First treatment period of 28 days b) Off-drug period of 28 days c) Second treatment period of 28 days | ||
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End point title |
efficacy endpoint | |||||||||
End point description |
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End point type |
Primary
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End point timeframe |
over the 6 months of the observation period
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Statistical analysis title |
mean of number of episodes RTI (LRTI+URTI) | |||||||||
Comparison groups |
paspat v placebo
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Number of subjects included in analysis |
203
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Analysis specification |
Pre-specified
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Analysis type |
superiority [1] | |||||||||
P-value |
= 0.77551 | |||||||||
Method |
ANCOVA | |||||||||
Confidence interval |
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| Notes [1] - By considering 203 patients who completed the 6 months of the observation period, the mean number of episodes (LRTI + URTI) was 1.02 ± 1.30, ranging from 0 to 6. Paspat and placebo groups showed similar values (respectively 1.03 ± 1.39 episodes with duration from 2 to 28 days,and 1.01 ± 1.21 episodes with duration from 2 to 22 days). No statistically significant difference between groups was revealed by comparing the total number of episodes (p = 0.7751). |
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Adverse events information
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Timeframe for reporting adverse events |
overall
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Adverse event reporting additional description |
During the study period,458 AEs were recorded:209 (45.63%)in the Paspat group and 249(54.36%) in placebo group.6 out of 458 AEs were reported as SAE, none of them related to the study drug.Regarding the severity,225 were considered mild,whereas the remaining 233(50.9%)were reported as moderate or severe.The severity profile resulted equal to 2group
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
23
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Reporting groups
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Reporting group title |
summary AE
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Reporting group description |
206 (98.6%) AEs occurred in the Paspat group were considered unlikely related or not related to the study drug. In the placebo group a total of 238 (95.6%) AEs were reported as unlikely related or not related to the treatment.Eleven AEs (2.4%) were considered related to the study drug(8 in the placebo group and 3 for patients assuming Paspat). Seven of them occurred during the treatment period (TEAEs): two in 2 patients assuming Paspat (flatulence and URTI) and5 TEAEs in 3 patients assuming placebo (abdominal pain, headache, dysmenorrhoea, pruritus and one rush). 3 AEs possibly related with study drug were reported, all from patients assuming placebo.No AE that occurred in the Paspat group determined the discontinuation of the study drug,whereas in the placebo group one event caused a temporarily discontinuation and another one resulted in a definitely discontinuation of the study drug. Both events were URTI infections. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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18 Nov 2016 |
The CTP was reviewed with 3 SAs: 1)CTP v.1.1,16/04/2016:-Changes of exclusion criterion N.#8: the exclusion of chronic use of corticosteroids has been restricted only to the systemic administration.In fact, inhaled corticosteroids andbronchodilators are necessary for the management of recurrences of Chronic ObstructivePulmonary Diseases and, on the other hand, there is no clinical evidence that temporarily use of inhaled corticosteroids and bronchodilators have effects on thesystemic immune response.-Changes of exclusion criterion N.#17: it has been corrected a discrepancy (6 months instead of 3 months) in the wash-out from any previous treatment active on the immune system; -Changes of exclusion criterion N.#18: it has been clarified that the exclusion from participation in another studies at the time of the randomization or within 4 weeks before, was only restricted to interventional studies.2)CTP v. 1.2,26/10/2016:In reference to the protocol version 1.1, the NCA raised some objections. The CA questioned if the combined use of an effective inhaled anti-inflammatory and/or bronchodilator regimen and the immuno-modulating oral bacterial lysates might lead to an additive or even better protection against COPD. In particular, the protocol has been updated with the following substantial changes:1)in the efficacy analysis the use of inhaled corticosteroids or bronchodilators has been included as covariate;2)regarding one of the Secondary Criteria - insurgence of asthma -, in the efficacy supportive analysis has been specified how the concomitant use of Paspat 3mg tablets and inhaled corticosteroids or bronchodilators would be evaluated for the possible impact on efficacy results;3)CTP v.1.3: the subgroup analyses of the patient affected by asthma and needing treatment of inhaled corticosteroids had to be performed in compliance with EMA rules guidelines. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
