Clinical Trial Results:
Efficacy of atazanavir/ritonavir monotherapy as maintenance in patients with viral suppression. Randomized, open label non inferiority trial. (MODAt STUDY)
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Summary
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EudraCT number |
2010-020442-10 |
Trial protocol |
IT |
Global end of trial date |
24 Jun 2015
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Results information
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Results version number |
v1(current) |
This version publication date |
04 Mar 2020
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First version publication date |
04 Mar 2020
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Other versions |
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Summary report(s) |
Modat1 Modat2 Modat3 Modat4 |
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 |
MODAt
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Additional study identifiers
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ISRCTN number |
ISRCTN01511809 | ||
US NCT number |
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WHO universal trial number (UTN) |
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Sponsors
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Sponsor organisation name |
Ospedale San Raffaele
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Sponsor organisation address |
Via Stamira d'Ancona 20, Milan, Italy,
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Public contact |
Castagna Antonella, Ospedale San Raffaele, 0039 0226437934, castagna.antonella1@hsr.it
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Scientific contact |
Castagna Antonella, Ospedale San Raffaele, 0039 0226437934, castagna.antonella1@hsr.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 |
30 Oct 2015
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
31 Jul 2013
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Global end of trial reached? |
Yes
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Global end of trial date |
24 Jun 2015
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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 non-inferiority of virological efficacy at week 48 of a monotherapy strategy with atazanavir/ritonavir vs atazanavir/ritonavir-based HAART, in patients treated with an ATV/r-based HAART since at least 48 weeks, fully suppressed since at least 24 weeks and with no previous virologic failures.
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Protection of trial subjects |
Helsinky Declaration, CEE Regulations, GCP for trials on medical products in the European Coomunity, Italian ICH.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
05 Oct 2010
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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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: 103
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Worldwide total number of subjects |
103
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EEA total number of subjects |
103
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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) |
103
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Inclusion criteria: - age > 18 years - HIV infected patients - First line ATV/r based HAART with ATV/r plus 2 NRTIs for at least 48 weeks - Virological suppression (HIV-RNA<50 c/ml) by at least 24 weeks with ATV/r plus 2 NRTIs - CD4 cells nadir >100 cells/µL - PPI and H2-receptor antagonists as follows: the PPI were not allowed | ||||||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
Inclusion criteria: - age > 18 years - HIV infected patients - First line ATV/r based HAART with ATV/r plus 2 NRTIs for at least 48 weeks - Virological suppression (HIV-RNA<50 c/ml) by at least 24 weeks with ATV/r plus 2 NRTIs - CD4 cells nadir >100 cells/µL - PPI and H2-receptor antagonists as follows: the PPI were not allowed | ||||||||||||||||||||||||||||||
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Period 1
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Period 1 title |
Atazanavir/ritonavir monotherapy (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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ATV/RTV monotherapy | ||||||||||||||||||||||||||||||
Arm description |
Simplify therapy to ATV/RTV 300 mg/100 mg OD as a monotherapy | ||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
ATV/RTV 300 mg/100 mg OD as a monotherapy
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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 |
ATV/RTV 300 mg/100 mg OD as a monotherapy
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Arm title
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Control Arm ATV/r 300/100 mg QD + 2 NRTI | ||||||||||||||||||||||||||||||
Arm description |
Control Arm ATV/r 300/100 mg QD + 2 NRTI | ||||||||||||||||||||||||||||||
Arm type |
Active comparator | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
Control Arm ATV/r 300/100 mg QD + 2 NRTI
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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 |
Control Arm ATV/r 300/100 mg QD + 2 NRTI
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| Notes [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: The stop of the enrollment in the trial was the object of a specific amendment during the study (Amendment dated 22 Jul 2013). |
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Baseline characteristics reporting groups
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Reporting group title |
Atazanavir/ritonavir monotherapy
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Primary efficacy analysis at week 48
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Subject analysis set type |
Intention-to-treat | |||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Assessment of noninferiority of ATV/r compared with
ATV/r along with two NRTIs was done with a twosided
95% confidence interval (95% CI) of the difference
in percentage of patients with treatment success
(monotherapy – triple therapy): a lower limit of the
95% CI of the difference between the two proportions
below the prespecified margin of noninferiority of
10% would establish inferiority.
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End points reporting groups
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Reporting group title |
ATV/RTV monotherapy
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Reporting group description |
Simplify therapy to ATV/RTV 300 mg/100 mg OD as a monotherapy | ||
Reporting group title |
Control Arm ATV/r 300/100 mg QD + 2 NRTI
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Reporting group description |
Control Arm ATV/r 300/100 mg QD + 2 NRTI | ||
Subject analysis set title |
Primary efficacy analysis at week 48
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
Assessment of noninferiority of ATV/r compared with
ATV/r along with two NRTIs was done with a twosided
95% confidence interval (95% CI) of the difference
in percentage of patients with treatment success
(monotherapy – triple therapy): a lower limit of the
95% CI of the difference between the two proportions
below the prespecified margin of noninferiority of
10% would establish inferiority.
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End point title |
Proportion of patient with treatment success at week 48 | |||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Intention to treat week 48
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Statistical analysis title |
Assessment of non inferiority of monoth. ATV/RTV | |||||||||
Statistical analysis description |
Assessment of noninferiority of ATV/r compared with
ATV/r along with two NRTIs was done with a twosided
95% confidence interval (95% CI) of the difference
in percentage of patients with treatment success
(monotherapy – triple therapy): a lower limit of the
95% CI of the difference between the two proportions
below the prespecified margin of noninferiority of
10% would establish inferiority.
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Comparison groups |
Control Arm ATV/r 300/100 mg QD + 2 NRTI v ATV/RTV monotherapy
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Number of subjects included in analysis |
101
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority | |||||||||
P-value |
< 0.05 | |||||||||
Method |
Mantel-Haenszel | |||||||||
Confidence interval |
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Adverse events information
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Timeframe for reporting adverse events |
from baseline to 96 weeks
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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 |
21.0
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Reporting groups
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Reporting group title |
AE of ATV/RTV monotherapy Arm
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Reporting group description |
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Reporting group title |
AE in control arm triple therapy
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 2% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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26 Oct 2011 |
In order to facilitate the enrollment of patients in the national study as much as possible, the inclusion criteria are changed, making it possible to include patients under treatment with atazanavir / ritonavir 300/100 mg plus 2 NRTIs for at least 48 weeks with viral load suppressed (HIV-RNA <50 copies) for at least 24 weeks in the absence of previous virological failure after starting antiretroviral treatment. Patients with previous treatment schedules modified for toxicity or therapeutic simplification will be admitted provided that this has occurred during virological suppression and that there is such documentation available in the folder.
The inclusion criterion in which the documentation of the genotype present at the beginning of the HAART certifying the absence of resistance to atazanavir was mandatory for entry into the study is eliminated. |
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29 Oct 2012 |
Following the slow enrollment of the satellite centers involved in the study and on the basis of the illustrated data, in order to protect the patients already enrolled, it is believed to amend the protocol in order to anticipate the interim evaluations confirming the effectiveness of the experimental treatment. Therefore, the sample size on which the interim analysis will be carried out is changed, reducing it from 171 to 100 patients. |
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03 Dec 2012 |
country specific amendment to include Spain in the enrollments (never enrollment were obtain) |
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22 Jul 2013 |
In consideration of the DSMB communication that assessed the interim analysis of the data carried out at week 48 of the first 103 patients enrolled, the protocol is amended in order to specify that no other patients will be screened and enrolled in the study. Based on DSMB recommendations, patients enrolled in the study to date (117) will be able to remain in the study and continue follow-up until the last patient has reached the 96th week of the study. Patients will therefore continue after week 96 to go to the center every 12 weeks for scheduled visits, agreeing to stay in the study by signing the new informed consent form for the patient version of 07/22/2013. The atazanavir drug for the arm of patients on monotherapy will continue to be supplied by BMS as per the existing contract. |
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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 | |||
