Human Immunodeficiency Virus 1Phase 2NCT00919854
A Safety Study to Evaluate the Antiviral Activity of Darunavir in Combination With Ritonavir in HIV 1 Infected Children
A Phase 2 study testing Darunavir and Ritonavir in people with Human Immunodeficiency Virus 1, run by Tibotec Pharmaceuticals, Ireland at 8 sites in 5 countries.
Trial summary
The purpose of this study is to evaluate the pharmacokinetics (what the body does to the medication), safety and antiviral activity to support dose recommendations by body weight of darunavir with low-dose ritonavir (DRV/rtv), in combination with other antiretroviral drugs (ARVs), in treatment-experienced Human… Read more about this study
- Who is it for?
- Ages 3 to 6 years
- Conditions the study is for
- Human Immunodeficiency Virus 1
- What is being tested?
- Darunavir and Ritonavir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 8 sitesin 5 countries
- Study dates
- Sep 2009to Feb 2011
- 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 3 to 6 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Participants with a documented HIV 1 infection (by any of the local standard diagnostic methods, such as HIV PCR-DNA, ELISA or western blot (WB) test for HIV antibodies, etc.)
- Body weight from 10 kg to less than 20 kg at screening
- Participants currently on stable ART (anti retroviral therapy) for at least 12 weeks, who need to change their ARV regimen because it is currently failing, with a viral load of greater than 1000 copies/mL
- Screening genotype resistance test results showing less than 3 DRV resistance-associated mutations
- Parents or legal representative willing and able to give consent
Who cannot join
- Participants with presence of any currently active conditions included in the listing of WHO ( World Health Organisation) Clinical Stage 4 and participants with presence of a non-HIV encephalopathy
- Administration of any ARV (antiretroviral) or non-ARV investigational medication or investigational vaccine within 30 days prior to screening, except for those medications where dose recommendations for children are available
- Life expectancy less than 6 months, according to the judgment of the investigator
- Co-enrollment in other clinical and/or cohort trials without written permission of the Sponsor
- Participants with any active clinically significant disease (eg, tuberculosis [TB], cardiac dysfunction, pancreatitis, acute viral infections) or findings during screening of medical history or physical examination that, in the investigator's opinion, would compromise the subject's safety or outcome of the study
Trial locations and contacts
8 sites in 5 countries.
8 sites in 5 countries
South Africa3 sites
Study site
Durban
Study site
Johannesburg
Study site
Johannesburg Gauteng
About this study
Official title: A Phase II, Open Label Trial, to Evaluate Pharmacokinetics, Safety, Tolerability and Antiviral Activity of DRV in Combination With Low-Dose Ritonavir (DRV/Rtv) in Treatment-Experienced HIV-1 Infected Children From 3 Years to Below 6 Years of Age
The purpose of this study is to evaluate the pharmacokinetics (what the body does to the medication), safety and antiviral activity to support dose recommendations by body weight of darunavir with low-dose ritonavir (DRV/rtv), in combination with other antiretroviral drugs (ARVs), in treatment-experienced Human immunodeficiency virus 1 (HIV 1) infected children.
Read the detailed description
This is an open-label (all people know the identity of the intervention), study to evaluate the pharmacokinetics, safety and antiviral activity. Approximately 24 HIV-1 infected children will be enrolled in this study. The study consists of a 4-week screening period, a 48-week treatment period, and a 4-week follow-up period. Participants will receive DRV/rtv according to their body weight. Safety evaluations will include assessment of adverse events, laboratory tests, physical Examination, neurologic examination, vital signs, and electrocardiogram. The total duration of the study will be 56 weeks.
- Conditions
- Human Immunodeficiency Virus 1
- Being tested
- Darunavir, Ritonavir
- Keywords
- Human immunodeficiency virus 1, HIV-1, Darunavir, Ritonavir, Norvir
- Medical subject headings
- Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DarunavirDrug
Darunavir oral suspension (100 mg/mL) will be administered as 20 mg per kg body weight twice daily for children weighing between 10 and <20 kg before dose adjustment. Darunavir oral suspension will be administered 25 mg per kg body weight twice daily if weight less than 15 kg, and fixed dose of 375 mg darunavir tablets twice daily if weight more than or equal to 15 kg after dose adjustment.
RitonavirDrug
Ritonavir oral solution (80 mg/mL) will be administered as 3 mg per kg body weight twice daily before dose adjustment and after dose adjustment fixed dose of 50 mg twice daily if weight more than or equal to 15 kg.
| Study group | Role | What they receive |
|---|---|---|
| Darunavir (DRV)+Ritonavir (rtv) | Experimental | Before dose adjustment, oral darunavir suspension (100 mg/mL): 20 mg per kg body weight twice daily for children weighing between 10 and <20 kg. After dose adjustment, 25 mg per kg body weight twice daily if weight less than 15 kg, and fixed dose of 375 mg twice daily if weight more than or equal to 15 kg. Before dose adjustment, oral ritonavir solution (80 mg/mL): 3 mg per kg body weight twice daily and after dose adjustment fixed dose of 50 mg twice daily if weight more than or equal to 15 kg. Receives: Drug: Darunavir; Drug: Ritonavir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Virological Response (Viral Load Less Than 50 Copies/mL) at Week 24 - Time to Loss of Virologic Response (TLOVR)
The TLOVR algorithm was used to derive response, ie, response and loss of response needed to be confirmed at 2 consecutive visits and participants who permanently discontinued were considered nonresponders after discontinuation. Participants with intermittent missing viral load values were considered responders if the preceeding and succeeding visits indicated response. In all other cases, intermittent values were imputed with nonresponse. Resuppression after confirmed virologic failure was considered as failure in this algorithm.
Measured: Week 24
Secondary outcomes (5)
Number of Participants With Virological Response (Viral Load Less Than 50 Copies/mL) at Week 48
Measured: Week 48
Number of Participants With Virological Response (Viral Load Less Than 400 Copies/mL) at Week 24 and Week 48
Measured: Week 24 and Week 48
Number of Participants With Less Than or Equal to 1 log10 Decrease in Plasma Viral Load at Week 24 and Week 48
Measured: Week 24 and Week 48
Mean Change From Baseline to Week 24 and Week 48 in Plasma log10 Viral Load
Measured: Baseline, Week 24 and Week 48
Mean Change From Baseline to Week 24 and Week 48 in CD4+ Percentage
Measured: Baseline, Week 24 and Week 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jun 2009 (estimated)
- Study startSep 2009
- Primary completionAug 2010
- Study completionFeb 2011
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Human Immunodeficiency Virus 1Studies of the same condition, open and under way.
- 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
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tibotec Pharmaceuticals, Ireland
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Tibotec Pharmaceutical Limited
- Responsible party
- Sponsor
- Investigators
- Tibotec Pharmaceuticals, Ireland Clinical Trial, Study director, Tibotec Pharmaceuticals, Ireland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00919854
- Sponsor's protocol ID
- CR012553
- Other IDs
- TMC114-TiDP29-C228
- Status last verified
- Apr 2014
- First submitted
- 11 Jun 2009
- Last updated
- 23 Apr 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Violari A, Bologna R, Kumarasamy N, Pilotto JH, Hendrickx A, Kakuda TN, Lathouwers E, Opsomer M, Van de Casteele T, Tomaka FL. Safety and efficacy of darunavir/ritonavir in treatment-experienced pediatric patients: week 48 results of the ARIEL trial. Pediatr Infect Dis J. 2015 May;34(5):e132-7. doi: 10.1097/INF.0000000000000644.
PubMed 25719453
Study at a glance
From the registry record, last updated by the sponsor on 23 Apr 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Open Label Trial, to Evaluate Pharmacokinetics, Safety, Tolerability and Antiviral Activity of DRV in Combination With Low-Dose Ritonavir (DRV/Rtv) in Treatment-Experienced HIV-1 Infected Children From 3 Years to Below 6 Years of Age
- ClinicalTrials.gov ID
- NCT00919854
- Acronym / sponsor ID
- CR012553
- Conditions
- Human Immunodeficiency Virus 1
- Keywords
- Human immunodeficiency virus 1, HIV-1, Darunavir, Ritonavir, Norvir
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Tibotec Pharmaceuticals, IrelandIndustry (pharma, biotech, devices)
- Collaborators
- Tibotec Pharmaceutical Limited
- Study start
- Sep 2009
- Primary completion
- Aug 2010 (actual)
- Study completion
- Feb 2011 (actual)
- First posted
- 12 Jun 2009 (estimated)
- Results
- Posted 24 Jun 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the pharmacokinetics (what the body does to the medication), safety and antiviral activity to support dose recommendations by body weight of darunavir with low-dose ritonavir (DRV/rtv), in combination with other antiretroviral drugs (ARVs), in treatment-experienced Human immunodeficiency virus 1 (HIV 1) infected children.
Detailed description
This is an open-label (all people know the identity of the intervention), study to evaluate the pharmacokinetics, safety and antiviral activity. Approximately 24 HIV-1 infected children will be enrolled in this study. The study consists of a 4-week screening period, a 48-week treatment period, and a 4-week follow-up period. Participants will receive DRV/rtv according to their body weight. Safety evaluations will include assessment of adverse events, laboratory tests, physical Examination, neurologic examination, vital signs, and electrocardiogram. The total duration of the study will be 56 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Darunavir (DRV)+Ritonavir (rtv) | Experimental | Drug: Darunavir, Drug: RitonavirBefore dose adjustment, oral darunavir suspension (100 mg/mL): 20 mg per kg body weight twice daily for children weighing between 10 and <20 kg. After dose adjustment, 25 mg per kg body weight twice daily if weight less than 15 kg, and fixed dose of 375 mg twice daily if weight more than or equal to 15 kg. Before dose adjustment, oral ritonavir solution (80 mg/mL): 3 mg per kg body weight twice daily and after dose adjustment fixed dose of 50 mg twice daily if weight more than or equal to 15 kg. |
Who may qualify
- Ages
- 3 to 6 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- Participants with a documented HIV 1 infection (by any of the local standard diagnostic methods, such as HIV PCR-DNA, ELISA or western blot (WB) test for HIV antibodies, etc.)
- Body weight from 10 kg to less than 20 kg at screening
- Participants currently on stable ART (anti retroviral therapy) for at least 12 weeks, who need to change their ARV regimen because it is currently failing, with a viral load of greater than 1000 copies/mL
- Screening genotype resistance test results showing less than 3 DRV resistance-associated mutations
- Parents or legal representative willing and able to give consent
Key exclusion criteria (5 listed)
- Participants with presence of any currently active conditions included in the listing of WHO ( World Health Organisation) Clinical Stage 4 and participants with presence of a non-HIV encephalopathy
- Administration of any ARV (antiretroviral) or non-ARV investigational medication or investigational vaccine within 30 days prior to screening, except for those medications where dose recommendations for children are available
- Life expectancy less than 6 months, according to the judgment of the investigator
- Co-enrollment in other clinical and/or cohort trials without written permission of the Sponsor
- Participants with any active clinically significant disease (eg, tuberculosis [TB], cardiac dysfunction, pancreatitis, acute viral infections) or findings during screening of medical history or physical examination that, in the investigator's opinion, would compromise the subject's safety or outcome of the study
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 |
|---|---|---|
| DarunavirDarunavir oral suspension (100 mg/mL) will be administered as 20 mg per kg body weight twice daily for children weighing between 10 and <20 kg before dose adjustment. Darunavir oral suspension will be administered 25 mg per kg body weight twice daily if weight less than 15 kg, and fixed dose of 375 mg darunavir tablets twice daily if weight more than or equal to 15 kg after dose adjustment. | Drug | Darunavir (DRV)+Ritonavir (rtv) |
| RitonavirRitonavir oral solution (80 mg/mL) will be administered as 3 mg per kg body weight twice daily before dose adjustment and after dose adjustment fixed dose of 50 mg twice daily if weight more than or equal to 15 kg. | Drug | Darunavir (DRV)+Ritonavir (rtv) |
Primary outcome
Number of Participants With Virological Response (Viral Load Less Than 50 Copies/mL) at Week 24 - Time to Loss of Virologic Response (TLOVR)
Time frame: Week 24
The TLOVR algorithm was used to derive response, ie, response and loss of response needed to be confirmed at 2 consecutive visits and participants who permanently discontinued were considered nonresponders after discontinuation. Participants with intermittent missing viral load values were considered responders if the preceeding and succeeding visits indicated response. In all other cases, intermittent values were imputed with nonresponse. Resuppression after confirmed virologic failure was considered as failure in this algorithm.
5 secondary outcomes
Number of Participants With Virological Response (Viral Load Less Than 50 Copies/mL) at Week 48
Time frame: Week 48
Number of Participants With Virological Response (Viral Load Less Than 400 Copies/mL) at Week 24 and Week 48
Time frame: Week 24 and Week 48
Number of Participants With Less Than or Equal to 1 log10 Decrease in Plasma Viral Load at Week 24 and Week 48
Time frame: Week 24 and Week 48
Mean Change From Baseline to Week 24 and Week 48 in Plasma log10 Viral Load
Time frame: Baseline, Week 24 and Week 48
Mean Change From Baseline to Week 24 and Week 48 in CD4+ Percentage
Time frame: Baseline, Week 24 and Week 48
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Apr 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 25719453Violari A, Bologna R, Kumarasamy N, Pilotto JH, Hendrickx A, Kakuda TN, Lathouwers E, Opsomer M, Van de Casteele T, Tomaka FL. Safety and efficacy of darunavir/ritonavir in treatment-experienced pediatric patients: week 48 results of the ARIEL trial. Pediatr Infect Dis J. 2015 May;34(5):e132-7. doi: 10.1097/INF.0000000000000644.
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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.
Tibotec Pharmaceuticals, Ireland Clinical Trial study director
Tibotec Pharmaceuticals, Ireland
8 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Darunavir and Ritonavir in people with Human Immunodeficiency Virus 1, run by Tibotec Pharmaceuticals, Ireland at 8 sites in 5 countries.
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 5 inclusion and 5 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 23 Apr 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in South Africa, Brazil, Argentina, India, Kenya. 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 24 Jun 2013). 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 Virological Response (Viral Load Less Than 50 Copies/mL) at Week 24 - Time to Loss of Virologic Response (TLOVR) (time frame: Week 24). 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 NCT00919854, which also lists 1 linked publication.
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 23 Apr 2014.