Plain English Summary
Background and study aims
Dolutegravir is new medication being used to treat HIV-positive adults. It is strong, safe, has low toxicity (few or no side effects) and only needs to be taken once a day. It has not yet been tested in children, and could be an excellent option for them if it works as well in them as it does in adults. The aim of this study is to compare dolutegravir treatment to the standard of care treatment for HIV to find out whether is as effective and has fewer side effects.
Who can participate?
Children under 18 years of age with a confirmed diagnosis of HIV infection.
What does the study involve?
Children will be randomly allocated to one of two groups. The usual care group will receive the usual, nationally approved HIV medication for either their first set of medication or if they are changing medicine for the first time. The dolutegravir group will take a combination of medication that includes dolutegravir. Children will be on the study for a minimum time of 2 years. To begin with they will be closely monitored. Once the doctor is happy that the child has no side effects and is doing well, they will go back to having their regular appointments. In addition to the normal clinical tests, a small amount of additional blood will be collected and stored at each visit. These will be tested at the end of the study to look at the effects of different HIV medicines in the blood.
What are the possible disadvantages and risks of taking part in this study?
We cannot promise that participating in the study will directly help your child. Your child will have three extra visits to the clinic even if they get usual care. All the information we get will help children and young people with HIV around the world and in the future it may mean your child has the chance to change to medicines that are easier to take. Dolutegravir has been shown to be very effective with less side effects in adults, but we dont know how it will work in children, which is why we need to do this study. Therefore, there may be unknown side effects, which is why the doctor needs to follow you closely.
Where is the study run from?
Not provided at time of registration.
When is the study starting and how long is it expected to run for?
The study will start in June 2015 and will run for 4 years.
Who is funding the study?
Viiv Healthcare (UK).
Who is the main contact?
Dr Pablo Rojo Conejo
pablorojoconejo@aim.com
Study website
Additional identifiers
EudraCT/CTIS number
2014-002632-14
IRAS number
179128
ClinicalTrials.gov number
NCT02259127
Protocol/serial number
ODYSSEY (PENTA 20)
Study information
Scientific title
A randomised trial of dolutegravir (DTG)-based antiretroviral therapy vs standard of care (SOC) in children with HIV infection starting first-line or switching to second-line ART
Acronym
ODYSSEY
Study hypothesis
Dolutegravir plus two NRTIs is non-inferior to standard of care (NNRTI or PI plus two or three NRTIs) in terms of efficacy and superior in terms of toxicity profile.
Ethics approval(s)
Not provided at time of registration
Study design
Open label multi-centre randomised non-inferiority phase II/III two-arm trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Study setting(s)
Other
Study type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
HIV infection
Intervention
Dolutegravir plus two NRTIs (dolutegravir arm) vs standard of care (SOC arm) in first-line and second-line antiretroviral regimens
Intervention type
Drug
Pharmaceutical study type(s)
Phase
Phase II/III
Drug/device/biological/vaccine name(s)
Dolutegravir
Primary outcome measure
Difference in proportion with clinical or virological failure at 96 weeks, estimated using time to the first occurrence of any of the following components:
1. Insufficient virological response defined as < 1 log drop at week 24
2. VL>400 copies/ml at or after 36 weeks confirmed by next visit
3. Death due to any cause
4. Any new or recurrent AIDS-defining event (CDC C or WHO 4) or severe/modified CDC B/WHO 3 events, adjudicated by the Endpoint Review Committee (ERC)
Secondary outcome measures
Secondary efficacy outcomes:
1. Difference in proportion with clinical or virological failure over 48 weeks
2. Time to any new or recurrent AIDS-defining event (CDC C or WHO 4) or severe/modified CDC B/WHO 3 events after 24 weeks from randomisation, adjudicated by the Endpoint Review Committee (ERC)
3. Proportion of children with VL suppression <50 copies/ml at 48 and 96 weeks
4. Proportion of children with VL suppression <400 copies/ml at 48 and 96 weeks
5. Rate of clinical events over 96 weeks: CDC C/WHO 4, severe CDC B/WHO 3 events and death
6. Change in CD4 count and percentage from baseline to weeks 48 and 96
7. Proportion developing new resistance mutations in those with viral load > 400 c/ml
Secondary safety outcomes:
1. Change in total cholesterol, triglycerides and lipid fractions (LDL, HDL) from baseline to weeks 48 and 96 These safety outcomes will be used to formally assess superiority of dolutegravir-based regimen vs standard of care
2. Incidence of serious adverse events
3. Incidence of new clinical and laboratory grade 3 and 4 adverse events
4. Incidence of adverse events (of any grade) leading to treatment modification
Overall study start date
30/06/2015
Overall study end date
30/06/2019
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Children <18 years with confirmed HIV-1 infection
2. Dolutegravir dose known for childs age/weight-band
3. Parents/carers and children, where applicable, give informed written consent
4. Girls aged 12 years or older who have reached menses must have a negative pregnancy test at screening and be willing to adhere to effective methods of contraception if sexually active
5. In settings where HLA B5701 is available, participants starting ABC as part of the NRTI backbone must be or have been screened and be negative for the HLA-B*5701 allele
6. Children with co-infections who need to start ART can be enrolled into ODYSSEY according to local/national guidelines
7. Parents/carers and children, where applicable, willing to adhere to a minimum of 96 weeks' follow-up
In addition to that, if about to start second-line therapy defined as switch of at least two ART drugs due to treatment failure:
9. At least one NRTI with predicted preserved activity available for a background regimen
10. In settings where resistance tests are routinely available, at least one new active NRTI from TDF, ABC or ZDV should have preserved activity based on cumulative results of resistance tests within 3 months
11. In settings where resistance tests are not routinely available, children who are due to switch according to national guidelines should have at least one new NRTI available from TDF, ABC or ZDV
12. Viral load >1000 copies/ml at screening visit
Participant type(s)
Patient
Age group
Child
Upper age limit
18 Years
Sex
Both
Target number of participants
700
Total final enrolment
707
Participant exclusion criteria
1. Alanine aminotransferase (ALT) > 5 times the upper limit of normal (ULN)
2. History or presence of allergy to the study drugs or their components
Recruitment start date
30/06/2015
Recruitment end date
30/06/2019
Locations
Countries of recruitment
Albania, Spain
Study participating centre
Hospital Universitario 12 de Octubre
Madrid
28041
Spain
Sponsor information
Organisation
The PENTA Foundation (Fondazione PENTA Onlus) (Italy)
Sponsor details
Corso Stati Uniti 4
c/o Torre di Ricerca Pediatrica
Padova
35127
Italy
Sponsor type
Research organisation
Website
ROR
Funders
Funder type
Industry
Funder name
Viiv Healthcare (UK)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Individual participant data (IPD) sharing plan
Not provided at registration
IPD sharing plan summary
Not provided at time of registration
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Other publications | Study design | 04/01/2021 | 30/12/2021 | Yes | No |
| Results article | 30/12/2021 | 30/12/2021 | Yes | No | |
| Results article | Results of pharmacokinetic and safety substudies in children weighing 20 to 40 kg | 01/08/2021 | 30/12/2021 | Yes | No |
| Results article | Nested pharmacokinetic and safety substudy in children with HIV-associated TB | 25/07/2022 | Yes | No |