ODYSSEY: Once daily Dolutegravir in Young people vS Standard thErapY
| ISRCTN | ISRCTN91737921 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN91737921 |
| EudraCT/CTIS number | 2014-002632-14 |
| IRAS number | 179128 |
| ClinicalTrials.gov number | NCT02259127 |
| Secondary identifying numbers | ODYSSEY (PENTA 20) |
- Submission date
- 16/07/2014
- Registration date
- 08/08/2014
- Last edited
- 23/05/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Infections and Infestations
Plain English summary of protocol
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
Contact information
Scientific
Hospital Universitario 12 de Octubre
Consulta de inmunodeficiencias pediatricas
Planta 6
Avenida de Cordoba s/n
Madrid
28041
Spain
Study information
| 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 |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| 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 |
| Study acronym | ODYSSEY |
| Study objectives | 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 |
| Health condition(s) or problem(s) studied | 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 |
| Completion date | 30/06/2019 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Child |
| Upper age limit | 18 Years |
| Sex | Both |
| Target number of participants | 700 |
| Total final enrolment | 707 |
| Key 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 |
| Key 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 |
| Date of first enrolment | 30/06/2015 |
| Date of final enrolment | 30/06/2019 |
Locations
Countries of recruitment
- Albania
- Spain
Study participating centre
28041
Spain
Sponsor information
Research organisation
Corso Stati Uniti 4
c/o Torre di Ricerca Pediatrica
Padova
35127
Italy
"ROR" |
https://ror.org/00d7mpc92 |
|---|
Funders
Funder type
Industry
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 | Not provided at 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 | |
| Results article | results from the below 14 kg cohort | 01/09/2022 | 23/05/2024 | Yes | No |
Editorial Notes
23/05/2024: Publication reference added.
25/07/2022: Publication reference added.
30/12/2021: The following changes have been made:
1. Publication references added.
2. The final enrolment number has been added from the reference.
3. The NCT number has been added from the reference.
4. The IRAS number has been added.
