ODYSSEY (PENTA 20)

NCT02259127 | Completed Phase 2 Results DMC

• 2 other identifiers: ODYSSEY (PENTA 20)2014-002632-14
• Study Type: interventional
• Target: 792
• Locations: 8 countries
• Sites: 28

Brief Summary

A new anti-HIV medicine (Dolutegravir) combined with 2 currently used anti-HIV medicines is non-inferior to the standard combination of medicines used in terms of efficacy and better in terms of toxicity.

Conditions

HIV Infection

Outcome Measures

Primary Outcomes (1)

• Difference in Proportion With Failure (Clinical or Virological)

  Treatment failure by 96 weeks. Estimated using time to the first occurrence of any of the following components: * Insufficient virological response defined as \< 1 log10 drop at week 24 and switch to second/third line ART for treatment failure * Viral Load (VL)\>400 c/ml at or after 36 weeks confirmed by next visit * Death due to any cause * Any new or recurrent AIDS defining event (WHO 4) or severe WHO 3 events, adjudicated by the Endpoint Review Committee

  96 weeks post randomisation

Secondary Outcomes (25)

• HIV-1 RNA <50c/ml at 96 Weeks

  96 weeks post randomisation

• HIV-1 RNA <400c/mL at 96 Weeks

  96 weeks post randomisation

• Mean Change in CD4 Count From Baseline to Week 96

  96 weeks post randomisation

• Mean Change in Total Cholesterol From Baseline to Week 96

  96 weeks post randomisation

• Serious Adverse Events

  Randomised phase: follow-up was censored when the last participant reached 96 weeks of follow-up (142 weeks (IQR:124 to 159) in ≥14kg cohort and 124 weeks (112 to 137) in <14kg cohort).

Other Outcomes (2)

• Mean Change in Weight From Baseline

  96 weeks post randomisation

• Mean Change in BMI-for-age Z-score From Baseline

  96 weeks post randomisation

Study Arms (2)

SOC arm

ACTIVE COMPARATOR

Standard of Care (SOC) for ODYSSEY A is defined as a PI or non nucleoside transcriptase inhibitors + 2 or 3 nucleoside transcriptase inhibitor SOC for ODYSSEY B is defined as a PI or non nucleoside transcriptase inhibitor+ 2 nucleoside transcriptase inhibitors

Drug: Standard of Care

DTG arm

EXPERIMENTAL

DTG + 2 nucleoside transcriptase inhibitors

Drug: Dolutegravir

Interventions

Dolutegravir DRUG

Also known as: DTG

DTG arm

Standard of Care DRUG

PI or non nucleoside transcriptase inhibitors

Also known as: SOC

SOC arm

Eligibility Criteria

• Age: 28 Days - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• ALL PATIENTS:
• Children ≥28 days and \<18 years weighing ≥3kg with confirmed HIV-1 infection
• Parents/carers and children, where applicable, give informed written consent
• 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
• Children with co-infections who need to start ART can be enrolled into ODYSSEY according to local/national guidelines
• Parents/carers and children, where applicable, willing to adhere to a minimum of 96 weeks' follow-up
• Children weighing 3 to \<14kg must be eligible and willing to participate in the Weight band (WB)-Pharmacokinetics (PK)1 substudy unless direct enrolment for the child's weight band has opened following the WB-PK1 substudy and/or dosing information has become available from the IMPAACT P1093 DTG dose-finding study.
• ADDITIONAL CRITERIA FOR ODYSSEY A:
• Planning to start first-line ART
• ADDITIONAL CRITERIA FOR ODYSSEY B:
• Planning to start second-line ART defined as either: (i) switch of at least 2 ART drugs due to treatment failure; or (ii) switch of only the third agent due to treatment failure where drug sensitivity tests show no mutations conferring Nucleoside Reverse Transcriptase Inhibitor (NRTI) resistance
• Treated with only one previous ART regimen. Single drug substitutions for toxicity, simplification, changes in national guidelines or drug availability are allowed
• At least one NRTI with predicted preserved activity available for a background regimen
• In settings where resistance tests are routinely available, at least one new active NRTI from tenofovir disoproxil fumarate, abacavir or zidovudine should have preserved activity based on cumulative results of resistance tests
• 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 predicted to be available from tenofovir disoproxil fumarate, abacavir or zidovudine

You may not qualify if:

• History or presence of known allergy or contraindications to dolutegravir
• History or presence of known allergy or contraindications to proposed available NRTI backbone or proposed available SOC third agent.
• Alanine aminotransferase (ALT) ≥ 5 times the upper limit of normal, OR ALT ≥3x upper limit of normal and bilirubin ≥2x upper limit of normal
• Patients with severe hepatic impairment or unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, or persistent jaundice), known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
• Anticipated need for Hepatitis C virus (HCV) therapy during the study
• Pregnancy or breastfeeding
• Evidence of lack of susceptibility to integrase inhibitors or more than a 2-week exposure to antiretrovirals of this class

Sponsors & Collaborators

• PENTA Foundation: lead
• Institut National de la Santé Et de la Recherche Médicale, France: collaborator
• Program for HIV Prevention and Treatment (PHPT): collaborator
• ViiV Healthcare: collaborator
• MRC CTU at UCL: collaborator

Study Sites (28)

Universitata Frankfurt

Frankfurt, Germany

Location

UkE Eppendorf Hamburg

Hamburg, Germany

Location

Centro Materno-Infantil de Norte

Porto, Portugal

Location

King Edward VIII Hospital

Durban, South Africa

Location

Africa Health Research Institute (AHRI)

Hlabisa, South Africa

Location

PHRU Klerksdorp

Klerksdorp, South Africa

Location

Kid-Cru

Parow, South Africa

Location

PHRU

Soweto, South Africa

Location

Hospital San Joan de Defu

Barcelona, Spain

Location

Hospital 12 de Octubre

Madrid, Spain

Location

Hospital La Paz

Madrid, Spain

Location

Prapokklao Hospital

Chanthaburi, Thailand

Location

Nakornping Hospital

Chiang Mai, Thailand

Location

Chiangrai Prachanukroh Hospital

Chiang Rai, Thailand

Location

Khon Kaen Hospital

Khon Kaen, Thailand

Location

Mahasarakam Hospital

Maha Sarakham, Thailand

Location

Phayao Hospital

Phayao, Thailand

Location

Baylor

Kampala, Uganda

Location

JCRC

Kampala, Uganda

Location

MUJHU

Kampala, Uganda

Location

JCRC

Mbarara, Uganda

Location

Birmingham Heartlands Hospital

Birmingham, United Kingdom

Location

Leeds General Infirmary

Leeds, United Kingdom

Location

Leicester Royal Infirmary

Leicester, United Kingdom

Location

Great Ormand Street Hospital

London, United Kingdom

Location

Kings College Hospital

London, United Kingdom

Location

St Mary's Hospital

London, United Kingdom

Location

UZCRC

Harare, Zimbabwe

Location

Related Publications (9)

• Turkova A, White E, Mujuru HA, Kekitiinwa AR, Kityo CM, Violari A, Lugemwa A, Cressey TR, Musoke P, Variava E, Cotton MF, Archary M, Puthanakit T, Behuhuma O, Kobbe R, Welch SB, Bwakura-Dangarembizi M, Amuge P, Kaudha E, Barlow-Mosha L, Makumbi S, Ramsagar N, Ngampiyaskul C, Musoro G, Atwine L, Liberty A, Musiime V, Bbuye D, Ahimbisibwe GM, Chalermpantmetagul S, Ali S, Sarfati T, Wynne B, Shakeshaft C, Colbers A, Klein N, Bernays S, Saidi Y, Coelho A, Grossele T, Compagnucci A, Giaquinto C, Rojo P, Ford D, Gibb DM; ODYSSEY Trial Team. Dolutegravir as First- or Second-Line Treatment for HIV-1 Infection in Children. N Engl J Med. 2021 Dec 30;385(27):2531-2543. doi: 10.1056/NEJMoa2108793.

  PMID: 34965338 RESULT

• Amuge P, Lugemwa A, Wynne B, Mujuru HA, Violari A, Kityo CM, Archary M, Variava E, White E, Turner RM, Shakeshaft C, Ali S, Nathoo KJ, Atwine L, Liberty A, Bbuye D, Kaudha E, Mngqibisa R, Mosala M, Mumbiro V, Nanduudu A, Ankunda R, Maseko L, Kekitiinwa AR, Giaquinto C, Rojo P, Gibb DM, Turkova A, Ford D; ODYSSEY Trial Team. Once-daily dolutegravir-based antiretroviral therapy in infants and children living with HIV from age 4 weeks: results from the below 14 kg cohort in the randomised ODYSSEY trial. Lancet HIV. 2022 Sep;9(9):e638-e648. doi: 10.1016/S2352-3018(22)00163-1.

  PMID: 36055295 RESULT

• Turkova A, White E, Violari A, Mujuru HA, Kekitiinwa AR, Lugemwa A, Kaudha E, Na-Rajsima S, Ahimbisibwe GM, Variavae E, Archary M, Akhalwaya Y, Puthanakit T, Bwakura-Dangarembizi M, Bbuye D, Kasozi M, Liberty A, Konigs C, Welch SB, Riault Y, Bamford A, Cressey TR, Musoke P, Kityo C, Ferrand R, Giaquinto C, Rojo P, Gibb DM, Ford D; ODYSSEY trial team. Weight gain, body composition, and metabolic parameters of dolutegravir-based antiretroviral therapy versus standard of care in children and adolescents: an ancillary analysis of the ODYSSEY trial. Lancet Child Adolesc Health. 2026 Jan 21:S2352-4642(25)00339-6. doi: 10.1016/S2352-4642(25)00339-6. Online ahead of print.

  PMID: 41579881 DERIVED

• White E, Kityo C, Spyer MJ, Mujuru HA, Nankya I, Kekitiinwa AR, Lugemwa A, Kaudha E, Liberty A, Cassim H, Archary M, Cotton MF, Ahimbisibwe GM, Cressey TR, Ngampiyaskul C, Srirompotong U, Behuhuma O, Saidi Y, Bamford A, Kobbe R, Nastouli E, Rojo P, Giaquinto C, Gibb DM, Ford D, Turkova A; ODYSSEY trial team. Virological outcomes and genotypic resistance on dolutegravir-based antiretroviral therapy versus standard of care in children and adolescents: a secondary analysis of the ODYSSEY trial. Lancet HIV. 2025 Mar;12(3):e201-e213. doi: 10.1016/S2352-3018(24)00155-3. Epub 2025 Feb 17.

  PMID: 39978387 DERIVED

• Barlow-Mosha LN, Ahimbisibwe GM, Chappell E, Amuge PM, Nanduudu A, Kaudha E, Amukele T, Balamusani D, Kafufu B, Nimwesiga A, Kataike H, Namwanje R, Kasangaki G, Mulindwa A, Muzorah GA, Bbuye D, Musiime V, Mujyambere E, Ssenyonga M, Mulima D, Kyambadde RC, Namusanje J, Isabirye R, Nabalamba M, Nakirya BM, Kityo C, Kekitiinwa AR, Giaquinto C, Copp A, Gibb DM, Ford D, Musoke P, Turkova A; ODYSSEY trial team. Effect of dolutegravir on folate, vitamin B12 and mean corpuscular volume levels among children and adolescents with HIV: a sub-study of the ODYSSEY randomized controlled trial. J Int AIDS Soc. 2023 Sep;26(9):e26174. doi: 10.1002/jia2.26174.

  PMID: 37766505 DERIVED

• Turkova A, Waalewijn H, Chan MK, Bollen PDJ, Bwakura-Dangarembizi MF, Kekitiinwa AR, Cotton MF, Lugemwa A, Variava E, Ahimbisibwe GM, Srirompotong U, Mumbiro V, Amuge P, Zuidewind P, Ali S, Kityo CM, Archary M, Ferrand RA, Violari A, Gibb DM, Burger DM, Ford D, Colbers A; ODYSSEY Trial Team. Dolutegravir twice-daily dosing in children with HIV-associated tuberculosis: a pharmacokinetic and safety study within the open-label, multicentre, randomised, non-inferiority ODYSSEY trial. Lancet HIV. 2022 Sep;9(9):e627-e637. doi: 10.1016/S2352-3018(22)00160-6. Epub 2022 Jul 19.

  PMID: 35868341 DERIVED

• Singh RP, Adkison KK, Baker M, Parasrampuria R, Wolstenholme A, Davies M, Sewell N, Brothers C, Buchanan AM. Development of Dolutegravir Single-entity and Fixed-dose Combination Formulations for Children. Pediatr Infect Dis J. 2022 Mar 1;41(3):230-237. doi: 10.1097/INF.0000000000003366.

  PMID: 34817414 DERIVED

• Moore CL, Turkova A, Mujuru H, Kekitiinwa A, Lugemwa A, Kityo CM, Barlow-Mosha LN, Cressey TR, Violari A, Variava E, Cotton MF, Archary M, Compagnucci A, Puthanakit T, Behuhuma O, Saiotadi Y, Hakim J, Amuge P, Atwine L, Musiime V, Burger DM, Shakeshaft C, Giaquinto C, Rojo P, Gibb DM, Ford D; ODYSSEY Trial Team. ODYSSEY clinical trial design: a randomised global study to evaluate the efficacy and safety of dolutegravir-based antiretroviral therapy in HIV-positive children, with nested pharmacokinetic sub-studies to evaluate pragmatic WHO-weight-band based dolutegravir dosing. BMC Infect Dis. 2021 Jan 4;21(1):5. doi: 10.1186/s12879-020-05672-6.

  PMID: 33446115 DERIVED

• Bollen PDJ, Moore CL, Mujuru HA, Makumbi S, Kekitiinwa AR, Kaudha E, Parker A, Musoro G, Nanduudu A, Lugemwa A, Amuge P, Hakim JG, Rojo P, Giaquinto C, Colbers A, Gibb DM, Ford D, Turkova A, Burger DM; ODYSSEY trial team. Simplified dolutegravir dosing for children with HIV weighing 20 kg or more: pharmacokinetic and safety substudies of the multicentre, randomised ODYSSEY trial. Lancet HIV. 2020 Aug;7(8):e533-e544. doi: 10.1016/S2352-3018(20)30189-2.

  PMID: 32763217 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

dolutegravir; Standard of Care

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Limitations and Caveats

None reported

Results Point of Contact

• Title: Prof Diana M Gibb (Chief Investigator)
• Organization: MRC CTU at UCL

diana.gibb@ucl.ac.uk

+44 (0) 207 670 4700

Study Officials

• Diana Gibb

  Medical Research Council Clinical Trials Unit at UCL

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 30, 2014
• First Posted: October 8, 2014
• Study Start: September 20, 2016
• Primary Completion: March 2, 2021
• Study Completion: December 7, 2023
• Last Updated: July 29, 2025
• Results First Posted: July 29, 2025

Record last verified: 2025-07

Locations

TH (6); ZI (1); DE (2); GB (6); UG (4); PT (1); ZA (5); ES (3)