Dolutegravir Plus 2 NRTIs, in Treatment-Naïve HIV-2 Infected Subjects

NCT03224338 | Completed Phase 2

• 1 other identifier: DTG-01-01
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 6

Brief Summary

Multicenter, single-arm, open-label clinical trial to evaluate the efficacy, the safety and the tolerability of 50 mg dolutegravir once daily (q.d.) given in combination with 2 NRTIs backbone in HIV-2 positive, treatment-naïve subjects.

Conditions

HIV II Infection

Outcome Measures

Primary Outcomes (1)

• Efficacy analysis- treatment efficacy, as measured by the "overall treatment success defined as proportion of patients with "global success" at week 48.

  The primary objective of this study is to evaluate the efficacy of DTG in combination with two NRTIs \[ABC/3TC or TDF/FTC\] in the treatment of HIV-2 treatment-naïve subjects, as measured by the proportion of subjects achieving a plasma viral load of \<40 copies/mL and/or by the change from baseline in CD4 cell count and in CD4/CD8 ratio at Week 48. Global success" is a composite variable defined as a plasma HIV-2 RNA viral load \<40 copies/mL and a delta of CD4 depending on the initial CD4 count (CD4 delta \>+100 cells/mm3 for initial CD4s ≤ 500 cells/mm3; or CD4delta \> +50 cells/mm3 for initial CD4s \> 500 cells/mm3).

  48 Weeks

Secondary Outcomes (3)

• Study treatment immunological effect

  12, 24 and 48 Weeks

• Study treatment immunological effect

  12, 24 and 48 Weeks

• Safety and tolerability of the study treatment, as assessed by review of the accumulated safety data.

  24 weeks or rebounder at least one week apart afte rinitial response

Other Outcomes (2)

• Antiretroviral activity

  48 Weeks

• Antiretroviral activity

  48 Weeks

Study Arms (1)

: Dolutegravir (DTG)

EXPERIMENTAL

Drug: Dolutegravir 50 mg

Interventions

Dolutegravir 50 mg DRUG

Dolutegravir will be used in combination with 2 nucleoside reverse transcriptase inhibitors (NRTIs). The NRTIs used in combination with DTG will be abacavir (ABC) plus lamivudine (3TC) or tenofovir (TDF) plus emtricitabine (FTC), which is in line with the current standard of care. The combination ABC/3TC/DTG will be preferential except in case of hepatitis B co-infection or in case the subject has a positive HLA-B\*5701 allele screening assessment.

: Dolutegravir (DTG)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to understand and willing to comply with all the requirements of the study, as confirmed by giving voluntary written informed consent for participation.
• Male or female gender.
• Age ≥ 18 years on the day of signing the informed consent.
• HIV-2 positive as determined by a positive result in the respective assay.
• CD4 count ≤500 cells/mm3 (in case of undetectable baseline HIV-2 viral load); and/or classified as B- or C-stage, by the HIV disease staging and classification system of Centers for Disease Control and Prevention (CDC); and/or have detectable viral load irrespective of CD4 count; and/or have other medical conditions / co-morbidities in which treatment is considered, according to European AIDS Clinical Society (EACS) and national guidelines;
• Naïve to ART including investigational antiretroviral agents .
• Considered clinically stable with no signs or symptoms of active infection, at the time of entry into the study (i.e., clinical status and all chronic medications should be unchanged for at least 2 weeks prior to the start of treatment in this study), in the opinion of the investigator.
• If woman or man with reproductive potential, agrees to adopt one of the following effective contraceptive methods throughout the study:
• True abstinence, if this is in line with the preferred and usual lifestyle of the subject \[Period abstinence (e.g., abstinence only on certain calendar days, abstinence only during ovulation period, use of symptothermal method, use of post-ovulation methods) and withdrawal are not acceptable methods of contraception\].
• Use of an acceptable method of birth control throughout the study (either by subject or subject's partner). Acceptable methods of birth control are: oral contraceptive, intrauterine device (IUD), diaphragm with spermicide, contraceptive sponge, condom, vasectomy. All forms of hormonal contraception are acceptable. However, the investigator should consult local prescribing information for guidance on the use of hormonal contraceptives with background ART as some antiretrovirals have clinically significant drug interactions with these products.
• NOTE: A subject who is not of reproductive potential , is not sexually active, whose current partner(s) is/are not of reproductive potential, or whose sexual activity is exclusively homosexual is eligible without requiring the use of contraception. However, use of barrier methods of contraception is strongly encouraged to reduce the risk of HIV-2 transmission during sexual contact.

You may not qualify if:

• History or presence of allergy to the study drugs or their components.
• HIV-1 infection or HIV-1/HIV-2 dual infection.
• History or current evidence of any condition, therapy, laboratory abnormality or other circumstance that might confound the results of the study, or interfere with the subject's participation for the full duration of the study, such that it is not in the best interest of the subject to participate.
• Documented or known resistance to DTG and/or NRTIs.
• Treatment with systemic immunosuppressive therapy or immune modulators within 30 days prior to treatment in this study or is anticipated to need them during the course of the study.
• NOTE: "Short courses" of corticosteroids (e.g., as for asthma exacerbation) will be allowed. "Short courses" mean a use of corticosteroids for less than 7 days.
• Requiring or is anticipated to require any of the prohibited medications while in the study (dofetilide, inducers of CYP3A4, including phenobarbital, phenytoin, carbamazepine and rifampicin).
• NOTE: Subjects must discontinue phenobarbital, phenytoin, carbamazepine, and rifampicin at least 14 days prior to the treatment phase of the study.
• Current (active) diagnosis of tuberculosis.
• Alanine aminotransferase (ALT) ≥5 times the upper limit of normal (ULN), or ALT ≥3xULN and bilirubin ≥1.5xULN (with \>35% direct bilirubin).
• Moderate to severe hepatic impairment (Class B or greater) as determined by Child-Pugh classification .
• If subject eligible to receive Tivicay®: Unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice), cirrhosis, known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• Estimated creatinine clearance \<50 mL/min at time of screening, based on Cockcroft-Gault equation .
• Current (active) diagnosis of acute hepatitis due to any cause. NOTE: Subjects with chronic hepatitis B and C may enter the study as long as they fulfil all entry criteria, have stable liver function tests, and have no significant impairment of hepatic synthetic function (significant impairment of hepatic synthetic function is defined as a serum albumin \<2.8 g/dL in the absence of another explanation for the abnormal laboratory value) at the time of enrollment.
• Under treatment for a viral infection other than HIV-2, such as hepatitis B, with an agent that may be active against HIV-2, including but not limited to 3TC, TDF or entecavir, unless the treatment with these agents occurred prior to the diagnosis of HIV.

Sponsors & Collaborators

• Blueclinical, Ltd.: lead

Study Sites (6)

Centro Hospitalar de Lisboa Central Hospital Curry Cabral

Lisbon, Portugal

Location

Centro Hospitalar de Lisboa Ocidental Hospital de Egas Moniz

Lisbon, Portugal

Location

Centro Hospitalar Lisboa Norte Hospital de Santa Maria

Lisbon, Portugal

Location

Hospital Beatriz Ângelo Loures

Lisbon, Portugal

Location

Hospital Garcia de Orta

Lisbon, Portugal

Location

Hospital Professor Doutor Fernando Fonseca Amadora

Lisbon, Portugal

Location

Related Publications (1)

• Pacheco P, Marques N, Rodrigues P, Mansinho K, Maltez F, Janeiro N, Franco C, Trigo D, Batista J, Duque L, Lopes MJ, Aleixo MJ, Silva AR, Tavares R, Alves J, Peres S, Povoas D, Lino S, Gomes P, Araujo V, Lopes C. Safety and Efficacy of Triple Therapy With Dolutegravir Plus 2 Nucleoside Reverse Transcriptase Inhibitors in Treatment-Naive Human Immunodeficiency Virus Type 2 Patients: Results From a 48-Week Phase 2 Study. Clin Infect Dis. 2023 Sep 11;77(5):740-748. doi: 10.1093/cid/ciad339.

  PMID: 37288954 DERIVED

MeSH Terms

Interventions

dolutegravir

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 6, 2017
• First Posted: July 21, 2017
• Study Start: April 5, 2017
• Primary Completion: July 2, 2019
• Study Completion: July 2, 2019
• Last Updated: September 3, 2019

Record last verified: 2019-08

Locations

PT (6)