HIV II Infection
Conditions
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.
Detailed description
Subjects who fulfill all inclusion criteria and none of the exclusion criteria, after giving informed consent, will be eligible for participation in this study. At the Visit 2 (Day1) subjects will receive the study medication and instructions for its administration. Thereafter, subjects will return to the investigational site at week 4, 12, 24, 36 and 48, for efficacy and safety assessments. Subjects who meet the virologic failure criteria will return to the investigational site approximately one week later to repeat viral RNA testing (Virologic Failure Confirmation visit). If virologic failure is confirmed and the viral load meets the criteria for resistance testing, viral resistance testing will then be performed.
Interventions
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.
Sponsors
Blueclinical, Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* A subject is eligible for the study if he/she fulfills all of the following inclusion criteria: 1. Able to understand and willing to comply with all the requirements of the study, as confirmed by giving voluntary written informed consent for participation. 2. Male or female gender. 3. Age ≥ 18 years on the day of signing the informed consent. 4. HIV-2 positive as determined by a positive result in the respective assay. 5. 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; 6. Naïve to ART including investigational antiretroviral agents . 7. 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. 8. If woman or man with reproductive potential, agrees to adopt one of the following effective contraceptive methods throughout the study: 1. True abstinence, if this is in line with the preferred and usual lifestyle of the subject \[Period abstinence (e.g., abstinence only on certain calendar days, abstinence only during ovulation period, use of symptothermal method, use of post-ovulation methods) and withdrawal are not acceptable methods of contraception\]. 2. 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.
Exclusion criteria
* A subject is not eligible for the trial if he/she fulfills any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy analysis- treatment efficacy, as measured by the overall treatment success defined as proportion of patients with global success at week 48. | 48 Weeks | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Study treatment immunological effect | 12, 24 and 48 Weeks | To evaluate the study treatment immunological effect, as measured by the change from baseline in CD4 cell count and the CD4/CD8 ratio at Week 48. as measured by the change from baseline in CD4 cell count and the CD4/CD8 ratio at Week 48. Change from Baseline in CD4 Cell Count and CD4/CD8 ratio Change from baseline in CD4 cell count and the CD4/CD8 ratio will be estimated at each time point with CD4 and CD8 cell count collection with a key interest at Week 12, 24 and 48. |
| 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 | The following clinical and laboratory adverse experiences will be summarized: Subjects with at least one adverse experience. Subjects with at least one drug related adverse experience. Subjects with at least one serious adverse experience. Subjects with at least one serious and drug related adverse experience, Subjects who discontinued study therapy due to an adverse experience. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Antiretroviral activity | 48 Weeks | The exploratory objective of this study is to evaluate the antiretroviral activity of DTG in combination with two NRTIs \[ABC/3TC or TDF/FTC\] against HIV-2, as measured by the Time to Virologic Response (TVR) |
Countries
Portugal
Outcome results
None listed