A Prospective, Open-label Trial of Two ABC/3TC Based Regimens in Late Presenter naïve Patients (CD4 <200 Cells/µL)

NCT ID: NCT01900106

Last Updated: 2019-04-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 47 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-11-30
• Study Completion Date: 2017-12-31

Brief Summary

1. PROTOCOL SUMMARY This is a prospective, randomized open-label, 2 arm, 3-phase trial to compare the 48-weeks virological response of two different regimens containing abacavir/lamivudine (abacavir/lamivudine +darunavir/ritonavir (DRV/r) vs abacavir/lamivudine + raltegravir (RAL) in antiretroviral therapy naive, HIV+ individuals presenting for care with CD4+ counts < 200/mm3.

1.1 Clinical Objectives: Primary Objective: To compare the 48-week virological response to two different regimens containing abacavir/lamivudine (abacavir/lamivudine +darunavir/ritonavir (DRV/r) vs abacavir/lamivudine + raltegravir (RAL) in antiretroviral therapy naive, HIV+ individuals presenting for care with CD4+ counts < 200/mm3.

Secondary Objective: a) To compare immunological response at 48 weeks; b) To determine the safety and tolerability of the 2 regimens.

1.2 Study population: 350 in/out patients 1.3 Outcome Primary Endpoint

• Proportion of patients with HIV RNA<50 copies/mL after 48 weeks Secondary Endpoints(s)
• Change in CD4+ cell count from baseline through week 48
• Time to virological rebound 1.4 Study design: Multicentre, parallel group, randomised, open label, non-inferiority study 1.5 Treatment regimens: Arm A: abacavir/lamivudine 1 tablet once a day + raltegravir 400 mg (1 tablet twice a day) Arm B: abacavir/lamivudine 1 tablet once a day + ritonavir 100 mg + darunavir 800 mg once a day.

All drugs have been approved for the treatment of HIV infection. The study population will consist of 350 HIV-positive, HLA B5701-negative patients. At baseline, patients will be randomized 1:1 to start abacavir/lamivudine plus either raltegravir or darunavir/ritonavir. Randomization will be stratified on the basis of the screening CD4+ cell count (≤100 vs ≥100 cells/µL), to ensure balance across treatments groups 1.7 Criteria for Safety: Adverse events and laboratory assessments. 1.8 Statistical analysis: As this is a non-inferiority trial, we will calculate the difference in the proportions of patients experiencing the primary outcome in the two treatment arms and will calculate a 95% confidence interval for this. Non-inferiority of the raltegravir arm will be demonstrated if the lower limit of the 95% confidence interval is greater than -12%. In case non-inferiority will be met, analyses for superiority will be performed.

Detailed Description

1. PROTOCOL SUMMARY This is a prospective, randomized open-label, 2 arm, 3-phase trial to compare the 48-weeks virological response of two different regimens containing abacavir/lamivudine (abacavir/lamivudine +darunavir/ritonavir (DRV/r) vs abacavir/lamivudine + raltegravir (RAL) in antiretroviral therapy naive, HIV+ individuals presenting for care with CD4+ counts < 200/mm3.

1.1 Clinical Objectives: Primary Objective: To compare the 48-week virological response to two different regimens containing abacavir/lamivudine (abacavir/lamivudine +darunavir/ritonavir (DRV/r) vs abacavir/lamivudine + raltegravir (RAL) in antiretroviral therapy naive, HIV+ individuals presenting for care with CD4+ counts < 200/mm3.

Secondary Objective:

1. To compare immunological response at 48 weeks;

2. To determine the safety and tolerability of the 2 regimens. 1.2 Study population: 350 inpatients or outpatients will be randomized 1.3 Outcome Primary Endpoint

• Proportion of patients with undetectable viremia (HIV RNA<50 copies/mL) after 48 weeks Secondary Endpoints(s)
• Change in CD4+ cell count from baseline through week 48
• Time to virological rebound Safety endpoints
• Incidence of adverse events (AEs)
• Incidence of serious adverse events (SAEs)
• Discontinuations due to adverse events
• Incidence of grade 3 or 4 laboratory abnormalities. 1.4 Study design Multicentre, parallel group, randomised, open label, non-inferiority study 1.5 Planned sample size: The planned sample size for this trial is 350 patients 1.6 Treatment regimens: Arm A: abacavir/lamivudine 1 tablet once a day + raltegravir 400 mg (1 tablet twice a day) Arm B: abacavir/lamivudine 1 tablet once a day + ritonavir 100 mg + darunavir 800 mg once a day.

All drugs have been approved for the treatment of HIV infection. Administration: oral The study population will consist of 350 HIV-positive, HLA B5701-negative patients. At baseline, patients will be randomized 1:1 to start abacavir/lamivudine plus either raltegravir or darunavir/ritonavir. Randomization will be stratified on the basis of the screening CD4+ cell count (≤100 vs ≥100 cells/µL), to ensure balance across treatments groups 1.7 Criteria for Safety: Adverse events and laboratory assessments. 1.8 Statistical analysis: As this is a non-inferiority trial, we will calculate the difference in the proportions of patients experiencing the primary outcome in the two treatment arms and will calculate a 95% confidence interval for this. Non-inferiority of the raltegravir arm will be demonstrated if the lower limit of the 95% confidence interval is greater than -12%. In case non-inferiority will be met, analyses for superiority will be performed.

Conditions

HIV Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

abacavir/lamivudine + raltegravir

abacavir/lamivudine + raltegravir

Group Type: EXPERIMENTAL

abacavir/lamivudine + raltegravir

Intervention Type: DRUG

abacavir/lamivudine + raltegravir

ABC/3TC + DRV/r

abacavir/lamivudine + darunavir/ritonavir

Group Type: ACTIVE_COMPARATOR

abacavir/lamivudine + darunavir/ritonavir

Intervention Type: DRUG

abacavir/lamivudine + darunavir/ritonavir

Interventions

abacavir/lamivudine + raltegravir

abacavir/lamivudine + raltegravir

Intervention Type: DRUG

abacavir/lamivudine + darunavir/ritonavir

abacavir/lamivudine + darunavir/ritonavir

Intervention Type: DRUG

Other Intervention Names

Kivexa; Isentress; Kivexa; Prezista; Norvir

Eligibility Criteria

Inclusion Criteria

1. Males or females (inpatients or outpatients) aged 18-64 years who are HIV-1 antibody seropositive, with a CD4 count <200 cells/uL.

2. All patients should be antiretroviral-naive

3. All patients should be HLA B57 or HLA B5701 negative

4. Patients must have an HIV RNA level <500,000 copies/mL

5. Patients with an active opportunistic infection could be enrolled as long as this was diagnosed more than 2 weeks prior to screening.

6. Patients must meet the following laboratory criteria. Neutrophil count > 1,000 cells/mm3 Haemoglobin > 9.0 grams/dl (men and women) Platelet count ≥ 75,000 cells/mm3 Alkaline phosphatase < 3.0 the upper limit of normal ALT and AST < 3.9 times the upper limit of normal Total bilirubin < 1.5 times the upper limit of normal.

7. Female patients of childbearing potential must be willing to use a reliable form of contraception, which will include a medically approved form of barrier contraception.

8. Patients must be able to provide written consent to comply with study requirements.

Exclusion Criteria

1. Patients with genotypic mutations for any of the study drugs.

2. Patients with an opportunistic infection diagnosed in the 2 weeks prior to screening.

3. Female patients who are pregnant or breastfeeding.

4. Patients who are receiving any investigational drug or anti-neoplastic radiotherapy/chemotherapy other than local skin radiotherapy within 12 weeks before randomization.

5. Patients with a current history of intravenous drug abuse, alcohol or substance abuse.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 64 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Modena and Reggio Emilia

OTHER

Sponsor Role: lead

Responsible Party

Cristina Mussini

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Cristina Mussini, Professor

Role: PRINCIPAL_INVESTIGATOR

University of Modena and ReggioEmilia

Locations

University of Modena and Reggio Emilia

Modena, , Italy

Countries

Italy

Other Identifiers

2011-005973-21

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

RTLP (PRADAR)

Identifier Type: -

Identifier Source: org_study_id