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

NCT01900106 | Completed Phase 3

• 2 other identifiers: RTLP (PRADAR)2011-005973-21
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 1

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.

Conditions

HIV Infection

Keywords

late presenter; naïve; advanced HIV disease

Outcome Measures

Primary Outcomes (1)

• HIV RNA Viral Load

  The proportion of patients attaining an HIV RNA level \<50 copies/mL after 48 weeks will be the primary outcome.

  baseline and week 48

Study Arms (2)

abacavir/lamivudine + raltegravir

EXPERIMENTAL

abacavir/lamivudine + raltegravir

Drug: abacavir/lamivudine + raltegravir

ABC/3TC + DRV/r

ACTIVE COMPARATOR

abacavir/lamivudine + darunavir/ritonavir

Drug: abacavir/lamivudine + darunavir/ritonavir

Interventions

abacavir/lamivudine + raltegravir DRUG

abacavir/lamivudine + raltegravir

Also known as: Kivexa, Isentress

abacavir/lamivudine + raltegravir

abacavir/lamivudine + darunavir/ritonavir DRUG

abacavir/lamivudine + darunavir/ritonavir

Also known as: Kivexa, Prezista, Norvir

ABC/3TC + DRV/r

Eligibility Criteria

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

You may qualify if:

• Males or females (inpatients or outpatients) aged 18-64 years who are HIV-1 antibody seropositive, with a CD4 count \<200 cells/uL.
• All patients should be antiretroviral-naive
• All patients should be HLA B57 or HLA B5701 negative
• Patients must have an HIV RNA level \<500,000 copies/mL
• Patients with an active opportunistic infection could be enrolled as long as this was diagnosed more than 2 weeks prior to screening.
• 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.
• 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.
• Patients must be able to provide written consent to comply with study requirements.

You may not qualify if:

• Patients with genotypic mutations for any of the study drugs.
• Patients with an opportunistic infection diagnosed in the 2 weeks prior to screening.
• Female patients who are pregnant or breastfeeding.
• Patients who are receiving any investigational drug or anti-neoplastic radiotherapy/chemotherapy other than local skin radiotherapy within 12 weeks before randomization.
• Patients with a current history of intravenous drug abuse, alcohol or substance abuse.

Sponsors & Collaborators

• University of Modena and Reggio Emilia: lead

Study Sites (1)

University of Modena and Reggio Emilia

Modena, 41124, Italy

Location

MeSH Terms

Conditions

HIV Infections

Interventions

abacavir; Lamivudine; Raltegravir Potassium; abacavir, lamivudine drug combination; Darunavir; Ritonavir

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)

Zalcitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Dideoxynucleosides; Pyrrolidinones; Pyrrolidines; Sulfonamides; Amides; Organic Chemicals; Carbamates; Acids, Acyclic; Carboxylic Acids; Sulfones; Sulfur Compounds; Furans; Thiazoles; Azoles

Study Officials

• Cristina Mussini, Professor

  University of Modena and ReggioEmilia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 5, 2013
• First Posted: July 16, 2013
• Study Start: November 1, 2013
• Primary Completion: December 1, 2017
• Study Completion: December 1, 2017
• Last Updated: April 23, 2019

Record last verified: 2019-04

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)