Safety & Efficacy of Dual Therapy With Raltegravir/Lamivudine (RALAM)

Pilot 24week Clinical Trial to Assess the Safety, Tolerability and Efficacy of Dual Therapy With Raltegravir/Lamivudine Combination, Replacing Standard Combination Therapy in HIV-infected Pts With Prolonged Virological Suppression.

A pilot 24-week open-label, randomized, controlled clinical trial to assess the safety, tolerability and efficacy of dual therapy with Raltegravir/Lamivudine combination when replacing standard combination therapy in HIV-infected patients with prolonged virological suppression

Study Overview

• Status: Unknown
• Conditions: AIDS
• Intervention / Treatment: Drug: Raltegravir/3TC; Drug: EFV/TDF/FTC; Drug: ATV/r + TDF/FTC or DRV/r + TDF/FTC; Drug: DTG+ABC/3TC DTG+TDF/FTC EVG/cobi/TDF/FTC RAL+TDF/FTC; Drug: EFV plus ABC/3TC or RPV/TDF/FTC; Drug: ATV/r plus ABC/3TC; Drug: DRV/r + ABC/3TC or LPV/r + ABC/3TC or LPV/r + TDF/FTC; Drug: RAL plus ABC/3TC; Drug: Other ART regimens

• Study Type: Interventional
• Enrollment (Anticipated): 75
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Esteban Martinez, MD PhD; Phone Number: 3310 +34932275400; Email: estebanm@clinic.ub.es

Study Locations

• Spain
  • Barcelona, Spain, 08036
    • Recruiting
    • Hospital Clínic
    • Contact: Joan Albert Arnaiz, MD; Phone Number: 932279838; Email: jaarnaiz@clinic.cat

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Eligible patients will be males or females at least 18 years of age. Women of childbearing potential must have a negative pregnancy test within 10 days prior to randomization into the study.
2. Patients seropositive for HIV-1 using standard diagnostic criteria.
3. Patients virologically suppressed during at least 12 months prior to inclusion (viral load <50 copies/mL).
4. Patients on combination antiretroviral therapy (at least 2 antiretroviral drugs) for at least 12 months before being randomized in this study.
5. Patients who are clinically stable in the opinion of the investigator at study entry (clinical status and chronic medication must not have not been modified at least 14 days prior to randomization).
6. Patients who have signed informed consent to participate in the study.

Exclusion Criteria:

1. Pregnancy, lactation, or planned pregnancy during the study period.
2. Previous failure to an integrase inhibitor-containing regimen.
3. Previous failure to a 3TC or FTC-containing regimen.
4. Resistance mutations to 3TC or integrase inhibitor if any resistance test had been previously performed.
5. Any disease or history of disease which, in the opinion of the investigator, might confound the results of the study or pose additional risk to patient treatment.
6. Chronic hepatitis B.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1 Raltegravir / 3TC (MK0518B; Raltegravir / 3TC (MK0518B ) (50 patients)	Drug: Raltegravir/3TC; MK0518B (Raltegravir/3TC) (300mg/150mg) twice daily, administered orally in the 300/150 mg film-coated tablets according to instructions in the prescribing information.
Active Comparator: Group 2 standard combination therapy; NNRTI-Based Regimen: • EFV/TDF/FTC PI-Based Regimens: ATV/r + TDF/FTC or DRV/r + TDF/FTC INSTI-Based Regimens: DTG+ABC/3TC DTG+TDF/FTC EVG/cobi/TDF/FTC RAL+TDF/FTC NNRTI-Based Regimens: EFV plus ABC/3TC or RPV/TDF/FTC PI-Based Regimen: ATV/r plus ABC/3TC PI-Based Regimens: DRV/r + ABC/3TC or LPV/r + ABC/3TC or LPV/r + TDF/FTC INSTI-Based Regimen: RAL plus ABC/3TC And other ART regimens	Drug: EFV/TDF/FTC; standard combination therapy; Other Names: NNRTI-Based Regimen; Drug: ATV/r + TDF/FTC or DRV/r + TDF/FTC; Other Names: PI-Based Regimens; Drug: DTG+ABC/3TC DTG+TDF/FTC EVG/cobi/TDF/FTC RAL+TDF/FTC; Other Names: INSTI-Based Regimens; Drug: EFV plus ABC/3TC or RPV/TDF/FTC; Other Names: NNRTI-Based Regimens; Drug: ATV/r plus ABC/3TC; Other Names: PI-Based Regimen; Drug: DRV/r + ABC/3TC or LPV/r + ABC/3TC or LPV/r + TDF/FTC; Other Names: PI-Based Regimens; Drug: RAL plus ABC/3TC; Other Names: INSTI-Based Regimen; Drug: Other ART regimens

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy in virological suppression assessed with standard plasma HIV-1 RNA detection	Efficacy in virological suppression assessed with standard plasma HIV-1 RNA detection	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy in virological suppression assessed with ultrasensitive HIV-1 RNA detection (limit of detection 1 copy/mL)	efficacy in virological suppression assessed with ultrasensitive HIV-1 RNA detection (limit of detection 1 copy/mL)	24 weeks
changes in peripheral mononuclear blood cells HIV-1 reservoir		24 weeks
changes in insulin resistance (HOMA-IR)	Composite measure	24 weeks
changes in body fat composition	Composite measure	24 weeks
changes in plasma 25-OH vitamin D levels		24 weeks
changes in estimated glomerular filtration rate (CKD-EPI)	Composite measure	24 weeks
changes in CD38		24 weeks
changes in IL-6		24 weeks
changes in sleep quality (Pittsburgh Sleep Quality Index)		24 weeks
changes in adherence in both treatment arms (Morisky-Green Test)overall tolerability		24 weeks
Changes in total cholesterol		24 weeks
Changes in HDL cholesterol		24 weeks
Changes in LDL cholesterol		24 weeks
Changes in triglycerides		24 weeks
Changes in bone mineral density	DEXA	24 weeks
Changes in urine beta-2-microglobulin		24 weeks
changes in HLA-DR		24 weeks
Changes in high sensitivity C-reactive protein		24 weeks
Changes in mononuclear activation SD-14		24 weeks
Changes in mononuclear activation SD-163		24 weeks

Collaborators and Investigators

• Sponsor: Juan A. Arnaiz
• Investigators: Principal Investigator: Esteban Martinez, MD PhD, Hospital Clinic of Barcelona

Study record dates

Study Major Dates

• Study Start: January 1, 2015
• Primary Completion (Anticipated): December 1, 2016
• Study Completion (Anticipated): December 1, 2016

Study Registration Dates

• First Submitted: October 28, 2014
• First Submitted That Met QC Criteria: November 3, 2014
• First Posted (Estimate): November 5, 2014

Study Record Updates

• Last Update Posted (Estimate): June 30, 2016
• Last Update Submitted That Met QC Criteria: June 29, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; HIV Integrase Inhibitors; Integrase Inhibitors; Raltegravir Potassium; Lamivudine
• Other Study ID Numbers: RALAM; 2014-003142-27 (EudraCT Number)