Kaletra and Maraviroc in Antiretroviral Therapy (ART)-Naive Patients (KALMAR Study) (KALMAR)

Kaletra and Maraviroc in Antiretroviral Therapy-Naïve Patients - KALMAR Study -Version 1.0 Amendment 2

The primary objective of this pilot study is to assess the efficacy of lopinavir/ritonavir (Kaletra, a protease inhibitor, PI) when used in combination with maraviroc (Selzentry, an HIV entry inhibitor) for the treatment of antiretroviral naïve HIV infected patients. Twenty patients will be enrolled and studied for 48 weeks.

Study Overview

• Status: Terminated
• Conditions: HIV Infections
• Intervention / Treatment: Drug: lopinavir/ritonavir plus maraviroc

Detailed Description

As patients with HIV are living longer it is important to explore antiretroviral treatments which may reduce the development of long term complications while preserving future HIV treatment options. This trial explores an antiretroviral treatment regimen which does not include the nucleoside reverse transcriptase inhibitor class which is thought to have long-term toxicity. This is a non-randomized, open label trial in participants meeting entry requirements.

Participants will be evaluated at screening, baseline,and weeks 4, 8, 12, 24, 36, and 48 to include clinical assessments as well as laboratory assessments.

An interim analysis will be performed when all patients have reached the week 24 visit.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple General Internal Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• The patient has signed and dated approved informed consent form.
• There is confirmed laboratory diagnosis of HIV infection (positive ELISA HIV antibody test confirmed by Western blot, p24 antigen assay, quantitative HIV-1 RNA assay, or HIV culture).
• The patient is at least 18 years of age.
• ART-naïve, lopinavir/ritonavir susceptible on genotypic testing, CCR5-tropic virus on Trofile testing (ESTA).
• Negative pregnancy test within 72 hours prior to start of study for women of childbearing potential.
• Females of childbearing potential and males must utilize effective barrier contraception.
• HIV RNA greater than 1,000 copies per mL at entry.
• Liver enzymes (AST, ALT) < 3 times the upper limit of normal.

Exclusion Criteria:

• Patients who are pregnant or breast-feeding.
• Active alcohol or substance abuse sufficient, in the Investigator's opinion that makes compliance to the study protocol unlikely.
• Suspected or active HIV-related opportunistic infection or condition requiring acute therapy within 30 days of entry into the trial.
• Patients on therapy for hepatitis B.
• Patients with hepatitis B surface antigen, or any evidence of active hepatitis B such as positive hepatitis B DNA and/or presence of hepatitis e antigen or e antibody.
• Acute hepatitis B or C within 60 days of entry.
• Patients harboring preexistent co-receptor CXCR4 tropic or dual-or mixed-tropic HIV.
• Patients harboring HIV resistant to lopinavir/ritonavir on genotypic testing.
• The presence of decompensated heart failure, myocardial infarction within 1 year, bypass surgery, severe vascular disease, or active hepatobiliary disease.
• Concomitant use of rifampin, ergot derivatives (i.e. dihydroergotamine, ergotamine), cisapride, lovastatin, simvastatin, triazolam, orally administered midazolam, carbamazepine, phenytoin, St. John's wort, ketoconazole, itraconazole, clarithromycin, telithromycin, amiodarone, bepridil, flecainide, propafenone, quinidine, voriconazole or nefazodone.
• Patients with concomitant diagnosis of malignancy or cancer other than basal cell carcinoma within the past 5 years.
• Concomitant use of investigational agents including the use of any investigational vaccines.
• Any other clinical conditions or prior therapy that, in the opinion of the investigator, would make the patient unsuitable for study, or unable to comply with the dosing requirements.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: open label single arm; Drug: lopinavir/ritonavir plus maraviroc	Drug: lopinavir/ritonavir plus maraviroc; Lopinavir/ritonavir 400 mg/100 mg two tablets twice daily with Maraviroc 150 mg one tablet twice daily will be administered for 48 weeks to participants meeting entry criteria.; Other Names: Lopinavir/ritonavir (Kaletra); Maraviroc (Selzentry); Nucleoside sparing regimen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Assess Proportion of Participants With HIV RNA Levels <50 and < 400 Copies/mL.	week 48

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of Participants With HIV RNA < 50 and <400 Copies/ml.	week 24
Assess the Proportion of Participants at Study Termination With VL < 50 Copies/ml.	week 48
Determine the Time to Viral Suppression (VL < 50 Copies/ml).	48 weeks
Determine the Median Change in VL From Baseline to Week 24, to Week 48 and to Study Termination.	week 24, week 48
Assess the Changes in CD4+ T Cell Count.	week 24, 48
Assess Development of HIV Resistance Mutations and in HIV Co-receptor Tropism Changes in Participants Who Develop Virologic Rebound.	week 48

Collaborators and Investigators

• Sponsor: Temple University
• Collaborators: Pfizer; Abbott
• Investigators: Principal Investigator: Mary van den Berg-Wolf, MD, Temple University

Study record dates

Study Major Dates

• Study Start: April 1, 2010
• Primary Completion (Actual): December 1, 2010
• Study Completion (Actual): December 1, 2010

Study Registration Dates

• First Submitted: February 12, 2010
• First Submitted That Met QC Criteria: February 12, 2010
• First Posted (Estimate): February 15, 2010

Study Record Updates

• Last Update Posted (Actual): November 2, 2020
• Last Update Submitted That Met QC Criteria: October 8, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: HIV; Protease Inhibitor; treatment naive; CCR5 Co-receptor Antagonist
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; HIV Fusion Inhibitors; Viral Fusion Protein Inhibitors; CCR5 Receptor Antagonists; Ritonavir; Lopinavir; Maraviroc
• Other Study ID Numbers: Temple IRB 12848