Kaletra-isentress Treatment Evaluation (KITE)

A Pilot Study to Assess the Safety, Efficacy, and PK Profile of a Switch in Antiretroviral Therapy to a RTI Sparing Combination of LPV/r and RAL in Virologically Suppressed HIV-infected Patients

This study will examine the effectiveness and safety of raltegravir (isentress) when used together with lopinavir/ritonavir (kaletra) for the treatment of HIV-infection. Isentress is a recently, Food and Drug Administration (FDA) approved, HIV medication that has strong effects against the HIV virus. Isentress has been shown in other studies to be safe and well tolerated by HIV patients. Combining this drug with kaletra might enable us to construct a HIV regimen that does not include the more toxic drugs of the nucleoside reverse transcriptase inhibitor class.

Eligible volunteers will undergo the following as part of the study procedure:

1. Sign the study consent form and the HIPAA Authorization Form.
2. Two-third of subjects, the intervention group (selected by random chance) will have their HIV drug treatment changed to kaletra + isentress.
3. The other one-third will continue their usual HIV medications (this will be the control group).
4. Make 9 study related visits to the Ponce clinic during the 48 weeks study period. During these visits, medical information will be collected, and blood tests will be performed.
5. Perform Dexa-scan on two separate occasions at Emory University Hospital Radiology.

Information collected will be used to assess the effectiveness of this treatment in keeping the HIV virus suppressed, how well these two drugs together is tolerated by HIV-infected patients, and the blood levels of these two drugs when given together.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Kaletra + Isentress; Drug: Pre-study antiretroviral regimen

Detailed Description

RATIONALE: Virologic failure and adverse effects associated with current highly active antiretroviral therapy (HAART) warrant continuing search for novel combination therapeutic options. Raltegravir's (RAL) was recently shown to be a potent antiretroviral (ARV) agent with a favorable safety profile. If future reports continue to show positive data on this first-in-class integrase inhibitor, there may be a paradigm shift in the currently recommended first line HAART to regimens that will include integrase inhibitors.

Combining RAL with a drug that has a high genetic barrier to resistance, such as lopinavir/ritonavir (LPV/r) may offer a number of advantages. Both agents are potent and should produce durable virologic suppression. Because their combination is reverse transcriptase inhibitor (RTI) class sparing, its tolerability might be superior. In addition, RAL is not metabolized by the cytochrome P-450 enzymes, therefore, a compatible pharmacokinetic profile is expected with this combination. Pairing LPV/r with RAL in early ARV regimens as is proposed in this application may provide a HAART regimen that is highly efficacious and durable, with less resistance and adverse drug events.

DESIGN: This is single center, open label, randomized, controlled, study designed to assess the tolerability, pharmacokinetic compatibility, and the durability of virologic suppression of the RTI sparing combination therapy of LPV/r + RAL. HIV-infected subjects who are virologically suppressed (HIV-RNA PCR < 50 copies/ml) on current HAART regimen will be randomized in a 2:1 fashion to be switched to a regimen consisting of LPV/r + RAL, intervention arm A (n=40), or to be continued on their pre-study HAART regimen, control arm B (n=20). The primary endpoint will be proportion of subjects with sustained virologic suppression (HIV-1 RNA PCR < 50 copies/ml) through week 48. The immunoreconstitution, toxicity profile, and pharmacokinetic profile of the RAL and LPV/r in this novel combination therapy will be evaluated.

DURATION: 48 weeks after the enrollment of the last participant. Enrollment is expected to take about 10 months.

SAMPLE SIZE: 60 subjects.

POPULATION: HIV-infected individuals (male and female), Age > 18 years, who are virologically suppressed (HIV-RNA PCR < 50 copies/ml) on their current HAART regimen for > 6 months.

REGIMEN: For Arm A= LPV/r 400/100 mg (2 tablets) twice daily + RAL 400 mg (1 tablet) twice daily taken by mouth. For Arm B=Pre-study HAART regimen.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Grady Infectious Diseases Program (Ponce Clinic)

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:

• HIV-1-infected individuals receiving HAART regimen (if on PI-based regimen, must be 1st PI-containing HAART).
• They must have been on and tolerating current HAART regimen for > 6-months.
• Plasma HIV-1 viral load < 50 copies/ml at study entry.
• Men and women age > 18 years (sex is defined as sex at birth).

• Laboratory values obtained within 30 days prior to study entry:

  • Hemoglobin > 9.4 g/dl
  • Creatinine < 2 mg/dl
  • AST (SGOT) < 2 x ULN
  • ALT (SGPT) < 2 x ULN
• Ability and willingness of subject or legal guardian/representative to give written informed consent.
• No CD4 T-cell counts requirement

Exclusion Criteria:

• Subjects with a history of previous intolerance to or virological failure to LPV/r
• Concomitant drugs (including alternative therapies) that may affect PI or RAL plasma concentrations (inducers or inhibitors of the CYP 3A4 or UDP-glucuronosyltransferase iso-enzymes).
• A known history of noncompliance with medications or a known history of noncompliance with scheduled physician and clinic visits.
• Investigational ARV drug.
• Pregnancy/Breast feeding.
• HBV-coinfected patients receiving nucleoside analogue for both HIV and HBV suppression.
• Active drug or alcohol use or dependence which, in the Investigator's opinion, may interfere with adherence to study requirements or endanger subject's health while on the study.
• Serious illness requiring systemic treatment and/or hospitalization within 30 days prior to the screening visit.

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: Kaletra + Isentress	Drug: Kaletra + Isentress; Kaletra 400/100 mg + Isentress 400 mg BID; Other Names: Raltegravir; Lopinavir/ritonavir
Active Comparator: Standard HAART; Pre-study Antiretroviral regimen	Drug: Pre-study antiretroviral regimen; Standard doses of pre-study antiretroviral regimen; Other Names: HAART

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Viral Loads (HIV-1 RNA PCR)	Percentage subjects with undetectable Plasma viral loads	baseline to week 48

Secondary Outcome Measures

Outcome Measure	Time Frame
To Compare Plasma Triglyceride Levels at 48 Weeks Between LPV/r + RAL and Standard HAART Treated Subjects	48 weeks

Collaborators and Investigators

• Sponsor: Emory University
• Collaborators: Merck Sharp & Dohme LLC; Abbott

Publications and helpful links

General Publications

• Ofotokun I, Sheth AN, Sanford SE, Easley KA, Shenvi N, White K, Eaton ME, Del Rio C, Lennox JL. A switch in therapy to a reverse transcriptase inhibitor sparing combination of lopinavir/ritonavir and raltegravir in virologically suppressed HIV-infected patients: a pilot randomized trial to assess efficacy and safety profile: the KITE study. AIDS Res Hum Retroviruses. 2012 Oct;28(10):1196-206. doi: 10.1089/AID.2011.0336. Epub 2012 Apr 20.

Study record dates

Study Major Dates

• Study Start: June 1, 2008
• Primary Completion (Actual): January 1, 2011
• Study Completion (Actual): January 1, 2011

Study Registration Dates

• First Submitted: June 16, 2008
• First Submitted That Met QC Criteria: June 17, 2008
• First Posted (Estimate): June 18, 2008

Study Record Updates

• Last Update Posted (Estimate): December 12, 2014
• Last Update Submitted That Met QC Criteria: November 25, 2014
• Last Verified: November 1, 2014

More Information

Terms related to this study

• Keywords: Treatment Experienced; raltegravir; HAART; lopinavir/ritonavir; HIV/AIDS patients on HAART
• 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; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Integrase Inhibitors; Integrase Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Raltegravir Potassium; Ritonavir; Lopinavir; Anti-Retroviral Agents
• Other Study ID Numbers: IRB00006876; KITE-6876 (Other Identifier: Other)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No