Switch to Maraviroc + Integrase Inhibitor

• Sponsor: University of Maryland, Baltimore (Other)
• Overall Status: Completed
• CT.gov ID: NCT01896921
• Collaborator: (none)
• Enrollment: 7
• Location: 1
• Arm: 1
• Actual Duration (Months): 63
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This clinical study proposes to evaluate the combination of maraviroc with an integrase strand transfer inhibitor (either raltegravir or dolutegravir) in antiretroviral-experienced patients to document the efficacy, safety, and tolerability of this combination in order to provide clinicians with a treatment regimen that minimizes the risk of metabolic complications by avoidance of NRTI/NNRTIs and PIs. The development of an alternative ART regimen which lessens the risk of metabolic complications could improve long-term adherence and reduce the risk of certain co-morbidities associated with long-term ART use. If this new combination is found to be as efficacious as the standard regimen with enhanced tolerability and improved metabolic effects, there is great potential for altering the current practice of HIV medicine.

Condition or Disease	Intervention/Treatment	Phase
HIV	Drug: Switch to Maraviroc + Raltegravir or Dolutegravir	Phase 3

Detailed Description

Description of the study design:

The study will enroll 30 HIV-infected patients on a stable ART regimen with a suppressed HIV RNA < 50 copies/ml for at least one year. Patients will be switched to the experimental regimen (maraviroc 300 mg twice a day plus either raltegravir 400 mg twice a day or dolutegravir 50 mg once a-day) and followed for 96 weeks. The decision to use raltegravir or dolutegravir will be left to investigator/subject preference, as the two integrate inhibitors are largely interchangeable aside from twice daily (raltegravir) vs. daily (dolutegravir) dosing.

Primary endpoint:

• The primary endpoint is the proportion of patients virologically suppressed (HIV RNA < 50 copies/ml) at 48 weeks.

Definitions:

• Virologic suppression is an HIV RNA < 50 copies/ml.

• Virologic failure is an HIV RNA ≥ 50 copies/ml confirmed on 2 separate occasions, separated by > 1 week after viral suppression.

Secondary endpoints:

• The percent change in total cholesterol, LDL, and HDL at 48 and 96 weeks.

• The number of adverse events.

• The proportion of patients who are virologically suppressed (HIV RNA < 50 copies/ml) at 96 weeks.

Exploratory endpoints:

• Telomerase activity and telomere length measured at baseline and 24, 48, and 96 weeks.

Study Design

• Study Type: Interventional
• Actual Enrollment: 7 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Switch to Maraviroc and Integrase Strand Transfer Inhibitor Combination Therapy (a Triple Class-Sparing Regimen) for the Treatment of HIV-1-Infected Patients on Suppressive Antiretroviral Regimens
• Actual Study Start Date: Sep 1, 2013
• Actual Primary Completion Date: Dec 1, 2018
• Actual Study Completion Date: Dec 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Maraviroc + Raltegravir or Dolutegravir Maraviroc 300 mg tablet twice a day plus Raltegravir 400 mg tablet twice a day or Dolutegravir 50 mg tablet once a day for 48 weeks	Drug: Switch to Maraviroc + Raltegravir or Dolutegravir; Change HIV-infected patients on stable, suppressed ART regimens for at least 1 year to experimental regimen of Maraviroc + Raltegravir or Dolutegravir for 48 weeks

Outcome Measures

Primary Outcome Measures

1. Number of Patients Virologically Suppressed (HIV RNA <50 Copies/ml) at 48 Weeks. [48 weeks]

   Number of patients virologically suppressed (HIV RNA <50 copies/ml) at 48 weeks.

Secondary Outcome Measures

1. Number of Participants With Adverse Events [96 weeks]

   Number of participants with adverse events

2. Number of Patients Who Are Virologically Suppressed (HIV RNA < 50 Copies/ml) [96 weeks]

   Number of patients who are virologically suppressed (HIV RNA < 50 copies/ml)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• HIV-1 infection

• Age between 18 and 75 years

• CD4 count nadir ≥ 250 cells/mm3

• HIV RNA ≤ 50 copies/ml for ≥ 12 months while taking any ART regimen

o One virologic blip ≤ 400 copies/ml permissible within the 12 months

• CCR5 tropic virus as defined by:

• trofile/tropism testing if available, OR

• DNA trofile if no trofile/tropism test available and CD4 nadir 250-499 cells/mm3, OR

• CD4 nadir ≥ 500 cells/mm3

Exclusion Criteria:

• Age < 18 or > 75 years

• CD4 count nadir < 250 cells/mm3

• Dual/mixed or X4 tropic virus if tested prior to viral suppression or if performed by DNA trofile testing at any time

• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2.5 times the upper limits of normal

• Women who:

• are currently pregnant or breastfeeding

• are of child-bearing age and do not agree to remain abstinent or use (or have their partner use) an acceptable method of birth control throughout the study. Acceptable method of birth control is defined as intrauterine device (IUD), diaphragm with spermicide, contraceptive sponge, condom, vasectomy.

• History of any malignancy except non-melanoma skin cancer

• Concomitant use of drugs known to impact or be impacted in terms of pharmacokinetics or drug-drug interactions with either raltegravir or maraviroc. This includes:

• Inducers of UGT1A1 (such as rifampin, phenytoin, phenobarbital rifabutin, St. John's wort)

• CYP3A inhibitors (such as ketoconazole, itraconazole, clarithromycin, nefazodone, and telithromycin)

• CYP3A inducers (such as rifampin, carbamazepine, phenobarbital and phenytoin)

• Subject requires or is anticipated to require any of the prohibited medications noted in the protocol

• Enrollment in an experimental protocol having received investigational agents (antiretroviral or non-antiretroviral) within 30 days of study enrollment

• Chronic active hepatitis B infection as defined by presence of HBsAg

• Subject has a history or current evidence of any condition, therapy, laboratory abnormality or other circumstance that might interfere with the patient's participation for the full duration of the study, such that it is not in the best interest of the patient to participate.

• Subject is unlikely to adhere to the study procedures, keep appointments, or is planning to relocate during the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Maryland, Institute of Human Virology	Baltimore	Maryland	United States	21201

Sponsors and Collaborators

• University of Maryland, Baltimore

Investigators

• Principal Investigator: David J Riedel, MD, University of Maryland, College Park

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - May 26, 2014

More Information

Publications

None provided.

• Responsible Party: David Riedel, Assistant Professor, University of Maryland, Baltimore
• ClinicalTrials.gov Identifier: NCT01896921
• Other Study ID Numbers: HP-00056162
• First Posted: Jul 11, 2013
• Last Update Posted: Oct 20, 2021
• Last Verified: Oct 1, 2021

• Keywords provided by David Riedel, Assistant Professor, University of Maryland, Baltimore: HIV
• Additional relevant MeSH terms: Raltegravir Potassium; Maraviroc; Dolutegravir

Study Results

Participant Flow

Arm/Group Title	Maraviroc + Raltegravir or Dolutegravir
Arm/Group Description	Maraviroc 300 mg tablet twice a day plus Raltegravir 400 mg tablet twice a day or Dolutegravir 50 mg tablet once a day for 48 weeks Switch to Maraviroc + Raltegravir or Dolutegravir: Change HIV-infected patients on stable, suppressed ART regimens for at least 1 year to experimental regimen of Maraviroc + Raltegravir or Dolutegravir for 48 weeks
Period Title: Overall Study
STARTED	7
COMPLETED	5
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Maraviroc + Raltegravir or Dolutegravir
Arm/Group Description	Maraviroc 300 mg tablet twice a day plus Raltegravir 400 mg tablet twice a day or Dolutegravir 50 mg tablet once a day for 48 weeks Switch to Maraviroc + Raltegravir or Dolutegravir: Change HIV-infected patients on stable, suppressed ART regimens for at least 1 year to experimental regimen of Maraviroc + Raltegravir or Dolutegravir for 48 weeks
Overall Participants	7
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	6 85.7%
>=65 years	1 14.3%
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	58
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	7 100%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	6 85.7%
White	1 14.3%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	7 100%

Outcome Measures

1. Primary Outcome

Title	Number of Patients Virologically Suppressed (HIV RNA <50 Copies/ml) at 48 Weeks.
Description	Number of patients virologically suppressed (HIV RNA <50 copies/ml) at 48 weeks.
Time Frame	48 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Maraviroc + Raltegravir or Dolutegravir
Arm/Group Description	Maraviroc 300 mg tablet twice a day plus Raltegravir 400 mg tablet twice a day or Dolutegravir 50 mg tablet once a day for 48 weeks Switch to Maraviroc + Raltegravir or Dolutegravir: Change HIV-infected patients on stable, suppressed ART regimens for at least 1 year to experimental regimen of Maraviroc + Raltegravir or Dolutegravir for 48 weeks
Measure Participants	7
Count of Participants [Participants]	5 71.4%

2. Secondary Outcome

Title	Number of Participants With Adverse Events
Description	Number of participants with adverse events
Time Frame	96 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Maraviroc + Raltegravir or Dolutegravir
Arm/Group Description	Maraviroc 300 mg tablet twice a day plus Raltegravir 400 mg tablet twice a day or Dolutegravir 50 mg tablet once a day for 48 weeks Switch to Maraviroc + Raltegravir or Dolutegravir: Change HIV-infected patients on stable, suppressed ART regimens for at least 1 year to experimental regimen of Maraviroc + Raltegravir or Dolutegravir for 48 weeks
Measure Participants	7
Count of Participants [Participants]	3 42.9%

3. Secondary Outcome

Title	Number of Patients Who Are Virologically Suppressed (HIV RNA < 50 Copies/ml)
Description	Number of patients who are virologically suppressed (HIV RNA < 50 copies/ml)
Time Frame	96 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Maraviroc + Raltegravir or Dolutegravir
Arm/Group Description	Maraviroc 300 mg tablet twice a day plus Raltegravir 400 mg tablet twice a day or Dolutegravir 50 mg tablet once a day for 48 weeks Switch to Maraviroc + Raltegravir or Dolutegravir: Change HIV-infected patients on stable, suppressed ART regimens for at least 1 year to experimental regimen of Maraviroc + Raltegravir or Dolutegravir for 48 weeks
Measure Participants	7
Count of Participants [Participants]	4 57.1%

Adverse Events

Time Frame	96 weeks
Arm/Group Title	Maraviroc + Raltegravir or Dolutegravir
Arm/Group Description	Maraviroc 300 mg tablet twice a day plus Raltegravir 400 mg tablet twice a day or Dolutegravir 50 mg tablet once a day for 48 weeks Switch to Maraviroc + Raltegravir or Dolutegravir: Change HIV-infected patients on stable, suppressed ART regimens for at least 1 year to experimental regimen of Maraviroc + Raltegravir or Dolutegravir for 48 weeks
All Cause Mortality
	Maraviroc + Raltegravir or Dolutegravir
	Affected / at Risk (%)	# Events
Total	0/7 (0%)
Serious Adverse Events
	Maraviroc + Raltegravir or Dolutegravir
	Affected / at Risk (%)	# Events
Total	3/7 (42.9%)
Cardiac disorders
Chest pain	1/7 (14.3%)	1
Endocrine disorders
Hyperglycemia	1/7 (14.3%)	1
Musculoskeletal and connective tissue disorders
Mechanical fall	1/7 (14.3%)	1
Other (Not Including Serious) Adverse Events
	Maraviroc + Raltegravir or Dolutegravir
	Affected / at Risk (%)	# Events
Total	0/7 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.