MIDAS: Maraviroc Plus Darunavir/Ritonavir for Treatment-Naïve Patients Infected With R5-tropic HIV-1

• Sponsor: Northwestern University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00993148
• Collaborator: Pfizer (Industry), Tibotec, Inc (Industry)
• Enrollment: 25
• Locations: 5
• Arm: 1
• Duration (Months): 35
• Patients Per Site: 5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The objective of this study is to evaluate the safety and efficacy of a novel combination antiretroviral therapy regimen consisting of maraviroc plus darunavir/ritonavir in treatment-naive patients infected with R5-tropic HIV-1. The hypothesis is that in treatment-naive subjects infected with R5-tropic HIV-1, combination antiretroviral therapy with maraviroc plus darunavir/ritonavir is well tolerated and efficacious.

Condition or Disease	Intervention/Treatment	Phase
HIV-1 Infection; HIV Infections	Drug: maraviroc; Drug: darunavir; Drug: ritonavir	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 25 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Maraviroc Plus Darunavir/Ritonavir Study for Treatment-Naïve Patients Infected With R5-tropic HIV-1 Based on Enhanced Sensitivity Trofile
• Study Start Date: May 1, 2010
• Actual Primary Completion Date: Apr 1, 2013
• Actual Study Completion Date: Apr 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Maraviroc plus darunavir/ritonavir Single arm open label trial of maraviroc 150 mg plus darunavir/ritonavir 800/100 mg once daily for 96 weeks	Drug: maraviroc; 150 mg tab by mouth once daily for 96 weeks; Other Names: Selzentry ; Drug: darunavir; 800 mg tab by mouth once daily for 96 weeks; Other Names: Prezista ; Drug: ritonavir; 100 mg capsule by mouth once daily for 96 weeks; Other Names: norvir

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Plasma HIV-1 RNA >50 [24 weeks]

   Percentage of participants with confirmed plasma HIV-1 RNA > 50 copies/mL

Secondary Outcome Measures

1. Percentage of Participants With Virologic Failure or Off Study Treatment Regimen [24 weeks]

   Percentage of participants with virologic failure (confirmed plasma HIV-1 RNA > 50 copies/mL) or off study treatment regimen (composite end point)

2. Percentage of Participants With Plasma HIV-1 RNA >50 Copies/mL [48 weeks]

   Percentage of participants with confirmed plasma HIV-1 RNA level >50 copies/mL

3. Signs/Symptoms or Laboratory Toxicities of Grade 3 or Higher [96 weeks]

   Signs/symptoms or laboratory toxicities of Grade 3 or higher, or of any grade which led to a permanent change or discontinuation of study treatment regimen

4. Drug Resistance Mutations and Co-receptor Tropism Assessed by Trofile ES [At study entry and at the time of virologic failure]

5. Drug Adherence, Number of Participants With Missed Doses [Week 24]

   Drug adherence, assessed as number of participants with missed doses over four-day recall

6. Trough Concentrations (Ctrough) of Maraviroc [24 hours]

   Average trough concentration (Ctrough) of maraviroc

7. Median CD4 Count Change From Baseline [96 weeks]

   Median changes from baseline in peripheral CD4+ T-cell count

8. Proportion of Participants With Plasma HIV-1 RNA >50 Copies/mL [96 weeks]

   Proportion of participants with confirmed plasma HIV-1 RNA level >50 copies/mL

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• HIV-1 infection, as documented by any licensed HIV test kit and confirmed by Western blot, HIV-1 culture, HIV-1 antigen, plasma HIV-1 RNA, or a second antibody test by a method other than ELISA any time prior to study entry

• Plasma HIV-1 RNA 5, 000 to 500,000 copies/mL obtained within 90 days prior to study entry

• Exclusive R5 tropism based on enhanced sensitivity Trofile assay done within 90 days prior to entry

• CD4 cell count > 100 cells/mm3 within 90 days prior to study entry

• HIV genotype (for RT and protease) performed at any time before study entry (Subjects with single or combination NNRTI or NRTI RAM(s) at screening are permitted)

• ARV drug-naïve, defined as no previous ARV treatment at any time prior to study entry

• Negative result from a hepatitis B surface antigen test performed within 90 days prior to study entry

• Negative result from a hepatitis C antibody test performed within 90 days prior to study entry

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

• ANC >=750/mm3

• Hemoglobin >=10 g/dL

• Platelets >=50,000/mm3

• AST (SGOT), ALT (SGPT), and alkaline phosphatase <=5 x ULN

• Calculated creatinine clearance (CrCl) >=30 mL/min, as estimated by the Cockcroft-Gault equation*

• Negative serum or urine pregnancy test within 48 hours prior to study entry for women with reproductive potential

• If participating in sexual activity that could lead to pregnancy, the study subjects with reproductive potential must use one form of contraceptive while receiving protocol-specified medications and for 60 days after stopping the medications.

• Men and women age >=18 years

• Ability and willingness of subject or legal guardian/representative to provide informed consent

Exclusion Criteria:

• Serious illness requiring systemic treatment and/or hospitalization until candidate either completes therapy or is clinically stable on therapy, in the opinion of the site investigator, for at least 7 days prior to study entry

• Screening HIV genotype obtained any time prior to study entry with any DRV RAM (V11I, V32I, L33F, I47V, I50V, I54L, I54M, T74P, L76V, I84V, and L89V)

• Treatment within 30 days prior to study entry with immune modulators such as systemic steroids, interleukins, interferons, granulocyte colony-stimulating factor (G-CSF), erythropoietin, or any investigational therapy. NOTE: Subjects receiving stable physiologic glucocorticoid doses (defined as prednisone ≤10 mg/day [or equivalent] as a stable or tapering dose) are permitted. Subjects receiving corticosteroids for acute therapy for PCP or asthma exacerbation, or receiving a short course (defined as ≤2 weeks of pharmacologic glucocorticoid therapy) are permitted

• Breast-feeding

• Requirement for any medication that is prohibited with a study medication

• Known allergy/sensitivity to study drugs or their formulations. A history of sulfa allergy is not an exclusion

• Active drug or alcohol use or dependence that could interfere with adherence to study requirements

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Quest Clinical Research	San Francisco	California	United States
2	University of Miami	Miami	Florida	United States
3	Northwestern University	Chicago	Illinois	United States	60611
4	CORECenter	Chicago	Illinois	United States	60612
5	University of Nebraska	Omaha	Nebraska	United States

Sponsors and Collaborators

• Northwestern University
• Pfizer
• Tibotec, Inc

Investigators

• Principal Investigator: Babafemi Taiwo, MD, Northwestern University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Babafemi Taiwo, Associate Professor, Northwestern University
• ClinicalTrials.gov Identifier: NCT00993148
• Other Study ID Numbers: MIDAS
• First Posted: Oct 12, 2009
• Last Update Posted: Sep 5, 2014
• Last Verified: Aug 1, 2014

• Keywords provided by Babafemi Taiwo, Associate Professor, Northwestern University: Treatment naive
• Additional relevant MeSH terms: Infections; Communicable Diseases; Ritonavir; Darunavir; Maraviroc

Study Results

Participant Flow

Arm/Group Title	Maraviroc + Darunavir/Ritonavir
Arm/Group Description	maraviroc 150 mg plus darunavir/ritonavir 800/100 mg once daily
Period Title: Overall Study
STARTED	25
COMPLETED	22
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	Maraviroc + Darunavir/Ritonavir
Arm/Group Description	maraviroc 150 mg plus darunavir/ritonavir 800/100 mg once daily
Overall Participants	25
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	38
Sex: Female, Male (Count of Participants)
Female	3 12%
Male	22 88%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 4%
Not Hispanic or Latino	23 92%
Unknown or Not Reported	1 4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	3 12%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	5 20%
White	15 60%
More than one race	0 0%
Unknown or Not Reported	2 8%
Region of Enrollment (participants) [Number]
United States	25 100%
Median HIV-1 RNA (log 10 copies) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [log 10 copies]	4.62

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Plasma HIV-1 RNA >50
Description	Percentage of participants with confirmed plasma HIV-1 RNA > 50 copies/mL
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Maraviroc + Darunavir/Ritonavir
Arm/Group Description	maraviroc 150 mg plus darunavir/ritonavir 800/100 mg once daily
Measure Participants	24
Number (95% Confidence Interval) [percentage of participants]	12.5 50%

2. Secondary Outcome

Title	Percentage of Participants With Virologic Failure or Off Study Treatment Regimen
Description	Percentage of participants with virologic failure (confirmed plasma HIV-1 RNA > 50 copies/mL) or off study treatment regimen (composite end point)
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Maraviroc + Darunavir/Ritonavir
Arm/Group Description	maraviroc 150 mg plus darunavir/ritonavir 800/100 mg once daily
Measure Participants	24
Number (95% Confidence Interval) [percentage of participants]	12.5 50%

3. Secondary Outcome

Title	Percentage of Participants With Plasma HIV-1 RNA >50 Copies/mL
Description	Percentage of participants with confirmed plasma HIV-1 RNA level >50 copies/mL
Time Frame	48 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Maraviroc + Darunavir/Ritonavir
Arm/Group Description	maraviroc 150 mg plus darunavir/ritonavir 800/100 mg once daily
Measure Participants	24
Number (95% Confidence Interval) [percentage of participants]	8.3 33.2%

4. Secondary Outcome

Title	Signs/Symptoms or Laboratory Toxicities of Grade 3 or Higher
Description	Signs/symptoms or laboratory toxicities of Grade 3 or higher, or of any grade which led to a permanent change or discontinuation of study treatment regimen
Time Frame	96 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Maraviroc + Darunavir/Ritonavir
Arm/Group Description	maraviroc 150 mg plus darunavir/ritonavir 800/100 mg once daily
Measure Participants	24
Number [participants]	1 4%

5. Secondary Outcome

Title	Drug Resistance Mutations and Co-receptor Tropism Assessed by Trofile ES
Time Frame	At study entry and at the time of virologic failure

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Maraviroc + Darunavir/Ritonavir
Arm/Group Description	maraviroc 150 mg plus darunavir/ritonavir 800/100 mg once daily
Measure Participants	24
Number [participants]	0 0%

6. Secondary Outcome

Title	Drug Adherence, Number of Participants With Missed Doses
Description	Drug adherence, assessed as number of participants with missed doses over four-day recall
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Maraviroc + Darunavir/Ritonavir
Arm/Group Description	maraviroc 150 mg plus darunavir/ritonavir 800/100 mg once daily
Measure Participants	24
Number [participants]	0 0%

7. Secondary Outcome

Title	Trough Concentrations (Ctrough) of Maraviroc
Description	Average trough concentration (Ctrough) of maraviroc
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Maraviroc + Darunavir/Ritonavir
Arm/Group Description	maraviroc 150 mg plus darunavir/ritonavir 800/100 mg once daily
Measure Participants	24
Mean (Standard Deviation) [ng/mL]	39.3 (22.8)

8. Secondary Outcome

Title	Median CD4 Count Change From Baseline
Description	Median changes from baseline in peripheral CD4+ T-cell count
Time Frame	96 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Maraviroc + Darunavir/Ritonavir
Arm/Group Description	maraviroc 150 mg plus darunavir/ritonavir 800/100 mg once daily
Measure Participants	24
Median (Inter-Quartile Range) [cells per mm^3]	247

9. Secondary Outcome

Title	Proportion of Participants With Plasma HIV-1 RNA >50 Copies/mL
Description	Proportion of participants with confirmed plasma HIV-1 RNA level >50 copies/mL
Time Frame	96 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Maraviroc + Darunavir/Ritonavir
Arm/Group Description	maraviroc 150 mg plus darunavir/ritonavir 800/100 mg once daily
Measure Participants	20
Number (95% Confidence Interval) [percentage of participants]	10 40%

Adverse Events

Arm/Group Title	Maraviroc + Darunavir/Ritonavir
Arm/Group Description	maraviroc 150 mg plus darunavir/ritonavir 800/100 mg once daily
All Cause Mortality
	Maraviroc + Darunavir/Ritonavir
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Maraviroc + Darunavir/Ritonavir
	Affected / at Risk (%)	# Events
Total	0/25 (0%)
Other (Not Including Serious) Adverse Events
	Maraviroc + Darunavir/Ritonavir
	Affected / at Risk (%)	# Events
Total	0/25 (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.