Integrase and Maraviroc Intensification in Neurocognitive Dysfunction (InMIND)

NCT02519777 | Completed Phase 4 Results DMC FDA Drug

• 2 other identifiers: A532411909
• Study Type: interventional
• Target: 191
• Locations: 5 countries
• Sites: 30

Brief Summary

People infected with HIV often have cognitive dysfunction even if they are on antiretroviral therapy (ART) and have undetectable viral loads. The study evaluated if the addition of maraviroc (MVC) and dolutegravir (DTG) (which are two antiretroviral \[ARV\] medications) to participants' existing ART regimens improved participants' neurocognitive performance.

Conditions

HIV Infections

Keywords

HIV-Associated Neurocognitive Disorder

Outcome Measures

Primary Outcomes (1)

• Change in Normalized Composite Neurocognitive Test Score at Week 48 From Baseline

  The normalized composite neurocognitive test score (total z-score) was defined as the average of the z-scores from the following tests: Domestic (US-based) and International Participants: * Grooved pegboard dominant * Grooved pegboard non-dominant * Hopkins Verbal Learning Test (HVLT-R) Learning trials * HVLT-R Delayed recall * HVLT-R Delayed recognition * Semantic verbal fluency Domestic only: * Stroop color naming * Stroop word reading * Stroop interference trial * Letter fluency * Trail Making A * Trail Making B * WAIS-III Symbol search * Digit Symbol International only: * Timed Gait * Finger Tapping Dominant * Finger Tapping Non-dominant * Color Trail 1 Z-scores were calculated using a demographically appropriate norming process. Higher z-scores correspond with better neurocognitive performance. Change was calculated as the total z-score at Week 48 minus the total z-score at Baseline.

  Measured at Baseline and Week 48

Secondary Outcomes (16)

• Number of Participants With Treatment Related Adverse Events (AEs)

  Measured from treatment initiation through Week 96

• Change in Normalized Composite Neurocognitive Test Score at Weeks 24, 72, and 96 From Baseline

  Measured at Baseline and Weeks 24, 72, and 96

• Change in Functional Status Scores

  Measured at Baseline and Weeks 24, 48, 72, and 96

• Number of Participants With Plasma HIV-1 RNA Greater Than or Equal to 50 Copies/mL

  Measured at Weeks 24, 48, and 96

• CD4+ T-cell Counts

  Measured at Weeks 24, 48, and 96

Other Outcomes (3)

• Changes in Cell-associated HIV-1 RNA/DNA/2-long Terminal Repeat Sequences (LTR) Circles and Single Copy Assay (SCA)

  Measured at Baseline and Week 48

• Changes in T Cell and Monocyte Activation

  Measured at Baseline and Week 48

• Changes in Residual Viremia

  Measured at Baseline and Week 48

Study Arms (3)

Arm A: Placebo MVC and placebo DTG

PLACEBO COMPARATOR

In addition to their existing ART regimens, participants in Arm A received placebo for MVC and placebo for DTG.

Drug: Placebo for maraviroc (MVC); Drug: Placebo for dolutegravir (DTG)

Arm B: DTG and placebo MVC

EXPERIMENTAL

In addition to their existing ART regimens, participants in Arm B received DTG and placebo for MVC.

Drug: Placebo for maraviroc (MVC); Drug: Dolutegravir (DTG)

Arm C: MVC and DTG

EXPERIMENTAL

In addition to their existing ART regimens, participants in Arm C received MVC and DTG

Drug: Dolutegravir (DTG); Drug: Maraviroc (MVC)

Interventions

Placebo for maraviroc (MVC) DRUG

Administered orally as one 150 mg tablet BID OR two 300 mg tablet BID OR one 300 mg tablet BID depending upon background ARV regimen

Arm A: Placebo MVC and placebo DTG; Arm B: DTG and placebo MVC

Placebo for dolutegravir (DTG) DRUG

Administered orally as one 50 mg tablet BID OR one 50 mg tablet QD depending upon background ARV regimen

Arm A: Placebo MVC and placebo DTG

Dolutegravir (DTG) DRUG

Administered orally as one 50 mg tablet BID OR one 50 mg tablet QD depending upon background ARV regimen

Arm B: DTG and placebo MVC; Arm C: MVC and DTG

Maraviroc (MVC) DRUG

Administered orally as one 150 mg tablet BID OR two 300 mg tablet BID OR one 300 mg tablet BID depending upon background ARV regimen

Arm C: MVC and DTG

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• HIV-1 infection, documented by:
• a licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen or plasma HIV-1 RNA viral load. NOTE: The term "licensed" refers to a United States Food and Drug Administration (FDA)-approved kit, which is required for all IND studies, or for sites located in countries other than the United States, a kit that has been certified or licensed by an oversight body within that country and validated internally. Non-US sites are encouraged to use US FDA-approved methods for IND studies. WHO (World Health Organization) and CDC (Centers for Disease Control and Prevention) guidelines mandate that confirmation of the initial test result must use a test that is different from the one used for the initial assessment. A reactive initial rapid test should be confirmed by either another type of rapid assay or an E/CIA that is based on a different antigen preparation and/or different test principle (eg, indirect versus competitive), or a Western blot or a plasma HIV-1 RNA. OR
• Documentation of HIV diagnosis in the medical record by a healthcare provider.
• On current ART for at least 6 months prior to study entry with no interruption in treatment of greater than or equal to 7 consecutive days. Note: The following ART changes are allowed:
• Tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide fumarate (TAF)/TAF-containing fixed-dose combination regimens
• Ritonavir (RTV) to cobicistat (COBI)/COBI-containing fixed-dose combination regimens
• No plans to change ART while on study. Note: The following planned ART changes are allowed:
• TDF to TAF/TAF-containing fixed-dose combination regimens
• RTV to COBI/COBI-containing fixed-dose combination regimens
• HIV-1 plasma RNA less than 50 copies/mL obtained within 90 days prior to study entry by any FDA-approved assay at any United States laboratory that has a Clinical Laboratory Improvement Amendments (CLIA) certification or its equivalent, or at any network-approved non-US laboratory that operates in accordance with Good Clinical Laboratory Practices (GCLP) and participates in appropriate external quality assurance programs.
• No more than one HIV-1 plasma RNA greater than or equal to 50 and less than 200 copies/mL (only one "blip") in the past 6 months with a subsequent HIV-1 plasma RNA less than 50 copies/mL. NOTE: There should be no plasma HIV-1 RNA greater than 200 copies/mL within the 6 months prior to study entry.
• HAND diagnosis (ANI, MND, or HAD) within 60 days prior to study entry. HAND is defined as at least mild impairment on neurocognitive testing (more than one standard deviation below appropriate normative data in two domains of functioning) and no severely confounding factors.
• Screening laboratory values obtained within 60 days prior to study entry by any US laboratory that has a CLIA certification or its equivalent, or at any network-approved non-US laboratory that operates in accordance with GCLP and participates in appropriate external quality assurance programs:
• Absolute neutrophil count (ANC) greater than or equal to 500/mm\^3
• Hemoglobin greater than or equal to 7.5 g/dL

You may not qualify if:

• Current or past medical condition(s) that in the opinion of the investigator prevents attribution of the cause of cognitive impairment to HIV. For example:
• Major depressive disorder with psychotic features
• Traumatic Brain Injury (TBI) with a clear impact on activities of daily living
• Developmental delay, intellectual deficit, and/or severe educational disability resulting in some dependence for activities of daily living
• Ongoing substance use disorder with significant impact on activities of daily living. Difficult or impossible to determine whether cognitive or functional decline is due to substance use or HIV, or both
• Evidence of intoxication or withdrawal during the screening evaluation
• Central nervous system (CNS) infections or opportunistic conditions: brain abscess (bacterial, mycobacterial, fungal or Toxoplasma), meningitis with persistent neurologic impairment, primary CNS lymphoma, progressive multifocal leukoencephalopathy (PML), or another structural brain lesion with neurological sequelae
• Other CNS conditions: non-opportunistic primary or metastatic brain tumors, uncontrolled seizure disorder, progressive multiple sclerosis, stroke with neurological sequelae, or dementia due to causes other than HIV (eg, Alzheimer's disease)
• Constitutional illness (eg, persistent unexplained fever, diarrhea, significant weight loss, disabling weakness) within 30 days of screening
• Known untreated B12 deficiency or malnutrition (body mass index \[BMI\] less than 18) at screening
• Evidence of current hepatitis C virus infection (HCV) (ie, HCV antibody \[Ab\] positive within 90 days prior to study entry unless also shown to be plasma HCV RNA negative within the same time period)
• Unstable and advanced liver disease (as defined by the presence of at least one of the following: ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice)
• Prior or current use of any CCR5 antagonist (such as MVC and cenicriviroc \[CVC\]) and integrase inhibitor (such as RAL, DTG, and elvitegravir \[EVG\])
• Current use of any medication, including antiretrovirals, prohibited in the study (refer to the A5324 protocol-specific web page \[PSWP\] for the prohibited medications)
• Breastfeeding

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (30)

UCLA CARE Center CRS

Los Angeles, California, 90035, United States

Location

UCSD Antiviral Research Center CRS

San Diego, California, 92103, United States

Location

Harbor-UCLA CRS

Torrance, California, 90502, United States

Location

Whitman-Walker Health CRS

Washington D.C., District of Columbia, 20005, United States

Location

Northwestern University CRS

Chicago, Illinois, 60611, United States

Location

Johns Hopkins University CRS

Baltimore, Maryland, 21205, United States

Location

Washington University Therapeutics (WT) CRS

St Louis, Missouri, 63110-1010, United States

Location

New Jersey Medical School Clinical Research Center CRS

Newark, New Jersey, 07103, United States

Location

Weill Cornell Chelsea CRS

New York, New York, 10010, United States

Location

Weill Cornell Uptown CRS

New York, New York, 10065, United States

Location

University of Rochester Adult HIV Therapeutic Strategies Network CRS

Rochester, New York, 14642, United States

Location

Chapel Hill CRS

Chapel Hill, North Carolina, 27599, United States

Location

Greensboro CRS

Greensboro, North Carolina, 27401, United States

Location

Cincinnati Clinical Research Site

Cincinnati, Ohio, 45219, United States

Location

Case Clinical Research Site

Cleveland, Ohio, 44106, United States

Location

Ohio State University CRS

Columbus, Ohio, 43210, United States

Location

Penn Therapeutics, CRS

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pittsburgh CRS

Pittsburgh, Pennsylvania, 15213, United States

Location

The Miriam Hospital Clinical Research Site (TMH CRS) CRS

Providence, Rhode Island, 02906, United States

Location

Vanderbilt Therapeutics (VT) CRS

Nashville, Tennessee, 37204, United States

Location

Trinity Health and Wellness Center CRS

Dallas, Texas, 75208, United States

Location

Houston AIDS Research Team CRS

Houston, Texas, 77030, United States

Location

University of Washington AIDS CRS

Seattle, Washington, 98104-9929, United States

Location

Instituto de Pesquisa Clinica Evandro Chagas (IPEC) CRS

Rio de Janeiro, 21040-360, Brazil

Location

Puerto Rico AIDS Clinical Trials Unit CRS

San Juan, 00935, Puerto Rico

Location

Wits Helen Joseph Hospital CRS (Wits HJH CRS)

Johannesburg, Gauteng, 2092, South Africa

Location

Durban International Clinical Research Site CRS

Durban, KwaZulu-Natal, 4052, South Africa

Location

Famcru Crs

Tygerberg, Western Cape, 7505, South Africa

Location

Thai Red Cross AIDS Research Centre (TRC-ARC) CRS

Bangkok, 10330, Thailand

Location

Chiang Mai University HIV Treatment (CMU HIV Treatment) CRS

Chiang Mai, 50200, Thailand

Location

Related Links

• The Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Corrected Version 2.1, July 2017
• Manual for Expedited Reporting of Adverse Events to DAIDS (DAIDS EAE Manual), Version 2.0, January 2010

MeSH Terms

Conditions

HIV Infections

Interventions

Maraviroc; dolutegravir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: ACTG Clinicaltrials.gov Coordinator
• Organization: ACTG Network Coordinating Center, Social and Scientific Systems, a DLH Holdings Company

ACTGCT.gov@fstrf.org

(301) 628-3348

Study Officials

• Kevin Robertson, PhD

  University of North Carolina

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 6, 2015
• First Posted: August 11, 2015
• Study Start: April 21, 2016
• Primary Completion: December 2, 2019
• Study Completion: January 5, 2021
• Last Updated: April 22, 2022
• Results First Posted: March 2, 2022

Record last verified: 2022-04

Locations

ZA (3); TH (2); BR (1); US (23); PR (1)