Chloroquine for Reducing Immune Activation in HIV- Infected Individuals

NCT00819390 | Completed Phase 2 Results DMC

• 2 other identifiers: ACTG A52581U01AI068636
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 15

Brief Summary

HIV is characterized by frequent immune system activation. Early in the course of infection the body establishes an immune activation "set point" related to the amount of HIV in the blood stream. This set point affects the rate of CD4 cell loss. Without CD4 cells, or with very low levels of CD4 cells, the body cannot fight off illness. This is known as immunodeficiency. If left untreated HIV can lead to extreme immunodeficiency and AIDS. Evidence suggests that by decreasing the rate of immune system activation, immune deficiency progression could be prevented. The purpose of this study is to learn how well chloroquine can reduce the level of immune activation and to test the safety and tolerance of chloroquine in people infected with HIV.

Conditions

HIV Infections

Outcome Measures

Primary Outcomes (1)

• Change in Percent CD8 HLA-DR+/CD38+ From Baseline to Week 12

  The baseline percent CD8 HLA-DR+/CD38+ (mean of pre-entry and entry percent CD8 HLA-DR+/CD38+) was subtracted from the mean of week 10 and week 12 percent CD8 HLA-DR+/CD38+.

  At pre-entry, entry, weeks 10 and 12

Secondary Outcomes (28)

• Change in Percent CD8 HLA-DR+/CD38+ From Start to End of the 12-week Chloroquine Treatment Period

  For Arms A and C: Pre-entry, entry, weeks 10 and 12. For Arms B and D: Weeks 10, 12, 22 and 24

• Change in Percent CD8 HLA-DR+/CD38+ From Week 12 to Week 24

  At Weeks 10, 12, 22 and 24

• Change in Percent CD8 HLA-DR+/CD38+ From Baseline to Week 24 in Arm A and Arm C

  At Pre-entry, entry, Weeks 22 and 24

• Change in Total CD4 T Cell Count From Baseline to Week 12

  At pre-entry, entry, weeks 10 and 12

• Number of Participants With Events Grade 3 or Higher

  From start of study treatment to study completion at week 28

Study Arms (4)

A: Chloroquine then Placebo for Off-ART Participants

EXPERIMENTAL

Participants received chloroquine treatment from Day 0 through the Week 12 study visit and then began chloroquine placebo treatment until the Week 24 study visit.

Drug: Chloroquine; Drug: Placebo

B: Placebo then Chloroquine for Off-ART Participants

EXPERIMENTAL

Participants received chloroquine placebo treatment from Day 0 through the Week 12 study visit and then began chloroquine treatment until the Week 24 study visit.

Drug: Chloroquine; Drug: Placebo

C: Chloroquine then Placebo for On-ART Participants

EXPERIMENTAL

Participants received chloroquine treatment from Day 0 through the Week 12 study visit and then began chloroquine placebo treatment until the Week 24 study visit.

Drug: Chloroquine; Drug: Placebo

D: Placebo then Chloroquine for On-ART Participants

EXPERIMENTAL

Participants received chloroquine placebo treatment from Day 0 through the Week 12 study visit and then began chloroquine treatment until the Week 24 study visit.

Drug: Chloroquine; Drug: Placebo

Interventions

Chloroquine DRUG

Taken orally, once daily, at a dose of 250 mg for 12 weeks.

A: Chloroquine then Placebo for Off-ART Participants; B: Placebo then Chloroquine for Off-ART Participants; C: Chloroquine then Placebo for On-ART Participants; D: Placebo then Chloroquine for On-ART Participants

Placebo DRUG

Taken orally, once daily for 12 weeks.

A: Chloroquine then Placebo for Off-ART Participants; B: Placebo then Chloroquine for Off-ART Participants; C: Chloroquine then Placebo for On-ART Participants; D: Placebo then Chloroquine for On-ART Participants

Eligibility Criteria

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

You may qualify if:

• HIV-1 infected
• Certain specified laboratory values obtained within 30 days prior to study entry. More information on this criterion can be found in the study protocol.
• Documentation that pre-entry specimen for the primary immune activation endpoint responses has been obtained
• Female participants of reproductive potential must have a negative pregnancy test performed within 24 hours prior to study entry
• If engaging in sexual activity, female participants must use adequate forms of contraception while receiving study treatment and for 4 weeks after stopping the treatment. More information on this criterion can be found in the study protocol.
• Ability and willingness to provide informed consent
• No antiretroviral therapy (ART) for at least 6 months prior to study entry and not likely to start within the 6 months after study entry
• CD4 cell count greater than or equal to 400 cells/mm3 at screening, obtained within 30 days prior to study entry
• For participants with previous ART use, documentation or recall of nadir CD4 cell count greater than or equal to 200 cells/mm3
• HIV-1 RNA viral load greater than or equal to 1,000 copies/mL obtained within 30 days prior to study entry
• No history of CDC category C AIDS-related opportunistic infections
• Karnofsky performance score greater than or equal to 70 within 30 days prior to study entry
• Receiving ART, defined as a regimen that includes three or more antiretroviral medications, for at least 24 months prior to study entry
• Required documentation that all HIV-1 viral loads (at least two) were below 400 copies/mL. More information on this criterion can be found in the study protocol.
• Screening HIV-1 RNA \<200 copies/mL within 30 days prior to study entry. More information on this criterion can be found in the study protocol.

You may not qualify if:

• Continuous use of certain specified medication for more than 3 days within 30 days prior to study entry. More information on this criterion can be found in the study protocol.
• Use of chloroquine or hydroxychloroquine within 3 months prior to study entry
• Known history of hypersensitivity to 4-aminoquinoline compounds (such as chloroquine or hydroxychloroquine)
• Active drug or alcohol use or dependence that, in the opinion of the investigator would interfere with adherence to study requirements
• Serious illness requiring systemic treatment and/or hospitalization within 30 days prior to study entry
• Renal insufficiency, defined as serum creatinine greater than 1.5 mg/dL, within 30 days prior to study entry
• History of retinal disease (i.e. confirmed retinopathy by ophthalmologic examination)
• History of neoplasm, within 5 years prior to study entry, other than treated in situ carcinoma or basal-cell or localized squamous cell carcinoma of the skin
• Glucose-6-phosphate dehydrogenase (G6PD) deficiency at screening
• History of porphyria
• History of psoriasis
• History of cirrhosis
• History of seizure disorder
• History of tinnitus (ear and/or head noise lasting more than 5 minutes that occurs more often than once per week) or history of sudden hearing loss
• History of myopathy

Sponsors & Collaborators

• Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (15)

Alabama Therapeutics CRS (5801)

Birmingham, Alabama, 35294, United States

Location

Ucsd, Avrc Crs (701)

San Diego, California, 92103, United States

Location

University of Colorado Hospital CRS (6101)

Aurora, Colorado, 80045, United States

Location

Georgetown University CRS (GU CRS) (1008)

Washington D.C., District of Columbia, 20007, United States

Location

Johns Hopkins Adult AIDS CRS (201)

Baltimore, Maryland, 21205, United States

Location

Massachusetts General Hospital ACTG CRS (101)

Boston, Massachusetts, 02114, United States

Location

Washington University CRS (2101)

St Louis, Missouri, 63110, United States

Location

Cornell CRS (7804)

New York, New York, 10011, United States

Location

Unc Aids Crs (3201)

Chapel Hill, North Carolina, 27514, United States

Location

Univ. of Cincinnati CRS (2401)

Cincinnati, Ohio, 45267, United States

Location

Case CRS (2501)

Cleveland, Ohio, 44106, United States

Location

MetroHealth CRS (2503)

Cleveland, Ohio, 44109, United States

Location

Hosp. of the Univ. of Pennsylvania CRS (6201)

Philadelphia, Pennsylvania, 19104, United States

Location

Pittsburgh CRS (1001)

Pittsburgh, Pennsylvania, 15213, United States

Location

Vanderbilt Therapeutics CRS (3652)

Nashville, Tennessee, 37204, United States

Location

Related Publications (4)

• Neely M, Kalyesubula I, Bagenda D, Myers C, Olness K. Effect of chloroquine on human immunodeficiency virus (HIV) vertical transmission. Afr Health Sci. 2003 Aug;3(2):61-7.

  PMID: 12913796 BACKGROUND

• Savarino A, Boelaert JR, Cassone A, Majori G, Cauda R. Effects of chloroquine on viral infections: an old drug against today's diseases? Lancet Infect Dis. 2003 Nov;3(11):722-7. doi: 10.1016/s1473-3099(03)00806-5.

  PMID: 14592603 BACKGROUND

• Semrau K, Kuhn L, Kasonde P, Sinkala M, Kankasa C, Shutes E, Vwalika C, Ghosh M, Aldrovandi G, Thea DM. Impact of chloroquine on viral load in breast milk. Trop Med Int Health. 2006 Jun;11(6):800-3. doi: 10.1111/j.1365-3156.2006.01645.x.

  PMID: 16772000 BACKGROUND

• Jacobson JM, Bosinger SE, Kang M, Belaunzaran-Zamudio P, Matining RM, Wilson CC, Flexner C, Clagett B, Plants J, Read S, Purdue L, Myers L, Boone L, Tebas P, Kumar P, Clifford D, Douek D, Silvestri G, Landay AL, Lederman MM. The Effect of Chloroquine on Immune Activation and Interferon Signatures Associated with HIV-1. AIDS Res Hum Retroviruses. 2016 Jul;32(7):636-47. doi: 10.1089/AID.2015.0336. Epub 2016 Apr 19.

  PMID: 26935044 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

Chloroquine

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)

Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

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

ACTGCT.Gov@s-3.com

(301) 628-3313

Study Officials

• Jeffrey M Jacobson, MD

  Drexel University College of Medicine

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 8, 2009
• First Posted: January 9, 2009
• Study Start: March 1, 2009
• Primary Completion: February 1, 2013
• Study Completion: May 1, 2013
• Last Updated: October 13, 2014
• Results First Posted: September 5, 2014

Record last verified: 2014-10

Locations

US (15)