Interferon Alpha 2b Intensification in HIV-Positive Individuals on Antiretroviral Therapy

NCT01295515 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: 11005711-I-0057
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 2

Brief Summary

Background:

• Antiretroviral therapy (ART) has been able to improve the lifespan of individuals infected with human immunodeficiency virus type 1 (HIV-1), but ART requires continuous treatment that has substantial consequences on quality of life. Recent research is attempting to determine whether this persistent infection stems from a low-level infection where new cells are continually infected with HIV, or from cells that live for a long time after infection. ART is very active against the virus in new cells, but has no effect on long-lived cells that are already infected with HIV-1 at the start of ART. As a result, new strategies may be necessary to reduce or eradicate these 'reservoir' cells.
• Interferon is a natural substance made by the body to combat virus infections, and can be made as an injectable drug known as PEGINTRON. Researchers are interested in determining whether PEGINTRON therapy will also reduce the residual low levels of HIV in patients who are already taking ART. Objectives: \- To evaluate the effectiveness of PEGINTRON injections on HIV levels in participants currently undergoing antiretroviral therapy. Eligibility: \- Individuals at least 18 years of age who have been diagnosed with HIV, are currently undergoing antiretroviral therapy, and have maintained HIV virus blood counts that are not detectable by current commercial tests for at least 12 months before the start of the study. Design:
• This study will involve separate screening and treatment processes.
• Participants will be screened with a physical examination and medical history, including blood and urine samples. The screening analysis to determine study eligibility will take several weeks. Participants will have apheresis to provide sufficient numbers of blood cells for evaluation by the study researchers.
• Eligible participants will begin a 4-week course of PEGINTRON injections using the standard dose of PEGINTRON that is approved for treatment of chronic hepatitis C. Participants will have weekly injections and have frequent blood tests to measure HIV virus levels.
• Participants who experience problems in maintaining safe numbers of white blood cells during the study may receive injections of filgrastim to increase their white blood cell count.
• After the 4 weeks of treatment, participants will return for additional blood tests on study days 28, 35, 42, 49, 56, and 84, and Weeks 16, 24, 36, and 48 (i.e., through the end of 1 year after the start of the study).

Conditions

HIV Infection

Keywords

HIV; Replication; Antiretroviral; Interferon; Reservoirs

Outcome Measures

Primary Outcomes (2)

• Pre- and Post- Interferon Alpha on Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA)

  Cell associated HIV nucleic acid levels were measured using a single copy assay, and numbers of cells were quantified using a polymerase chain reaction method that detects RNA.

  week 4 (post) compared to week 0 (pre)

• Pre- and Post- Interferon Alpha on Human Immunodeficiency Virus Type 1 (HIV-1) Deoxyribonucleic Acid (DNA)

  Cell associated HIV nucleic acid levels were measured using a single copy assay, and numbers of cells were quantified using a polymerase chain reaction method that detects C-C chemokine receptor type 5 (CCR5) DNA.

  week 4 (post) compared to week 0 (pre)

Secondary Outcomes (3)

• Fold Change in Ribonucleic Acid (RNA) and Deoxyribonucleic Acid (DNA) in Human Immunodeficiency Virus Type 1 (HIV-1) Genetic Variation in Individuals Undergoing Interferon Therapy

  week 4 (post) and week 0 (pre)

• Pre-and Post- Plasma Human Immunodeficiency Virus (HIV) Ribonucleic Acid (RNA) in HIV-infected Individuals

  week 4 (post) compared to week 0 (pre)

• Count of Participants With Serious and Non-serious Adverse Events Assessed by the Division of Acquired Immune Deficiency Syndrome (AIDS) Table for Grading Adult Adverse Events.

  Date consent signed to date off study, approximately 66 months and 2 days.

Study Arms (1)

Interferon treatment

EXPERIMENTAL

Interferon treatment The intervention is administration of Pegylated Interferon Alpha 2b (PEGINTRON) weekly for four weeks

Drug: Pegylated Interferon Alpha 2b (PEGINTRON)

Interventions

Pegylated Interferon Alpha 2b (PEGINTRON) DRUG

pegylated preparation of interferon alpha 2b

Also known as: PEGINTRON

Interferon treatment

Eligibility Criteria

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

You may qualify if:

• Age greater than or equal to 18 years.
• Documentation of human immunodeficiency virus type 1 (HIV-1) infection by any licensed enzyme-linked immunosorbent assay (ELISA) test and confirmed by a Western Blot.
• Receiving a Department of Health and Human Services (DHHS)-approved antiretroviral (ARV) regimen.
• Level of cell-associated HIV ribonucleic acid (RNA) greater than or equal to 5 copies/million peripheral blood mononuclear cells (PBMC) done at screening visit 1.
• HIV-1 RNA levels less than detectable by current commercial means (e.g., Roche Amplicor, b-deoxyribonycleic acid (DNA) test) for a minimum of 12 months prior to screening at all time points, and with at least 2 measurements in this 12 month window.
• Cluster of differentiation 4 (CD4) greater than or equal to 300 cells/mm(3) at pre-entry visit within 14 days prior to enrollment.
• Ability to sign informed consent and willingness to comply with the study requirements and clinic policies.
• No evidence of viral hepatitis co-infection as assessed by Hepatitis C antibody, HCV RNA, and hepatitis B surface antigen; determinations at pre-entry visit within 28 days prior to enrollment.
• No history of or evidence of autoimmune hepatitis or other autoimmune disorders at screening, or Antinuclear antibody (ANA \> 3 times upper limit of normal.
• Laboratory values at pre-entry visit within 14 days prior to enrollment:
• Alkaline phosphatase \<2.0 times upper limit of normal
• Alanine transaminase (ALT) \<2.0 times upper limit of normal
• Total bilirubin \< 2.5 mg/dL (\< 40 mg/dL if on Atazanavir)
• Creatinine clearance greater than or equal to 60 mL/min as estimated by the Cockcroft-Gault equation
• Neutrophil count greater than or equal 1500 cells/mm(3)

You may not qualify if:

• A volunteer will be ineligible to participate in this study if any of the following criteria are met:
• History of neoplastic disease requiring cytotoxic therapy including hydroxyurea.
• Use of long-term systemic corticosteroids, immunosuppressive agents, or cytotoxic agents within 60 days prior to enrollment.
• Any vaccination within 30 days prior to enrollment. Individuals interested in participating who require vaccination will delay screening until 30 day period is completed.
• Any febrile illness (\>38 degrees C) in the 3 weeks prior to enrollment or any acute therapy for a serious infection completed within 30 days prior to enrollment.
• Current pregnancy or lactation, history of pregnancy in the last 4 months.
• Preexisting autoimmune disorders including inflammatory bowel diseases, psoriasis, idiopathic thrombocytopenic purpura, lupus erythematous, autoimmune hemolytic anemia, scleroderma, severe psoriasis, rheumatoid arthritis, and optic neuritis.
• History of severe retinopathy or evidence of severe retinopathy judged by pre-entry ophthalmologic examination.
• Known allergy/sensitivity to study drug or its formulation.
• History of seizure disorders or current anticonvulsant use.
• Any history of medical conditions associated with chronic liver disease (genetic hemochromatosis, alcoholic liver disease, toxin exposures, and autoimmune hepatitis) or documented cirrhosis due to any cause.
• History of pulmonary disease associated with functional limitation.
• Documented history of thyroid disease.
• Active drug or alcohol use or dependence, which in the opinion of the investigator, would interfere with complying with the study requirements.
• Known hypersensitivity to Escherichia coli-derived products such as filgrastim.

Sponsors & Collaborators

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

Study Sites (2)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15261, United States

Location

Related Publications (4)

• Palmer S, Maldarelli F, Wiegand A, Bernstein B, Hanna GJ, Brun SC, Kempf DJ, Mellors JW, Coffin JM, King MS. Low-level viremia persists for at least 7 years in patients on suppressive antiretroviral therapy. Proc Natl Acad Sci U S A. 2008 Mar 11;105(10):3879-84. doi: 10.1073/pnas.0800050105. Epub 2008 Mar 10.

  PMID: 18332425 BACKGROUND

• Maldarelli F, Palmer S, King MS, Wiegand A, Polis MA, Mican J, Kovacs JA, Davey RT, Rock-Kress D, Dewar R, Liu S, Metcalf JA, Rehm C, Brun SC, Hanna GJ, Kempf DJ, Coffin JM, Mellors JW. ART suppresses plasma HIV-1 RNA to a stable set point predicted by pretherapy viremia. PLoS Pathog. 2007 Apr;3(4):e46. doi: 10.1371/journal.ppat.0030046.

  PMID: 17411338 BACKGROUND

• Dinoso JB, Kim SY, Wiegand AM, Palmer SE, Gange SJ, Cranmer L, O'Shea A, Callender M, Spivak A, Brennan T, Kearney MF, Proschan MA, Mican JM, Rehm CA, Coffin JM, Mellors JW, Siliciano RF, Maldarelli F. Treatment intensification does not reduce residual HIV-1 viremia in patients on highly active antiretroviral therapy. Proc Natl Acad Sci U S A. 2009 Jun 9;106(23):9403-8. doi: 10.1073/pnas.0903107106. Epub 2009 May 22.

  PMID: 19470482 BACKGROUND

• Somsouk M, Dunham RM, Cohen M, Albright R, Abdel-Mohsen M, Liegler T, Lifson J, Piatak M, Gorelick R, Huang Y, Wu Y, Hsue PY, Martin JN, Deeks SG, McCune JM, Hunt PW. The immunologic effects of mesalamine in treated HIV-infected individuals with incomplete CD4+ T cell recovery: a randomized crossover trial. PLoS One. 2014 Dec 29;9(12):e116306. doi: 10.1371/journal.pone.0116306. eCollection 2014.

  PMID: 25545673 RESULT

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

HIV Infections

Interventions

peginterferon alfa-2b

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

Results Point of Contact

• Title: Dr. Frank Maldarelli
• Organization: National Cancer Institute

frank_maldarelli@nih.gov

301- 846-5611

Study Officials

• Frank Maldarelli, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 11, 2011
• First Posted: February 14, 2011
• Study Start: February 11, 2011
• Primary Completion: May 31, 2017
• Study Completion: May 31, 2017
• Last Updated: April 23, 2019
• Results First Posted: April 23, 2019

Record last verified: 2019-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)