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NCT01295515

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

Completed Phase 1, PHASE2 Results posted Last updated 23 April 2019
What this trial tests

Phase 1, PHASE2 trial testing Pegylated Interferon Alpha 2b (PEGINTRON) in HIV Infection in 7 participants. Completed in 31 May 2017.

Timeline
11 February 2011
Primary endpoint
31 May 2017
31 May 2017

Quick facts

Lead sponsorNational Cancer Institute (NCI)
PhasePhase 1, PHASE2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment7
Start date11 February 2011
Primary completion31 May 2017
Estimated completion31 May 2017
Sites2 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

National Cancer Institute (NCI)

Who can join

18 and older, any sex, with HIV Infection. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Pre- and Post- Interferon Alpha on Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) Primary · week 4 (post) compared to week 0 (pre)

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.

Patient #1 HIV RNA Pre
GroupValue95% CI
Interferon Treatment670
Patient #1 HIV RNA Post
GroupValue95% CI
Interferon Treatment180
Patient #2 HIV RNA Pre
GroupValue95% CI
Interferon Treatment90
Patient #2 HIV RNA Post
GroupValue95% CI
Interferon Treatment130
Patient #3 HIV RNA Pre
GroupValue95% CI
Interferon Treatment810
Patient #3 HIV RNA Post
GroupValue95% CI
Interferon Treatment420
Patient #4 HIV RNA Pre
GroupValue95% CI
Interferon Treatment450
Patient #4 HIV RNA Post
GroupValue95% CI
Interferon Treatment390
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 Secondary · week 4 (post) and week 0 (pre)

The outcome measure is the fold change in the ratio of HIV RNA to HIV DNA. For the pre and post interferon time point, the level of HIV RNA is divided by the level of HIV DNA and this ratio of the HIV RNA/DNA pre and post interferon is calculated to yield the fold change in HIV RNA/DNA levels. Fold change does not have units.

Patient #1
GroupValue95% CI
Interferon Treatment0.408
Patient #2
GroupValue95% CI
Interferon Treatment1.44
Patient #3
GroupValue95% CI
Interferon Treatment0.684
Patient #4
GroupValue95% CI
Interferon Treatment1.12
Patient #5
GroupValue95% CI
Interferon Treatment2.24
Patient #6
GroupValue95% CI
Interferon Treatment4.37
Patient #7
GroupValue95% CI
Interferon Treatment1.05
Pre-and Post- Plasma Human Immunodeficiency Virus (HIV) Ribonucleic Acid (RNA) in HIV-infected Individuals Secondary · week 4 (post) compared to week 0 (pre)

The outcome measure is copies of HIV RNA per ml of plasma. HIV RNA levels are measured using a polymerase chain reaction method.

Patient #1 Pre
GroupValue95% CI
Interferon Treatment0.7± 0.8
Patient #1 Post
GroupValue95% CI
Interferon Treatment3.8± 1.9
Patient #2 Pre
GroupValue95% CI
Interferon Treatment0.2± 0.4
Patient #2 Post
GroupValue95% CI
Interferon Treatment.02± 0
Patient #3 Pre
GroupValue95% CI
Interferon Treatment3.8± 1.9
Patient #3 Post
GroupValue95% CI
Interferon Treatment0.8± 0.9
Patient #4 Pre
GroupValue95% CI
Interferon Treatment.02± 0
Patient #4 Post
GroupValue95% CI
Interferon Treatment1.5± 1.2
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. Secondary · Date consent signed to date off study, approximately 66 months and 2 days.

Here is the 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 for severity (mild/moderate/severe), expectedness (expected/unexpected), and relatedness to study drug (definitely, probably, possibly, unlikely, or unrelated).

GroupValue95% CI
Interferon Treatment7
Pre- and Post- Interferon Alpha on Human Immunodeficiency Virus Type 1 (HIV-1) Deoxyribonucleic Acid (DNA) Primary · week 4 (post) compared to week 0 (pre)

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.

Patient #1 HIV DNA Pre
GroupValue95% CI
Interferon Treatment1200
Patient #1 HIV DNA Post
GroupValue95% CI
Interferon Treatment790
Patient #2 HIV DNA Pre
GroupValue95% CI
Interferon Treatment150
Patient #2 HIV DNA Post
GroupValue95% CI
Interferon Treatment150
Patient #3 HIV DNA Pre
GroupValue95% CI
Interferon Treatment660
Patient #3 HIV DNA Post
GroupValue95% CI
Interferon Treatment500
Patient #4 HIV DNA Pre
GroupValue95% CI
Interferon Treatment400
Patient #4 HIV DNA Post
GroupValue95% CI
Interferon Treatment310

Adverse events — posted to ClinicalTrials.gov

Time frame: The adverse events were collected from date of consent to date off study, approximately 66 months and 2 days.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Interferon Treatment
Serious: 1/7 (14%)
Deaths: 0/7

Serious adverse events (1 terms)

ReactionSystemInterferon Treatment
Craniocerebral injuryInjury, poisoning and procedural complications
Other adverse events (37 terms — click to expand)

ReactionSystemInterferon Treatment
MyalgiaMusculoskeletal and connective tissue disorders
Neutrophil count decreasedInvestigations
PyrexiaGeneral disorders
ArthralgiaMusculoskeletal and connective tissue disorders
FatigueGeneral disorders
Abdominal painGastrointestinal disorders
Alanine aminotransferase increasedInvestigations
Aspartate aminotransferase increasedInvestigations
DiarrheaGastrointestinal disorders
Dry mouthGastrointestinal disorders
HeadacheNervous system disorders
HyperglycemiaMetabolism and nutrition disorders
HypocalcemiaMetabolism and nutrition disorders
HypokalaemiaMetabolism and nutrition disorders
Injection site reactionInjury, poisoning and procedural complications
NauseaGastrointestinal disorders
Platelet count decreasedInvestigations
VomitingGastrointestinal disorders
White blood cell count decreasedInvestigations
Blood cholesterol increasedInvestigations
Blood pressure increasedVascular disorders
ChillsGeneral disorders
DermatophytosisSkin and subcutaneous tissue disorders
Gastroesophageal reflux diseaseGastrointestinal disorders
Hemoglobin decreasedInvestigations
HyperkalemiaMetabolism and nutrition disorders
HypersensitivityImmune system disorders
Injection site erythemaInjury, poisoning and procedural complications
InjuryInjury, poisoning and procedural complications
InsomniaPsychiatric disorders
Nasal congestionRespiratory, thoracic and mediastinal disorders
Night sweatsSkin and subcutaneous tissue disorders
Oropharyngeal painRespiratory, thoracic and mediastinal disorders
PainGeneral disorders
Productive coughRespiratory, thoracic and mediastinal disorders
Prothrombin time prolongedInvestigations
RhinorrheaRespiratory, thoracic and mediastinal disorders

Most-reported serious reactions: Craniocerebral injury.

Data from ClinicalTrials.gov NCT01295515 adverse events section.

Sponsor's own description

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).

Publications & conference data

5 peer-reviewed publications reference this trial (live from Europe PMC):

  1. HIV-1 transcription and latency: an update.
    Van Lint C, Bouchat S, Marcello A. · · 2013 · cited 256× · PMID 23803414 · DOI 10.1186/1742-4690-10-67
  2. Barriers to a cure for HIV: new ways to target and eradicate HIV-1 reservoirs.
    Katlama C, Deeks SG, Autran B, Martinez-Picado J, et al · · 2013 · cited 228× · PMID 23541541 · DOI 10.1016/s0140-6736(13)60104-x
  3. HIV-1 Eradication: Early Trials (and Tribulations).
    Spivak AM, Planelles V. · · 2016 · cited 93× · PMID 26691297 · DOI 10.1016/j.molmed.2015.11.004
  4. Interferon-α Subtypes in an Ex Vivo Model of Acute HIV-1 Infection: Expression, Potency and Effector Mechanisms.
    Harper MS, Guo K, Gibbert K, Lee EJ, et al · · 2015 · cited 88× · PMID 26529416 · DOI 10.1371/journal.ppat.1005254
  5. Ongoing Clinical Trials of Human Immunodeficiency Virus Latency-Reversing and Immunomodulatory Agents.
    Delagrèverie HM, Delaugerre C, Lewin SR, Deeks SG, et al · · 2016 · cited 68× · PMID 27757411 · DOI 10.1093/ofid/ofw189

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing