A Randomized, Dose-ranging Study of Alferon LDO in Asymptomatic HIV+ Subjects

Tracking Information
First Submitted Date ICMJE	September 16, 2005
First Posted Date ICMJE	September 22, 2005
Last Update Posted Date	September 4, 2013
Study Start Date ICMJE	July 2005
Actual Primary Completion Date	April 2009 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: April 16, 2013)	Gene expression analysis [ Time Frame: Days 0, 2, 5, 11, 12 and 16 ]
Original Primary Outcome Measures ICMJE	Not Provided
Change History	Complete list of historical versions of study NCT00215852 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: April 16, 2013)	CD4 Level [ Time Frame: Days 0, 11 and 16 ]
Original Secondary Outcome Measures ICMJE	Not Provided
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	A Randomized, Dose-ranging Study of Alferon LDO in Asymptomatic HIV+ Subjects
Official Title ICMJE	A Randomized, Dose-Ranging Study of Alferon® LDO [Low Dose Interferon Alfa-n3 (Human Leukocyte Derived)] in Asymptomatic HIV+ Subjects
Brief Summary	To conduct a randomized dose-ranging study to evaluate the safety and activity of orally administered low dose interferon alfa-n3 as an immunomodulator in subjects with asymptomatic HIV-1 infection. The primary endpoints of the study will include an increase or upregulation in genes known to be mediators of interferon response. Secondary endpoints will include the absolute CD4 count and plasma HIV RNA levels.
Detailed Description	This study will be an open-label, randomized outpatient study in HIV infected subjects using a range of doses of Alferon LDO. The first nine (9) patients enrolled will not be randomized. Instead, the first three (3) patients will receive 500 IU, the second three (3) patients will receive 1000 IU, and the final three (3) patients will receive 2000 IU. Once three (3) patients at a given dose level have received at least 8 doses without grade 3 toxicity, patients may be enrolled at the next higher dose level. Following enrollment of the first nine (9) patients, additional patients will be randomized to receive one of the three (3) dose levels of Alferon® LDO. The Alferon LDO (natural interferon alfa-n3) will be in a buffer solution and taken orally once each day for 10 consecutive days at doses equal to 500 IU, 1000 IU, or 2000 IU. Pretherapy baseline evaluations will be performed within the three (3) week period prior to randomization. Drug will be dispensed for a ten day treatment period, during which time any clinical symptoms and adverse events will be evaluated. Laboratory samples (2.5 ml blood) for microarray analysis evaluations will be made twice during baseline and 12-14 hours following doses 1, 4, and 10 on study days 2, 5, and 11, respectively.
Study Type ICMJE	Interventional
Study Phase	Phase 2
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	HIV Infections
Intervention ICMJE	Drug: Alferon LDO; 500 IU, taken orally each evening, for 10 consecutive days while holding in the mouth for at least 2 minutes prior to swallowing, for 10 daysday 5 of each 28 day cycle.
Study Arms	Active Comparator: 1 500 IU Intervention: Drug: Alferon LDO; Active Comparator: 2 1000 IU Intervention: Drug: Alferon LDO; Active Comparator: 3 2000 IU Intervention: Drug: Alferon LDO
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Terminated
Actual Enrollment ICMJE; (submitted: April 16, 2013)	17
Original Enrollment ICMJE; (submitted: September 16, 2005)	60
Actual Study Completion Date	April 2009
Actual Primary Completion Date	April 2009 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: 18 years of age or older.; HIV-1 plasma RNA > 500 copies/ml (Roche Amplicor assay) or similar assay within 45 days of starting oral dosing.; Karnofsky performance status of 100; Subjects must be asymptomatic with regard to HIV related clinical symptoms including the following opportunistic infections: Oral candidiasis (thrush), cutaneous herpes simplex, fever, diarrhea, weight loss ≥ 10% of body weight, seborrheic dermatitis, chronic mucocutaneous fungal infections or Kaposi's sarcoma. Subjects with a history of AIDS are not eligible.; Serum creatinine ≤ 1.5 ULN; serum bilirubin ≤ 2.0 ULN.; Total WBC ≥ 3000/mm3, platelet count ≥ 100,000/mm3 and granulocytes ≥ 1500 mm3.; Absolute CD4 cell count greater than 400 (based on the average CD4 count from the two pretherapy tests).; Hemoglobin > 10.0 g/dl.; AST < 4 times upper normal limit.; ALT < 4 times upper normal limit.; Serum Albumin > 2.0 g/dl.; Written informed consent.; Females must either be of non-child bearing potential, or utilize an effective form of contraception and have a negative pregnancy test within 14 days of entry.; For those subjects who are on antiretroviral therapy, they must have been on a stable dose schedule for at least 90 days prior to study entry and must continue on the same schedule during the treatment phase of this study. Exclusion Criteria: Pregnant or nursing women, or women not using an effective form of contraception.; Less than 18 years of age.; Active IV drug users.; Absolute CD4 ≤ 400 mm3 (based on the average CD4 counts from the two pretherapy tests).; Receipt of any immunosuppressive agent, chemotherapy, or systemic steroids within 45 days of study entry.; Receipt of any immunomodulator such as BCG vaccine, isoprinosine, or similar experimental agents within 45 days of study entry.; Evidence of chronic hepatitis, or other active gastrointestinal, renal, respiratory, endocrine, hematologic, cardiovascular, neurological, or psychiatric disorder that would limit the subject's ability to complete the study period.; Unlikely or unable to comply with the requirements of the protocol.; Patients unwilling or unable to give informed consent.; Patients on any other concurrent experimental medication.; Concurrent, chronic prophylactic use of any systemic antifungal medication (e.g. ketoconazole, fluconazole, clotrimazole) or of any systemic anti-viral (e.g. acyclovir or ganciclovir) except for antiretroviral therapy.; Patients using any form of interferon therapy during the 6 weeks prior to study entry. If prior interferon therapy has been received, the subject must not have known development of antibodies to interferon.; Hospitalized subjects, or those with an active viral infection other than HIV, within 2 weeks of study entry.; Transfusion dependent subjects (subjects requiring > 1 unit of packed RBC per month within the 3 months prior to study entry).; Subjects who are symptomatic of their HIV infection at study entry.
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years and older (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT00215852
Other Study ID Numbers ICMJE	LDO-101
Has Data Monitoring Committee	No
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Hemispherx Biopharma
Study Sponsor ICMJE	Hemispherx Biopharma
Collaborators ICMJE	Not Provided
Investigators ICMJE	Study Director: David R Strayer, MD Hemispherx Biopharma
PRS Account	Hemispherx Biopharma
Verification Date	August 2013
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP