LDO 101
A Randomized, Dose-Ranging Study of Alferon LDO in Asympotmatic HIV+
Subject
Design:
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 AlferonŽ 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.
Number of Subjects:
The overall number of
subjects who will be enrolled in the study is 60
(20/dose level).
Objectives:
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.
Patient Eligibility:
HIV+ subjects satisfying the
inclusion and the exclusion criteria listed below
will be admitted to the study after the nature and
purpose of the protocol have been explained to them
and after they have voluntarily granted written
informed consent to participate.
Inclusion Criteria:
a. 18 years of age or older.
b. HIV-1 plasma RNA > 500
copies/ml (Roche Amplicor assay) or similar assay
within 45 days of starting oral dosing.
c. Karnofsky performance
status of 100
d. 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.
e. Serum creatinine ≤ 1.5
ULN; serum bilirubin ≤ 2.0 ULN.
f. Total WBC ≥ 3000/mm3,
platelet count ≥ 100,000/mm3 and
granulocytes ≥ 1500 mm3.
g. Absolute CD4 cell count greater
than 400 (based on the average CD4 count from the
two pretherapy tests).
h. Hemoglobin > 10.0 g/dl.
i. AST < 4 times upper
normal limit.
j. ALT < 4 times upper
normal limit.
k. Serum Albumin >
2.0 g/dl.
l. Written informed consent.
m. 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.
n. 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
a. Pregnant or nursing women, or women not using an
effective form of contraception.
b. Less than 18 years of age.
c. Active IV drug users.
d. Absolute CD4 ≤ 400 mm3 (based on the
average CD4 counts from the two pretherapy tests).
e. Receipt of any immunosuppressive agent,
chemotherapy, or systemic steroids within 45 days of
study entry.
f. Receipt of any immunomodulator such as BCG
vaccine, isoprinosine, or similar experimental
agents within 45 days of study entry.
g. 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.
h. Unlikely or unable to comply with the
requirements of the protocol.
i. Patients unwilling or unable to give informed
consent.
j. Patients on any other concurrent experimental
medication.
k. 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.
l. 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.
m. Hospitalized subjects, or those with an
active viral infection other than HIV, within 2
weeks of study entry.
n. Transfusion dependent subjects (subjects
requiring > 1 unit of packed RBC per month within
the 3 months prior to study entry).
o. Subjects who are symptomatic of their HIV
infection at study entry.Status:
The study is open to enrollment.
Locations:
Drexel University, Philadelphia, PA
Please contact Hemispherx Biopharma in writing for additional information regarding trial locations and site contacts:
| By Fax: |
215-988-1739 |
| By E-Mail: |
trialinfo@hemispherx.net |
| By Mail: |
Hemispherx Biopharma, Inc.
One Penn Center
1617 JFK Blvd., 6th Floor
Philadelphia, PA 19103 |
|
