Clinical trial NCT00917813: A Study of Anti-HIV Monoclonal Antibody KD-247
Official title: A Study of the Safety, Tolerability, and Pharmacokinetics of KD-247, a Humanized Monoclonal Antibody That Recognizes the Principal Neutralizing Determinant of HIV-1, in Asymptomatic HIV-1 Seropositive Individuals Who Are Not Receiving Concurrent Antiretroviral Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV Infections
Keywords: HIV
monoclonal antibody
KD-247
treatment naive
Lead sponsor: The Chemo-Sero-Therapeutic Research Institute
Sponsor class: INDUSTRY
First posted: 2009-06-10
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety and tolerability of 3 infusions of KD-247 over 2 weeks in HIV-1 seropositive individuals; to determine the pharmacokinetic parameters of KD-247 when administered as above; and to assess the effect of KD-247 infusions on plasma HIV-1 ribonucleic acid (RNA) load and on CD4+ T cell counts.

Detailed description: A minimum of 6 active subjects and 3 placebo subjects for each dose cohort will complete 2 weeks of infusions. A maximum of 27 total subjects will be dosed with KD-247 and up to 9 total will receive placebo. Per cohort subjects randomized to active treatment will receive iv infusions of KD 247 over 2 hours at each dosing visit. Subjects randomized to placebo will receive 2-hour iv infusions of saline solution at each dosing visit. Following the first infusion of KD-247 (or placebo) for each subject in the study, there will be a 24-hour in-patient observation period before the next subject can be randomized within the study. Dose escalation will proceed only after safety data through Day 18 for all subjects in the lower-dose cohort is reviewed.

Eligibility criteria: Inclusion Criteria:

1. Have HIV-1 infection confirmed by enzyme immunoassay (EIA) and immunoblot.
2. Are male or female subjects, age 18-64 years.
3. Demonstrate an HIV-1 RNA copy number between 1000 and 100,000 copies/mL on 2 measurements at least 2 weeks apart. Measurements taken during screening and/or on a prior non-study related medical visit within 3 to 6 weeks of Study Day 1 may be considered.
4. Have CD4+ T cell count \>350 cells/mm3 on 2 measurements at least 2 weeks apart. Measurements taken during screening and on one prior non-study medical visit within 3 to 6 weeks of Study Day 1 may be considered.
5. Are treatment naïve or have been off antiretroviral drugs for at least 8 weeks prior to screening.
6. By genotyping, have a sequence of the portion of the HIV envelope gene encoding the principal neutralizing determinant that is consistent with neutralization by KD-247.
7. Weigh 45-120 kg.
8. Have an absolute neutrophil count \>1000 cells/uL, hemoglobin (Hgb) \>10 g/dL, and platelets \>100,000/uL.
9. Have serum creatinine ≤1.5 mg/dL and alanine transaminase (ALT) \<2.5 times the upper limit of normal.
10. Have a 12-lead electrocardiogram (ECG) without clinically significant abnormalities in the opinion of the investigator.
11. Female subjects must be:

    * Women of non-childbearing potential, defined as either surgically sterile or at least 1-year post-menopausal (no menstrual periods for at least 2 years), or
    * Women of childbearing potential using a highly effective method of contraception, and
    * Women of childbearing potential with a negative serum beta human chorionic gonadotropin (β-HCG) test result at screening and within the 24 hours prior to administration of study drug. A negative urine pregnancy test within the 24 hours prior to administration of study drug will be acceptable, if the serum pregnancy test result is not yet available.
12. For heterosexual male subjects, the subject and the subject's sexual partner must agree to use acceptable methods of contraception during the entire study. Acceptable methods include, but are not limited to, intrauterine device, diaphragm with spermicide, condoms, or abstinence. Oral contraceptives alone are not an acceptable method of birth control.
13. Be willing and able to provide written informed consent.

Exclusion Criteria:

1. Have a history of an acquired immune deficiency syndrome (AIDS)-defining illness or symptomatic HIV disease (i.e., Centers for Disease Control \[CDC\] Class B or C).
2. Have received monoclonal antibody therapy of any kind in the past.
3. Received vaccinations in the past 15 days prior to study entry.
4. Received antihistamines in the 6 weeks prior to study entry.
5. Received non-steroidal anti-inflammatory drugs (NSAIDs) in the 5-6 days prior to skin test.
6. Any history of anaphylaxis, asthma, hypersensitivity reaction to a vaccine or drug infusion, angioedema, or urticaria.
7. Have been treated with any of the following within the 3 months prior to screening: interferons, cytokines, or other immunomodulators; immunoglobulin therapy; systemic corticosteroids; cytotoxic drugs; or ionizing radiation.
8. Have received any investigational agent within 60 days prior to screening.
9. Have any condition which, in the judgment of the investigator, may make the subject's participation in this study too risky; interfere with the collection of or interpretation of PK data; or interfere with the ability of the subject to adhere to and complete the study. Such conditions may include, but are not limited to, cardiovascular, respiratory, gastrointestinal/hepatic, neurologic, and genitourinary disorders.
10. Current alcohol or drug use that, in the judgment of the investigator, will interfere with the subject's ability to comply with the protocol requirements.
11. Have an unexplained positive urine drug screen test for an illicit drug.
12. Have a confirmed positive hepatitis B surface antigen (HBsAg) or antibody to hepatitis C virus (HCV).
13. Have used any prescription within 14 days of study initiation or any over-the-counter (OTC) medication within 3 days of study initiation which, in the judgment of the investigator, would place the individual at risk or interfere with safety, tolerability, or PK data.
14. Have dosages/amounts of drugs that have changed, or are scheduled to use new drugs which, in the judgment of the investigator, would place the individual at risk or interfere with safety, tolerability, or PK data.
15. Have a recent history of major surgery, internal organ biopsy, or major trauma.
16. Females who are pregnant or breast-feeding, or who plan to become pregnant during the study.
17. Have a mental condition rendering the subject unable to understand the nature, scope, and possible consequences of the study.
18. Show a positive reaction to the prick test for KD-247, i.e., ≥3 mm in diameter greater than the negative control.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Beverly Hills
country: United States
facility: Pacific Oaks Medical Group
state: California
city: Burbank
country: United States
facility: Providence Clinical Research
state: California
city: Los Angeles
country: United States
facility: Peter J. Ruane, MD, Inc.
state: California
city: Washington, DC
country: United States
facility: Washington Hospital Center CAR
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: Gary Richmond, MD, PA
state: Florida
city: Orlando
country: United States
facility: Orlando Immunology Center
state: Florida
city: Tamarac
country: United States
facility: Vita Research Solutions, Inc.
state: Florida
city: Atlanta
country: United States
facility: AIDS Research Consortium of Atlanta
state: Georgia
city: Chicago
country: United States
facility: Northstar Medical
state: Illinois
city: Baltimore
country: United States
facility: Institute of Human Virology, University of Maryland
state: Maryland
city: Albany
country: United States
facility: Albany Medical Center
state: New York
city: New York
country: United States
facility: Aaron Diamond AIDS Research Center (ADARC)
state: New York
city: Austin
country: United States
facility: Central Texas Clinical Research
state: Texas
city: Houston
country: United States
facility: Therapeutic Concepts, P.A.
state: Texas
city: Longview
country: United States
facility: DCOL Center for Clinical Research
state: Texas
Study officials:
References: