Succinylated Human Serum Albumin (Suc-HSA) for HIV-1 Infection

A Phase 1 & 2, Randomized Open-Label Study to Evaluate the Pharmacokinetics, Safety and Antiretroviral Activity of Succinylated Human Serum Albumin (Suc-HSA) in Treatment Naïve HIV-1 Infected Subjects

The primary objective of the study is to evaluate the pharmacokinetic behavior of Suc-HSA after consecutive daily intravenous (i.v.) doses. The secondary objectives are to evaluate the safety and tolerability and the antiretroviral and immunological effects of consecutive daily i.v. doses of Suc-HSA.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: succinylated human serum albumin

Detailed Description

This is a single centre, single arm study. Subjects will receive 5 consecutive daily doses of Suc-HSA at a dose of 10 mg/kg on days 0, 1, 2, 3 and 4 on the Special Investigation Unit (SIU), with a safety follow up on the SIU for 4 hours on day 1 and 2 hours on the next days. There will be follow-up visits on week 1, 2, 4 and 12. Standard safety parameters (physical examination, clinical symptoms, laboratory hematology and biochemistry) will be followed until week 12. Plasma HIV-1 RNA and CD4+/CD8+ cell counts will be assessed at every visit. Plasma drug levels (trough and peak) will be measured from baseline until week 2.

6 patients will be included in this study as described in this protocol amendment.

Eligible subjects are chronic HIV-1 infected patients who have never been treated with antiretroviral treatment and for whom there is no need to start antiretroviral treatment.

Test Product: Suc-HSA, a candidate HIV-1 fusion inhibitor.

Duration of treatment: 5 days

Criteria for evaluation:

• Safety: symptoms, signs at physical examination, standard hematology and chemistry laboratory parameters- Efficacy: changes in plasma HIV-1 RNA and CD4+ T cell count
• Pharmacokinetics: plasma levels of Suc-HSA: Cmin, Cmax and AUC

• Study Type: Interventional
• Enrollment: 6
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • NH
    • Amsterdam, NH, Netherlands, 1105AZ
      • Academic Medical Center, University of Amsterdam

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patient is ≥ 18 years of age;
2. Voluntarily signed informed consent;
3. Patient has a proven HIV-1 infection (with positive antibodies against HIV-1 and a detectable plasma HIV-1 RNA);
4. Patient is HIV-1 treatment naïve;
5. CD4+ T-cell count ≥ 350 x 10^6/L;
6. Plasma HIV-1 RNA level at screening visit of at least 5.000 copies/ml, and not varying more than ± 0.5 log10 copies during the preceding 6 month period;
7. Patient was participant in part 1 of the original Suc-HSA study (protocol no. 2003-002, version 2.4, dated 18 November 2003) and the administration of Suc-HSA occurred more than 8 weeks ago, OR patient was not participant in this study;

8. Patient is one of the following:

   • not heterosexually active, OR
   • a heterosexually active female, agreeing to use an effective method of contraception with her partner (combined oral contraceptive pill; injectable contraceptive; intrauterine contraceptive device (IUCD); consistent use of condoms if using these; physiological or anatomical sterility in herself or her partner) from 14 days prior to the first administration of study medication until 4 months after the last, and willing to undergo urine pregnancy tests prior to the first and last administration, OR
   • a heterosexually active male, agreeing to use an effective method of contraception with his partner from the day of the first administration until 4 months after the last administration.

Exclusion Criteria:

1. History of an AIDS defining event;
2. Use of antiretroviral or immunomodulatory therapy;
3. Any reason to start antiretroviral therapy at the time of enrolment or which is expected to occur during the course of the study at the time of enrolment;
4. Presence of active, replicating hepatitis B and/or C virus co-infection;
5. ASAT and/or ALAT > 3 times upper limit of normal (ULN) (AIDS Clinical Trials Group [ACTG] toxicity scale);
6. Serum creatinine measuring > 1.5 x ULN;
7. Total bilirubin > 2x ULN;
8. Neutropenia (absolute neutrophil count < 1000/mm3);
9. Presence of any clinically significant disease or findings during screening, that in the opinion of the investigator could compromise the safety of the subject;
10. Patient is female and (willing to become) pregnant or breast-feeding;
11. Any other condition which, in the opinion of the investigator, may interfere with the evaluation of the study objectives.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
To evaluate the pharmacokinetic behavior of Suc-HSA after consecutive daily i.v. doses.

Secondary Outcome Measures

Outcome Measure
To evaluate the safety and tolerability and the antiretroviral and immunological effects of consecutive daily i.v. doses of Suc-HSA.

Collaborators and Investigators

• Sponsor: International Antiviral Therapy Evaluation Center
• Collaborators: University Medical Center Groningen; Prothya Biosolutions
• Investigators: Study Chair: Joep MA Lange, MD PhD, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA); Principal Investigator: Jan Prins, MD PhD, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: August 1, 2005
• Study Completion (Actual): June 1, 2006

Study Registration Dates

• First Submitted: August 8, 2005
• First Submitted That Met QC Criteria: August 8, 2005
• First Posted (Estimate): August 9, 2005

Study Record Updates

• Last Update Posted (Estimate): April 24, 2007
• Last Update Submitted That Met QC Criteria: April 23, 2007
• Last Verified: April 1, 2007

More Information

Terms related to this study

• Keywords: HIV-1; Treatment Naive; succinylated human serum albumin
• Additional Relevant MeSH Terms: Infections
• Other Study ID Numbers: 04-IAT-0047