Safety Study of a Dual Anti-HIV Gene Transfer Construct to Treat HIV-1 Infection

• Status: Completed
• Trial end date: 2017-11-01
• Target enrollment: 0
• Participant gender: All

Summary

This is an early phase research study looking at whether an experimental gene transfer, LVsh5/C46 (also known as Cal-1), is safe and if it can protect the immune system from the effects of HIV without the use of antiretroviral drugs.

Cal-1 is an experimental gene transfer agent designed to inhibit HIV infection through 2 active parts:

1. Removing a protein named CCR5 from bone marrow and white blood cells

2. Producing a protein named C46 on bone marrow and white blood cells

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Calimmune, Inc.
• Treatments: Busulfan

Criteria

Inclusion Criteria:

• Prior to any study-related procedures, signed informed consent indicating that they understand the purpose, risks and procedures required for the study and are willing to participate in the study

• Individuals aged 18 to 65 years of age (inclusive) at time of consent

• Documented HIV-1 infection ≥ 6 months prior to Screening 1

• Previous treatment with antiretroviral agents that had a demonstrated suppressive effect (defined as plasma HIV RNA ≤ 50 copies/ml)

• A documented viable ART regimen option, as determined by the Investigator, taking into account prior ART experience and HIV geno/phenotyping analyses

• Not taking antiretroviral therapy for ≥ 6 weeks prior to Screening 1, for one or more of the following reasons:

i) Concerns over short-term or long-term toxicities associated with antiretroviral agents, or ii) Treatment fatigue from the daily regimen of life-long therapy

• Plasma HIV-1 viral RNA ≥ 5,000 copies/mL and ≤ 100,000 copies/ml at Screening 1 and Screening 2

• CD4+ T lymphocyte count ≥ 500 cells/µl at Screening 1 and Screening 2

Exclusion Criteria:

• Abnormal hematology at Screening 1: Absolute neutrophil count (ANC) < 1.5 x 109/L, Platelet count < 100 x 109/L, Hemoglobin < 10 g/dL

• Abnormal biochemistry at Screening 1: Alanine aminotransferase (ALT) > 2.5 x Upper Limit of Normal (ULN), Total bilirubin > 1.5 x ULN, Serum creatinine > 1.5 x ULN

• Detection of any CXCR4-tropic HIV-1 at Screening 1

• Evidence of co-infection with hepatitis B virus, hepatitis C virus, West Nile Virus, or HTLV-1 as detected at Screening 2

• Evidence of active TB infection determined by positive QuantiFERON®-TB Gold/IGRA test result and clinical confirmation at Screening 2

• ART or other antiretroviral therapy within 6 weeks of Screening 1 or any time during the pre-infusion period

• Documented history of CD4+ T lymphocyte count < 250 cells/µl

• Any previous or current AIDS-defining illnesses (CDC Category C), including AIDS-related dementia, with the exception of Kaposi's sarcoma confined to the skin

• History of malignancy or systemic chemotherapy within the last 5 years (i.e., subjects with prior malignancy must be disease-free for 5 years), except curatively-treated basal cell carcinoma, cutaneous squamous cell carcinoma, or cervical or anal intra-epithelial neoplasia

• History of steroid-dependent asthma in the past 5 years

• History of seizure

• Any clinical history of hematologic diseases including leukemia, myelodysplasia, myeloproliferative disease, thromboembolic disease, sickle cell disorder, thrombocytopenia or leukopenia

• Class II-IV heart failure, according to the New York Heart Association classification

• Inadequate venous access for apheresis, as assessed at Screening 1

• Current or planned systemic immunosuppressive or immunomodulatory medication

• Taking warfarin, aspirin or any medication that is likely to affect platelet function or other aspects of blood coagulation, and unable to safely cease this medication for a period of 1 week prior, during, and 1 week after administration of G-CSF (a total period of 19 days)

• Participation in any study involving any investigational drug or medical device within 30 days prior to Screening 1

• Receipt of a vaccine for HIV-1 or any gene transfer product at any time

• Prior treatment with recombinant G-CSF or busulfan or other stem-cell mobilizing or modulating agent within the previous 12 months

• Known hypersensitivity to busulfan, G-CSF (Neupogen™) or E. coli-derived proteins

• Subjects who will not accept transfusions of blood products

• Pregnant or breast-feeding at any time between Screening 1 and Baseline (infusion)

• History of alcohol or drug abuse within the 12 months prior to Screening 1

• Inability to understand and provide informed consent