Overview

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