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

NCT01734850 | Completed Phase 1 Results DMC

• 1 other identifier: CAL-USA-11
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 2

Brief 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. 1.Removing a protein named CCR5 from bone marrow and white blood cells
2. 2.Producing a protein named C46 on bone marrow and white blood cells

Conditions

Human Immunodeficiency Virus

Keywords

HIV-1

Outcome Measures

Primary Outcomes (8)

• Number of Participants With Severe and Life-threatening Adverse Events (AEs)

  Up to 48 weeks

• Number of Participants With Severe or Life-threatening AEs Related to CSL202

  Up to 48 weeks

• Number of Participants With the Presence of Replication-competent Retrovirus

  Up to 48 weeks

• Number of Participants With Predominant Integration Site Analysis

  Vector Integration Site Analysis performed only when Cal-1 Marking is \>= 1%.

  Up to 48 weeks

• Mean Cell Dose for CD4+ Cells (Ttn)

  Up to 48 weeks

• Mean Cell Dose for CD34+ Cells (HSPCtn)

  Up to 48 weeks

• Percent Transduction Efficiency of CD4+ Cells (Ttn) and CD34+ Cells (HSPCtn) of Final Cell Product

  Up to 48 weeks

• Total Area Under the Curve (AUC) for Busulfan

  Cohort 3: Total AUC = first dose AUC value + second dose AUC value

  Up to 48 weeks

Secondary Outcomes (9)

• Percent Cal-1 Marking in Peripheral Blood

  Up to 48 weeks

• Cal-1 Marking in Gut-associated Lymphoid Tissue (GALT) (10-15 cm)

  Up to 48 weeks

• Cal-1 Marking in GALT (25-35 cm)

  Up to 48 weeks

• Cal-1 Marking in Bone Marrow

  Up to 48 weeks

• Cal-1 C46 Expression in Peripheral Blood

  Up to 48 weeks

Study Arms (3)

No busulfan pre-conditioning

EXPERIMENTAL

Cal-1 modified HSPC and Cal-1 modified CD4+ T lymphocytes without busulfan preconditioning

Biological: Cal-1 modified HSPC; Biological: Cal-1 modified CD4+ T lymphocytes

1 x 4mg/kg busulfan preconditioning

EXPERIMENTAL

Cal-1 modified HSPC and Cal-1 modified CD4+ T lymphocytes, with single 4mg/kg busulfan dose administered as pre-conditioning for transplant

Drug: Busulfan; Biological: Cal-1 modified HSPC; Biological: Cal-1 modified CD4+ T lymphocytes

2 x 4mg/kg busulfan pre-conditioning

EXPERIMENTAL

Cal-1 modified HSPC and Cal-1 modified CD4+ T lymphocytes, with two 4mg/kg busulfan doses administered as pre-conditioning for transplant

Drug: Busulfan; Biological: Cal-1 modified HSPC; Biological: Cal-1 modified CD4+ T lymphocytes

Interventions

Busulfan DRUG

Intravenous busulfan

Also known as: Busulfex

1 x 4mg/kg busulfan preconditioning; 2 x 4mg/kg busulfan pre-conditioning

Cal-1 modified HSPC BIOLOGICAL

Hematopoietic progenitor/stem cells (HSPC) modified with LVsh5/C46 (Cal-1)

Also known as: LVsh5/C46 modified HSPC

1 x 4mg/kg busulfan preconditioning; 2 x 4mg/kg busulfan pre-conditioning; No busulfan pre-conditioning

Cal-1 modified CD4+ T lymphocytes BIOLOGICAL

CD4+ T lymphocytes modified with LVsh5/C46 (Cal-1)

Also known as: LVsh5/C46 modified CD4+ T lymphocytes

1 x 4mg/kg busulfan preconditioning; 2 x 4mg/kg busulfan pre-conditioning; No busulfan pre-conditioning

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Calimmune, Inc.: lead

Study Sites (2)

UCLA CARE Center

Los Angeles, California, 90035, United States

Location

Quest Clinical Research

San Francisco, California, 94115, United States

Location

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

Busulfan

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Results Point of Contact

• Title: Trial Registration Coordinator
• Organization: CSL Behring

clinicaltrials@cslbehring.com

484-878-4000

Study Officials

• Ronald Mitsuyasu, M.D.

  University of California, Los Angeles

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 19, 2012
• First Posted: November 28, 2012
• Study Start: April 1, 2013
• Primary Completion: September 1, 2017
• Study Completion: November 1, 2017
• Last Updated: August 6, 2020
• Results First Posted: August 6, 2020

Record last verified: 2020-07

Locations

US (2)