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Vacc-4x + Lenalidomide vs. Vacc-4x +Placebo in HIV-1-infected Subjects on Antiretroviral Therapy (ART)

Information source: Bionor Immuno AS
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: HIV-1 Infection

Intervention: Part A: lenalidomide dose escalation (Drug); Part B: lenalidomide (Drug); Part B: lenalidomide placebo (Drug)

Phase: Phase 1/Phase 2

Status: Completed

Sponsored by: Bionor Immuno AS

Official(s) and/or principal investigator(s):
Kim Krogsgaard, Study Director, Affiliation: Bionor Pharma ASA, Kronprinsesse Märthas Plass 1, P.O. Box 1477 Vika, NO-0116 Oslo, Norway

Summary

During the course of HIV infection the number of CD4 cells decreases, resulting in a reduced immunological response and ultimately immune deficiency. Vacc-4x is a peptide-based HIV immunotherapy and the primary objective is to strengthen the immune system's response to HIV p24. By adding Lenalidomide, an immunomodulatory agent, as a supporting drug, it is anticipated that the effect of Vacc-4x might be enhanced.

Clinical Details

Official title: A Double-blind Placebo Controlled Immunogenicity Study of Vacc-4x + Lenalidomide Versus Vacc-4x With an Initial Open-label Dose Escalation Assessment of Lenalidomide in HIV-1-infected Subjects on Antiretroviral Therapy (ART).

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Supportive Care

Primary outcome:

Endpoint Part A: find maximum tolerated dose (MTD) of lenalidomide

Endpoints Part B: evaluate the immunomodulatory effect of Lenalidomide/placebo under immunization with Vacc-4x on change in CD4 count

Endpoints Part B: evaluate the immunomodulatory effect of Lenalidomide/placebo under immunization with Vacc-4x on change in mean T-cell response

Endpoints Part B: evaluate the immunomodulatory effect of Lenalidomide/placebo under immunization with Vacc-4x on antibody titer to vacc-4x and p24

Endpoints Part B: evaluate the immunomodulatory effect of Lenalidomide/placebo under immunization with Vacc-4x on increase in antibody titer

Secondary outcome:

Endpoints Part B: change in CD4

Endpoints Part B: change in CD8

Endpoints Part B: change in HIV viral load

Endpoints Part B: DTH induration and erythema

Detailed description: Human immunodeficiency virus (HIV) infects the CD4 subset of T-cells that are critical for initiating immune responses to infection. The level of CD4 cells in the blood is a marker of a patient's immunological status. The number of CD4 cells decreases in the course of the HIV infection and results in a reduced immunological response and eventually immune deficiency. Vacc-4x is one of the few peptide-based therapeutic vaccines tested, and consists of four, slightly modified HIV Gag p24 consensus peptides. Vacc-4x was first tested by intradermal injections using GM-CSF as adjuvant. A recent multinational placebo-controlled study found improvement of vaccine-specific T cell immunity and decrease in viral loads (presented at the AIDS vaccine 2011 conference, Bangkok). Lenalidomide (CC-5013) is a substance in the class of immunomodulatory agents. The lenalidomide mechanism of action includes anti-neoplastic, pro-erythropoietic, and immunomodulatory properties. Lenalidomide inhibits proliferation of certain hematopoietic tumor cells, enhances T cell- and Natural Killer (NK) cell-mediated immunity and increases the number of NK T cells. The anti-HIV p24 immune response resulting from Vacc-4x immunization could in combination with ART potentially improve immune reconstitution in patients who have not fully regained a healthy CD4 level (> 600 x106/L). Adding the immunomodulatory agent Lenalidomide (CC-5013) to Vacc-4x immunization could enhance the immune response to Vacc-4x and further strengthen immune reconstitution.

Eligibility

Minimum age: 18 Years. Maximum age: 55 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- 1. Men, age ≥ 18 and ≤ 55 years at the time of screening.

- 2. Women, age ≥ 50 and ≤ 55 years at the time of screening, who are not of

childbearing potential (see Exclusion criteria, point 9). Childbearing status must be documented.

- 3. Clinically stable on ART for the last 18 months (changes in therapy are allowed as

long as the viral load is stable).

- 4. Well controlled with no treatment failure due to ART resistance in the past

- 5. Screening plasma viral load (HIV-1 RNA) less than 50 copies/mL for the last six

months. If screening value is between 50-500 copies/mL rescreening is allowed. Single blips (up to 500 copies/mL) are allowed.

- 6. Screening CD4 cell count ≥ 200x106/L and ≤500x106/L. (Rescreening is allowed)

- 7. Laboratory test results within these ranges: Absolute neutrophil count (ANC)

>1. 0x10 9 /L, Platelet count >75x10 9 /L and eGRF (MDRD) >60 mL/min

- 8. Signed informed consent

- 9. Willingness to adhere to Global Pregnancy Prevention Risk Management Plan

Lenalidomide Exclusion Criteria:

- 1. Reported pre-study AIDS-defining illness within the previous year

- 2. Malignant disease.

- 3. On chronic treatment with immunosuppressive therapy.

- 4. Autoimmune disorders, present or in the past if there is an increased risk of

disease exacerbation.

- 5. Unacceptable values of the hematologic and clinical chemistry parameters

(including those associated with hemophilia), as judged by the Investigator or the Sponsor (or designee), including creatinine values >1. 5x upper limit of normal (ULN), and AST (SGOT), ALT (SGPT), and alkaline phosphatase values >2. 5x ULN.

- 6. Concurrent chronic active infection such as viral hepatitis B or C or

tuberculosis.

- 7. Previous thromboembolic events or patient is currently immobilized

- 8. Sexually active subjects who do not adhere to Global Pregnancy Prevention Risk

Management Plan Lenalidomide

- 9. Current participation in other clinical therapeutic studies.

- 10. Females of childbearing potential will be excluded from this trial. A female of

childbearing potential (FCBP) is a sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i. e. has had menses at any time in the preceding 24 consecutive months).

- 11. The development of erythema nodosum if characterized by a desquamating rash while

previously

- 12. Incapability of compliance to the treatment protocol, in the opinion of the

Investigator.

Locations and Contacts

Charite Campus, Virchow-Klinikum Medizinische Klinik mit Schwerpunkt Infektiologie Station 59 (Suedring 11) Augustenburger Platz 1, Berlin 13353, Germany

EIPMED - Gesellschaft fűr epidemiologische und klinische Forschung in der Medizin mbH Rubensstrasse 125, Berlin 12157, Germany

University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany

Klinik I für Innere Medizin Klinikum Der Universität zu Köln, Köln 50937, Germany

Additional Information

Related publications:

Asjö B, Stavang H, Sørensen B, Baksaas I, Nyhus J, Langeland N. Phase I trial of a therapeutic HIV type 1 vaccine, Vacc-4x, in HIV type 1-infected individuals with or without antiretroviral therapy. AIDS Res Hum Retroviruses. 2002 Dec 10;18(18):1357-65.

Kran AM, Sørensen B, Nyhus J, Sommerfelt MA, Baksaas I, Bruun JN, Kvale D. HLA- and dose-dependent immunogenicity of a peptide-based HIV-1 immunotherapy candidate (Vacc-4x). AIDS. 2004 Sep 24;18(14):1875-83.

Kvale D, Kran AM, Sommerfelt MA, Nyhus J, Baksaas I, Bruun JN, Sørensen B. Divergent in vitro and in vivo correlates of HIV-specific T-cell responses during onset of HIV viraemia. AIDS. 2005 Mar 24;19(6):563-7.

Sommerfelt MA, Nyhus J, Sørensen B. Novel peptide-based HIV-1 immunotherapy. Expert Opin Biol Ther. 2004 Mar;4(3):349-61. Review.

Starting date: September 2012
Last updated: October 13, 2014

Page last updated: August 23, 2015

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