Clinical trial NCT01704781: Vacc-4x + Lenalidomide vs. Vacc-4x +Placebo in HIV-1-infected Subjects on Antiretroviral Therapy (ART)
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: HIV-1 Infection
Keywords: CD4
Clinical trial
Dose escalation assessment lenalidomide
Human immunodeficiency virus-1 (HIV-1)
HIV
Immunomodulatory
Infection
Lenalidomide
Phase I/II
Vaccine
Vacc-4x
Lead sponsor: Bionor Immuno AS
Sponsor class: INDUSTRY
Collaborators: name: Celgene Corporation
First posted: 2012-10-11
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief 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.

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 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 ≥ 200x10\^6 cells/L and ≤500x10\^6 cells/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.

Primary outcomes:
measure: Part A: To Establish Highest Tolerated Dose of Lenalidomide, Dose-Limiting Toxicity
timeFrame: 31 days
measure: Part A: To Establish Highest Tolerated Dose of Lenalidomide, CD4 Counts Over Time
timeFrame: 31 days
measure: Part B: Change in CD4 Count
timeFrame: Week 26
Secondary outcomes:
measure: Part B: Change in CD8 Count
timeFrame: 26 weeks
measure: Part B: Evaluate the Effect on HIV Viral Load
timeFrame: 26 weeks
measure: Part B: Incidents of Delayed-type Hypersensitivity
timeFrame: 26 weeks
measure: Part A and B: Safety and Tolerability
timeFrame: Part A: 31 days and Part B: 26 weeks
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: EIPMED - Gesellschaft fűr epidemiologische und klinische Forschung in der Medizin mbH Rubensstrasse 125
city: Berlin
country: Germany
facility: Charite Campus, Virchow-Klinikum Medizinische Klinik mit Schwerpunkt Infektiologie Station 59 (Suedring 11) Augustenburger Platz 1
city: Hamburg
country: Germany
facility: University Medical Center Hamburg-Eppendorf
city: Köln
country: Germany
facility: Klinik I für Innere Medizin Klinikum Der Universität zu Köln
Study officials:
affiliation: Bionor Pharma ASA, Kronprinsesse Märthas Plass 1, P.O. Box 1477 Vika, NO-0116 Oslo, Norway
name: Kim Krogsgaard
role: STUDY_DIRECTOR
References:
citation: Asjo B, Stavang H, Sorensen 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. doi: 10.1089/088922202320935438.
citation: Kran AM, Sorensen 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. doi: 10.1097/00002030-200409240-00003.
citation: Kvale D, Kran AM, Sommerfelt MA, Nyhus J, Baksaas I, Bruun JN, Sorensen 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. doi: 10.1097/01.aids.0000163932.76531.c6.
citation: Sommerfelt MA, Nyhus J, Sorensen B. Novel peptide-based HIV-1 immunotherapy. Expert Opin Biol Ther. 2004 Mar;4(3):349-61. doi: 10.1517/14712598.4.3.349.