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

HIV-1 Infection Clinical Trial

— IMID  

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).

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01704781
• Other study ID #: CT-BI Vacc-4x/IMiD-2010/1
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: September 11, 2012
• Last updated: October 13, 2014
• Start date: September 2012
• Est. completion date: August 2014

Study information

• Verified date: October 2014
• Source: Bionor Immuno AS
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical DevicesUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: August 2014
• Est. primary completion date: August 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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.

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

Related Conditions & MeSH terms

• HIV-1 Infection

Intervention

Drug:
• Part A: lenalidomide dose escalation
Dose escalation (3+3 design) Dose level -1: 2.5 mg Lenalidomide (CC-5013) in the event Dose level 1 is nontolerated dose (NTD) Dose level 1(start): 5 mg Lenalidomide (CC-5013) Dose level 2: 10 mg Lenalidomide (CC-5013) Dose level 3: 25 mg Lenalidomide (CC-5013) and Vacc-4x/GM-CSF.
• Part B: lenalidomide
Part B continue with lenalidomide MTD found in Part A in combination with Vacc-4x.
• Part B: lenalidomide placebo
Part B continue with placebo in combination with Vacc-4x.

Locations

Country	Name	City	State
Germany	Charite Campus, Virchow-Klinikum Medizinische Klinik mit Schwerpunkt Infektiologie Station 59 (Suedring 11) Augustenburger Platz 1	Berlin
Germany	EIPMED - Gesellschaft fur epidemiologische und klinische Forschung in der Medizin mbH Rubensstrasse 125	Berlin
Germany	University Medical Center Hamburg-Eppendorf	Hamburg
Germany	Klinik I für Innere Medizin Klinikum Der Universität zu Köln	Köln

Sponsors (2)

Lead Sponsor	Collaborator
Bionor Immuno AS	Celgene Corporation

Country where clinical trial is conducted

Germany, 

References & Publications (4)

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. — View Citation

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. — View Citation

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. — View Citation

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Endpoint Part A: find maximum tolerated dose (MTD) of lenalidomide		Part A: 6 weeks	Yes
Primary	Endpoints Part B: evaluate the immunomodulatory effect of Lenalidomide/placebo under immunization with Vacc-4x on change in CD4 count		26 weeks - Several points throughout the study	Yes
Primary	Endpoints Part B: evaluate the immunomodulatory effect of Lenalidomide/placebo under immunization with Vacc-4x on change in mean T-cell response		26 weeks - Several points throughout the study	No
Primary	Endpoints Part B: evaluate the immunomodulatory effect of Lenalidomide/placebo under immunization with Vacc-4x on antibody titer to vacc-4x and p24		26 weeks - Several points throughout the study	No
Primary	Endpoints Part B: evaluate the immunomodulatory effect of Lenalidomide/placebo under immunization with Vacc-4x on increase in antibody titer		26 weeks - Several points throughout the study	No
Secondary	Endpoints Part B: change in CD4		26 weeks - Several points throughout the study	Yes
Secondary	Endpoints Part B: change in CD8	- Change (and percent change) in CD8 count from study start (mean of Screening and Week 1[Visit 2]) to Weeks 4, 12, 13, 21 and 26 (Termination).	26 weeks	No
Secondary	Endpoints Part B: change in HIV viral load		26 weeks - Several points throughout the study	Yes
Secondary	Endpoints Part B: DTH induration and erythema		26 weeks -Several points throughout the study	No