Trial record 13 of 31 for:    " August 19, 2012":" September 18, 2012"[FIRST-RECEIVED-DATE]AND HIV[CONDITION]

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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Celgene Corporation
Information provided by (Responsible Party):
Bionor Immuno AS
ClinicalTrials.gov Identifier:
NCT01704781
First received: September 11, 2012
Last updated: May 12, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
HIV-1 Infection
Drug: Part A: lenalidomide dose escalation
Drug: Part B: lenalidomide
Drug: Part B: lenalidomide placebo
Phase 1
Phase 2

Study Type: Interventional
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
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).

Resource links provided by NLM:


Further study details as provided by Bionor Immuno AS:

Primary Outcome Measures:
  • Endpoint Part A: find maximum tolerated dose (MTD) of lenalidomide [ Time Frame: Part A: 6 weeks ] [ Designated as safety issue: Yes ]
  • Endpoints Part B: evaluate the immunomodulatory effect of Lenalidomide/placebo under immunization with Vacc-4x on change in CD4 count [ Time Frame: 26 weeks - Several points throughout the study ] [ Designated as safety issue: Yes ]
  • Endpoints Part B: evaluate the immunomodulatory effect of Lenalidomide/placebo under immunization with Vacc-4x on change in mean T-cell response [ Time Frame: 26 weeks - Several points throughout the study ] [ Designated as safety issue: No ]
  • Endpoints Part B: evaluate the immunomodulatory effect of Lenalidomide/placebo under immunization with Vacc-4x on antibody titer to vacc-4x and p24 [ Time Frame: 26 weeks - Several points throughout the study ] [ Designated as safety issue: No ]
  • Endpoints Part B: evaluate the immunomodulatory effect of Lenalidomide/placebo under immunization with Vacc-4x on increase in antibody titer [ Time Frame: 26 weeks - Several points throughout the study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Endpoints Part B: change in CD4 [ Time Frame: 26 weeks - Several points throughout the study ] [ Designated as safety issue: Yes ]
  • Endpoints Part B: change in CD8 [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]
    - 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).

  • Endpoints Part B: change in HIV viral load [ Time Frame: 26 weeks - Several points throughout the study ] [ Designated as safety issue: Yes ]
  • Endpoints Part B: DTH induration and erythema [ Time Frame: 26 weeks -Several points throughout the study ] [ Designated as safety issue: No ]

Estimated Enrollment: 36
Study Start Date: September 2012
Estimated Study Completion Date: August 2014
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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 non tolerated 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.
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.
Other Name: Lenalidomide dose escalation maximum tolerated dose (MTD).
Experimental: Part B: lenalidomide
Vacc-4x/GM-CSF 6 immunizations (week 2, 3, 4, 5, 6 and 7) & lenalidomide two days prior to and at the day of immunization.
Drug: Part B: lenalidomide
Part B continue with lenalidomide MTD found in Part A in combination with Vacc-4x.
Other Name: Part B: MTD lenalidomide in comb. with Vacc-4x.
Placebo Comparator: Part B: lenalidomide placebo
Vacc-4x/GM-CSF & lenalidomide placebo. Vacc-4x/GM-CSF 6 immunizations (week 2, 3, 4, 5, 6 and 7) & lenalidomide placebo two days prior to and at the day of immunization.
Drug: Part B: lenalidomide placebo
Part B continue with placebo in combination with Vacc-4x.
Other Name: lenalidomide placebo

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

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01704781

Locations
Germany
EIPMED - Gesellschaft fűr epidemiologische und klinische Forschung in der Medizin mbH Rubensstrasse 125
Berlin, Germany, 12157
Charite Campus, Virchow-Klinikum Medizinische Klinik mit Schwerpunkt Infektiologie Station 59 (Suedring 11) Augustenburger Platz 1
Berlin, Germany, 13353
University Medical Center Hamburg-Eppendorf
Hamburg, Germany, 20246
Klinik I für Innere Medizin Klinikum Der Universität zu Köln
Köln, Germany, 50937
Sponsors and Collaborators
Bionor Immuno AS
Celgene Corporation
Investigators
Study Director: Vidar Wendel-Hansen, Dr. med Bionor Pharma ASA, Kronprinsesse Märthas Plass 1, P.O. Box 1477 Vika, NO-0116 Oslo, Norway
  More Information

Publications:
Responsible Party: Bionor Immuno AS
ClinicalTrials.gov Identifier: NCT01704781     History of Changes
Other Study ID Numbers: CT-BI Vacc-4x/IMiD-2010/1
Study First Received: September 11, 2012
Last Updated: May 12, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices
United States: Food and Drug Administration

Keywords provided by Bionor Immuno AS:
Human immunodeficiency virus-1 (HIV-1)
HIV
CD4
Clinical trial
Dose escalation assessment lenalidomide
Immunomodulatory
Infection
Lenalidomide
Phase I/II
Vaccine
Vacc-4x

Additional relevant MeSH terms:
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Lenalidomide
Thalidomide
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors

ClinicalTrials.gov processed this record on July 10, 2014