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

This study has been completed.
Sponsor:
Collaborator:
Celgene Corporation
Information provided by (Responsible Party):
Bionor Immuno AS
ClinicalTrials.gov Identifier:
NCT01704781
First received: September 11, 2012
Last updated: January 16, 2017
Last verified: October 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: Lenalidomide Drug: Lenalidomide placebo Drug: Vacc-4X Drug: rhuGM-CSF Phase 1 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, 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:
  • Part A: To Establish Highest Tolerated Dose of Lenalidomide, Dose-Limiting Toxicity [ Time Frame: 31 days ]
    Number of participants in each of the three groups that experienced any dose-limiting toxicity.

  • Part A: To Establish Highest Tolerated Dose of Lenalidomide, CD4 Counts Over Time [ Time Frame: 31 days ]
  • Part B: Change in CD4 Count [ Time Frame: Week 26 ]
    Change in CD4 count from baseline to Week 26.


Secondary Outcome Measures:
  • Part B: Change in CD8 Count [ Time Frame: 26 weeks ]
    Change in CD8 count from baseline to week 26.

  • Part B: Evaluate the Effect on HIV Viral Load [ Time Frame: 26 weeks ]
    Results BLQ (<20 HIV copies/mL) have been replaced with BLQ/2 = 10 HIV copies/mL while 'not detected' results have been replaced with 0 HIV copies/mL.

  • Part B: Incidents of Delayed-type Hypersensitivity [ Time Frame: 26 weeks ]
    Delayed-type hypersensitivity measured by induration and erythema.

  • Part A and B: Safety and Tolerability [ Time Frame: Part A: 31 days and Part B: 26 weeks ]

Enrollment: 36
Study Start Date: September 2012
Study Completion Date: August 2014
Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part A: lenalidomide dose escalation

All patient receive intradermal Vacc-4x (1.2 mg) given with Leukine® (rhu-GM-CSF) (0.06 mg) and oral lenalidomide in a 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)

Drug: Lenalidomide
In Part A a dose escalation design is used (2,5; 5; 10; 25 mg). Part B will use the dose confirmed by Part A
Other Name: Lenalidomide capsule
Drug: Vacc-4X
Vacc-4x is a peptide-based HIV immunotherapy administered intradermally. Vacc-4x peptides are reconstituted in sterile water.
Other Name: Combination of Vacc-10, Vacc-11, Vacc-12 and Vacc-13.
Drug: rhuGM-CSF
Granulocyte macrophage colony stimulating factor as a local adjuvant
Other Name: Leukine®
Experimental: Part B: lenalidomide
Intradermal Vacc-4x (1.2 mg) given with Leukine® (rhu-GM-CSF) (0.06 mg) and oral lenalidomide for 6 immunizations (visit 2, 3, 4, 5, 6 and 7) & lenalidomide (dose determined in Part A) two days prior to and at the day of immunization.
Drug: Lenalidomide
In Part A a dose escalation design is used (2,5; 5; 10; 25 mg). Part B will use the dose confirmed by Part A
Other Name: Lenalidomide capsule
Drug: Vacc-4X
Vacc-4x is a peptide-based HIV immunotherapy administered intradermally. Vacc-4x peptides are reconstituted in sterile water.
Other Name: Combination of Vacc-10, Vacc-11, Vacc-12 and Vacc-13.
Drug: rhuGM-CSF
Granulocyte macrophage colony stimulating factor as a local adjuvant
Other Name: Leukine®
Placebo Comparator: Part B: lenalidomide placebo
Intradermal Vacc-4x (1.2 mg) given with Leukine® (rhu-GM-CSF) (0.06 mg) and oral lenalidomide for 6 immunizations (visit 2, 3, 4, 5, 6 and 7) & lenalidomide placebo two days prior to and at the day of immunization.
Drug: Lenalidomide placebo
Capsules are identical to the active Lenalidomide capsules used.
Other Name: placebo
Drug: Vacc-4X
Vacc-4x is a peptide-based HIV immunotherapy administered intradermally. Vacc-4x peptides are reconstituted in sterile water.
Other Name: Combination of Vacc-10, Vacc-11, Vacc-12 and Vacc-13.
Drug: rhuGM-CSF
Granulocyte macrophage colony stimulating factor as a local adjuvant
Other Name: Leukine®

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   (Adult)
Sexes Eligible for Study:   All
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 ≥ 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.
  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: Kim Krogsgaard Bionor Pharma ASA, Kronprinsesse Märthas Plass 1, P.O. Box 1477 Vika, NO-0116 Oslo, Norway
  More Information

Additional 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
Results First Received: January 16, 2017
Last Updated: January 16, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Participants have not provided informed consent for their anonymized individual data to be made available beyond that described in the patient information sheet.

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:
Lenalidomide
Thalidomide
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents
Immunosuppressive Agents
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on September 19, 2017