- ICH GCP
- US-Register für klinische Studien
- Klinische Studie NCT01704781
Vacc-4x + Lenalidomide vs. Vacc-4x +Placebo in HIV-1-infected Subjects on Antiretroviral Therapy (ART) (IMID)
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).
Studienübersicht
Status
Bedingungen
Intervention / Behandlung
Detaillierte Beschreibung
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.
Studientyp
Einschreibung (Tatsächlich)
Phase
- Phase 2
- Phase 1
Kontakte und Standorte
Studienorte
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Berlin, Deutschland, 12157
- EIPMED - Gesellschaft fűr epidemiologische und klinische Forschung in der Medizin mbH Rubensstrasse 125
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Berlin, Deutschland, 13353
- Charite Campus, Virchow-Klinikum Medizinische Klinik mit Schwerpunkt Infektiologie Station 59 (Suedring 11) Augustenburger Platz 1
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Hamburg, Deutschland, 20246
- University Medical Center Hamburg-Eppendorf
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Köln, Deutschland, 50937
- Klinik I für Innere Medizin Klinikum Der Universität zu Köln
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Teilnahmekriterien
Zulassungskriterien
Studienberechtigtes Alter
Akzeptiert gesunde Freiwillige
Studienberechtigte Geschlechter
Beschreibung
Inclusion Criteria:
- Men, age ≥ 18 and ≤ 55 years at the time of screening.
- 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.
- Clinically stable on ART for the last 18 months (changes in therapy are allowed as long as the viral load is stable).
- Well controlled with no treatment failure due to ART resistance in the past
- 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.
- Screening CD4 cell count ≥ 200x10^6 cells/L and ≤500x10^6 cells/L. (Rescreening is allowed)
- 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
- Signed informed consent
- Willingness to adhere to Global Pregnancy Prevention Risk Management Plan Lenalidomide
Exclusion Criteria:
- Reported pre-study AIDS-defining illness within the previous year
- Malignant disease.
- On chronic treatment with immunosuppressive therapy.
- Autoimmune disorders, present or in the past if there is an increased risk of disease exacerbation.
- 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.
- Concurrent chronic active infection such as viral hepatitis B or C or tuberculosis.
- Previous thromboembolic events or patient is currently immobilized
- Sexually active subjects who do not adhere to Global Pregnancy Prevention Risk Management Plan Lenalidomide
- Current participation in other clinical therapeutic studies.
- 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).
- The development of erythema nodosum if characterized by a desquamating rash while previously
- Incapability of compliance to the treatment protocol, in the opinion of the Investigator.
Studienplan
Wie ist die Studie aufgebaut?
Designdetails
- Hauptzweck: Unterstützende Pflege
- Zuteilung: Zufällig
- Interventionsmodell: Parallele Zuordnung
- Maskierung: Vervierfachen
Waffen und Interventionen
Teilnehmergruppe / Arm |
Intervention / Behandlung |
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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) |
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
Andere Namen:
Vacc-4x is a peptide-based HIV immunotherapy administered intradermally.
Vacc-4x peptides are reconstituted in sterile water.
Andere Namen:
Granulocyte macrophage colony stimulating factor as a local adjuvant
Andere Namen:
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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.
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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
Andere Namen:
Vacc-4x is a peptide-based HIV immunotherapy administered intradermally.
Vacc-4x peptides are reconstituted in sterile water.
Andere Namen:
Granulocyte macrophage colony stimulating factor as a local adjuvant
Andere Namen:
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Placebo-Komparator: 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.
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Vacc-4x is a peptide-based HIV immunotherapy administered intradermally.
Vacc-4x peptides are reconstituted in sterile water.
Andere Namen:
Granulocyte macrophage colony stimulating factor as a local adjuvant
Andere Namen:
Capsules are identical to the active Lenalidomide capsules used.
Andere Namen:
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Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
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Part A: To Establish Highest Tolerated Dose of Lenalidomide, Dose-Limiting Toxicity
Zeitfenster: 31 days
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Number of participants in each of the three groups that experienced any dose-limiting toxicity.
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31 days
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Part A: To Establish Highest Tolerated Dose of Lenalidomide, CD4 Counts Over Time
Zeitfenster: 31 days
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31 days
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Part B: Change in CD4 Count
Zeitfenster: Week 26
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Change in CD4 count from baseline to Week 26.
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Week 26
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Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
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Part B: Change in CD8 Count
Zeitfenster: 26 weeks
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Change in CD8 count from baseline to week 26.
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26 weeks
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Part B: Evaluate the Effect on HIV Viral Load
Zeitfenster: 26 weeks
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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.
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26 weeks
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Part B: Incidents of Delayed-type Hypersensitivity
Zeitfenster: 26 weeks
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Delayed-type hypersensitivity measured by induration and erythema.
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26 weeks
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Part A and B: Safety and Tolerability
Zeitfenster: Part A: 31 days and Part B: 26 weeks
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Part A: 31 days and Part B: 26 weeks
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Mitarbeiter und Ermittler
Sponsor
Mitarbeiter
Ermittler
- Studienleiter: Kim Krogsgaard, Bionor Pharma ASA, Kronprinsesse Märthas Plass 1, P.O. Box 1477 Vika, NO-0116 Oslo, Norway
Publikationen und hilfreiche Links
Allgemeine Veröffentlichungen
- 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.
- 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.
- 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.
- 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.
Studienaufzeichnungsdaten
Haupttermine studieren
Studienbeginn
Primärer Abschluss (Tatsächlich)
Studienabschluss (Tatsächlich)
Studienanmeldedaten
Zuerst eingereicht
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
Zuerst gepostet (Schätzen)
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Tatsächlich)
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
Zuletzt verifiziert
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Schlüsselwörter
Zusätzliche relevante MeSH-Bedingungen
Andere Studien-ID-Nummern
- CT-BI Vacc-4x/IMiD-2010/1
Plan für individuelle Teilnehmerdaten (IPD)
Planen Sie, individuelle Teilnehmerdaten (IPD) zu teilen?
Beschreibung des IPD-Plans
Diese Informationen wurden ohne Änderungen direkt von der Website clinicaltrials.gov abgerufen. Wenn Sie Ihre Studiendaten ändern, entfernen oder aktualisieren möchten, wenden Sie sich bitte an register@clinicaltrials.gov. Sobald eine Änderung auf clinicaltrials.gov implementiert wird, wird diese automatisch auch auf unserer Website aktualisiert .
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