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

NCT01704781 | Completed Phase 1 Results DMC

• 1 other identifier: CT-BI Vacc-4x/IMiD-2010/1
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 4

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.

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

Outcome Measures

Primary Outcomes (3)

• Part A: To Establish Highest Tolerated Dose of Lenalidomide, Dose-Limiting Toxicity

  Number of participants in each of the three groups that experienced any dose-limiting toxicity.

  31 days

• Part A: To Establish Highest Tolerated Dose of Lenalidomide, CD4 Counts Over Time

  31 days

• Part B: Change in CD4 Count

  Change in CD4 count from baseline to Week 26.

  Week 26

Secondary Outcomes (4)

• Part B: Change in CD8 Count

  26 weeks

• Part B: Evaluate the Effect on HIV Viral Load

  26 weeks

• Part B: Incidents of Delayed-type Hypersensitivity

  26 weeks

• Part A and B: Safety and Tolerability

  Part A: 31 days and Part B: 26 weeks

Study Arms (3)

Part A: lenalidomide dose escalation

EXPERIMENTAL

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; Drug: Vacc-4X; Drug: rhuGM-CSF

Part B: lenalidomide

EXPERIMENTAL

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; Drug: Vacc-4X; Drug: rhuGM-CSF

Part B: lenalidomide placebo

PLACEBO COMPARATOR

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; Drug: Vacc-4X; Drug: rhuGM-CSF

Interventions

Lenalidomide DRUG

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

Also known as: Lenalidomide capsule

Part A: lenalidomide dose escalation; Part B: lenalidomide

Lenalidomide placebo DRUG

Capsules are identical to the active Lenalidomide capsules used.

Also known as: placebo

Part B: lenalidomide placebo

Vacc-4X DRUG

Vacc-4x is a peptide-based HIV immunotherapy administered intradermally. Vacc-4x peptides are reconstituted in sterile water.

Also known as: Combination of Vacc-10, Vacc-11, Vacc-12 and Vacc-13.

Part A: lenalidomide dose escalation; Part B: lenalidomide; Part B: lenalidomide placebo

rhuGM-CSF DRUG

Granulocyte macrophage colony stimulating factor as a local adjuvant

Also known as: Leukine®

Part A: lenalidomide dose escalation; Part B: lenalidomide; Part B: lenalidomide placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Men, age ≥ 18 and ≤ 55 years at the time of screening.

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Bionor Immuno AS: lead
• Celgene Corporation: collaborator

Study Sites (4)

University Medical Center Hamburg-Eppendorf

Hamburg, Hamburg, 20246, Germany

Location

EIPMED - Gesellschaft fűr epidemiologische und klinische Forschung in der Medizin mbH Rubensstrasse 125

Berlin, State of Berlin, 12157, Germany

Location

Charite Campus, Virchow-Klinikum Medizinische Klinik mit Schwerpunkt Infektiologie Station 59 (Suedring 11) Augustenburger Platz 1

Berlin, State of Berlin, 13353, Germany

Location

Klinik I für Innere Medizin Klinikum Der Universität zu Köln

Cologne, 50937, Germany

Location

Related Publications (4)

• 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.

  PMID: 12487807 BACKGROUND

• 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.

  PMID: 15353973 BACKGROUND

• 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.

  PMID: 15802974 BACKGROUND

• 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.

  PMID: 15006729 BACKGROUND

MeSH Terms

Conditions

Infections

Interventions

Lenalidomide; Vacc-4x; sargramostim

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Maja Sommerfelt
• Organization: Bionor Pharma ASA

ms@bionorpharma.com

+4723010960

Study Officials

• Kim Krogsgaard

  Bionor Pharma ASA, Kronprinsesse Märthas Plass 1, P.O. Box 1477 Vika, NO-0116 Oslo, Norway

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 11, 2012
• First Posted: October 11, 2012
• Study Start: September 1, 2012
• Primary Completion: August 1, 2014
• Study Completion: August 1, 2014
• Last Updated: March 8, 2017
• Results First Posted: March 8, 2017

Record last verified: 2014-10

Data Sharing

• IPD Sharing: Will not share

Locations

DE (4)