Drugs

Vacc-4x

Vacc-4x

Drug Class: Therapeutic Vaccines Organization: Bionor Holding AS Phase of Development: Vacc-4x is in Phase II development as a therapeutic HIV vaccine.

(Compound details obtained from Treatment Action Group website,1 Bionor Holding AS website,2 and EU Clinical Trials Register3)

What is Vacc-4x?

What is Vacc-4x?

Vacc-4x is an investigational vaccine being studied as a possible strategy to treat people living with HIV.1 Vacc-4x belongs to a group of HIV vaccines called therapeutic HIV vaccines.

To learn how investigational vaccines and drugs are tested during clinical trials, read the AIDSinfo What is an Investigational HIV Drug? and HIV/AIDS Clinical Trials fact sheets.

How do therapeutic HIV vaccines work?

How do therapeutic HIV vaccines work?

A therapeutic HIV vaccine is a type of vaccine that’s designed to improve the body’s immune response to HIV in a person living with HIV.4 Therapeutic vaccines work by strengthening the immune system to recognize and eliminate HIV from the body. To learn more, read the AIDSinfo What is a Therapeutic HIV Vaccine? fact sheet.

There are several types of therapeutic vaccines currently being studied to treat HIV. Vacc-4x is a peptide-based therapeutic HIV vaccine, which means that it is made up of HIV peptides (pieces of HIV proteins). The HIV peptides help the body produce an immune response to fight the virus.5

Which clinical trials are studying Vacc-4x?

Which clinical trials are studying Vacc-4x?

Study Names: REDUC; NCT02092116
Phase: Ib/IIa
Status: This study has been completed.
Location: Denmark
Purpose: The REDUC trial was a two-part study. Part A was designed to find a safe and effective dose of the investigational drug romidepsin to give with Vacc-4x in the second part of the study. Part B was designed to evaluate the effect of Vacc-4x when combined with romidepsin, on the amount of inactive HIV hiding in the body (known as latent HIV) and viral load levels during a planned break from ART.6

Study Names: CT-BI Vacc-4x 2007/1; NCT00659789
Phase: II
Status: This study has been completed.
Locations: Germany, Italy, Spain, United Kingdom, United States
Purpose: The purpose of this study was to evaluate the safety of Vacc-4x and its ability to produce an immune response in the body. The study also looked at what effects Vacc-4x would have while participants were on a planned break from ART.7

Study Names: CT-BI Vacc-4x 2012/1; NCT01712256
Phase: II
Status: This study has been completed.
Locations: Germany, Italy, Spain, United Kingdom, United States
Purpose: The purpose of this study was to evaluate the effect of two additional Vacc-4x injections on the immune responses and viral loads levels of participants who received Vacc-4x in a previous study.8

Study Names: BIOSKILL; EudraCT 2015-003186-28
Phase: II
Status: This study is ongoing.
Locations: Australia, Europe, United States
Purpose: The purpose of this study is to evaluate the safety and effectiveness of Vacc-4x when given before the investigational drug romidepsin. The researchers will measure the effects of Vacc-4x on viral load, latent HIV, and the body’s immune responses.3

For more details on the studies listed above, see the Health Professional version of this drug summary.

A number of other studies have evaluated the effects of Vacc-4x in participants with HIV. These include:
  • A Phase II study that looked at the safety of Vacc-4x and its ability to produce an immune response in the body. Some participants from this study were followed for more than 7 years after their last injection.9,10
  • A Phase I/II study (NCT01704781) that evaluated whether using Vacc-4x along with a drug called lenalidomide could improve participants’ CD4 counts.11
  • A Phase I/II study (NCT01473810) that looked at an intranasal form of Vacc-4x, which is given to participants through the nose rather than through an injection. Researchers evaluated the safety of intranasal Vacc-4x and its ability to produce an immune response in the body.12

What side effects might Vacc-4x cause?

What side effects might Vacc-4x cause?

One goal of HIV research is to identify new drugs that have fewer side effects. The following side effects were observed in some of the studies of Vacc-4x listed above.

REDUC (NCT02092116):

In this study, one participant dropped out early because of side effects that may have been related to Vacc-4x. Most of the side effects associated with Vacc-4x or the drug that was given to boost Vacc-4x’s effects, called an adjuvant, were mild in severity. The most common side effects related to Vacc-4x and its adjuvant were temporary redness and itching at the location where the injection was given. No serious side effects related to a study drug were reported. Other notable side effects were related to romidepsin or to the planned break from ART.6,13

CT-BI Vacc-4x 2007/1 (NCT00659789):

In this study, the majority of participants who received Vacc-4x plus an adjuvant had a side effect that the researchers thought might be related to treatment. Participants who received Vacc-4x plus an adjuvant had reactions at the injection location more often than participants who did not receive the vaccine. These reactions included itchiness, reddening, or hardening of the skin. Five serious side effects occurred in the Vacc-4x group but only one may have been caused by Vacc-4x.7,14

CT-BI Vacc-4x 2012/1 (NCT01712256):

In this study, no participants discontinued treatment or withdrew from the study because of a side effect. Except for reactions at the injection location, side effects associated with Vacc-4x and its adjuvant were uncommon. Itchiness was the most commonly report treatment-related reaction at the injection location, and most cases were either mild or moderate in intensity.8,15

CTN-Vacc-4x/L3-2011/1 (NCT01473810):

No serious side effects related to Vacc-4x were reported in this study. However, participants in all of the study groups, including the group that did not receive Vacc-4x, frequently experienced mild and temporary soreness inside their noses.12,16

Because Vacc-4x is still being studied, information on possible side effects of the vaccine is not complete. As testing of Vacc-4x continues, additional information on possible side effects will be gathered.

Where can I get more information about clinical trials studying Vacc-4x?

Where can I get more information about clinical trials studying Vacc-4x?

More information about Vacc-4x-related research studies is available from the AIDSinfo database of ClinicalTrials.gov study summaries. Click on the title of any trial in the list to see the ClinicalTrials.gov trial summary and more information about the study.

Some clinical trials may be looking for volunteer participants. Your health care provider can help you decide whether participating in a clinical trial is right for you. For information, visit NIH Clinical Research Trials and You.

References

References

  1. Treatment Action Group website. Research toward a cure trials. http://www.treatmentactiongroup.org/cure/trials. Accessed March 4, 2019.
  2. Bionor Holding AS website. About us. https://bionorholding.com/about-us/. Accessed March 4, 2019.
  3. EU Clinical Trials Register. EudraCT Number: 2015-003186-28; BIOSKILL: studying Vacc-4x, an HIV therapeutic vaccine, an assessment of immune-mediated anti-viral effects, when administered with adjuvant GM-CSF prior to HIV latent reservoir activation by the HDAC inhibitor, romidepsin. https://www.clinicaltrialsregister.eu/ctr-search/trial/2015-003186-28/DK. Accessed March 4, 2019.
  4. The History of Vaccines website. The development of HIV vaccines. https://www.historyofvaccines.org/content/articles/development-hiv-vaccines. Accessed March 4, 2019.
  5. Kran A-M, Jonassen TO, Sommerfelt MA, Løvgården G, Sørensen B, Kvale D. Low frequency of amino acid alterations following therapeutic immunization with HIV-1 Gag p24-like peptides. AIDS. 2010;24(17):2609-2618.
  6. Bionor Immuno AS. An open Phase I/IIa study to evaluate the safety and effect of therapeutic HIV-1 immunization using Vacc-4x + rhuGM-CSF, and HIV-1 reactivation using romidepsin, on the viral reservoir in virologically suppressed HIV-1 infected adults on cART. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on March 3, 2014. NLM Identifier: NCT02092116. https://clinicaltrials.gov/ct2/show/NCT02092116. Accessed March 4, 2019.
  7. Bionor Immuno AS. A Phase II, randomized, double-blind, multicenter, immunogenicity study of Vacc-4x versus placebo in patients infected with HIV-1 who have maintained an adequate response to ART. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on April 14, 2008. NLM Identifier: NCT00659789. https://clinicaltrials.gov/ct2/show/NCT00659789. Accessed March 4, 2019.
  8. Bionor Immuno AS. Re-boosting of subjects previously included in the CT BI-Vacc-4x 2007/1 study. An open, multicenter, immunogenicity, follow-up re-boosting study with Vacc-4x in subjects infected with HIV-1 who have maintained an adequate response to ART. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on October 16, 2012. NLM Identifier: NCT01712256. https://clinicaltrials.gov/ct2/show/NCT01712256. Accessed March 4, 2019.
  9. Kran A-M, Sørensen B, Nyhus J, et al. HLA- and dose-dependent immunogenicity of a peptide-based HIV-1 immunotherapy candidate (Vacc-4x). AIDS. 2004;18(14):1875-1883.
  10. Lind A, Sommerfelt M, Holmberg JO, Baksaas I, Sørensen B, Kvale D. Intradermal vaccination of HIV-infected patients with short HIV Gag p24-like peptides induces CD4 + and CD8 + T cell responses lasting more than seven years. Scand J Infect Dis. 2012;44(8):566-572. doi:10.3109/00365548.2011.653581
  11. Bionor Immuno AS. 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). In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on September 11, 2012. NLM Identifier: NCT01704781. https://clinicaltrials.gov/ct2/show/NCT01704781. Accessed March 4, 2019.
  12. Oslo University Hospital. Immunotherapy of HIV-infected patients: a single-blinded, randomized, immunogenicity, pilot study of intranasal administration of Vacc-4x with Endocine as adjuvant. In: ClinicalTrials.gov. Bethesda (MD): National Library of Medicine (US). Registered on November 1, 2011. NLM Identifier: NCT01473810. https://clinicaltrials.gov/ct2/show/NCT01473810. Accessed March 4, 2019.
  13. Leth S, Schleimann MH, Nissen SK, et al. Combined effect of Vacc-4x, recombinant human granulocyte macrophage colony-stimulating factor vaccination, and romidepsin on the HIV-1 reservoir (REDUC): a single-arm, phase 1B/2A trial. Lancet HIV. 2016;3(10):e463-72.
  14. Pollard RB, Rockstroh JK, Pantaleo G, et al. Safety and efficacy of the peptide-based therapeutic vaccine for HIV-1, Vacc-4x: A phase 2 randomised, double-blind, placebo-controlled trial. Lancet Infect Dis. 2014;14(4):291-300.
  15. Rockstroh JK, Asmuth D, Pantaleo G, et al. Re-boost immunizations with the peptide-based therapeutic HIV vaccine, Vacc-4x, restores geometric mean viral load set-point during treatment interruption. PLoS ONE. 2019;14(1). doi:10.1371/journal.pone.0210965
  16. Brekke K, Lind A, Holm-Hansen C, et al. Intranasal administration of a therapeutic HIV vaccine (Vacc-4x) induces dose-dependent systemic and mucosal immune responses in a randomized controlled trial. PLoS One. 2014;9(11). doi:10.1371/journal.pone.0112556

Last Reviewed: March 4, 2019