HPV Vaccine for Cervical Cell Changes

(PVX-6 Trial)

Recruiting at 1 trial location

Overseen By Yung-Nien Chang, Ph.D.

Age: 18+

Sex: Female

Trial Phase: Phase 1

Sponsor: PapiVax Biotech, Inc.

Must not be taking: Steroids, Immunosuppressants, others

Disqualifiers: Immunosuppression, Autoimmune disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

Duration: 8 weeks

30 Participants Needed

Trial Summary

What is the purpose of this trial?

Phase I clinical trial to assess safety of pNGVL4aCRTE6E7L2 DNA and TA-CIN protein vaccinations, and to seek the appropriate dose of the pNGVL4aCRTE6E7L2 DNA vaccine

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you are on immunosuppressive medications or other investigational agents, you may need to stop them before joining the trial.

What data supports the effectiveness of the treatment pNGVL4aCRTE6E7L2 DNA vaccine for cervical cell changes?

Research on a similar treatment, TA-CIN, shows that it can trigger immune responses against HPV16, which is linked to cervical diseases. In trials, TA-CIN led to significant immune cell activity and complete lesion regression in some patients, suggesting potential effectiveness in treating HPV-related conditions. ^{1 2 3 4 5}

Is the HPV vaccine TA-CIN safe for humans?

In clinical trials, the TA-CIN vaccine was tested on healthy volunteers and showed no serious side effects, indicating it is generally safe for humans. ^{1 2 4 6 7}

How is the HPV vaccine treatment for cervical cell changes different from other treatments?

The HPV vaccine treatment, pNGVL4aCRTE6E7L2, TA-CIN, is unique because it targets specific HPV proteins (E6 and E7) that are consistently expressed in HPV-associated cancer cells, aiming to boost the body's immune response to fight the virus. Unlike standard preventive vaccines, this treatment is designed to be therapeutic, potentially benefiting those already exposed to HPV by enhancing T-cell responses to control and possibly clear HPV-related lesions. ^{1 4 5 8 9}

Eligibility Criteria

This trial is for individuals over 19 years old with persistent HPV16+ ASC-US/LSIL cervical lesions. They must have good organ function, agree to use two forms of contraception, and be able to follow the study schedule. Excluded are those with more advanced cervical changes, immunosuppression, other serious health issues, pregnancy or breastfeeding, certain infections (HIV/HCV/HBV), prior malignancy within 5 years (except some skin cancers), previous LEEP/conization procedures or HPV vaccinations.

Inclusion Criteria

Subject is able to adhere to the study visit schedule and other protocol requirements.

Total bilirubin <3 X the institutional limit of normal

Absolute neutrophil count > 1,000

Exclusion Criteria

I have had a LEEP or cervical conization procedure before.

I have been cancer-free for over 5 years, or I had skin cancer removed within this time.

I am able and willing to understand and sign the consent form.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pNGVL4aCRTE6E7L2 DNA vaccine and TA-CIN protein vaccinations. The pNGVL4aCRTE6E7L2 DNA is administered at weeks 0, 4, and 8, and the TA-CIN protein is administered at week 8.

8 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety, feasibility, and immune response post-vaccination

12 months

Treatment Details

Interventions

• pNGVL4aCRTE6E7L2
• TA-CIN

Trial Overview The trial is testing the safety and proper dosage of pNGVL4aCRTE6E7L2 DNA vaccine and TA-CIN protein vaccination in patients with specific types of precancerous cervical lesions caused by HPV16. It's a Phase I study which means it's early in the clinical trials process focusing on safety.

Participant Groups

Group I: pNGVL4aCRTE6E7L2 3 mg dose Experimental Treatment 1 Intervention

High dose of pNGVL4aCRTE6E7L2 plasmid DNA is administered by intramuscular injection at weeks 0, 4 and 8.

Group II: pNGVL4aCRTE6E7L2 1 mg dose Experimental Treatment 1 Intervention

Intermediate dose of pNGVL4aCRTE6E7L2 plasmid DNA is administered by intramuscular injection at weeks 0, 4 and 8.

Group III: pNGVL4aCRTE6E7L2 0.3mg dose Experimental Treatment 1 Intervention

Low dose of pNGVL4aCRTE6E7L2 plasmid DNA is administered by intramuscular injection at weeks 0, 4 and 8.

Group IV: PVX-6 Experimental Treatment 2 Interventions

Selected dose of pNGVL4aCRTE6E7L2 plasmid DNA is administered by intramuscular injection at weeks 0 and 4, and the TA-CIN protein is administered by intramuscular injection at week 8.

Who Is Running the Clinical Trial?

PapiVax Biotech, Inc.

Lead Sponsor

Trials

6

Recruited

120+

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

Johns Hopkins University

Collaborator

Trials

2,366

Recruited

15,160,000+

Findings from Research

The TA-CIN vaccine, which targets HPV16 E6, E7, and L2 proteins, successfully triggered strong immune responses in a pre-clinical mouse model, including the production of HPV16-specific T-cells and antibodies.

Using TA-CIN in combination with the TA-HPV vaccine enhanced the immune response, effectively preventing the growth of HPV16-positive tumors, suggesting a promising approach for future human trials in treating cervical intraepithelial neoplasia and cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pre-clinical safety and efficacy of TA-CIN, a recombinant HPV16 L2E6E7 fusion protein vaccine, in homologous and heterologous prime-boost regimens. van der Burg, SH., Kwappenberg, KM., O'Neill, T., et al.[2022]

The TA-CIN vaccine, which targets HPV type 16, was found to be safe in a phase I study involving 40 healthy volunteers, with no serious adverse events reported after administration.

The vaccine successfully induced both antibody and T-cell immune responses against HPV16 oncoproteins, particularly at the highest dose of 533 micrograms, indicating its potential effectiveness in preventing HPV-related tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhancement of human papillomavirus (HPV) type 16 E6 and E7-specific T-cell immunity in healthy volunteers through vaccination with TA-CIN, an HPV16 L2E7E6 fusion protein vaccine. de Jong, A., O'Neill, T., Khan, AY., et al.[2022]

In a phase II trial involving 192 women with confirmed CIN2/3, the tipapkinogen sovacivec (TS) vaccine demonstrated a significantly higher rate of complete resolution of CIN2/3 compared to placebo (24% vs. 10%), indicating its efficacy in treating high-risk HPV-related lesions.

The vaccine was well tolerated, with injection site reactions being the most common side effect, suggesting a favorable safety profile over a 30-month period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and safety of Tipapkinogen Sovacivec therapeutic HPV vaccine in cervical intraepithelial neoplasia grades 2 and 3: Randomized controlled phase II trial with 2.5 years of follow-up. Harper, DM., Nieminen, P., Donders, G., et al.[2022]

TA-CIN, a therapeutic HPV vaccine targeting HPV16, has shown promise in mouse models by inducing strong immune responses, specifically CD4 and CD8 T-cell activation, which are crucial for fighting HPV-related diseases.

In a phase II trial, combining TA-CIN with imiquimod led to significant immune cell infiltration and complete regression of lesions in 63% of patients with vulval intraepithelial neoplasia, indicating its potential effectiveness in treating HPV-associated conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TA-CIN, a vaccine incorporating a recombinant HPV fusion protein (HPV16 L2E6E7) for the potential treatment of HPV16-associated genital diseases. Hibbitts, S.[2020]

The TA-HPV vaccine was well tolerated in a Phase II study involving 12 women with high-grade HPV-positive lesions, showing promising safety and immunogenicity results.

42% of participants experienced at least a 50% reduction in lesion size over 24 weeks, with an overall average decrease of 40%, indicating potential efficacy in treating anogenital intraepithelial neoplasia associated with HPV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vaccinia-expressed human papillomavirus 16 and 18 e6 and e7 as a therapeutic vaccination for vulval and vaginal intraepithelial neoplasia. Baldwin, PJ., van der Burg, SH., Boswell, CM., et al.[2022]

The plasmid vaccine pNGVL4a-CRT-E7(detox) was found to be well-tolerated in a study of 32 patients with HPV16-associated CIN2/3, with most adverse events being mild and related to the injection site.

When administered directly into the cervical lesion, the vaccine showed the strongest immune response and resulted in histologic regression to CIN 1 or less in 30% of patients who completed the treatment, suggesting potential clinical efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pilot study of pNGVL4a-CRT/E7(detox) for the treatment of patients with HPV16+ cervical intraepithelial neoplasia 2/3 (CIN2/3). Alvarez, RD., Huh, WK., Bae, S., et al.[2022]

Combining the HPV16 E6E7L2 fusion protein (TA-CIN) with the adjuvant GPI-0100 significantly enhances immune responses, including increased neutralizing antibodies and CD8+ T cell activity, in mice vaccinated against HPV16-related tumors.

Administering TA-CIN/GPI-0100 after cisplatin chemotherapy not only slows tumor growth but also leads to tumor regression and extended survival in 80% of treated mice, demonstrating a potent therapeutic effect in a murine model of HPV16+ cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sequential cisplatin therapy and vaccination with HPV16 E6E7L2 fusion protein in saponin adjuvant GPI-0100 for the treatment of a model HPV16+ cancer. Peng, S., Wang, JW., Karanam, B., et al.[2020]

A codon-optimized HPV-16 E6 DNA vaccine (pNGVL4a-E6/opt) was developed, showing highly efficient translation and significantly enhancing E6-specific CD8+ T cell immune responses in vaccinated mice.

Vaccination with this optimized E6 DNA vaccine resulted in strong protective and therapeutic anti-tumor effects against HPV-associated tumors, suggesting it could improve the effectiveness of HPV vaccines in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A DNA vaccine encoding a codon-optimized human papillomavirus type 16 E6 gene enhances CTL response and anti-tumor activity. Lin, CT., Tsai, YC., He, L., et al.[2006]

Cervicovaginal vaccination with the TA-HPV vaccine, following an initial DNA vaccine, significantly increased the accumulation of HPV-specific CD8 T cells in the cervicovaginal tract compared to intramuscular vaccination, suggesting a more effective immune response in targeting cervical cancer.

The study demonstrated that cervicovaginal vaccination can induce strong local immune responses against HPV-16 E7, regardless of the route of the initial DNA vaccine, supporting the potential for this method in clinical applications for treating cervical cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Local HPV Recombinant Vaccinia Boost Following Priming with an HPV DNA Vaccine Enhances Local HPV-Specific CD8+ T-cell-Mediated Tumor Control in the Genital Tract. Sun, YY., Peng, S., Han, L., et al.[2021]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Pre-clinical safety and efficacy of TA-CIN, a recombinant HPV16 L2E6E7 fusion protein vaccine, in homologous and heterologous prime-boost regimens. [2022]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Enhancement of human papillomavirus (HPV) type 16 E6 and E7-specific T-cell immunity in healthy volunteers through vaccination with TA-CIN, an HPV16 L2E7E6 fusion protein vaccine. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

The efficacy and safety of Tipapkinogen Sovacivec therapeutic HPV vaccine in cervical intraepithelial neoplasia grades 2 and 3: Randomized controlled phase II trial with 2.5 years of follow-up. [2022]

4. England pubmed.ncbi.nlm.nih.gov

TA-CIN, a vaccine incorporating a recombinant HPV fusion protein (HPV16 L2E6E7) for the potential treatment of HPV16-associated genital diseases. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

Vaccinia-expressed human papillomavirus 16 and 18 e6 and e7 as a therapeutic vaccination for vulval and vaginal intraepithelial neoplasia. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

A pilot study of pNGVL4a-CRT/E7(detox) for the treatment of patients with HPV16+ cervical intraepithelial neoplasia 2/3 (CIN2/3). [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Sequential cisplatin therapy and vaccination with HPV16 E6E7L2 fusion protein in saponin adjuvant GPI-0100 for the treatment of a model HPV16+ cancer. [2020]

8. England pubmed.ncbi.nlm.nih.gov

A DNA vaccine encoding a codon-optimized human papillomavirus type 16 E6 gene enhances CTL response and anti-tumor activity. [2006]

9. United States pubmed.ncbi.nlm.nih.gov

Local HPV Recombinant Vaccinia Boost Following Priming with an HPV DNA Vaccine Enhances Local HPV-Specific CD8+ T-cell-Mediated Tumor Control in the Genital Tract. [2021]