ASC-USPhase 2PVX2NCT03911076
Phase II Study of Treatment for HPV16+ ASC-US, ASC-H and LSIL
A Phase 2 study testing PVX-2 in people with ASC-US and ASC-H, run by PapiVax Biotech, Inc. at 6 sites in United States.
Trial summary
To evaluate the safety and tolerability of the dual IM pNGVL4a Sig/E7(detox)/HSP70 DNA and single IM TA-CIN immunization regimen To evaluate the efficacy of dual IM pNGVL4a-Sig/E7(detox)/HSP70 DNA and single IM TA-CIN immunization regimen on Human Papillomavirus (HPV) 16 clearance by Month 6 Read more about this study
- Who is it for?
- Ages 25 to 70 years, women only
- What is being tested?
- PVX-2
- Type of treatment
- Vaccines
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 16 participants
- Where
- 6 sitesUnited States
- Study dates
- 22 May 2019to 8 Jun 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 25 to 70 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Female subjects age 25-70 years with confirmation of ASC-US, ASC-H, or LSIL by liquid-based cytology
- HIV uninfected
- Patients whose cytologic specimen is HPV16+ by Aptima HPV 16 18/45 Genotype Assay
- Body Mass Index ≤ 32 kg/m2
- Hepatitis B surface antigen negative
- Anti-hepatitis C virus antibody (anti-HCV) negative or negative HCV PCR if anti-HCV positive
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- Patients who are able and willing to comply with all study procedures and voluntarily sign an informed consent form, and with anticipated availability for the planned follow-up period of one year
- Patients who are of childbearing potential agree to remain sexually abstinent, use methods of contraception (e.g. oral contraception, barrier methods, spermicide, intrauterine device (IUD)), or have a partner who is sterile (i.e., vasectomy) through 6 months.
- Patients must have adequate organ function at the time of enrollment as defined by the following parameters: white blood cell count >3,000/mcL; lymphocyte number >500/mcL; absolute neutrophil count >1,000/mcL; platelets >90,000/mcL; hemoglobin >9 g/dL; total bilirubin <3 X the institutional limit of normal; aspartate aminotransferase (AST [SGOT]) / alanine aminotransferase (ALT [SGPT]) <3 X the institutional limit of normal; creatinine <2.5X the institutional limit of normal.
- Histologic diagnosis of <CIN2 upon screening colposcopic examination with mandatory ECC, and cervical biopsy(ies) as clinically indicated.
Who cannot join
- Patients who are attempting pregnancy within 6 months, pregnant, or breastfeeding.
- Patients with immunodeficiency, or treatment with immunosuppressive medications
- Administration of any blood product within 3 months of enrollment.
- Administration of any licensed vaccine within 2 weeks of enrollment (4weeks for measles vaccine)
- Participation in a study with an investigational compound or device within 30 days of signing informed consent.
- History of seizures (unless seizure free for 5 years)
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- Patients with positive serological test for human immunodeficiency virus (HIV).
- Previous cancer history within the past 5 years.
- Patients who have had chemotherapy, radiation, biological cancer therapy, or other investigational agents within 28 days prior to the first dose of study drug.
- Patients who have had surgery within 28 days, excluding minor procedures (dental work, skin biopsy, etc).
- Patients with an uncontrolled intercurrent illness including, but not limited to, ongoing, or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Patients who have an active autoimmune disease (e.g., rheumatoid arthritis, systemic lupus erythematosus (SLE), ulcerative colitis, Crohn's Disease, multiple sclerosis (MS), ankylosing spondylitis).
- Patients with a recognized immunodeficiency disease including cellular immunodeficiencies, hypogammaglobulinemia, or dysgammaglobulinemia; patients who have acquired, hereditary, or congenital immunodeficiencies; patients being chronically treated with immunosuppressive drugs such as cyclosporin, adrenocorticotropic hormone (ACTH), or systemic corticosteroids
- Previous cervical conization or LEEP procedure or previous total hysterectomy due to cervical lesions at enrollment.
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
Austin Area Obstetrics, Gynecology, and Fertility
Austin, Texas, 78758
Corpus Christi Women's Clinic (Elligo Health Research, Inc.)
Corpus Christi, Texas, 78412
Obstetrics & Gynecology Associates, Inc.
Fairfield, Ohio, 45014
MacArthur Medical Center
Irving, Texas, 75062
University Hospital, Rutgers New Jersey Medical School
Newark, New Jersey, 07103
Health Awareness, Inc.
Port Saint Lucie, Florida, 33458
About this study
Official title: A Randomized Double-Blind, Placebo-controlled Phase II Trial With Safety Run-In of Intramuscular pNGVL4a-Sig/E7(Detox)/HSP70 and TA-CIN for the Treatment of Patients With HPV16+ Atypical Squamous Cells of Undetermined Significance (ASC-US) or Cannot Exclude High Grade SIL (ASC-H) Cytology or Low-grade Squamous Intraepithelial Lesion (LSIL)
- To evaluate the safety and tolerability of the dual IM pNGVL4a Sig/E7(detox)/HSP70 DNA and single IM TA-CIN immunization regimen
- To evaluate the efficacy of dual IM pNGVL4a-Sig/E7(detox)/HSP70 DNA and single IM TA-CIN immunization regimen on Human Papillomavirus (HPV) 16 clearance by Month 6
Read the detailed description
Patients with human papillomavirus type 16 (HPV16) infection and low-grade cervical dysplasia [low-grade squamous intraepithelial lesion (LSIL)/CIN1] or atypical squamous cells [atypical squamous cells of undetermined significance (ASC-US)/atypical squamous cells- cannot exclude high-grade squamous intraepithelial lesion (ASC-H)] require active surveillance for disease progression. A safe and effective immunotherapy to clear HPV16 is an unmet medical need. This study (NCT03911076) is a randomized double-blind, placebo-controlled phase II trial of PVX2 [vaccination twice with HPV16-targeting pNGVL4a-Sig/E7(detox)/HSP70 plasmid and once with the HPV16 L2E7E6 fusion protein "TA-CIN"] as immunotherapy for patients with HPV16+ ASC-US, ASC-H, or LSIL/CIN1. The primary objective of this cohort is to determine the safety and tolerability of PVX2 in three monthly immunizations. Subjects are confirmed to have HPV16 infection and LSIL/CIN1, ASC-US, or ASC-H. Adverse events are evaluated using Common Terminology Criteria for Adverse Events v5.0. HPV typing by HPV16 18/45 Aptima Assay is performed at baseline, month 6, and month 12, with simultaneous cytology analysis. Cervical biopsies and endocervical curettage are performed at baseline and month 6. In a safety run-in cohort 12 eligible patients are enrolled prior to the randomized phase.
- Being tested
- PVX-2, Placebo
- Medical subject headings
- Atypical Squamous Cells of the Cervix
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PVX-2Biological
pNGVL4a-Sig/E7(detox)/HSP70 (pBI-1, naked DNA plasmid priming vaccine) TA-CIN (HPV16 L2E7E6 fusion protein booster vaccine)
PlaceboOther
PBS and PGC
| Study group | Role | What they receive |
|---|---|---|
| PVX-2 | Experimental | Prime: 3 mg pNGVL4a-Sig/E7(detox)/HSP70 DNA Boost: 0.1 mg TA-CIN protein Receives: Biological: PVX-2 |
| Placebo | Placebo comparator | Prime: PBS (Phosphate Buffered Saline) Boost: PGC (Phosphate Glycine Cysteine Buffer) Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v5.0
To evaluate the safety and tolerability of the dual IM pNGVL4a Sig/E7(detox)/HSP70 DNA and single IM TA-CIN immunization regimen
Measured: 12 months
Percent of patients that have cleared HPV16 at Month 6
To evaluate the efficacy of dual IM pNGVL4a-Sig/E7(detox)/HSP70 DNA and single IM TA-CIN immunization regimen on Human Papillomavirus (HPV) 16 clearance by Month 6
Measured: 6 months
Secondary outcomes (2)
Percent of patients that have cleared HPV16 at Month 12
To evaluate the efficacy of dual IM pNGVL4a-Sig/E7(detox)/HSP70 DNA and single IM TA-CIN immunization regimen on maintenance of Human Papillomavirus (HPV) 16 clearance by Month 12
Measured: 12 months
Percent of patients that have normal cytology at Month 6
To evaluate the efficacy of dual IM pNGVL4a-Sig/E7(detox)/HSP70 DNA and single IM TA-CIN immunization regimen on regression to cytology with no evidence of intraepithelial lesion or malignancy (NILM) at Month 6
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Apr 2019
- Study start22 May 2019
- Primary completion8 Jun 2022
- Study completion8 Jun 2022
Why it stopped: Slow recruitment/funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for ASC-USStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Safety run-in followed by randomized double-blind, placebo-controlled study
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- PapiVax Biotech, Inc.
- Sponsor type
- University, hospital or other
- Collaborators
- Parexel
- Responsible party
- Sponsor
- Investigators
- Mark Einstein, MD, MS, Principal investigator, Professor and Chairman, Dept. of OBS&GYN, Rutgers New Jersey Medical School, Newark, NJ 07101
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03911076
- Sponsor's protocol ID
- PVX2TACIN17368
- Acronym
- PVX2
- Status last verified
- Jun 2024
- First submitted
- 5 Apr 2019
- Last updated
- 17 Jun 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Einstein MH, Roden RBS, Ferrall L, Akin M, Blomer A, Wu TC, Chang YN. Safety Run-in of Intramuscular pNGVL4a-Sig/E7(detox)/HSP70 DNA and TA-CIN Protein Vaccination as Treatment for HPV16+ ASC-US, ASC-H, or LSIL/CIN1. Cancer Prev Res (Phila). 2023 Apr 3;16(4):219-227. doi: 10.1158/1940-6207.CAPR-22-0413.
PubMed 36607735
Study at a glance
From the registry record, last updated by the sponsor on 17 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Double-Blind, Placebo-controlled Phase II Trial With Safety Run-In of Intramuscular pNGVL4a-Sig/E7(Detox)/HSP70 and TA-CIN for the Treatment of Patients With HPV16+ Atypical Squamous Cells of Undetermined Significance (ASC-US) or Cannot Exclude High Grade SIL (ASC-H) Cytology or Low-grade Squamous Intraepithelial Lesion (LSIL)
- ClinicalTrials.gov ID
- NCT03911076
- Acronym / sponsor ID
- PVX2 / PVX2TACIN17368
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow recruitment/funding
- Enrolment
- 16 participants (actual)
- Lead sponsor
- PapiVax Biotech, Inc.University, hospital or other
- Collaborators
- Parexel
- Study start
- 22 May 2019 (actual)
- Primary completion
- 8 Jun 2022 (actual)
- Study completion
- 8 Jun 2022 (actual)
- First posted
- 10 Apr 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
- To evaluate the safety and tolerability of the dual IM pNGVL4a Sig/E7(detox)/HSP70 DNA and single IM TA-CIN immunization regimen
- To evaluate the efficacy of dual IM pNGVL4a-Sig/E7(detox)/HSP70 DNA and single IM TA-CIN immunization regimen on Human Papillomavirus (HPV) 16 clearance by Month 6
Detailed description
Patients with human papillomavirus type 16 (HPV16) infection and low-grade cervical dysplasia [low-grade squamous intraepithelial lesion (LSIL)/CIN1] or atypical squamous cells [atypical squamous cells of undetermined significance (ASC-US)/atypical squamous cells- cannot exclude high-grade squamous intraepithelial lesion (ASC-H)] require active surveillance for disease progression. A safe and effective immunotherapy to clear HPV16 is an unmet medical need. This study (NCT03911076) is a randomized double-blind, placebo-controlled phase II trial of PVX2 [vaccination twice with HPV16-targeting pNGVL4a-Sig/E7(detox)/HSP70 plasmid and once with the HPV16 L2E7E6 fusion protein "TA-CIN"] as immunotherapy for patients with HPV16+ ASC-US, ASC-H, or LSIL/CIN1. The primary objective of this cohort is to determine the safety and tolerability of PVX2 in three monthly immunizations. Subjects are confirmed to have HPV16 infection and LSIL/CIN1, ASC-US, or ASC-H. Adverse events are evaluated using Common Terminology Criteria for Adverse Events v5.0. HPV typing by HPV16 18/45 Aptima Assay is performed at baseline, month 6, and month 12, with simultaneous cytology analysis. Cervical biopsies and endocervical curettage are performed at baseline and month 6. In a safety run-in cohort 12 eligible patients are enrolled prior to the randomized phase.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Safety run-in followed by randomized double-blind, placebo-controlled study
| Arm | Type | Receives |
|---|---|---|
| PVX-2 | Experimental | Biological: PVX-2Prime: 3 mg pNGVL4a-Sig/E7(detox)/HSP70 DNA Boost: 0.1 mg TA-CIN protein |
| Placebo | Placebo comparator | Other: PlaceboPrime: PBS (Phosphate Buffered Saline) Boost: PGC (Phosphate Glycine Cysteine Buffer) |
Who may qualify
- Ages
- 25 to 70 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Female subjects age 25-70 years with confirmation of ASC-US, ASC-H, or LSIL by liquid-based cytology
- HIV uninfected
- Patients whose cytologic specimen is HPV16+ by Aptima HPV 16 18/45 Genotype Assay
- Body Mass Index ≤ 32 kg/m2
- Hepatitis B surface antigen negative
Key exclusion criteria (14 listed)
- Patients who are attempting pregnancy within 6 months, pregnant, or breastfeeding.
- Patients with immunodeficiency, or treatment with immunosuppressive medications
- Administration of any blood product within 3 months of enrollment.
- Administration of any licensed vaccine within 2 weeks of enrollment (4weeks for measles vaccine)
- Participation in a study with an investigational compound or device within 30 days of signing informed consent.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PVX-2pNGVL4a-Sig/E7(detox)/HSP70 (pBI-1, naked DNA plasmid priming vaccine) TA-CIN (HPV16 L2E7E6 fusion protein booster vaccine) | Biological | PVX-2 |
| PlaceboPBS and PGC | Other | Placebo |
Primary outcome
Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v5.0
Time frame: 12 months
To evaluate the safety and tolerability of the dual IM pNGVL4a Sig/E7(detox)/HSP70 DNA and single IM TA-CIN immunization regimen
Percent of patients that have cleared HPV16 at Month 6
Time frame: 6 months
To evaluate the efficacy of dual IM pNGVL4a-Sig/E7(detox)/HSP70 DNA and single IM TA-CIN immunization regimen on Human Papillomavirus (HPV) 16 clearance by Month 6
2 secondary outcomes
Percent of patients that have cleared HPV16 at Month 12
Time frame: 12 months
Percent of patients that have normal cytology at Month 6
Time frame: 6 months
Results and safety
The study was stopped early (reason given: Slow recruitment/funding). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jun 2024.
- Results publication: PubMed 36607735Einstein MH, Roden RBS, Ferrall L, Akin M, Blomer A, Wu TC, Chang YN. Safety Run-in of Intramuscular pNGVL4a-Sig/E7(detox)/HSP70 DNA and TA-CIN Protein Vaccination as Treatment for HPV16+ ASC-US, ASC-H, or LSIL/CIN1. Cancer Prev Res (Phila). 2023 Apr 3;16(4):219-227. doi: 10.1158/1940-6207.CAPR-22-0413.
- Study reportLink provided by the sponsor.
- Individual participant dataSharing planned: No
Related trials for ASC-US
Not yet recruiting
Papilozumib Vaginal Gel for Exocervical Mucosal Restoration in Women With Human Papillomavirus (HPV)
Human Papillomavirus Infection, Human Papillomavirus Infections
Active, not recruiting
Dual-Modality Immunotherapy for HPV Clearance (DUAL-HPV)
Human Papillomavirus Infection, Cervical Intraepithelial Neoplasia (CIN)
RecruitingPhase 1
Study of Treatment for HPV16+ ASC-US or LSIL
ASC-US, LSIL
RecruitingPhase 2
Phase II Study of Dysplasix™ Intravaginal Suppositories in Patients Patients With High-Risk HPV and Mild Cervical Cytologic Abnormalities
High-risk HPV (Any Strain), LSIL, Low Grade Squamous Intraepithelial Lesion
Recruiting
Comparison Between Liquid-Based Cytology And Molecular Screening For Detecting Precursor Lesions and Cervical Cancer
I) Atypical Squamous Cells of Undetermined Significance (ASC-US), II) Atypical Glandular Cells of Uncertain Significance (AGUS)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mark Einstein, MD, MS principal investigator
Professor and Chairman, Dept. of OBS&GYN, Rutgers New Jersey Medical School, Newark, NJ 07101
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing PVX-2 in people with ASC-US and ASC-H, run by PapiVax Biotech, Inc. at 6 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 17 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Slow recruitment/funding). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v5.0 (time frame: 12 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03911076, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jun 2024.