CompletedNCT00988559Updated Jul 9, 2018Results posted

Therapeutic Vaccination for Patients With HPV16+ Cervical Intraepithelial Neoplasia (CIN2/3)

A Phase 1 interventional study of DNA vaccination and Gene gun vaccine in HPV16 Positive and Cervical Intraepithelial Neoplasia (CIN 2/3), sponsored by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins. Completed at 3 sites in United States. Open to female participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2018-07-09.

Sponsored by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins · Phase 1, Interventional, and Treatment

Phase: Phase 1
Study type: Interventional
Enrollment: 132
Allocation: Non-randomized
Ages: 18 Years and older
Sex: Female

Study summary

This study will test the efficacy and safety of different routes of administration of a DNA vaccine in patients with HPV16+ CIN2/3. Subjects will be enrolled in one of six treatment groups. Subjects enrolled in the first two groups will receive vaccination intradermally with a needle-free delivery device. Subjects enrolled in groups 3 and 4 will receive vaccination intramuscularly. Subjects enrolled in groups 5 and 6 will receive vaccine intralesionally.

Read the detailed description

Primary Objectives

To evaluate the feasibility and toxicity of vaccination in women with CIN2/3 caused by HPV16
To evaluate the effect of vaccination on histology
To compare immunogenicity of three different routes of administration: intradermal (ID), intramuscular (IM), intralesional (IL).

Secondary Objectives:

To evaluate changes in HPV viral load
To evaluate the cellular immune response to vaccination
To evaluate the humoral immune response to vaccination
To evaluate local tissue immune response
To correlate measures of immune response with clinical response
To correlate measures of immune response with those observed in the preclinical model

Conditions studied

HPV16 Positive
Cervical Intraepithelial Neoplasia (CIN 2/3)

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Keywords

high grade cervical dysplasia
treatment vaccine
therapeutic
HPV
DNA vaccine
gene therapy
gene gun
pre-cancerous

In context

Neoplasms

9,365 studies on the registry are indexed under Neoplasms; 2,489 are open to participants now.

This study's enrollment of 132 is above the median of 50 across 7,253 interventional studies indexed under Neoplasms.

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Lead sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins is the lead sponsor of 572 studies on the registry; 73 are open to participants now.

Of its 111 completed or terminated interventional studies of FDA-regulated products, 67 (60%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: Female
Accepts healthy volunteers: No

Inclusion criteria

patients with high grade cervical intraepithelial lesions (CIN2/3)
patients whose lesions are HPV16+
patients who are age 18 or older
patients who are able to give informed consent
patients who are immunocompetent
patients who are not pregnant, committed to using adequate contraception if of childbearing age
patients who have a minimum hemoglobin level of 9

Exclusion criteria

Exclusion Criteria:

Patients with cytologic evidence of glandular dysplasia
Patients with cytologic evidence of adenocarcinoma in situ
Patients who are pregnant
Patients with an active autoimmune disease
Patients who are taking immunosuppressive medication
Patients with concurrent malignancy except for nonmelanoma skin lesions
Patients who have an allergy to gold.
Patients with any evidence of damaged skin, or moles, scars, tattoos or marks at the proposed site(s) of administration that might interfere with the interpretation of local skin reactions.
History or evidence of a physician-diagnosed chronic or recurrent inflammatory skin disease (e.g. psoriasis, eczema, atopic dermatitis, hypersensitivity) at the proposed site of administration in the past 5 years.
Patients who have an active autoimmune disease or history of autoimmune disease requiring medical treatment with systemic immunosuppressants, including: inflammatory bowel disease, systemic vasculitis, scleroderma, psoriasis, multiple sclerosis, hemolytic anemic, or immune thrombocytopenia, rheumatoid arthritis, SLE, and Sjogren's syndrome, sarcoidosis. Asthma or COPD that does not require systemic corticosteroids or routine use of inhaled steroids is acceptable
Patients who have received prior chrysotherapy (administration of gold salts to treat rheumatoid arthritis).
Patients with a history of arterial or venous thrombosis
Patients with non-healed wounds.
Patients with a history of keloid formation ( ID delivery group only)
Patients with a history of hepatitis B with persistent infection.

Study design

Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 132 participants (actual)

Study arms

Experimental
PMED Delivery - groups 1 and 2
Subjects will receive pNGVL4a-CRT/E7(detox) via gene gun at weeks 0, 4, 8 prior to therapeutic resection of their lesion at week 15.
Biological: DNA vaccination · Device: Gene gun vaccine · Procedure: therapeutic resection of the lesion
Experimental
IM injections - groups 5 and 6
Subjects will receive pNGVL4a-CRT/E7(detox) intramuscularly at weeks 0, 4, 8 prior to therapeutic resection of their lesion at week 15.
Biological: DNA vaccination · Biological: intramuscular vaccination · Procedure: therapeutic resection of the lesion
Experimental
Intralesional delivery - group 3 and 4
Subjects will receive pNGVL4a-CRT/E7(detox) intra-mucosally at weeks 0, 4, 8 prior to therapeutic resection of their lesion at week 15.
Biological: DNA vaccination · Biological: intra-lesional vaccine administration · Procedure: therapeutic resection of the lesion
Experimental
Intralesional delivery + imiquimod - group 7
Subjects will receive pNGVL4a-CRT/E7(detox) intra-mucosally and imiquimod applied to the cervix at weeks 0, 4, 8 prior to therapeutic resection of their lesion at week 15.
Biological: DNA vaccination · Biological: intra-lesional vaccine administration · Procedure: therapeutic resection of the lesion · Drug: imiquimod

Interventions

BiologicalDNA vaccination
vaccination with pNGVL4a-CRT/E7(detox)
Also known as: Therapeutic vaccine
DeviceGene gun vaccine
8 micrograms (group 1) or 16 micrograms (group 2)
Also known as: PMED administration, ND10 device
Biologicalintramuscular vaccination
1mg (group 3) or 3mg (group 4) of pNGVLra-CRT/E7(detox) administered intramuscularly
Also known as: DNA vaccine
Biologicalintra-lesional vaccine administration
1mg (group 5) or 3mg (group 6) of pNGVL4a-CRT/E7(detox)administered intra-lesionally
Also known as: Intra-lesional DNA vaccination
Proceduretherapeutic resection of the lesion
at week 15, all residual lesions will be resected
Also known as: LEEP or cold knife conization
Drugimiquimod
imiquimod applied to the cervix by the physician

What researchers measure

Primary outcomes

Number of Participants With Related Serious Adverse Events
Presence of intervention-related serious adverse events as defined by CTCAE
Time frame: 9 months

Secondary outcomes

Absence of CIN2/3 Lesion by Week 15
Number of participants with no CIN2/3 lesion at the week 15 visit
Time frame: 15 weeks

Results

Posted Jul 9, 2018

Participant flow

Participant flow — Overall Study
Milestone	PMED Delivery - Groups 1 and 2	IM Injections - Groups 5 and 6	Intralesional Delivery - Group 3 and 4	Intralesional Delivery + Imiquimod - Group 7
Started	10	11	11	7
Completed	9	9	9	6
Not completed	1	2	2	1
Withdrew: Withdrawal by subject	1	1	0	1
Withdrew: Pregnancy	0	1	1	0
Withdrew: Lost to follow-up	0	0	1	0

Outcome measures

PrimaryNumber of Participants With Related Serious Adverse Events

Presence of intervention-related serious adverse events as defined by CTCAE

Time frame:: 9 months
Reported as:: Count of participants · Participants

Number of Participants With Related Serious Adverse Events
Participants	PMED Delivery - Groups 1 and 2	IM Injections - Groups 5 and 6	Intralesional Delivery - Group 3 and 4	Intralesional Delivery + Imiquimod - Group 7
Number of Participants With Related Serious Adverse Events	0	0	0	0

SecondaryAbsence of CIN2/3 Lesion by Week 15

Number of participants with no CIN2/3 lesion at the week 15 visit

Time frame:: 15 weeks
Reported as:: Count of participants · Participants

Absence of CIN2/3 Lesion by Week 15
Participants	PMED Delivery - Groups 1 and 2	IM Injections - Groups 5 and 6	Intralesional Delivery - Group 3 and 4	Intralesional Delivery + Imiquimod - Group 7
Absence of CIN2/3 Lesion by Week 15	2	3	3	1

Adverse events

Collected over 41 weeks. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
PMED Delivery - Groups 1 and 2	—	0/10 (0%)	10/10 (100%)
IM Injections - Groups 5 and 6	—	0/11 (0%)	11/11 (100%)
Intralesional Delivery - Group 3 and 4	—	0/11 (0%)	10/11 (90.9%)
Intralesional Delivery + Imiquimod - Group 7	—	0/7 (0%)	7/7 (100%)

Most frequent other events

Most frequent other events
Event	PMED Delivery - Groups 1 and 2	IM Injections - Groups 5 and 6	Intralesional Delivery - Group 3 and 4	Intralesional Delivery + Imiquimod - Group 7
General pain, fever, malaise/fatigueGeneral disorders	8/10	8/11	8/11	7/7
Injection site reactionsGeneral disorders	8/10	6/11	1/11	0/7
Vaginal bleeding/spottingReproductive system and breast disorders	0/10	0/11	3/11	1/7
RashInfections and infestations	0/10	2/11	0/11	1/7
DepressionPsychiatric disorders	1/10	0/11	0/11	1/7
Laryngeal inflammationRespiratory, thoracic and mediastinal disorders	0/10	1/11	0/11	1/7
Limb numbnessNervous system disorders	1/10	1/11	0/11	0/7

Baseline characteristics

Participants enrolled in the study who received at least one study intervention

Age, Continuous
Age, Continuous(years)	PMED Delivery - Groups 1 and 2	IM Injections - Groups 5 and 6	Intralesional Delivery - Group 3 and 4	Intralesional Delivery + Imiquimod - Group 7	Total
Median	25.5 (20 to 44)	26 (21 to 35)	26 (23 to 35)	26.14 (24 to 29)	25.91 (20 to 44)

Sex: Female, Male
Sex: Female, Male(Participants)	PMED Delivery - Groups 1 and 2	IM Injections - Groups 5 and 6	Intralesional Delivery - Group 3 and 4	Intralesional Delivery + Imiquimod - Group 7	Total
Female	10	11	11	7	39
Male	0	0	0	0	0

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	PMED Delivery - Groups 1 and 2	IM Injections - Groups 5 and 6	Intralesional Delivery - Group 3 and 4	Intralesional Delivery + Imiquimod - Group 7	Total
American Indian or Alaska Native	0	0	0	0	0
Asian	1	1	0	0	2
Native Hawaiian or Other Pacific Islander	0	0	0	0	0
Black or African American	0	5	2	4	11
White	9	5	9	3	26
More than one race	0	0	0	0	0
Unknown or Not Reported	0	0	0	0	0

Study locations

3 sites

University of Alabama at Birmingham
Birmingham, Alabama 35294, United States
Johns Hopkins Outpatient Center
Baltimore, Maryland 21205, United States
Johns Hopkins Bayview Medical Center
Baltimore, Maryland 21224, United States

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Jul 9, 2018, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT00988559
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators: National Institutes of Health (NIH), National Cancer Institute (NCI)
Responsible party: Sponsor
First posted: Oct 2, 2009
Start date: Sep 2009
Primary completion: Jul 2016
Completion: Jul 2016
Results posted: Jul 9, 2018
Last update: Jul 9, 2018

Study contacts

Cornelia L Trimble, MD

principal investigator · Johns Hopkins University

Oversight

Data monitoring committee: Yes

View the source record on ClinicalTrials.gov ↗

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