Cervical Intraepithelial Neoplasia Grade 2/3, High-risk HPV (Any Strain)
Conditions
Keywords
cervical dysplasia, HPV, Treatment, preinvasive, cervix, vaginal suppository, Cornelia Trimble, abnormal pap, CIN
Brief summary
This phase I research protocol is designed to assess immunogenicity and clinical endpoints in patients with human papillomavirus (HPV) 16 cervical intraepithelial neoplasia (CIN)2/3. The protocol tests the use of artesunate in suppository formulation applied intravaginally in patients with cervical dysplasia (CIN2/3). The primary endpoint is to determine and evaluate the safety, tolerability, and feasibility of intravaginal administration of artesunate in health women with CIN2/3.
Detailed description
Phase I open-label dose escalation study of intravaginal artesunate, formulated in suppositories, in adult females with biopsy-confirmed CIN2/3. Thirty (30) subjects will undergo up to a total of three cycles of intravaginal artesunate. The first cycle will be initiated on Day 0, the second at Week 4, and the third and final cycle at week 8.
Interventions
Sponsors
Frantz Viral Therapeutics, LLC
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* ≥ 18 years * Capable of informed consent * HPV-positive by DNA test * Histologically confirmed CIN 2, CIN 3, or CIN 2/3 * Body weight ≥ 50 kg * Immune competent
Exclusion criteria
* Pregnant and nursing women * HIV seropositive * Active autoimmune disease * Taking immunosuppressive medication * Evidence of concurrent adenocarcinoma in situ * Concurrent malignancy except for nonmelanoma skin lesions
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Serious Adverse Events | 41 weeks | Number of participants with serious adverse events or dose limiting toxicities related to the study intervention assessed using Common Terminology Criteria for Adverse Events (CTCAE) 4.0 criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Viral Clearance of HPV | 41 weeks | Number of participants whose human papillomavirus (HPV) genotypes present at study entry become undetectable without surgical intervention. HPV genotyping detects strains of HPV present at each timepoint. For this outcome, we evaluated whether strains of HPV detected at study entry became undetectable during the study participation. |
| Histologic Regression of CIN2/3 | 41 weeks | Number of participants who had histologic regression from cervical intraepithelial neoplasia (CIN) 2/3 to CIN 1 or less, as assessed by colposcopically-directed biopsies. Histologic regression is defined as disappearance of the high grade lesion (CIN2/3) without surgical intervention. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 50 mg Artesunate Suppositories, 1 Cycle Subjects enrolled in this cohort will receive 1 five day cycle of Artesunate suppositories prior to therapeutic resection of their lesion (if clinically indicated).
Artesunate Suppositories | 3 |
| 200 mg Artesunate Suppositories, 1 Cycle Subjects enrolled in this cohort will receive 1 five day cycle of Artesunate suppositories prior to therapeutic resection of their lesion (if clinically indicated).
Artesunate Suppositories | 9 |
| 200 mg Artesunate Suppositories,2 Cycles Subjects enrolled in this cohort will receive 2 five day cycles of Artesunate suppositories prior to therapeutic resection of their lesion (if clinically indicated).
Artesunate Suppositories | 10 |
| 200 mg Artesunate Suppositories,3 Cycles Subjects enrolled in this cohort will receive 3 five day cycles of Artesunate suppositories prior to therapeutic resection of their lesion (if clinically indicated).
Artesunate Suppositories | 8 |
| Total | 30 |
Baseline characteristics
| Characteristic | 200 mg Artesunate Suppositories, 1 Cycle | 200 mg Artesunate Suppositories,2 Cycles | 50 mg Artesunate Suppositories, 1 Cycle | 200 mg Artesunate Suppositories,3 Cycles | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants | 10 Participants | 3 Participants | 8 Participants | 30 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized Black | 2 Participants | 1 Participants | 0 Participants | 2 Participants | 5 Participants |
| Race/Ethnicity, Customized Hispanic | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 7 Participants | 7 Participants | 3 Participants | 4 Participants | 21 Participants |
| Region of Enrollment United States | 9 Participants | 10 Participants | 3 Participants | 8 Participants | 30 Participants |
| Sex: Female, Male Female | 9 Participants | 10 Participants | 3 Participants | 8 Participants | 30 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Type of HPV at baseline HPV16 and other genotypes | 2 Participants | 2 Participants | 0 Participants | 0 Participants | 4 Participants |
| Type of HPV at baseline HPV16 only | 3 Participants | 1 Participants | 0 Participants | 4 Participants | 8 Participants |
| Type of HPV at baseline Non-16 HPV genotypes | 4 Participants | 7 Participants | 3 Participants | 4 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 9 | 0 / 10 | 0 / 8 |
| other Total, other adverse events | 2 / 3 | 9 / 9 | 8 / 10 | 8 / 8 |
| serious Total, serious adverse events | 0 / 3 | 0 / 9 | 0 / 10 | 0 / 8 |
Outcome results
Primary
Number of Participants With Serious Adverse Events
Number of participants with serious adverse events or dose limiting toxicities related to the study intervention assessed using Common Terminology Criteria for Adverse Events (CTCAE) 4.0 criteria.
Time frame: 41 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 50 mg Artesunate Suppositories, 1 Cycle | Number of Participants With Serious Adverse Events | 0 Participants |
| 200 mg Artesunate Suppositories, 1 Cycle | Number of Participants With Serious Adverse Events | 0 Participants |
| 200 mg Artesunate Suppositories,2 Cycles | Number of Participants With Serious Adverse Events | 0 Participants |
| 200 mg Artesunate Suppositories,3 Cycles | Number of Participants With Serious Adverse Events | 0 Participants |
Secondary
Histologic Regression of CIN2/3
Number of participants who had histologic regression from cervical intraepithelial neoplasia (CIN) 2/3 to CIN 1 or less, as assessed by colposcopically-directed biopsies. Histologic regression is defined as disappearance of the high grade lesion (CIN2/3) without surgical intervention.
Time frame: 41 weeks
Population: All participants who received at least one dose of the interventional drug and on whom we have outcomes data. 2 participants did not have data collected for this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 50 mg Artesunate Suppositories, 1 Cycle | Histologic Regression of CIN2/3 | 2 Participants |
| 200 mg Artesunate Suppositories, 1 Cycle | Histologic Regression of CIN2/3 | 7 Participants |
| 200 mg Artesunate Suppositories,2 Cycles | Histologic Regression of CIN2/3 | 5 Participants |
| 200 mg Artesunate Suppositories,3 Cycles | Histologic Regression of CIN2/3 | 5 Participants |
Secondary
Viral Clearance of HPV
Number of participants whose human papillomavirus (HPV) genotypes present at study entry become undetectable without surgical intervention. HPV genotyping detects strains of HPV present at each timepoint. For this outcome, we evaluated whether strains of HPV detected at study entry became undetectable during the study participation.
Time frame: 41 weeks
Population: Subjects enrolled in the study who received at least one dose of the investigational drug, and on whom we have outcomes data. 2 participants did not have data collected for this outcome.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 50 mg Artesunate Suppositories, 1 Cycle | Viral Clearance of HPV | 1 Participants |
| 200 mg Artesunate Suppositories, 1 Cycle | Viral Clearance of HPV | 3 Participants |
| 200 mg Artesunate Suppositories,2 Cycles | Viral Clearance of HPV | 4 Participants |
| 200 mg Artesunate Suppositories,3 Cycles | Viral Clearance of HPV | 1 Participants |