Intravaginal Artesunate for the Treatment of HPV+ High Grade Cervical Intraepithelial Neoplasia (CIN2/3)
Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Other)
Overall Status
Completed
CT.gov ID
NCT02354534
Collaborator
Frantz Viral Therapeutics (Other)
30
3
4
45.1
10
0.2
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
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.
Study Design
Study Type:
Interventional
Actual Enrollment
:
30 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase I Study of Intravaginally Administered Artesunate In Women With High Grade Cervical Intraepithelial Neoplasia (CIN2/3)
Actual Study Start Date
:
Feb 1, 2015
Actual Primary Completion Date
:
Jul 1, 2018
Actual Study Completion Date
:
Nov 6, 2018
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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). |
Drug: Artesunate Suppositories
|
| Experimental: 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). |
Drug: Artesunate Suppositories
|
| Experimental: 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). |
Drug: Artesunate Suppositories
|
| Experimental: 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). |
Drug: Artesunate Suppositories
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
Female
Accepts 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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Johns Hopkins Outpatient Center | Baltimore | Maryland | United States | 21205 |
| 2 | Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Baltimore | Maryland | United States | 21231-2410 |
| 3 | Greater Baltimore Medical Center | Towson | Maryland | United States | 21204 |
Sponsors and Collaborators
- Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
- Frantz Viral Therapeutics
Investigators
- Principal Investigator: Cornelia L Trimble, MD, Johns Hopkins University
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
ClinicalTrials.gov Identifier:
NCT02354534
Other Study ID Numbers:
- J1498
- IRB00045376
First Posted:
Feb 3, 2015
Last Update Posted:
Apr 28, 2021
Last Verified:
Mar 1, 2021
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | 50 mg Artesunate Suppositories, 1 Cycle | 200 mg Artesunate Suppositories, 1 Cycle | 200 mg Artesunate Suppositories,2 Cycles | 200 mg Artesunate Suppositories,3 Cycles |
|---|---|---|---|---|
| Arm/Group Description | 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 | 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 | 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 | 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 |
| Period Title: Overall Study | ||||
| STARTED | 3 | 9 | 10 | 8 |
| COMPLETED | 3 | 9 | 9 | 8 |
| NOT COMPLETED | 0 | 0 | 1 | 0 |
Baseline Characteristics
| Arm/Group Title | 50 mg Artesunate Suppositories, 1 Cycle | 200 mg Artesunate Suppositories, 1 Cycle | 200 mg Artesunate Suppositories,2 Cycles | 200 mg Artesunate Suppositories,3 Cycles | Total |
|---|---|---|---|---|---|
| Arm/Group Description | 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 | 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 | 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 | 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 | Total of all reporting groups |
| Overall Participants | 3 | 9 | 10 | 8 | 30 |
| Age (Count of Participants) | |||||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
3
100%
|
9
100%
|
10
100%
|
8
100%
|
30
100%
|
| >=65 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
3
100%
|
9
100%
|
10
100%
|
8
100%
|
30
100%
|
| Male |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Race/Ethnicity, Customized (Count of Participants) | |||||
| Black |
0
0%
|
2
22.2%
|
1
10%
|
2
25%
|
5
16.7%
|
| White |
3
100%
|
7
77.8%
|
7
70%
|
4
50%
|
21
70%
|
| Asian |
0
0%
|
0
0%
|
2
20%
|
1
12.5%
|
3
10%
|
| Hispanic |
0
0%
|
1
11.1%
|
0
0%
|
1
12.5%
|
2
6.7%
|
| Region of Enrollment (Count of Participants) | |||||
| United States |
3
100%
|
9
100%
|
10
100%
|
8
100%
|
30
100%
|
| Type of HPV at baseline (Count of Participants) | |||||
| HPV16 only |
0
0%
|
3
33.3%
|
1
10%
|
4
50%
|
8
26.7%
|
| HPV16 and other genotypes |
0
0%
|
2
22.2%
|
2
20%
|
0
0%
|
4
13.3%
|
| Non-16 HPV genotypes |
3
100%
|
4
44.4%
|
7
70%
|
4
50%
|
18
60%
|
Outcome Measures
| Title | Number of Participants With Serious Adverse Events |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | 50 mg Artesunate Suppositories, 1 Cycle | 200 mg Artesunate Suppositories, 1 Cycle | 200 mg Artesunate Suppositories,2 Cycles | 200 mg Artesunate Suppositories,3 Cycles |
|---|---|---|---|---|
| Arm/Group Description | 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 | 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 | 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 | 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 |
| Measure Participants | 3 | 9 | 10 | 8 |
| Count of Participants [Participants] |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Viral Clearance of HPV |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | 50 mg Artesunate Suppositories, 1 Cycle | 200 mg Artesunate Suppositories, 1 Cycle | 200 mg Artesunate Suppositories,2 Cycles | 200 mg Artesunate Suppositories,3 Cycles |
|---|---|---|---|---|
| Arm/Group Description | 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 | 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 | 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 | 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 |
| Measure Participants | 3 | 9 | 8 | 8 |
| Count of Participants [Participants] |
1
33.3%
|
3
33.3%
|
4
40%
|
1
12.5%
|
| Title | Histologic Regression of CIN2/3 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | 50 mg Artesunate Suppositories, 1 Cycle | 200 mg Artesunate Suppositories, 1 Cycle | 200 mg Artesunate Suppositories,2 Cycles | 200 mg Artesunate Suppositories,3 Cycles |
|---|---|---|---|---|
| Arm/Group Description | 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 | 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 | 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 | 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 |
| Measure Participants | 3 | 9 | 8 | 8 |
| Count of Participants [Participants] |
2
66.7%
|
7
77.8%
|
5
50%
|
5
62.5%
|
Adverse Events
| Time Frame | 41 weeks | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | All adverse events reported by study participants from the time of study drug administration through 30 days after the final treatment, whether or not they are related to the study intervention. Participants filled out a symptom diary for each treatment cycle completed. Adverse events were also documented and assessed for causality by the study investigators at each study visit. | |||||||
| Arm/Group Title | 50 mg Artesunate Suppositories, 1 Cycle | 200 mg Artesunate Suppositories, 1 Cycle | 200 mg Artesunate Suppositories,2 Cycles | 200 mg Artesunate Suppositories,3 Cycles | ||||
| Arm/Group Description | 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 | 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 | 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 | 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 | ||||
All Cause Mortality |
||||||||
| 50 mg Artesunate Suppositories, 1 Cycle | 200 mg Artesunate Suppositories, 1 Cycle | 200 mg Artesunate Suppositories,2 Cycles | 200 mg Artesunate Suppositories,3 Cycles | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/3 (0%) | 0/9 (0%) | 0/10 (0%) | 0/8 (0%) | ||||
Serious Adverse Events |
||||||||
| 50 mg Artesunate Suppositories, 1 Cycle | 200 mg Artesunate Suppositories, 1 Cycle | 200 mg Artesunate Suppositories,2 Cycles | 200 mg Artesunate Suppositories,3 Cycles | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/3 (0%) | 0/9 (0%) | 0/10 (0%) | 0/8 (0%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| 50 mg Artesunate Suppositories, 1 Cycle | 200 mg Artesunate Suppositories, 1 Cycle | 200 mg Artesunate Suppositories,2 Cycles | 200 mg Artesunate Suppositories,3 Cycles | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/3 (66.7%) | 9/9 (100%) | 8/10 (80%) | 8/8 (100%) | ||||
| Ear and labyrinth disorders | ||||||||
| Tinnitus | 0/3 (0%) | 0 | 1/9 (11.1%) | 1 | 1/10 (10%) | 2 | 0/8 (0%) | 0 |
| Gastrointestinal disorders | ||||||||
| Bloating | 1/3 (33.3%) | 4 | 1/9 (11.1%) | 1 | 0/10 (0%) | 0 | 0/8 (0%) | 0 |
| Abdominal pain | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 1/10 (10%) | 1 | 0/8 (0%) | 0 |
| Diarrhea | 0/3 (0%) | 0 | 1/9 (11.1%) | 1 | 0/10 (0%) | 0 | 0/8 (0%) | 0 |
| Nausea | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 1/10 (10%) | 1 | 0/8 (0%) | 0 |
| Salivary duct inflammation | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 1/10 (10%) | 1 | 0/8 (0%) | 0 |
| General disorders | ||||||||
| Chills | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 1/8 (12.5%) | 2 |
| Fatigue | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 1/10 (10%) | 1 | 0/8 (0%) | 0 |
| Fever | 0/3 (0%) | 0 | 1/9 (11.1%) | 1 | 1/10 (10%) | 1 | 0/8 (0%) | 0 |
| Flu-like symptoms | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 1/8 (12.5%) | 1 |
| Infections and infestations | ||||||||
| Vaginal infection | 0/3 (0%) | 0 | 2/9 (22.2%) | 2 | 4/10 (40%) | 4 | 1/8 (12.5%) | 2 |
| Urinary tract infection | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 1/10 (10%) | 1 | 1/8 (12.5%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||||||
| Vaginal twitching | 0/3 (0%) | 0 | 1/9 (11.1%) | 1 | 0/10 (0%) | 0 | 0/8 (0%) | 0 |
| Nervous system disorders | ||||||||
| Dizziness | 1/3 (33.3%) | 2 | 2/9 (22.2%) | 6 | 3/10 (30%) | 5 | 3/8 (37.5%) | 3 |
| Headache | 1/3 (33.3%) | 2 | 5/9 (55.6%) | 9 | 3/10 (30%) | 3 | 2/8 (25%) | 2 |
| Psychiatric disorders | ||||||||
| Anxiety | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 1/10 (10%) | 1 | 0/8 (0%) | 0 |
| Insomnia | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 1/10 (10%) | 1 | 0/8 (0%) | 0 |
| Renal and urinary disorders | ||||||||
| Cystitis noninfective | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 1/8 (12.5%) | 1 |
| Reproductive system and breast disorders | ||||||||
| Uterine cramping | 2/3 (66.7%) | 5 | 1/9 (11.1%) | 3 | 1/10 (10%) | 1 | 2/8 (25%) | 2 |
| Dyspareunia | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 1/8 (12.5%) | 1 |
| pelvic pain | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 1/10 (10%) | 1 | 0/8 (0%) | 0 |
| Vaginal discharge | 0/3 (0%) | 0 | 3/9 (33.3%) | 3 | 1/10 (10%) | 4 | 3/8 (37.5%) | 4 |
| Vaginal dryness | 1/3 (33.3%) | 1 | 1/9 (11.1%) | 1 | 1/10 (10%) | 2 | 1/8 (12.5%) | 1 |
| Vaginal hemorrhage | 0/3 (0%) | 0 | 3/9 (33.3%) | 3 | 1/10 (10%) | 1 | 0/8 (0%) | 0 |
| vaginal inflammation | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 1/10 (10%) | 1 | 1/8 (12.5%) | 2 |
| vaginal pain/burning | 0/3 (0%) | 0 | 4/9 (44.4%) | 5 | 4/10 (40%) | 4 | 4/8 (50%) | 7 |
| Skin and subcutaneous tissue disorders | ||||||||
| rash | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 0/10 (0%) | 0 | 1/8 (12.5%) | 1 |
| pruritus | 0/3 (0%) | 0 | 0/9 (0%) | 0 | 1/10 (10%) | 1 | 0/8 (0%) | 0 |
| Vaginal pruritus | 0/3 (0%) | 0 | 3/9 (33.3%) | 3 | 5/10 (50%) | 5 | 6/8 (75%) | 11 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Cornelia L. Trimble, MD |
|---|---|
| Organization | Johns Hopkins University |
| Phone | 410-502-0512 |
| CervixDoctor@jhmi.edu |
Responsible Party:
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
ClinicalTrials.gov Identifier:
NCT02354534
Other Study ID Numbers:
- J1498
- IRB00045376
First Posted:
Feb 3, 2015
Last Update Posted:
Apr 28, 2021
Last Verified:
Mar 1, 2021