A Study of Amolimogene (ZYC101a) in Patients With High Grade Cervical Intraepithelial Lesions of the Uterine Cervix

Uterine Cervical Dysplasia Clinical Trial

Official title:

A Multi-Center, Double-Blind, Randomized, Placebo-Controlled Study of Amolimogene (ZYC101a) in the Treatment of High-Grade Cervical Intraepithelial Lesions (CIN 2/3) of the Uterine Cervix

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00264732
• Other study ID #: ZYC1-004
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: December 12, 2005
• Last updated: May 21, 2013
• Start date: July 2005
• Est. completion date: May 2009

Study information

• Verified date: May 2012
• Source: Eisai Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the efficacy and safety of amolimogene, in the treatment of patients with high-grade cervical intraepithelial lesions of the uterine cervix.

Description:

This is a double-blind study, so neither the patient not the doctor will know which treatment has been assigned.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 251
• Est. completion date: May 2009
• Est. primary completion date: May 2009
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 13 Years to 25 Years

Eligibility

Inclusion Criteria:

To be considered for enrollment, patients must:

1. Have an abnormal Pap smear (atypical squamous cells of undetermined significance [ASCUS], atypical squamous cells, cannot exclude high grade [ASC-H], low grade squamous intraepithelial lesion [LSIL], high grade squamous intraepithelial lesion [HSIL]) result within 6 months of screening visit.

2. Have a colposcopically visible lesion suspected to be high-grade that does not involve more than 75% of the cervix.

3. Have a CIN 2/3 consensus pathology diagnosis on tissue taken from a colposcopically-directed punch biopsy.

4. Not have evidence of cervical carcinoma on Pap smear or biopsy and not have a positive endocervical curettage.

5. Not have atypical endometrial cells or glandular-cell atypia on Pap smear or biopsy.

6. Have colposcopic visualization of entire squamocolumnar junction and of the entire lesion (i.e. cannot extend into canal).

7. Not have concomitant cancer, history of malignancies, including carcinoma of the cervix, except for non-melanoma skin cancer.

8. Be willing to sign an Institutional Review Board (IRB) approved informed consent. Minors must have the consent of a parent or legal guardian as required by local laws and regulations.

9. Agree to use 2 acceptable forms of contraception (e.g., double-method including at least one barrier and one hormonal method).

10. Be capable of complying with the protocol.

11. Not have other illnesses that would put the patient at undue risk for participation in the trial or would interfere with the required clinical observations.

12. Not have abnormalities of hematological, renal, or hepatic function as determined by clinical laboratory testing.

13. Not have immunologic disorder such as immunodeficiency, lupus, or other chronic auto-immune disease.

14. Not have an active systemic infection requiring treatment.

15. Not have ongoing systemic chronic steroid therapy or immunosuppressive medication (inhalers used for treating asthma and topical steroids are permitted).

16. Not be positive for HIV antibody.

17. Not be pregnant or lactating.

18. Not plan to use a cervical cap or diaphragm during the study.

19. Not have been treated with any investigational agent within 30 days prior to randomization in this trial.

20. Not have had prior gene therapy.

21. Not have had an excisional or ablative procedure performed on the cervix within one year of enrollment.

22. Be willing to consent to an excisional procedure, such as LEEP or cold-knife cone procedure, if indicated.

Please note: There may be additional inclusion/exclusion criteria. The study center will determine if patients meet all of the criteria. If patients do not qualify for the trial, study personnel will explain the reasons. If patients do qualify, study personnel will explain the trial in detail using an IRB-approved informed consent, and answer any questions. Patients can then decide if they wish to participate.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cervical Intraepithelial Neoplasia
• Uterine Cervical Dysplasia

Intervention

Drug:
• Amolimogene
1-dose amolimogene Group: Two intramuscular (IM) injections (100 micrograms ZYC101a per injection), one in each quadriceps, at Treatment Initiation. Single IM placebo injections (approximately 1 mL 0.9% sterile saline) at Weeks 3 and 6 in alternating quadriceps.
• Amolimogene
3-dose amolimogene Group: Two IM injections (100 micrograms ZYC101a per injection), one in each quadriceps, at Treatment Initiation. Single IM injections of 100 micrograms ZYC101a at Weeks 3 and 6 in alternating quadriceps.

Other:
• Placebo
Placebo Group: Two IM placebo injections at Treatment Initiation (1 injection in each quadriceps). Single placebo injections at Weeks 3 and 6 in alternating quadriceps. Each placebo injection consists of approximately 1 mL 0.9% sterile saline.

Locations

Country	Name	City	State
United States	Southwest Clinical Research	Albuquerque	New Mexico
United States	Medical College of Georgia, Department of Family Medicine	Augusta	Georgia
United States	University of Alabama	Birmingham	Alabama
United States	Visions Clinical Research	Boynton Beach	Florida
United States	Arrowhead Regional Medical Center	Colton	California
United States	UT Southwestern Medical Center at Dallas	Dallas	Texas
United States	Rosemark Women's Care Specialists	Idaho Falls	Idaho
United States	Physicians Research Options, LC	Lakewood	Colorado
United States	Sarah Cannon Research	Memphis	Tennessee
United States	University of Florida, Miami	Miami	Florida
United States	University of Minnesota	Minneapolis	Minnesota
United States	Michael Altenbern, MD	Nashville	Tennessee
United States	Centennial Hills OB-GYN Associaties	North Las Vegas	Nevada
United States	The University of Oklahoma Health Sciences Center, Center for Research in Women's Health	Oklahoma City	Oklahoma
United States	The Center for Advanced Research and Education, Inc.	Palm Springs	California
United States	Temple Center for Women's Health	Philadelphia	Pennsylvania
United States	Arizona Wellness Center for Women/Precision Trials, LLC	Phoenix	Arizona
United States	Physicians' Research Options	Pleasant Grove	Utah
United States	Medical Center for Clinical Research	San Diego	California
United States	Physicians' Research Options, LLC	Sandy	Utah
United States	Physician Care Clinical Research	Sarasota	Florida
United States	Insignia Clinical Research	Tampa	Florida
United States	University of Arizona	Tucson	Arizona
United States	Tidewater Clinical Research	Virginia Beach	Virginia
United States	Comprehensive Clinical Trials LLC	West Palm Beach	Florida
United States	Lyndhurst Gynecologic Associates	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Eisai Inc.

Country where clinical trial is conducted

United States, 

References & Publications (2)

Crum CP, Beach KJ, Hedley ML, Yuan L, Lee KR, Wright TC, Urban RG. Dynamics of human papillomavirus infection between biopsy and excision of cervical intraepithelial neoplasia: results from the ZYC101a protocol. J Infect Dis. 2004 Apr 15;189(8):1348-54. Epub 2004 Mar 30. — View Citation

Garcia F, Petry KU, Muderspach L, Gold MA, Braly P, Crum CP, Magill M, Silverman M, Urban RG, Hedley ML, Beach KJ. ZYC101a for treatment of high-grade cervical intraepithelial neoplasia: a randomized controlled trial. Obstet Gynecol. 2004 Feb;103(2):317-26. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cervical intraepithelial neoplasia (CIN) 2/3 resolution, defined as the histological evaluation of cervical tissue (presence or absence of CIN 2/3 as determined by pathology consensus diagnosis) at the End of Observation (EOO) period.		24 weeks after enrollment.	No
Secondary	Histology based on biopsy to determine the proportion of pts. w/resolution of CIN2/3. This is the same as primary efficacy variable in determination of presence or absence of CIN2/3, but excludes pts. with excisional procedure or cytology information.		24 weeks after enrollment.	No
Secondary	Histological resolution to normal to examine the proportion of patients with a histology result of "normal" versus "abnormal."		24 weeks after enrollment.	No
Secondary	Clearing or persistence of lesions based on colposcopic findings to examine the proportion of patients with "no lesion" versus "at least one lesion."		24 weeks after enrollment.	No
Secondary	Pap smear cytology.		24 weeks after enrollment.	No
Secondary	Clearing or persistence of original human papillomavirus (HPV) subtype as determined by HPV typing to present the number and percent of patients with absence of all HPV.		24 weeks after enrollment.	No