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

Sponsor

Eisai Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT00264732

Collaborator

(none)

251

Enrollment

Locations

Arms

Duration (Months)

9.7

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Uterine Cervical Dysplasia	Drug: Amolimogene Drug: Amolimogene Other: Placebo	Phase 2/Phase 3

Detailed Description

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

Study Design

Study Type:

Interventional

Actual Enrollment :

251 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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

Study Start Date :

Jul 1, 2005

Actual Primary Completion Date :

May 1, 2009

Actual Study Completion Date :

May 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1	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. Other Names: ZYC101a
Experimental: 2	Drug: 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 Names: ZYC101a
Placebo Comparator: 3	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.

Arm

Intervention/Treatment

Experimental: 1

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.

Other Names:

ZYC101a

Experimental: 2

Drug: 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 Names:

ZYC101a

Placebo Comparator: 3

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.

Outcome Measures

Primary Outcome Measures

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.]

Secondary Outcome Measures

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.]
Histological resolution to normal to examine the proportion of patients with a histology result of "normal" versus "abnormal." [24 weeks after enrollment.]
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.]
Pap smear cytology. [24 weeks after enrollment.]
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.]

Eligibility Criteria

Criteria

Ages Eligible for Study:

13 Years to 25 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

To be considered for enrollment, patients must:

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.
Have a colposcopically visible lesion suspected to be high-grade that does not involve more than 75% of the cervix.
Have a CIN 2/3 consensus pathology diagnosis on tissue taken from a colposcopically-directed punch biopsy.
Not have evidence of cervical carcinoma on Pap smear or biopsy and not have a positive endocervical curettage.
Not have atypical endometrial cells or glandular-cell atypia on Pap smear or biopsy.
Have colposcopic visualization of entire squamocolumnar junction and of the entire lesion (i.e. cannot extend into canal).
Not have concomitant cancer, history of malignancies, including carcinoma of the cervix, except for non-melanoma skin cancer.
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.
Agree to use 2 acceptable forms of contraception (e.g., double-method including at least one barrier and one hormonal method).
Be capable of complying with the protocol.
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.
Not have abnormalities of hematological, renal, or hepatic function as determined by clinical laboratory testing.
Not have immunologic disorder such as immunodeficiency, lupus, or other chronic auto-immune disease.
Not have an active systemic infection requiring treatment.
Not have ongoing systemic chronic steroid therapy or immunosuppressive medication (inhalers used for treating asthma and topical steroids are permitted).
Not be positive for HIV antibody.
Not be pregnant or lactating.
Not plan to use a cervical cap or diaphragm during the study.
Not have been treated with any investigational agent within 30 days prior to randomization in this trial.
Not have had prior gene therapy.
Not have had an excisional or ablative procedure performed on the cervix within one year of enrollment.
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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama	Birmingham	Alabama	United States	35205
2	Arizona Wellness Center for Women/Precision Trials, LLC	Phoenix	Arizona	United States	85032
3	University of Arizona	Tucson	Arizona	United States	85724
4	Arrowhead Regional Medical Center	Colton	California	United States	92324
5	The Center for Advanced Research and Education, Inc.	Palm Springs	California	United States	92262
6	Medical Center for Clinical Research	San Diego	California	United States	92108
7	Physicians Research Options, LC	Lakewood	Colorado	United States	80228
8	Visions Clinical Research	Boynton Beach	Florida	United States	33472
9	University of Florida, Miami	Miami	Florida	United States	33136
10	Physician Care Clinical Research	Sarasota	Florida	United States	34239
11	Insignia Clinical Research	Tampa	Florida	United States	33613
12	Comprehensive Clinical Trials LLC	West Palm Beach	Florida	United States	33409
13	Medical College of Georgia, Department of Family Medicine	Augusta	Georgia	United States	30912
14	Rosemark Women's Care Specialists	Idaho Falls	Idaho	United States	83404
15	University of Minnesota	Minneapolis	Minnesota	United States	55455
16	Centennial Hills OB-GYN Associaties	North Las Vegas	Nevada	United States	89030
17	Southwest Clinical Research	Albuquerque	New Mexico	United States	87102
18	Lyndhurst Gynecologic Associates	Winston-Salem	North Carolina	United States	27103
19	The University of Oklahoma Health Sciences Center, Center for Research in Women's Health	Oklahoma City	Oklahoma	United States	73104
20	Temple Center for Women's Health	Philadelphia	Pennsylvania	United States	19140
21	Sarah Cannon Research	Memphis	Tennessee	United States	38120
22	Michael Altenbern, MD	Nashville	Tennessee	United States	33437
23	UT Southwestern Medical Center at Dallas	Dallas	Texas	United States	75390
24	Physicians' Research Options	Pleasant Grove	Utah	United States	84062
25	Physicians' Research Options, LLC	Sandy	Utah	United States	84070
26	Tidewater Clinical Research	Virginia Beach	Virginia	United States	23456