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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eisai Inc.
ClinicalTrials.gov Identifier:
NCT00264732
First received: December 12, 2005
Last updated: May 21, 2013
Last verified: May 2012
  Purpose

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 Intervention Phase
Uterine Cervical Dysplasia
Drug: Amolimogene
Other: Placebo
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, 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

Resource links provided by NLM:


Further study details as provided by Eisai Inc.:

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. [ Time Frame: 24 weeks after enrollment. ] [ Designated as safety issue: No ]

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. [ Time Frame: 24 weeks after enrollment. ] [ Designated as safety issue: No ]
  • Histological resolution to normal to examine the proportion of patients with a histology result of "normal" versus "abnormal." [ Time Frame: 24 weeks after enrollment. ] [ Designated as safety issue: No ]
  • Clearing or persistence of lesions based on colposcopic findings to examine the proportion of patients with "no lesion" versus "at least one lesion." [ Time Frame: 24 weeks after enrollment. ] [ Designated as safety issue: No ]
  • Pap smear cytology. [ Time Frame: 24 weeks after enrollment. ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: 24 weeks after enrollment. ] [ Designated as safety issue: No ]

Enrollment: 251
Study Start Date: July 2005
Study Completion Date: May 2009
Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: 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.

Detailed Description:

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

  Eligibility

Ages Eligible for Study:   13 Years to 25 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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.

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00264732

  Show 26 Study Locations
Sponsors and Collaborators
Eisai Inc.
  More Information

Publications:
Responsible Party: Eisai Inc.
ClinicalTrials.gov Identifier: NCT00264732     History of Changes
Other Study ID Numbers: ZYC1-004
Study First Received: December 12, 2005
Last Updated: May 21, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Eisai Inc.:
cervical lesions
cervical dysplasia
Human papilloma virus
abnormal Pap
High-grade cervical intraepithelial lesions (CIN 2/3)

Additional relevant MeSH terms:
Uterine Cervical Dysplasia
Cervical Intraepithelial Neoplasia
Precancerous Conditions
Neoplasms
Uterine Cervical Diseases
Uterine Diseases
Genital Diseases, Female
Carcinoma in Situ
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on April 22, 2014