A Study of INO-3112 DNA Vaccine With Electroporation in Participants With Cervical Cancer

NCT02172911 | Completed Phase 1 Results FDA Drug FDA Device

• 1 other identifier: HPV-004
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 3

Brief Summary

This is an open-label study to evaluate the safety, tolerability, and immunogenicity of INO-3112 DNA vaccines delivered by electroporation (EP) to female participants with HPV-16 and/or 18-positive cervical carcinoma.

Conditions

Cervical Cancer

Keywords

Cervical cancer; Papillomavirus; Chemoradiation; Recurrent cervical cancer; Persistent cervical cancer

Outcome Measures

Primary Outcomes (14)

• Percentage of Participants With at Least 1 Treatment Emergent Adverse Event (TEAE)

  An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can include any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A TEAE is any AE either reported for the first time or worsening of a pre-existing event after the first dose of study drug.

  Up to 36 weeks

• Percentage of Participants With Grade 3 or Higher TEAEs Graded Per Common Terminology Criteria for Adverse Events, Version 4.03 (CTCAE, v 4.03)

  An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can include any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A TEAE is any AE either reported for the first time or worsening of a pre-existing event after the first dose of study drug. The severity of TEAEs was assessed by the National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events, version 4.03 (CTCAE,v 4.03). TEAEs were graded on a 5-point scale where 1 = Mild, 2 = Moderate, 3 = Severe, 4 = Potentially life-threatening and 5 = Death.

  Up to 36 weeks

• Percentage of Participants With Injection Site Reactions

  Injection site reactions and administration site pain were evaluated starting 30 minutes following injection/EP. Injection site reactions were assessed in accordance with the 'Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials' (Food and Drug Administration \[FDA\] Guidance for Industry, September 2007). Local reaction to the injectable product such as pain, tenderness, erythema/redness and induration/swelling were graded on a 4-point scale where: 1 = Mild, 2 = Moderate, 3 = Severe and 4 = Potentially life-threatening.

  Up to 36 weeks

• Rates of Acute Gastrointestinal, Genitourinary, or Other Chemoradiation Side Effects Above the Expected, Graded Per Acute Radiation Morbidity Scoring Criteria

  Up to 36 weeks

• Change From Baseline in Hematocrit at the Indicated Time Points

  Clinical laboratory parameters (hematology, serum chemistry, and creatine phosphokinase \[CPK\]) were analyzed using descriptive statistics for actual values and changes from baseline to each study visit.

  Baseline and Week 4, 8,12,16,24, 32 and 48

• Change From Baseline in Hemoglobin at the Indicated Time Points

  Clinical laboratory parameters (hematology, serum chemistry, creatine phosphokinase \[CPK\]) were analyzed using descriptive statistics for actual values and changes from baseline to each study visit.

  Baseline and Weeks 4, 8,12,16,24, 32 and 48

• Change From Baseline in Lymphocytes, Monocytes, Neutrophils and White Blood Cell (WBC) Count at the Indicated Time Points

  Clinical laboratory parameters (hematology, serum chemistry, creatine phosphokinase \[CPK\]) were analyzed using descriptive statistics for actual values and changes from baseline to each study visit. Hematology parameters analyzed for this outcome measure included: white blood cell (WBC) count, count of lymphocytes (L), monocytes (M) and neutrophils (N).

  Baseline and Weeks 4, 8,12,16,24, 32 and 48

• Change From Baseline in Platelet Count at the Indicated Time Points

  Clinical laboratory parameters (hematology, serum chemistry, creatine phosphokinase \[CPK\]) were analyzed using descriptive statistics for actual values and changes from baseline to each study visit.

  Baseline and Weeks 4,8,12,16,24,32 and 48

• Change From Baseline in Red Blood Cell (RBC) Count at the Indicated Time Points

  Clinical laboratory parameters (hematology, serum chemistry, creatine phosphokinase \[CPK\]) were analyzed using descriptive statistics for actual values and changes from baseline to each study visit.

  Baseline and Weeks 4 and 8

• Change From Baseline in Alkaline Phosphatase, Alanine Aminotransferase, and Aspartate Aminotransferase at the Indicated Time Points

  Clinical laboratory parameters (hematology, serum chemistry, creatine phosphokinase \[CPK\]) were analyzed using descriptive statistics for actual values and changes from baseline to each study visit. Clinical chemistry parameter assessed in this outcome measure included alkaline phosphatase (ALP), alanine amino transferase (ALT) and aspartate amino transferase (AST).

  Baseline and Weeks 4,8,12 and 16

• Change From Baseline in Bicarbonate, Glucose, Blood Urea Nitrogen (BUN), Calcium (Ca), Chloride (Cl), Potassium (K), Magnesium (Mg) and Sodium (Na) at the Indicated Time Points

  Clinical laboratory parameters (hematology, serum chemistry, creatine phosphokinase \[CPK\]) were analyzed using descriptive statistics for actual values and changes from baseline to each study visit.

  Baseline and Weeks 4,8,12 and 16

• Change From Baseline in Albumin and Total Protein at the Indicated Time Points

  Clinical laboratory parameters (hematology, serum chemistry, creatine phosphokinase \[CPK\]) were analyzed using descriptive statistics for actual values and changes from baseline to each study visit.

  Baseline and Weeks 4,8,12 and 16

• Change From Baseline in Creatine Phosphokinase (CPK) at the Indicated Time Points

  Clinical laboratory parameters (hematology, serum chemistry, creatine phosphokinase \[CPK\]) were analyzed using descriptive statistics for actual values and changes from baseline to each study visit.

  Baseline and Week 16

• Change From Baseline in Creatinine and Total Bilirubin at the Indicated Time Points

  Clinical laboratory parameters (hematology, serum chemistry, creatine phosphokinase \[CPK\]) were analyzed using descriptive statistics for actual values and changes from baseline to each study visit.

  Baseline and Weeks 4, 8,12 and 16

Secondary Outcomes (3)

• Change From Baseline in the Combined HPV-16 and HPV-18 E6 and E7 Antigen Specific Spot-Forming Units Per Million Peripheral Blood Mononuclear Cell (SFU/10^6 PBMC)

  Baseline and Weeks 2, 4, 6, 8, 10,12,14,16, 24, 32, 36, 40 and 48

• E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA)

  Baseline and Weeks 2, 4, 6, 8, 10,12,14,16, 24, 32, 36, 40 and 48

• E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA

  Baseline and Weeks 2, 4, 6, 8, 10, 12, 14, 16, 24, 32, 36, 40 and 48

Study Arms (2)

Cohort I: INO-3112: Curative Intent

EXPERIMENTAL

Cohort I included participants with biopsy-proven, stage IB-IVB inoperable, newly diagnosed invasive cervical carcinoma associated with HPV-16 and/or HPV-18 treated with standard chemoradiation therapy with curative intent. Participants received a 4-dose series of 1.1 mL IM injection of INO-3112 followed immediately by EP with CELLECTRA™-5P.

Biological: INO-3112; Device: CELLECTRA™-5P

Cohort II: INO-3112: Salvage Therapy

EXPERIMENTAL

Cohort II included participants with persistent and/or recurrent cervical carcinoma associated with HPV-16 and/or HPV-18 who had been treated with salvage therapy (chemotherapy and/or radiation therapy). Participants received a 4-dose series of 1.1 mL IM injection of INO-3112 followed immediately by EP with CELLECTRA™-5P.

Biological: INO-3112; Device: CELLECTRA™-5P

Interventions

INO-3112 BIOLOGICAL

1.1 mL intramuscular (IM) injection of INO-3112 (VGX-3100 + INO-9012) was administered followed immediately by electroporation (EP) with CELLECTRA™-5P on Day 0, Week 4, Week 8, and Week 12.

Also known as: VGX-3100, INO-9012

Cohort I: INO-3112: Curative Intent; Cohort II: INO-3112: Salvage Therapy

CELLECTRA™-5P DEVICE

CELLECTRA™-5P was used for EP following IM delivery of INO-3112 on Day 0, Week 4, Week 8, and Week 12.

Cohort I: INO-3112: Curative Intent; Cohort II: INO-3112: Salvage Therapy

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Only female participants with biopsy-proven, Stage IB-IVB inoperable invasive cervical carcinoma associated with HPV-16 and/or HPV-18 were included.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent.
• Histological diagnosis of squamous cell carcinoma, adenocarcinoma or adenosquamous cell carcinoma of the cervix. Not accepted are small cell, clear cell and other rare variants of the classical adenocarcinoma.
• Histologically confirmed, Stage IB-IVB, invasive cervical carcinoma associated with HPV 16 and/or 18 and meet the following eligibility criteria for either Cohort 1 or Cohort 2.
• Cohort 1
• Newly diagnosed inoperable cervical cancer treated with chemoradiation therapy with curative intent and life expectancy of at least 12 months as assessed by the investigator
• No CNS/spinal metastases
• Able to initiate study treatment within 2 weeks of completion of last chemoradiation treatment
• Cohort 2
• Persistent and/or recurrent cervical cancer
• No CNS/spinal metastases
• Able to initiate study treatment at least 2 weeks but no more than 4 weeks after completion of salvage therapy
• Life expectancy of at least 12 months as assessed by the investigator
• Electrocardiogram (ECG) with no clinically significant findings.
• Chemistry, liver function tests, renal function, total CPK and hematology lab results must be ≤ Grade 1 at the time of screening.
• Eastern Cooperative Oncology Group (ECOG) Performance status of ≤ 1.

You may not qualify if:

• Pregnancy or breastfeeding.
• History of previous therapeutic HPV vaccination.
• Prior exposure to an investigational agent or device within 30 days of signing the ICF. Of note, the participant may participate in observational studies.
• Positive serological test for HIV, Hep B or Hep C or history of HIV infection, Hepatitis B or Hepatitis C (women with cured HCV will be allowed; participant must have had a serologic test performed within 12 months of informed consent).
• Prior major surgery from which the participant has not yet recovered to baseline.
• High medical risks because of non-malignant systemic disease or with active uncontrolled infection.
• Current malignancies at other sites, with the exception of adequately treated basal or squamous cell carcinoma of the skin.
• Congestive heart failure or prior history of New York Heart Association (NYHA) class III/ IV cardiac disease.
• Use of topical corticosteroids at or near the intended administration site.
• Any cardiac pre-excitation syndromes (such as Wolff-Parkinson-White).
• History of seizures (unless seizure free for 5 years).
• Tattoos or scars within 2 cm of the intended site of injection or if there is implanted metal within the same limb. Any device implanted in the chest (e.g., cardiac pacemaker or defibrillator) excludes the use of the deltoid muscle on the same side of the body.
• Active drug or alcohol use or dependence.
• Imprisonment or compulsory detainment for treatment of either a psychiatric or physical (i.e. infectious disease) illness.
• History of immunosuppressive or autoimmune disease.

Sponsors & Collaborators

• Inovio Pharmaceuticals: lead

Study Sites (3)

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Related Publications (2)

• Bagarazzi ML, Yan J, Morrow MP, Shen X, Parker RL, Lee JC, Giffear M, Pankhong P, Khan AS, Broderick KE, Knott C, Lin F, Boyer JD, Draghia-Akli R, White CJ, Kim JJ, Weiner DB, Sardesai NY. Immunotherapy against HPV16/18 generates potent TH1 and cytotoxic cellular immune responses. Sci Transl Med. 2012 Oct 10;4(155):155ra138. doi: 10.1126/scitranslmed.3004414.

  PMID: 23052295 BACKGROUND

• Diehl MC, Lee JC, Daniels SE, Tebas P, Khan AS, Giffear M, Sardesai NY, Bagarazzi ML. Tolerability of intramuscular and intradermal delivery by CELLECTRA((R)) adaptive constant current electroporation device in healthy volunteers. Hum Vaccin Immunother. 2013 Oct;9(10):2246-52. doi: 10.4161/hv.24702. Epub 2013 Jun 4.

  PMID: 24051434 BACKGROUND

Related Links

• Sponsor's Website

MeSH Terms

Conditions

Uterine Cervical Neoplasms

Interventions

MEDI0457; VGX-3100; rocakinogene sifuplasmid

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Results Point of Contact

• Title: Study Director
• Organization: Inovio Pharmaceuticals

clinical.trials@inovio.com

267-440-4237

Study Officials

• Jeffrey Skolnik, MD

  Inovio Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 18, 2014
• First Posted: June 24, 2014
• Study Start: June 6, 2014
• Primary Completion: September 7, 2017
• Study Completion: September 7, 2017
• Last Updated: February 21, 2021
• Results First Posted: February 21, 2021

Record last verified: 2021-02

Locations

US (3)