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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.
This is a Phase I/IIa, open-label study to evaluate the safety, tolerability, and immunogenicity of INO-3112 [VGX-3100 and INO-9012] delivered intramuscularly by electroporation in approximately 30 female participants with biopsy-proven, Stage IB-IVB inoperable invasive cervical carcinoma associated with HPV 16 and/or 18 who have completed treatment with standard chemoradiation therapy with curative intent (Cohort I) or in participants with persistent and/or recurrent cervical cancer associated with HPV 16 and/or 18 following salvage therapy (Cohort II).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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) | Whole blood and serum samples to be tested for antibodies to the human papillomavirus (HPV) E6 and E7 proteins and/or T-lymphocytes producing interferon-gamma (IFN-γ) elicited by INO-3112 were assessed by enzyme-linked immunosorbent spot-forming assay (ELISpot). |
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Inclusion Criteria:
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
Cohort 2
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.
Adequate venous access for repeated blood sampling according to the study schedule.
Women of child-bearing potential must have a negative serum pregnancy test and agree to remain sexually abstinent, have a partner who is sterile (i.e., vasectomy), or use two medically effective methods of contraception (e.g., oral contraception, barrier methods, spermicide, intrauterine device [IUD]).
Able and willing to comply with all study procedures.
Exclusion Criteria:
Only female participants with biopsy-proven, Stage IB-IVB inoperable invasive cervical carcinoma associated with HPV-16 and/or HPV-18 were included.
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| Name | Affiliation | Role |
|---|---|---|
| Jeffrey Skolnik, MD | Inovio Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Chicago Medical Center | Chicago | Illinois | 60637 | United States | ||
| University of Michigan |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23052295 | Background | 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. | |
| 24051434 |
| Label | URL |
|---|---|
| Sponsor's Website | View source |
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Female participants with cervical cancer after chemoradiation for newly diagnosed disease or therapy for recurrent and/or persistent disease were enrolled in 2 study sites between 6th June 2014 to 7th September 2017.
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| ID | Title | Description |
|---|---|---|
| FG000 | Cohort I: INO-3112: Curative Intent | 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. |
| FG001 | Cohort II: INO-3112: Salvage Therapy | 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. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Cohort I: INO-3112: Curative Intent | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Safety population included all participants who received at least one dose of study treatment plus EP. | Posted | Number | 95% Confidence Interval | percentage of participants | Up to 36 weeks |
|
Up to 36 weeks
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Cohort I: INO-3112: Curative Intent | 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Disseminated Intravascular Coagulation | Blood and lymphatic system disorders | MedDRA Version 20.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA Version 20.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Inovio Pharmaceuticals | 267-440-4237 | clinical.trials@inovio.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Apr 27, 2016 | Jan 4, 2021 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D002583 | Uterine Cervical Neoplasms |
| ID | Term |
|---|---|
| D014594 | Uterine Neoplasms |
| D005833 | Genital Neoplasms, Female |
| D014565 | Urogenital Neoplasms |
| D009371 | Neoplasms by Site |
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| ID | Term |
|---|---|
| C000657484 | MEDI0457 |
| C000604121 | VGX-3100 |
| C000722693 | rocakinogene sifuplasmid |
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|
| 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. |
|
| 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 |
| 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) | Antigen-specific humoral responses against HPV E6 and E7 antigens induced by INO-3112 were measured using ELISA. Commercially available recombinant human HPV-16 and HPV-18 proteins were used to assess the induction of binding antibodies to each of the antigen components. | 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 | Antigen-specific humoral responses against HPV E6 and E7 antigens induced by INO-3112 were measured using ELISA. Commercially available recombinant human HPV-16 and HPV-18 proteins were used to assess the induction of binding antibodies to each of the antigen components. | Baseline and Weeks 2, 4, 6, 8, 10, 12, 14, 16, 24, 32, 36, 40 and 48 |
| Ann Arbor |
| Michigan |
| 48109 |
| United States |
| Columbia University Medical Center | New York | New York | 10032 | United States |
| 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. |
| Loss of insurance coverage |
|
| BG001 | Cohort II: INO-3112: Salvage Therapy | 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. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex/Gender, Customized | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
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.
| OG001 | Cohort II: INO-3112: Salvage Therapy | 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. |
|
|
| Primary | 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. | Safety population included all participants who received at least one dose of study treatment plus EP. | Posted | Number | 95% Confidence Interval | percentage of participants | Up to 36 weeks |
|
|
|
| Primary | 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. | Safety population included all participants who received at least one dose of study treatment plus EP. | Posted | Number | 95% Confidence Interval | percentage of participants | Up to 36 weeks |
|
|
|
| Primary | Rates of Acute Gastrointestinal, Genitourinary, or Other Chemoradiation Side Effects Above the Expected, Graded Per Acute Radiation Morbidity Scoring Criteria | The above-mentioned outcome could not be assessed as no data were captured that reflect the expected rates of acute gastrointestinal, genitourinary or other chemoradiation side effects, in order to compare those collected on this study with those from prior studies. While adverse event data related to study therapy were captured, these were not graded per acute radiation morbidity score because of the above-noted limitation. No comparison was thus possible that would reflect rates expected. | Posted | Up to 36 weeks |
|
|
| Primary | 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. | Safety population included all participants who received at least one dose of study treatment plus EP. Number analyzed is the number of participants with data available for analysis at a specified time-point. | Posted | Mean | Standard Deviation | percentage of blood | Baseline and Week 4, 8,12,16,24, 32 and 48 |
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|
| Primary | 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. | The safety population included all participants who received at least one dose of study treatment plus EP. Number analyzed is the number of participants with data available for analysis at a specified time-point. | Posted | Mean | Standard Deviation | gram per liter (g/L) | Baseline and Weeks 4, 8,12,16,24, 32 and 48 |
|
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| Primary | 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). | Safety population included all participants who received at least one dose of study treatment plus EP. Number analyzed is the number of participants with data available for analysis at a specified time-point. | Posted | Mean | Standard Deviation | 10^9 cells/liter (10^9/L) | Baseline and Weeks 4, 8,12,16,24, 32 and 48 |
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| Primary | 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. | Safety population included all participants who received at least one dose of study treatment plus EP. Number analyzed is the number of participants with data available for analysis at a specified time-point. | Posted | Mean | Standard Deviation | 10^9 cells/liter (10^9/L) | Baseline and Weeks 4,8,12,16,24,32 and 48 |
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| Primary | 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. | Safety population included all participants who received at least one dose of study treatment plus EP. Number analyzed is the number of participants with data available for analysis at a specified time-point. | Posted | Mean | Standard Deviation | 10^12 cells/liter | Baseline and Weeks 4 and 8 |
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| Primary | 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). | Safety population included all participants who received at least one dose of study treatment plus EP. Number analyzed is the number of participants with data available for analysis at a specified time-point. | Posted | Mean | Standard Deviation | units per liter (U/L) | Baseline and Weeks 4,8,12 and 16 |
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| Primary | 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. | Safety population included all participants who received at least one dose of study treatment plus EP. Number analyzed is the number of participants with data available for analysis at a specified time-point. | Posted | Mean | Standard Deviation | millimole per liter (mmol/L) | Baseline and Weeks 4,8,12 and 16 |
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| Primary | 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. | Safety population included all participants who received at least one dose of study treatment plus EP. Number analyzed is the number of participants with data available for analysis at a specified time-point. | Posted | Mean | Standard Deviation | grams per liter (g/L) | Baseline and Weeks 4,8,12 and 16 |
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| Primary | 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. | Safety population included all participants who received at least one dose of study treatment plus EP. Number analyzed is the number of participants with data available for analysis at a specified time-point. | Posted | Mean | Standard Deviation | units per liter (U/L) | Baseline and Week 16 |
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| Primary | 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. | Safety population included all participants who received at least one dose of study treatment plus EP. Number analyzed is the number of participants with data available for analysis at a specified time-point. | Posted | Mean | Standard Deviation | micromoles per liter (umol/L) | Baseline and Weeks 4, 8,12 and 16 |
|
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| Secondary | 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) | Whole blood and serum samples to be tested for antibodies to the human papillomavirus (HPV) E6 and E7 proteins and/or T-lymphocytes producing interferon-gamma (IFN-γ) elicited by INO-3112 were assessed by enzyme-linked immunosorbent spot-forming assay (ELISpot). | Modified intention-to-treat (mITT) population included all participants receiving at least one study treatment plus EP as assigned. Number analyzed is the number of participants with data available for analysis at a specified time-point. | Posted | Mean | Standard Deviation | SFU/10^6 PBMC | Baseline and Weeks 2, 4, 6, 8, 10,12,14,16, 24, 32, 36, 40 and 48 |
|
|
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| Secondary | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | Antigen-specific humoral responses against HPV E6 and E7 antigens induced by INO-3112 were measured using ELISA. Commercially available recombinant human HPV-16 and HPV-18 proteins were used to assess the induction of binding antibodies to each of the antigen components. | Modified intention-to-treat (mITT) population included all participants receiving at least one study treatment plus EP as assigned. Number analyzed is the number of participants with data available for analysis at a specified time-point. | Posted | Mean | Standard Deviation | log titer | Baseline and Weeks 2, 4, 6, 8, 10,12,14,16, 24, 32, 36, 40 and 48 |
|
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| Secondary | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | Antigen-specific humoral responses against HPV E6 and E7 antigens induced by INO-3112 were measured using ELISA. Commercially available recombinant human HPV-16 and HPV-18 proteins were used to assess the induction of binding antibodies to each of the antigen components. | Modified intention-to-treat (mITT) population included all participants receiving at least one study treatment plus EP as assigned. Number analyzed is the number of participants with data available for analysis at a specified time-point. | Posted | Mean | Standard Deviation | log titer | Baseline and Weeks 2, 4, 6, 8, 10, 12, 14, 16, 24, 32, 36, 40 and 48 |
|
|
|
| 0 |
| 7 |
| 3 |
| 7 |
| 7 |
| 7 |
| EG001 | Cohort II: INO-3112: Salvage Therapy | 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. | 1 | 3 | 2 | 3 | 3 | 3 |
| Abdominal Pain | Gastrointestinal disorders | MedDRA Version 20.0 | Systematic Assessment |
|
| Intestinal Perforation | Gastrointestinal disorders | MedDRA Version 20.0 | Systematic Assessment |
|
| Endometritis | Infections and infestations | MedDRA Version 20.0 | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA Version 20.0 | Systematic Assessment |
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| Neutropenia | Blood and lymphatic system disorders | MedDRA Version 20.0 | Systematic Assessment |
|
| Tachycardia | Cardiac disorders | MedDRA Version 20.0 | Systematic Assessment |
|
| Ear Pain | Ear and labyrinth disorders | MedDRA Version 20.0 | Systematic Assessment |
|
| Abdominal Pain | Gastrointestinal disorders | MedDRA Version 20.0 | Systematic Assessment |
|
| Abdominal Pain Lower | Gastrointestinal disorders | MedDRA Version 20.0 | Systematic Assessment |
|
| Abdominal Pain Upper | Gastrointestinal disorders | MedDRA Version 20.0 | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA Version 20.0 | Systematic Assessment |
|
| Defaecation Urgency | Gastrointestinal disorders | MedDRA Version 20.0 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA Version 20.0 | Systematic Assessment |
|
| Dry Mouth | Gastrointestinal disorders | MedDRA Version 20.0 | Systematic Assessment |
|
| Gastrointestinal Motility Disorder | Gastrointestinal disorders | MedDRA Version 20.0 | Systematic Assessment |
|
| Gastrooesophageal Reflux Disease | Gastrointestinal disorders | MedDRA Version 20.0 | Systematic Assessment |
|
| Haemorrhoids | Gastrointestinal disorders | MedDRA Version 20.0 | Systematic Assessment |
|
| Hiatus Hernia | Gastrointestinal disorders | MedDRA Version 20.0 | Systematic Assessment |
|
| Large Intestine Polyp | Gastrointestinal disorders | MedDRA Version 20.0 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA Version 20.0 | Systematic Assessment |
|
| Rectal Ulcer | Gastrointestinal disorders | MedDRA Version 20.0 | Systematic Assessment |
|
| Toothache | Gastrointestinal disorders | MedDRA Version 20.0 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA Version 20.0 | Systematic Assessment |
|
| Chest Pain | General disorders | MedDRA Version 20.0 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA Version 20.0 | Systematic Assessment |
|
| Injection Site Bruising | General disorders | MedDRA Version 20.0 | Systematic Assessment |
|
| Injection Site Discolouration | General disorders | MedDRA Version 20.0 | Systematic Assessment |
|
| Injection Site Erythema | General disorders | MedDRA Version 20.0 | Systematic Assessment |
|
| Injection Site Haemorrhage | General disorders | MedDRA Version 20.0 | Systematic Assessment |
|
| Injection Site Pain | General disorders | MedDRA Version 20.0 | Systematic Assessment |
|
| Injection Site Swelling | General disorders | MedDRA Version 20.0 | Systematic Assessment |
|
| Malaise | General disorders | MedDRA Version 20.0 | Systematic Assessment |
|
| Peripheral Swelling | General disorders | MedDRA Version 20.0 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA Version 20.0 | Systematic Assessment |
|
| Cholecystitis | Hepatobiliary disorders | MedDRA Version 20.0 | Systematic Assessment |
|
| Hepatic Steatosis | Hepatobiliary disorders | MedDRA Version 20.0 | Systematic Assessment |
|
| Influenza | Infections and infestations | MedDRA Version 20.0 | Systematic Assessment |
|
| Pyometra | Infections and infestations | MedDRA Version 20.0 | Systematic Assessment |
|
| Sinusitis | Infections and infestations | MedDRA Version 20.0 | Systematic Assessment |
|
| Urinary Tract Infection | Infections and infestations | MedDRA Version 20.0 | Systematic Assessment |
|
| Ligament Sprain | Injury, poisoning and procedural complications | MedDRA Version 20.0 | Systematic Assessment |
|
| Radiation Proctopathy | Injury, poisoning and procedural complications | MedDRA Version 20.0 | Systematic Assessment |
|
| Weight Decreased | Investigations | MedDRA Version 20.0 | Systematic Assessment |
|
| White Blood Cell Count Decreased | Investigations | MedDRA Version 20.0 | Systematic Assessment |
|
| Decreased Appetite | Metabolism and nutrition disorders | MedDRA Version 20.0 | Systematic Assessment |
|
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA Version 20.0 | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA Version 20.0 | Systematic Assessment |
|
| Back Pain | Musculoskeletal and connective tissue disorders | MedDRA Version 20.0 | Systematic Assessment |
|
| Bone Pain | Musculoskeletal and connective tissue disorders | MedDRA Version 20.0 | Systematic Assessment |
|
| Exostosis | Musculoskeletal and connective tissue disorders | MedDRA Version 20.0 | Systematic Assessment |
|
| Joint Swelling | Musculoskeletal and connective tissue disorders | MedDRA Version 20.0 | Systematic Assessment |
|
| Pain In Extremity | Musculoskeletal and connective tissue disorders | MedDRA Version 20.0 | Systematic Assessment |
|
| Pain In Jaw | Musculoskeletal and connective tissue disorders | MedDRA Version 20.0 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA Version 20.0 | Systematic Assessment |
|
| Dysgeusia | Nervous system disorders | MedDRA Version 20.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA Version 20.0 | Systematic Assessment |
|
| Neuropathy Peripheral | Nervous system disorders | MedDRA Version 20.0 | Systematic Assessment |
|
| Paraesthesia | Nervous system disorders | MedDRA Version 20.0 | Systematic Assessment |
|
| Parosmia | Nervous system disorders | MedDRA Version 20.0 | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA Version 20.0 | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA Version 20.0 | Systematic Assessment |
|
| Hydronephrosis | Renal and urinary disorders | MedDRA Version 20.0 | Systematic Assessment |
|
| Nocturia | Renal and urinary disorders | MedDRA Version 20.0 | Systematic Assessment |
|
| Pollakiuria | Renal and urinary disorders | MedDRA Version 20.0 | Systematic Assessment |
|
| Proteinuria | Renal and urinary disorders | MedDRA Version 20.0 | Systematic Assessment |
|
| Urge Incontinence | Renal and urinary disorders | MedDRA Version 20.0 | Systematic Assessment |
|
| Urinary Incontinence | Renal and urinary disorders | MedDRA Version 20.0 | Systematic Assessment |
|
| Coital Bleeding | Reproductive system and breast disorders | MedDRA Version 20.0 | Systematic Assessment |
|
| Dyspareunia | Reproductive system and breast disorders | MedDRA Version 20.0 | Systematic Assessment |
|
| Uterine Pain | Reproductive system and breast disorders | MedDRA Version 20.0 | Systematic Assessment |
|
| Uterine Prolapse | Reproductive system and breast disorders | MedDRA Version 20.0 | Systematic Assessment |
|
| Vaginal Haemorrhage | Reproductive system and breast disorders | MedDRA Version 20.0 | Systematic Assessment |
|
| Vaginal Stricture | Reproductive system and breast disorders | MedDRA Version 20.0 | Systematic Assessment |
|
| Vulvovaginal Pain | Reproductive system and breast disorders | MedDRA Version 20.0 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA Version 20.0 | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA Version 20.0 | Systematic Assessment |
|
| Dyspnoea Exertional | Respiratory, thoracic and mediastinal disorders | MedDRA Version 20.0 | Systematic Assessment |
|
| Oropharyngeal Pain | Respiratory, thoracic and mediastinal disorders | MedDRA Version 20.0 | Systematic Assessment |
|
| Excessive Granulation Tissue | Skin and subcutaneous tissue disorders | MedDRA Version 20.0 | Systematic Assessment |
|
| Rash Maculo-Papular | Skin and subcutaneous tissue disorders | MedDRA Version 20.0 | Systematic Assessment |
|
| Deep Vein Thrombosis | Vascular disorders | MedDRA Version 20.0 | Systematic Assessment |
|
| Hot Flush | Vascular disorders | MedDRA Version 20.0 | Systematic Assessment |
|
Not provided
| D009369 |
| Neoplasms |
| D002577 | Uterine Cervical Diseases |
| D014591 | Uterine Diseases |
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D000091662 | Genital Diseases |
| Abdominal Pain |
|
| Intestinal Perforation |
|
| Pneumonia |
|
| Pathological Fracture |
|
| Injection Site Erythema |
|
| Injection Site Haemorrhage |
|
| Injection Site Pain |
|
| Injection Site Swelling |
|
| Change from Baseline at Week 4 |
|
|
| Change from Baseline at Week 8 |
|
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| Change from Baseline at Week 12 |
|
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| Change from Baseline at Week 16 |
|
|
| Change from Baseline at Week 24 |
|
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| Change from Baseline at Week 32 |
|
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| Change from Baseline at Week 48 |
|
|
| Change from Baseline at Week 4 |
|
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| Change from Baseline at Week 8 |
|
|
| Change from Baseline at Week 12 |
|
|
| Change from Baseline at Week 16 |
|
|
| Change from Baseline at Week 24 |
|
|
| Change from Baseline at Week 32 |
|
|
| Change from Baseline at Week 48 |
|
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| L,Change from Baseline at Week 4 |
|
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| L,Change from Baseline at Week 8 |
|
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| L, Change from Baseline at Week 12 |
|
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| L, Change from Baseline at Week 16 |
|
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| L, Change From Baseline at Week 24 |
|
|
| L, Change from Baseline at Week 32 |
|
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| L, Change from Baseline at Week 48 |
|
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| M, Baseline |
|
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| M,Change from Baseline at Week 4 |
|
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| M,Change from Baseline at Week 8 |
|
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| M,Change from Baseline at Week 12 |
|
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| M,Change from Baseline at Week 16 |
|
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| M,Change from Baseline at Week 24 |
|
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| M,Change from Baseline at Week 32 |
|
|
| M,Change from Baseline at Week 48 |
|
|
| N, Baseline |
|
|
| N,Change from Baseline at Week 4 |
|
|
| N,Change from Baseline at Week 8 |
|
|
| N,Change from Baseline at Week 12 |
|
|
| N,Change from Baseline at Week 16 |
|
|
| N,Change from Baseline at Week 24 |
|
|
| N,Change from Baseline at Week 32 |
|
|
| N,Change from Baseline at Week 48 |
|
|
| WBC, Baseline |
|
|
| WBC, Change from Baseline at Week 4 |
|
|
| WBC, Change from Baseline at Week 8 |
|
|
| WBC, Change from Baseline at Week 12 |
|
|
| WBC, Change from Baseline at Week 16 |
|
|
| WBC, Change from Baseline at Week 24 |
|
|
| WBC, Change from Baseline at Week 32 |
|
|
| WBC, Change from Baseline at Week 48 |
|
|
| Platelet Count, Change from Baseline at Week 4 |
|
|
| Platelet Count, Change from Baseline at Week 8 |
|
|
| Platelet Count, Change from Baseline at Week 12 |
|
|
| Platelet Count, Change from Baseline at Week 16 |
|
|
| Platelet Count, Change From Baseline at Week 24 |
|
|
| Platelet Count, Change from Baseline at Week 32 |
|
|
| Platelet Count, Change from Baseline at Week 48 |
|
|
| RBC Count, Change from Baseline at Week 4 |
|
|
| RBC Count, Change from Baseline at Week 8 |
|
|
| ALP, Change from Baseline at Week 4 |
|
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| ALP, Change from Baseline at Week 8 |
|
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| ALP, Change from Baseline at Week 12 |
|
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| ALP, Change from Baseline at Week 16 |
|
|
| ALT, Baseline |
|
|
| ALT, Change from Baseline at Week 4 |
|
|
| ALT, Change from Baseline at Week 8 |
|
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| ALT, Change from Baseline at Week 12 |
|
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| ALT, Change from Baseline at Week 16 |
|
|
| AST, Baseline |
|
|
| AST, Change from Baseline at Week 4 |
|
|
| AST, Change from Baseline at Week 8 |
|
|
| AST, Change from Baseline at Week 12 |
|
|
| AST, Change from Baseline at Week 16 |
|
|
| Bicarbonate, Change from Baseline at Week 4 |
|
|
| Bicarbonate, Change from Baseline at Week 8 |
|
|
| Bicarbonate, Change from Baseline at Week 12 |
|
|
| Bicarbonate, Change from Baseline at Week 16 |
|
|
| Glucose, Baseline |
|
|
| Glucose, Change from Baseline at Week 4 |
|
|
| Glucose, Change from Baseline at Week 8 |
|
|
| Glucose, Change from Baseline at Week 12 |
|
|
| Glucose, Change from Baseline at Week 16 |
|
|
| BUN, Baseline |
|
|
| BUN, Change from Baseline at Week 4 |
|
|
| BUN, Change from Baseline at Week 8 |
|
|
| BUN, Change from Baseline at Week 12 |
|
|
| BUN, Change from Baseline at Week 16 |
|
|
| Ca, Baseline |
|
|
| Ca, Change from Baseline at Week 4 |
|
|
| Ca, Change from Baseline at Week 8 |
|
|
| Ca, Change from Baseline at Week 12 |
|
|
| Ca, Change from Baseline at Week 16 |
|
|
| Cl, Baseline |
|
|
| Cl, Change from Baseline at Week 4 |
|
|
| Cl, Change from Baseline at Week 8 |
|
|
| Cl, Change from Baseline at Week 12 |
|
|
| Cl, Change from Baseline at Week 16 |
|
|
| K, Baseline |
|
|
| K, Change from Baseline at Week 4 |
|
|
| K, Change from Baseline at Week 8 |
|
|
| K, Change from Baseline at Week 12 |
|
|
| K, Change from Baseline at Week 16 |
|
|
| Mg, Baseline |
|
|
| Na, Baseline |
|
|
| Na, Change from Baseline at Week 4 |
|
|
| Na, Change from Baseline at Week 8 |
|
|
| Na, Change from Baseline at Week 12 |
|
|
| Na, Change from Baseline at Week 16 |
|
|
| Albumin, Change from Baseline at Week 4 |
|
|
| Albumin, Change from Baseline at Week 8 |
|
|
| Albumin, Change from Baseline at Week 12 |
|
|
| Albumin, Change from Baseline at Week 16 |
|
|
| Total protein, Baseline |
|
|
| Total protein, Change from Baseline at Week 4 |
|
|
| Total protein, Change from Baseline at Week 8 |
|
|
| Total protein, Change from Baseline at Week 12 |
|
|
| Total protein, Change from Baseline at Week 16 |
|
|
| CPK, Change from Baseline at Week 16 |
|
|
| Creatinine, Change from Baseline at Week 4 |
|
|
| Creatinine, Change from Baseline at Week 8 |
|
|
| Creatinine, Change from Baseline at Week 12 |
|
|
| Creatinine, Change from Baseline at Week 16 |
|
|
| Total Bilirubin, Baseline |
|
|
| Total Bilirubin, Change from Baseline at Week 4 |
|
|
| Total Bilirubin, Change from Baseline at Week 8 |
|
|
| Total Bilirubin, Change from Baseline at Week 12 |
|
|
| Total Bilirubin, Change from Baseline at Week 16 |
|
|
| Increase from Baseline at Week 2 |
|
|
| Increase from Baseline at Week 4 |
|
|
| Increase from Baseline at Week 6 |
|
|
| Increase from Baseline at Week 8 |
|
|
| Increase from Baseline at Week 10 |
|
|
| Increase from Baseline at Week 12 |
|
|
| Increase from Baseline at Week 14 |
|
|
| Increase from Baseline at Week 16 |
|
|
| Increase from Baseline at Week 24 |
|
|
| Increase from Baseline at Week 32 |
|
|
| Increase from Baseline at Week 36 |
|
|
| Increase from Baseline at Week 40 |
|
|
| Increase from Baseline at Week 48 |
|
|
| HPV-16, Week 2 |
|
|
| HPV-16, Week 4 |
|
|
| HPV-16, Week 6 |
|
|
| HPV-16, Week 8 |
|
|
| HPV-16, Week 10 |
|
|
| HPV-16, Week 12 |
|
|
| HPV-16, Week 14 |
|
|
| HPV-16, Week 16 |
|
|
| HPV-16, Week 24 |
|
|
| HPV-16, Week 32 |
|
|
| HPV-16, Week 36 |
|
|
| HPV-16, Week 40 |
|
|
| HPV-16, Week 48 |
|
|
| HPV-18, Baseline |
|
|
| HPV-18, Week 2 |
|
|
| HPV-18, Week 4 |
|
|
| HPV-18, Week 6 |
|
|
| HPV-18, Week 8 |
|
|
| HPV-18, Week 10 |
|
|
| HPV-18, Week 12 |
|
|
| HPV-18, Week 14 |
|
|
| HPV-18, Week 16 |
|
|
| HPV-18, Week 24 |
|
|
| HPV-18, Week 32 |
|
|
| HPV-18, Week 36 |
|
|
| HPV-18, Week 40 |
|
|
| HPV-18, Week 48 |
|
|
| HPV-16, Week 2 |
|
|
| HPV-16, Week 4 |
|
|
| HPV-16, Week 6 |
|
|
| HPV-16, Week 8 |
|
|
| HPV-16, Week 10 |
|
|
| HPV-16, Week 12 |
|
|
| HPV-16, Week 14 |
|
|
| HPV-16, Week 16 |
|
|
| HPV-16, Week 24 |
|
|
| HPV-16, Week 32 |
|
|
| HPV-16, Week 36 |
|
|
| HPV-16, Week 40 |
|
|
| HPV-16, Week 48 |
|
|
| HPV-18, Baseline |
|
|
| HPV-18, Week 2 |
|
|
| HPV-18, Week 4 |
|
|
| HPV-18, Week 6 |
|
|
| HPV-18, Week 8 |
|
|
| HPV-18, Week 10 |
|
|
| HPV-18, Week 12 |
|
|
| HPV-18, Week 14 |
|
|
| HPV-18, Week 16 |
|
|
| HPV-18, Week 24 |
|
|
| HPV-18, Week 32 |
|
|
| HPV-18, Week 36 |
|
|
| HPV-18, Week 40 |
|
|
| HPV-18, Week 48 |
|
|