Cervical Cancer
Conditions
Keywords
Cervical cancer, Papillomavirus, Chemoradiation, Recurrent cervical cancer, Persistent cervical cancer
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.
Detailed description
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).
Interventions
BIOLOGICALINO-3112
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.
DEVICECELLECTRA™-5P
CELLECTRA™-5P was used for EP following IM delivery of INO-3112 on Day 0, Week 4, Week 8, and Week 12.
Sponsors
Inovio Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Written informed consent. 2. 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. 3. 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. 1. 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 2. 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 4. Electrocardiogram (ECG) with no clinically significant findings. 5. Chemistry, liver function tests, renal function, total CPK and hematology lab results must be ≤ Grade 1 at the time of screening. 6. Eastern Cooperative Oncology Group (ECOG) Performance status of ≤ 1. 7. Adequate venous access for repeated blood sampling according to the study schedule. 8. 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 \[IUD\]). 9. Able and willing to comply with all study procedures.
Exclusion criteria
1. Pregnancy or breastfeeding. 2. History of previous therapeutic HPV vaccination. 3. Prior exposure to an investigational agent or device within 30 days of signing the ICF. Of note, the participant may participate in observational studies. 4. 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). 5. Prior major surgery from which the participant has not yet recovered to baseline. 6. High medical risks because of non-malignant systemic disease or with active uncontrolled infection. 7. Current malignancies at other sites, with the exception of adequately treated basal or squamous cell carcinoma of the skin. 8. Congestive heart failure or prior history of New York Heart Association (NYHA) class III/ IV cardiac disease. 9. Use of topical corticosteroids at or near the intended administration site. 10. Any cardiac pre-excitation syndromes (such as Wolff-Parkinson-White). 11. History of seizures (unless seizure free for 5 years). 12. 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. 13. Active drug or alcohol use or dependence. 14. Imprisonment or compulsory detainment for treatment of either a psychiatric or physical (i.e. infectious disease) illness. 15. History of immunosuppressive or autoimmune disease. 16. Any other illnesses or conditions that in the opinion of the investigator may affect the safety of the participant or limit the evaluation of a participant or any study endpoint.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Creatinine and Total Bilirubin at the Indicated Time Points | Baseline and Weeks 4, 8,12 and 16 | 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. |
| 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 | Baseline and Weeks 4,8,12 and 16 | 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. |
| Change From Baseline in Albumin and Total Protein at the Indicated Time Points | Baseline and Weeks 4,8,12 and 16 | 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. |
| Change From Baseline in Creatine Phosphokinase (CPK) at the Indicated Time Points | Baseline and Week 16 | 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. |
| Change From Baseline in Hematocrit at the Indicated Time Points | Baseline and Week 4, 8,12,16,24, 32 and 48 | 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. |
| Percentage of Participants With at Least 1 Treatment Emergent Adverse Event (TEAE) | Up to 36 weeks | 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. |
| Percentage of Participants With Grade 3 or Higher TEAEs Graded Per Common Terminology Criteria for Adverse Events, Version 4.03 (CTCAE, v 4.03) | Up to 36 weeks | 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. |
| Percentage of Participants With Injection Site Reactions | Up to 36 weeks | 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. |
| 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 Hemoglobin at the Indicated Time Points | Baseline and Weeks 4, 8,12,16,24, 32 and 48 | 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. |
| Change From Baseline in Lymphocytes, Monocytes, Neutrophils and White Blood Cell (WBC) Count at the Indicated Time Points | Baseline and Weeks 4, 8,12,16,24, 32 and 48 | 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). |
| Change From Baseline in Platelet Count at the Indicated Time Points | Baseline and Weeks 4,8,12,16,24,32 and 48 | 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. |
| Change From Baseline in Red Blood Cell (RBC) Count at the Indicated Time Points | Baseline and Weeks 4 and 8 | 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. |
| Change From Baseline in Alkaline Phosphatase, Alanine Aminotransferase, and Aspartate Aminotransferase at the Indicated Time Points | Baseline and Weeks 4,8,12 and 16 | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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. |
| 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 | 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. |
| 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 | 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). |
Countries
United States
Participant flow
Recruitment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 7 |
| 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. | 3 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Loss of insurance coverage | 1 | 0 |
| Overall Study | Progression of Disease | 0 | 1 |
| Overall Study | Serious Adverse Event | 0 | 1 |
Baseline characteristics
| Characteristic | Cohort I: INO-3112: Curative Intent | Cohort II: INO-3112: Salvage Therapy | Total |
|---|---|---|---|
| Age, Continuous | 47.9 years STANDARD_DEVIATION 11.63 | 41.7 years STANDARD_DEVIATION 14.64 | 46.0 years STANDARD_DEVIATION 12.11 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 1 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 2 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) White | 5 Participants | 1 Participants | 6 Participants |
| Sex/Gender, Customized Female | 7 Participants | 3 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 1 / 3 |
| other Total, other adverse events | 7 / 7 | 3 / 3 |
| serious Total, serious adverse events | 3 / 7 | 2 / 3 |
Outcome results
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.
Time frame: Baseline and Weeks 4,8,12 and 16
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Albumin and Total Protein at the Indicated Time Points | Albumin, Baseline | 42.00 grams per liter (g/L) | Standard Deviation 2 |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Albumin and Total Protein at the Indicated Time Points | Total protein, Change from Baseline at Week 12 | 2.20 grams per liter (g/L) | Standard Deviation 5.805 |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Albumin and Total Protein at the Indicated Time Points | Total protein, Change from Baseline at Week 16 | 3.20 grams per liter (g/L) | Standard Deviation 5.357 |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Albumin and Total Protein at the Indicated Time Points | Total protein, Change from Baseline at Week 4 | 1.20 grams per liter (g/L) | Standard Deviation 2.168 |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Albumin and Total Protein at the Indicated Time Points | Albumin, Change from Baseline at Week 4 | -1.00 grams per liter (g/L) | Standard Deviation 1 |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Albumin and Total Protein at the Indicated Time Points | Albumin, Change from Baseline at Week 8 | 0.80 grams per liter (g/L) | Standard Deviation 1.304 |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Albumin and Total Protein at the Indicated Time Points | Albumin, Change from Baseline at Week 12 | 0.60 grams per liter (g/L) | Standard Deviation 2.191 |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Albumin and Total Protein at the Indicated Time Points | Albumin, Change from Baseline at Week 16 | 1.00 grams per liter (g/L) | Standard Deviation 1.871 |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Albumin and Total Protein at the Indicated Time Points | Total protein, Baseline | 68.86 grams per liter (g/L) | Standard Deviation 4.488 |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Albumin and Total Protein at the Indicated Time Points | Total protein, Change from Baseline at Week 8 | 2.80 grams per liter (g/L) | Standard Deviation 4.087 |
| Cohort II: INO-3112: Salvage Therapy | Change From Baseline in Albumin and Total Protein at the Indicated Time Points | Albumin, Change from Baseline at Week 16 | -1.00 grams per liter (g/L) | — |
| Cohort II: INO-3112: Salvage Therapy | Change From Baseline in Albumin and Total Protein at the Indicated Time Points | Total protein, Change from Baseline at Week 8 | -5.50 grams per liter (g/L) | Standard Deviation 3.536 |
| Cohort II: INO-3112: Salvage Therapy | Change From Baseline in Albumin and Total Protein at the Indicated Time Points | Albumin, Change from Baseline at Week 8 | -2.50 grams per liter (g/L) | Standard Deviation 3.536 |
| Cohort II: INO-3112: Salvage Therapy | Change From Baseline in Albumin and Total Protein at the Indicated Time Points | Total protein, Change from Baseline at Week 12 | -2.00 grams per liter (g/L) | — |
| Cohort II: INO-3112: Salvage Therapy | Change From Baseline in Albumin and Total Protein at the Indicated Time Points | Total protein, Change from Baseline at Week 4 | -2.67 grams per liter (g/L) | Standard Deviation 3.215 |
| Cohort II: INO-3112: Salvage Therapy | Change From Baseline in Albumin and Total Protein at the Indicated Time Points | Total protein, Change from Baseline at Week 16 | -2.00 grams per liter (g/L) | — |
| Cohort II: INO-3112: Salvage Therapy | Change From Baseline in Albumin and Total Protein at the Indicated Time Points | Albumin, Change from Baseline at Week 12 | -2.00 grams per liter (g/L) | — |
| Cohort II: INO-3112: Salvage Therapy | Change From Baseline in Albumin and Total Protein at the Indicated Time Points | Albumin, Baseline | 40.33 grams per liter (g/L) | Standard Deviation 3.215 |
| Cohort II: INO-3112: Salvage Therapy | Change From Baseline in Albumin and Total Protein at the Indicated Time Points | Total protein, Baseline | 73.67 grams per liter (g/L) | Standard Deviation 3.215 |
| Cohort II: INO-3112: Salvage Therapy | Change From Baseline in Albumin and Total Protein at the Indicated Time Points | Albumin, Change from Baseline at Week 4 | -1.00 grams per liter (g/L) | Standard Deviation 1 |
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).
Time frame: Baseline and Weeks 4,8,12 and 16
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Alkaline Phosphatase, Alanine Aminotransferase, and Aspartate Aminotransferase at the Indicated Time Points | ALP, Change from Baseline at Week 16 | 8.60 units per liter (U/L) | Standard Deviation 22.233 |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Alkaline Phosphatase, Alanine Aminotransferase, and Aspartate Aminotransferase at the Indicated Time Points | ALT, Change from Baseline at Week 12 | -1.60 units per liter (U/L) | Standard Deviation 6.229 |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Alkaline Phosphatase, Alanine Aminotransferase, and Aspartate Aminotransferase at the Indicated Time Points | ALP, Change from Baseline at Week 4 | 0.20 units per liter (U/L) | Standard Deviation 13.989 |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Alkaline Phosphatase, Alanine Aminotransferase, and Aspartate Aminotransferase at the Indicated Time Points | ALT, Change from Baseline at Week 16 | -2.20 units per liter (U/L) | Standard Deviation 3.768 |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Alkaline Phosphatase, Alanine Aminotransferase, and Aspartate Aminotransferase at the Indicated Time Points | ALT, Baseline | 20.14 units per liter (U/L) | Standard Deviation 6.793 |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Alkaline Phosphatase, Alanine Aminotransferase, and Aspartate Aminotransferase at the Indicated Time Points | AST, Baseline | 22.71 units per liter (U/L) | Standard Deviation 6.945 |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Alkaline Phosphatase, Alanine Aminotransferase, and Aspartate Aminotransferase at the Indicated Time Points | ALP, Change from Baseline at Week 12 | 4.00 units per liter (U/L) | Standard Deviation 26.448 |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Alkaline Phosphatase, Alanine Aminotransferase, and Aspartate Aminotransferase at the Indicated Time Points | AST, Change from Baseline at Week 4 | 3.20 units per liter (U/L) | Standard Deviation 8.526 |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Alkaline Phosphatase, Alanine Aminotransferase, and Aspartate Aminotransferase at the Indicated Time Points | ALT, Change from Baseline at Week 4 | 4.60 units per liter (U/L) | Standard Deviation 13.353 |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Alkaline Phosphatase, Alanine Aminotransferase, and Aspartate Aminotransferase at the Indicated Time Points | AST, Change from Baseline at Week 8 | -3.80 units per liter (U/L) | Standard Deviation 6.34 |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Alkaline Phosphatase, Alanine Aminotransferase, and Aspartate Aminotransferase at the Indicated Time Points | ALP, Change from Baseline at Week 8 | 3.00 units per liter (U/L) | Standard Deviation 20.273 |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Alkaline Phosphatase, Alanine Aminotransferase, and Aspartate Aminotransferase at the Indicated Time Points | AST, Change from Baseline at Week 12 | 1.20 units per liter (U/L) | Standard Deviation 13.461 |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Alkaline Phosphatase, Alanine Aminotransferase, and Aspartate Aminotransferase at the Indicated Time Points | ALT, Change from Baseline at Week 8 | -5.00 units per liter (U/L) | Standard Deviation 4.95 |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Alkaline Phosphatase, Alanine Aminotransferase, and Aspartate Aminotransferase at the Indicated Time Points | AST, Change from Baseline at Week 16 | -2.80 units per liter (U/L) | Standard Deviation 4.658 |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Alkaline Phosphatase, Alanine Aminotransferase, and Aspartate Aminotransferase at the Indicated Time Points | ALP, Baseline | 73.29 units per liter (U/L) | Standard Deviation 26.606 |
| Cohort II: INO-3112: Salvage Therapy | Change From Baseline in Alkaline Phosphatase, Alanine Aminotransferase, and Aspartate Aminotransferase at the Indicated Time Points | AST, Change from Baseline at Week 16 | -16.00 units per liter (U/L) | — |
| Cohort II: INO-3112: Salvage Therapy | Change From Baseline in Alkaline Phosphatase, Alanine Aminotransferase, and Aspartate Aminotransferase at the Indicated Time Points | ALP, Baseline | 81.33 units per liter (U/L) | Standard Deviation 10.017 |
| Cohort II: INO-3112: Salvage Therapy | Change From Baseline in Alkaline Phosphatase, Alanine Aminotransferase, and Aspartate Aminotransferase at the Indicated Time Points | ALP, Change from Baseline at Week 4 | 14.67 units per liter (U/L) | Standard Deviation 21.779 |
| Cohort II: INO-3112: Salvage Therapy | Change From Baseline in Alkaline Phosphatase, Alanine Aminotransferase, and Aspartate Aminotransferase at the Indicated Time Points | ALP, Change from Baseline at Week 8 | 54.00 units per liter (U/L) | Standard Deviation 65.054 |
| Cohort II: INO-3112: Salvage Therapy | Change From Baseline in Alkaline Phosphatase, Alanine Aminotransferase, and Aspartate Aminotransferase at the Indicated Time Points | ALP, Change from Baseline at Week 12 | 0.00 units per liter (U/L) | — |
| Cohort II: INO-3112: Salvage Therapy | Change From Baseline in Alkaline Phosphatase, Alanine Aminotransferase, and Aspartate Aminotransferase at the Indicated Time Points | ALP, Change from Baseline at Week 16 | 1.00 units per liter (U/L) | — |
| Cohort II: INO-3112: Salvage Therapy | Change From Baseline in Alkaline Phosphatase, Alanine Aminotransferase, and Aspartate Aminotransferase at the Indicated Time Points | ALT, Baseline | 13.00 units per liter (U/L) | Standard Deviation 9.849 |
| Cohort II: INO-3112: Salvage Therapy | Change From Baseline in Alkaline Phosphatase, Alanine Aminotransferase, and Aspartate Aminotransferase at the Indicated Time Points | ALT, Change from Baseline at Week 4 | -3.67 units per liter (U/L) | Standard Deviation 11.59 |
| Cohort II: INO-3112: Salvage Therapy | Change From Baseline in Alkaline Phosphatase, Alanine Aminotransferase, and Aspartate Aminotransferase at the Indicated Time Points | ALT, Change from Baseline at Week 8 | -4.50 units per liter (U/L) | Standard Deviation 14.849 |
| Cohort II: INO-3112: Salvage Therapy | Change From Baseline in Alkaline Phosphatase, Alanine Aminotransferase, and Aspartate Aminotransferase at the Indicated Time Points | ALT, Change from Baseline at Week 12 | -14.00 units per liter (U/L) | — |
| Cohort II: INO-3112: Salvage Therapy | Change From Baseline in Alkaline Phosphatase, Alanine Aminotransferase, and Aspartate Aminotransferase at the Indicated Time Points | ALT, Change from Baseline at Week 16 | -15.00 units per liter (U/L) | — |
| Cohort II: INO-3112: Salvage Therapy | Change From Baseline in Alkaline Phosphatase, Alanine Aminotransferase, and Aspartate Aminotransferase at the Indicated Time Points | AST, Baseline | 17.00 units per liter (U/L) | Standard Deviation 7.937 |
| Cohort II: INO-3112: Salvage Therapy | Change From Baseline in Alkaline Phosphatase, Alanine Aminotransferase, and Aspartate Aminotransferase at the Indicated Time Points | AST, Change from Baseline at Week 4 | -5.67 units per liter (U/L) | Standard Deviation 11.547 |
| Cohort II: INO-3112: Salvage Therapy | Change From Baseline in Alkaline Phosphatase, Alanine Aminotransferase, and Aspartate Aminotransferase at the Indicated Time Points | AST, Change from Baseline at Week 8 | -5.00 units per liter (U/L) | Standard Deviation 14.142 |
| Cohort II: INO-3112: Salvage Therapy | Change From Baseline in Alkaline Phosphatase, Alanine Aminotransferase, and Aspartate Aminotransferase at the Indicated Time Points | AST, Change from Baseline at Week 12 | -15.00 units per liter (U/L) | — |
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.
Time frame: Baseline and Weeks 4,8,12 and 16
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort I: INO-3112: Curative Intent | 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 | Ca, Change from Baseline at Week 12 | 0.01 millimole per liter (mmol/L) | Standard Deviation 0.086 |
| Cohort I: INO-3112: Curative Intent | 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 | Glucose, Baseline | 6.90 millimole per liter (mmol/L) | Standard Deviation 2.994 |
| Cohort I: INO-3112: Curative Intent | 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 | Ca, Change from Baseline at Week 16 | 0.04 millimole per liter (mmol/L) | Standard Deviation 0.121 |
| Cohort I: INO-3112: Curative Intent | 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 | BUN, Baseline | 4.18 millimole per liter (mmol/L) | Standard Deviation 1.897 |
| Cohort I: INO-3112: Curative Intent | 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 | Cl, Baseline | 91.57 millimole per liter (mmol/L) | Standard Deviation 28.757 |
| Cohort I: INO-3112: Curative Intent | 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 | Bicarbonate, Change from Baseline at Week 12 | -1.40 millimole per liter (mmol/L) | Standard Deviation 0.548 |
| Cohort I: INO-3112: Curative Intent | 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 | Cl, Change from Baseline at Week 4 | 15.40 millimole per liter (mmol/L) | Standard Deviation 34.53 |
| Cohort I: INO-3112: Curative Intent | 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 | BUN, Change from Baseline at Week 4 | 0.86 millimole per liter (mmol/L) | Standard Deviation 1.485 |
| Cohort I: INO-3112: Curative Intent | 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 | Cl, Change from Baseline at Week 8 | 14.60 millimole per liter (mmol/L) | Standard Deviation 35.494 |
| Cohort I: INO-3112: Curative Intent | 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 | Glucose, Change from Baseline at Week 4 | -0.60 millimole per liter (mmol/L) | Standard Deviation 0.736 |
| Cohort I: INO-3112: Curative Intent | 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 | Cl, Change from Baseline at Week 12 | 14.00 millimole per liter (mmol/L) | Standard Deviation 34.785 |
| Cohort I: INO-3112: Curative Intent | 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 | BUN, Change from Baseline at Week 8 | 0.50 millimole per liter (mmol/L) | Standard Deviation 1.568 |
| Cohort I: INO-3112: Curative Intent | 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 | Cl, Change from Baseline at Week 16 | 14.40 millimole per liter (mmol/L) | Standard Deviation 33.923 |
| Cohort I: INO-3112: Curative Intent | 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 | Bicarbonate, Change from Baseline at Week 8 | -0.60 millimole per liter (mmol/L) | Standard Deviation 2.074 |
| Cohort I: INO-3112: Curative Intent | 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 | K, Baseline | 4.20 millimole per liter (mmol/L) | Standard Deviation 0.383 |
| Cohort I: INO-3112: Curative Intent | 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 | BUN, Change from Baseline at Week 12 | 1.87 millimole per liter (mmol/L) | Standard Deviation 3.085 |
| Cohort I: INO-3112: Curative Intent | 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 | K, Change from Baseline at Week 4 | -0.16 millimole per liter (mmol/L) | Standard Deviation 0.503 |
| Cohort I: INO-3112: Curative Intent | 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 | Glucose, Change from Baseline at Week 8 | -0.57 millimole per liter (mmol/L) | Standard Deviation 0.839 |
| Cohort I: INO-3112: Curative Intent | 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 | K, Change from Baseline at Week 8 | -0.06 millimole per liter (mmol/L) | Standard Deviation 0.391 |
| Cohort I: INO-3112: Curative Intent | 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 | BUN, Change from Baseline at Week 16 | 1.29 millimole per liter (mmol/L) | Standard Deviation 1.686 |
| Cohort I: INO-3112: Curative Intent | 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 | K, Change from Baseline at Week 12 | -0.02 millimole per liter (mmol/L) | Standard Deviation 0.466 |
| Cohort I: INO-3112: Curative Intent | 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 | Bicarbonate, Change from Baseline at Week 16 | -0.40 millimole per liter (mmol/L) | Standard Deviation 1.14 |
| Cohort I: INO-3112: Curative Intent | 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 | K, Change from Baseline at Week 16 | -0.14 millimole per liter (mmol/L) | Standard Deviation 0.365 |
| Cohort I: INO-3112: Curative Intent | 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 | Ca, Baseline | 2.33 millimole per liter (mmol/L) | Standard Deviation 0.089 |
| Cohort I: INO-3112: Curative Intent | 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 | Mg, Baseline | 0.41 millimole per liter (mmol/L) | — |
| Cohort I: INO-3112: Curative Intent | 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 | Na, Baseline | 141.29 millimole per liter (mmol/L) | Standard Deviation 3.147 |
| Cohort I: INO-3112: Curative Intent | 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 | Glucose, Change from Baseline at Week 12 | -0.78 millimole per liter (mmol/L) | Standard Deviation 0.755 |
| Cohort I: INO-3112: Curative Intent | 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 | Na, Change from Baseline at Week 4 | 0.00 millimole per liter (mmol/L) | Standard Deviation 2.915 |
| Cohort I: INO-3112: Curative Intent | 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 | Ca, Change from Baseline at Week 4 | 0.05 millimole per liter (mmol/L) | Standard Deviation 0.077 |
| Cohort I: INO-3112: Curative Intent | 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 | Na, Change from Baseline at Week 8 | -0.20 millimole per liter (mmol/L) | Standard Deviation 1.924 |
| Cohort I: INO-3112: Curative Intent | 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 | Bicarbonate, Change from Baseline at Week 4 | 0.00 millimole per liter (mmol/L) | Standard Deviation 1 |
| Cohort I: INO-3112: Curative Intent | 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 | Na, Change from Baseline at Week 12 | -1.20 millimole per liter (mmol/L) | Standard Deviation 2.28 |
| Cohort I: INO-3112: Curative Intent | 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 | Ca, Change from Baseline at Week 8 | 0.02 millimole per liter (mmol/L) | Standard Deviation 0.045 |
| Cohort I: INO-3112: Curative Intent | 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 | Na, Change from Baseline at Week 16 | -0.60 millimole per liter (mmol/L) | Standard Deviation 1.517 |
| Cohort I: INO-3112: Curative Intent | 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 | Bicarbonate, Baseline | 25.00 millimole per liter (mmol/L) | Standard Deviation 1.633 |
| Cohort I: INO-3112: Curative Intent | 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 | Glucose, Change from Baseline at Week 16 | -0.46 millimole per liter (mmol/L) | Standard Deviation 0.308 |
| Cohort II: INO-3112: Salvage Therapy | 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 | Na, Change from Baseline at Week 16 | 3.00 millimole per liter (mmol/L) | — |
| Cohort II: INO-3112: Salvage Therapy | 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 | Bicarbonate, Baseline | 24.33 millimole per liter (mmol/L) | Standard Deviation 2.082 |
| Cohort II: INO-3112: Salvage Therapy | 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 | Bicarbonate, Change from Baseline at Week 4 | 3.33 millimole per liter (mmol/L) | Standard Deviation 0.577 |
| Cohort II: INO-3112: Salvage Therapy | 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 | Bicarbonate, Change from Baseline at Week 8 | 0.00 millimole per liter (mmol/L) | Standard Deviation 2.828 |
| Cohort II: INO-3112: Salvage Therapy | 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 | Bicarbonate, Change from Baseline at Week 12 | 2.00 millimole per liter (mmol/L) | — |
| Cohort II: INO-3112: Salvage Therapy | 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 | Bicarbonate, Change from Baseline at Week 16 | 4.00 millimole per liter (mmol/L) | — |
| Cohort II: INO-3112: Salvage Therapy | 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 | Glucose, Baseline | 5.25 millimole per liter (mmol/L) | Standard Deviation 1.042 |
| Cohort II: INO-3112: Salvage Therapy | 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 | Glucose, Change from Baseline at Week 4 | 1.18 millimole per liter (mmol/L) | Standard Deviation 0.946 |
| Cohort II: INO-3112: Salvage Therapy | 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 | Glucose, Change from Baseline at Week 8 | 2.69 millimole per liter (mmol/L) | Standard Deviation 2.237 |
| Cohort II: INO-3112: Salvage Therapy | 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 | Glucose, Change from Baseline at Week 12 | 0.39 millimole per liter (mmol/L) | — |
| Cohort II: INO-3112: Salvage Therapy | 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 | Glucose, Change from Baseline at Week 16 | -1.44 millimole per liter (mmol/L) | — |
| Cohort II: INO-3112: Salvage Therapy | 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 | BUN, Baseline | 4.17 millimole per liter (mmol/L) | Standard Deviation 1.687 |
| Cohort II: INO-3112: Salvage Therapy | 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 | BUN, Change from Baseline at Week 4 | -1.07 millimole per liter (mmol/L) | Standard Deviation 1.071 |
| Cohort II: INO-3112: Salvage Therapy | 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 | BUN, Change from Baseline at Week 8 | 0.18 millimole per liter (mmol/L) | Standard Deviation 0.757 |
| Cohort II: INO-3112: Salvage Therapy | 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 | BUN, Change from Baseline at Week 12 | -1.79 millimole per liter (mmol/L) | — |
| Cohort II: INO-3112: Salvage Therapy | 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 | BUN, Change from Baseline at Week 16 | -0.71 millimole per liter (mmol/L) | — |
| Cohort II: INO-3112: Salvage Therapy | 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 | Ca, Baseline | 2.37 millimole per liter (mmol/L) | Standard Deviation 0.014 |
| Cohort II: INO-3112: Salvage Therapy | 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 | Ca, Change from Baseline at Week 4 | -0.06 millimole per liter (mmol/L) | Standard Deviation 0.104 |
| Cohort II: INO-3112: Salvage Therapy | 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 | Ca, Change from Baseline at Week 8 | -0.16 millimole per liter (mmol/L) | Standard Deviation 0.088 |
| Cohort II: INO-3112: Salvage Therapy | 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 | Ca, Change from Baseline at Week 12 | -0.08 millimole per liter (mmol/L) | — |
| Cohort II: INO-3112: Salvage Therapy | 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 | Ca, Change from Baseline at Week 16 | -0.15 millimole per liter (mmol/L) | — |
| Cohort II: INO-3112: Salvage Therapy | 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 | Cl, Baseline | 100.00 millimole per liter (mmol/L) | Standard Deviation 3.464 |
| Cohort II: INO-3112: Salvage Therapy | 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 | Cl, Change from Baseline at Week 4 | -1.00 millimole per liter (mmol/L) | Standard Deviation 2.646 |
| Cohort II: INO-3112: Salvage Therapy | 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 | Cl, Change from Baseline at Week 8 | -1.00 millimole per liter (mmol/L) | Standard Deviation 1.414 |
| Cohort II: INO-3112: Salvage Therapy | 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 | Cl, Change from Baseline at Week 12 | 1.00 millimole per liter (mmol/L) | — |
| Cohort II: INO-3112: Salvage Therapy | 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 | Cl, Change from Baseline at Week 16 | 0.00 millimole per liter (mmol/L) | — |
| Cohort II: INO-3112: Salvage Therapy | 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 | K, Baseline | 4.37 millimole per liter (mmol/L) | Standard Deviation 0.252 |
| Cohort II: INO-3112: Salvage Therapy | 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 | K, Change from Baseline at Week 4 | -0.43 millimole per liter (mmol/L) | Standard Deviation 1.305 |
| Cohort II: INO-3112: Salvage Therapy | 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 | K, Change from Baseline at Week 8 | -0.65 millimole per liter (mmol/L) | Standard Deviation 1.061 |
| Cohort II: INO-3112: Salvage Therapy | 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 | K, Change from Baseline at Week 12 | -0.70 millimole per liter (mmol/L) | — |
| Cohort II: INO-3112: Salvage Therapy | 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 | K, Change from Baseline at Week 16 | -1.00 millimole per liter (mmol/L) | — |
| Cohort II: INO-3112: Salvage Therapy | 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 | Na, Baseline | 138.67 millimole per liter (mmol/L) | Standard Deviation 1.528 |
| Cohort II: INO-3112: Salvage Therapy | 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 | Na, Change from Baseline at Week 4 | 1.67 millimole per liter (mmol/L) | Standard Deviation 4.726 |
| Cohort II: INO-3112: Salvage Therapy | 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 | Na, Change from Baseline at Week 8 | -0.50 millimole per liter (mmol/L) | Standard Deviation 3.536 |
| Cohort II: INO-3112: Salvage Therapy | 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 | Na, Change from Baseline at Week 12 | 4.00 millimole per liter (mmol/L) | — |
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.
Time frame: Baseline and Week 16
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Creatine Phosphokinase (CPK) at the Indicated Time Points | CPK, Baseline | 46.9 units per liter (U/L) | Standard Deviation 9.3 |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Creatine Phosphokinase (CPK) at the Indicated Time Points | CPK, Change from Baseline at Week 16 | 18.8 units per liter (U/L) | Standard Deviation 15.8 |
| Cohort II: INO-3112: Salvage Therapy | Change From Baseline in Creatine Phosphokinase (CPK) at the Indicated Time Points | CPK, Baseline | 42.7 units per liter (U/L) | Standard Deviation 15.5 |
| Cohort II: INO-3112: Salvage Therapy | Change From Baseline in Creatine Phosphokinase (CPK) at the Indicated Time Points | CPK, Change from Baseline at Week 16 | 30.0 units per liter (U/L) | — |
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.
Time frame: Baseline and Weeks 4, 8,12 and 16
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Creatinine and Total Bilirubin at the Indicated Time Points | Creatinine, Baseline | 66.93 micromoles per liter (umol/L) | Standard Deviation 16.817 |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Creatinine and Total Bilirubin at the Indicated Time Points | Creatinine, Change from Baseline at Week 4 | 5.83 micromoles per liter (umol/L) | Standard Deviation 7.543 |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Creatinine and Total Bilirubin at the Indicated Time Points | Creatinine, Change from Baseline at Week 8 | -1.59 micromoles per liter (umol/L) | Standard Deviation 7.193 |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Creatinine and Total Bilirubin at the Indicated Time Points | Creatinine, Change from Baseline at Week 16 | 3.36 micromoles per liter (umol/L) | Standard Deviation 8.015 |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Creatinine and Total Bilirubin at the Indicated Time Points | Total Bilirubin, Baseline | 7.82 micromoles per liter (umol/L) | Standard Deviation 4.922 |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Creatinine and Total Bilirubin at the Indicated Time Points | Total Bilirubin, Change from Baseline at Week 4 | -1.71 micromoles per liter (umol/L) | Standard Deviation 4.837 |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Creatinine and Total Bilirubin at the Indicated Time Points | Total Bilirubin, Change from Baseline at Week 8 | -1.37 micromoles per liter (umol/L) | Standard Deviation 4.083 |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Creatinine and Total Bilirubin at the Indicated Time Points | Total Bilirubin, Change from Baseline at Week 12 | -1.03 micromoles per liter (umol/L) | Standard Deviation 5.353 |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Creatinine and Total Bilirubin at the Indicated Time Points | Total Bilirubin, Change from Baseline at Week 16 | -0.00 micromoles per liter (umol/L) | Standard Deviation 6.283 |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Creatinine and Total Bilirubin at the Indicated Time Points | Creatinine, Change from Baseline at Week 12 | 6.01 micromoles per liter (umol/L) | Standard Deviation 8.442 |
| Cohort II: INO-3112: Salvage Therapy | Change From Baseline in Creatinine and Total Bilirubin at the Indicated Time Points | Total Bilirubin, Baseline | 6.84 micromoles per liter (umol/L) | Standard Deviation 4.524 |
| Cohort II: INO-3112: Salvage Therapy | Change From Baseline in Creatinine and Total Bilirubin at the Indicated Time Points | Creatinine, Baseline | 70.72 micromoles per liter (umol/L) | Standard Deviation 8.84 |
| Cohort II: INO-3112: Salvage Therapy | Change From Baseline in Creatinine and Total Bilirubin at the Indicated Time Points | Total Bilirubin, Change from Baseline at Week 16 | 0.00 micromoles per liter (umol/L) | — |
| Cohort II: INO-3112: Salvage Therapy | Change From Baseline in Creatinine and Total Bilirubin at the Indicated Time Points | Creatinine, Change from Baseline at Week 4 | 2.95 micromoles per liter (umol/L) | Standard Deviation 5.104 |
| Cohort II: INO-3112: Salvage Therapy | Change From Baseline in Creatinine and Total Bilirubin at the Indicated Time Points | Total Bilirubin, Change from Baseline at Week 4 | -1.71 micromoles per liter (umol/L) | Standard Deviation 2.962 |
| Cohort II: INO-3112: Salvage Therapy | Change From Baseline in Creatinine and Total Bilirubin at the Indicated Time Points | Creatinine, Change from Baseline at Week 8 | 8.84 micromoles per liter (umol/L) | Standard Deviation 12.502 |
| Cohort II: INO-3112: Salvage Therapy | Change From Baseline in Creatinine and Total Bilirubin at the Indicated Time Points | Creatinine, Change from Baseline at Week 12 | -17.68 micromoles per liter (umol/L) | — |
| Cohort II: INO-3112: Salvage Therapy | Change From Baseline in Creatinine and Total Bilirubin at the Indicated Time Points | Total Bilirubin, Change from Baseline at Week 12 | 0.00 micromoles per liter (umol/L) | — |
| Cohort II: INO-3112: Salvage Therapy | Change From Baseline in Creatinine and Total Bilirubin at the Indicated Time Points | Creatinine, Change from Baseline at Week 16 | -8.84 micromoles per liter (umol/L) | — |
| Cohort II: INO-3112: Salvage Therapy | Change From Baseline in Creatinine and Total Bilirubin at the Indicated Time Points | Total Bilirubin, Change from Baseline at Week 8 | -1.71 micromoles per liter (umol/L) | Standard Deviation 4.837 |
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.
Time frame: Baseline and Week 4, 8,12,16,24, 32 and 48
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Hematocrit at the Indicated Time Points | Change from Baseline at Week 48 | 4.70 percentage of blood | — |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Hematocrit at the Indicated Time Points | Change from Baseline at Week 12 | 5.73 percentage of blood | Standard Deviation 3.722 |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Hematocrit at the Indicated Time Points | Change from Baseline at Week 16 | 5.97 percentage of blood | Standard Deviation 3.288 |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Hematocrit at the Indicated Time Points | Change from Baseline at Week 24 | 5.10 percentage of blood | — |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Hematocrit at the Indicated Time Points | Change from Baseline at Week 32 | 4.80 percentage of blood | — |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Hematocrit at the Indicated Time Points | Baseline | 30.87 percentage of blood | Standard Deviation 3.118 |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Hematocrit at the Indicated Time Points | Change from Baseline at Week 4 | 1.63 percentage of blood | Standard Deviation 2.553 |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Hematocrit at the Indicated Time Points | Change from Baseline at Week 8 | 3.49 percentage of blood | Standard Deviation 2.805 |
| Cohort II: INO-3112: Salvage Therapy | Change From Baseline in Hematocrit at the Indicated Time Points | Baseline | 35.03 percentage of blood | Standard Deviation 5.016 |
| Cohort II: INO-3112: Salvage Therapy | Change From Baseline in Hematocrit at the Indicated Time Points | Change from Baseline at Week 16 | 2.10 percentage of blood | — |
| Cohort II: INO-3112: Salvage Therapy | Change From Baseline in Hematocrit at the Indicated Time Points | Change from Baseline at Week 4 | -2.10 percentage of blood | Standard Deviation 2.8 |
| Cohort II: INO-3112: Salvage Therapy | Change From Baseline in Hematocrit at the Indicated Time Points | Change from Baseline at Week 12 | 1.60 percentage of blood | — |
| Cohort II: INO-3112: Salvage Therapy | Change From Baseline in Hematocrit at the Indicated Time Points | Change from Baseline at Week 8 | -5.90 percentage of blood | Standard Deviation 6.505 |
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.
Time frame: Baseline and Weeks 4, 8,12,16,24, 32 and 48
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Hemoglobin at the Indicated Time Points | Baseline | 103.29 gram per liter (g/L) | Standard Deviation 10.339 |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Hemoglobin at the Indicated Time Points | Change from Baseline at Week 16 | 20.29 gram per liter (g/L) | Standard Deviation 11.086 |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Hemoglobin at the Indicated Time Points | Change from Baseline at Week 24 | 17.00 gram per liter (g/L) | — |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Hemoglobin at the Indicated Time Points | Change from Baseline at Week 32 | 8.00 gram per liter (g/L) | — |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Hemoglobin at the Indicated Time Points | Change from Baseline at Week 48 | 7.00 gram per liter (g/L) | — |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Hemoglobin at the Indicated Time Points | Change from Baseline at Week 8 | 11.14 gram per liter (g/L) | Standard Deviation 12.402 |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Hemoglobin at the Indicated Time Points | Change from Baseline at Week 4 | 5.57 gram per liter (g/L) | Standard Deviation 10.048 |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Hemoglobin at the Indicated Time Points | Change from Baseline at Week 12 | 18.29 gram per liter (g/L) | Standard Deviation 13.889 |
| Cohort II: INO-3112: Salvage Therapy | Change From Baseline in Hemoglobin at the Indicated Time Points | Baseline | 112.00 gram per liter (g/L) | Standard Deviation 22.517 |
| Cohort II: INO-3112: Salvage Therapy | Change From Baseline in Hemoglobin at the Indicated Time Points | Change from Baseline at Week 12 | 4.00 gram per liter (g/L) | — |
| Cohort II: INO-3112: Salvage Therapy | Change From Baseline in Hemoglobin at the Indicated Time Points | Change from Baseline at Week 4 | -7.00 gram per liter (g/L) | Standard Deviation 9.165 |
| Cohort II: INO-3112: Salvage Therapy | Change From Baseline in Hemoglobin at the Indicated Time Points | Change from Baseline at Week 8 | -19.00 gram per liter (g/L) | Standard Deviation 24.042 |
| Cohort II: INO-3112: Salvage Therapy | Change From Baseline in Hemoglobin at the Indicated Time Points | Change from Baseline at Week 16 | 8.00 gram per liter (g/L) | — |
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).
Time frame: Baseline and Weeks 4, 8,12,16,24, 32 and 48
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Lymphocytes, Monocytes, Neutrophils and White Blood Cell (WBC) Count at the Indicated Time Points | L, Baseline | 0.93 10^9 cells/liter (10^9/L) | Standard Deviation 0.522 |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Lymphocytes, Monocytes, Neutrophils and White Blood Cell (WBC) Count at the Indicated Time Points | M,Change from Baseline at Week 24 | 0.00 10^9 cells/liter (10^9/L) | — |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Lymphocytes, Monocytes, Neutrophils and White Blood Cell (WBC) Count at the Indicated Time Points | M,Change from Baseline at Week 32 | -0.40 10^9 cells/liter (10^9/L) | — |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Lymphocytes, Monocytes, Neutrophils and White Blood Cell (WBC) Count at the Indicated Time Points | M,Change from Baseline at Week 48 | -0.20 10^9 cells/liter (10^9/L) | — |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Lymphocytes, Monocytes, Neutrophils and White Blood Cell (WBC) Count at the Indicated Time Points | N, Baseline | 2.60 10^9 cells/liter (10^9/L) | Standard Deviation 2.129 |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Lymphocytes, Monocytes, Neutrophils and White Blood Cell (WBC) Count at the Indicated Time Points | N,Change from Baseline at Week 4 | 0.43 10^9 cells/liter (10^9/L) | Standard Deviation 0.964 |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Lymphocytes, Monocytes, Neutrophils and White Blood Cell (WBC) Count at the Indicated Time Points | N,Change from Baseline at Week 8 | 0.09 10^9 cells/liter (10^9/L) | Standard Deviation 1.188 |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Lymphocytes, Monocytes, Neutrophils and White Blood Cell (WBC) Count at the Indicated Time Points | N,Change from Baseline at Week 12 | -0.03 10^9 cells/liter (10^9/L) | Standard Deviation 0.138 |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Lymphocytes, Monocytes, Neutrophils and White Blood Cell (WBC) Count at the Indicated Time Points | N,Change from Baseline at Week 16 | -0.07 10^9 cells/liter (10^9/L) | Standard Deviation 0.16 |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Lymphocytes, Monocytes, Neutrophils and White Blood Cell (WBC) Count at the Indicated Time Points | N,Change from Baseline at Week 24 | 0.00 10^9 cells/liter (10^9/L) | — |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Lymphocytes, Monocytes, Neutrophils and White Blood Cell (WBC) Count at the Indicated Time Points | N,Change from Baseline at Week 32 | -0.40 10^9 cells/liter (10^9/L) | — |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Lymphocytes, Monocytes, Neutrophils and White Blood Cell (WBC) Count at the Indicated Time Points | N,Change from Baseline at Week 48 | -0.20 10^9 cells/liter (10^9/L) | — |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Lymphocytes, Monocytes, Neutrophils and White Blood Cell (WBC) Count at the Indicated Time Points | WBC, Change from Baseline at Week 4 | 0.33 10^9 cells/liter (10^9/L) | Standard Deviation 0.966 |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Lymphocytes, Monocytes, Neutrophils and White Blood Cell (WBC) Count at the Indicated Time Points | WBC, Change from Baseline at Week 8 | 0.27 10^9 cells/liter (10^9/L) | Standard Deviation 1.237 |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Lymphocytes, Monocytes, Neutrophils and White Blood Cell (WBC) Count at the Indicated Time Points | WBC, Change from Baseline at Week 12 | 0.01 10^9 cells/liter (10^9/L) | Standard Deviation 1.771 |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Lymphocytes, Monocytes, Neutrophils and White Blood Cell (WBC) Count at the Indicated Time Points | WBC, Change from Baseline at Week 16 | 0.66 10^9 cells/liter (10^9/L) | Standard Deviation 1.279 |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Lymphocytes, Monocytes, Neutrophils and White Blood Cell (WBC) Count at the Indicated Time Points | WBC, Change from Baseline at Week 24 | 0.90 10^9 cells/liter (10^9/L) | — |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Lymphocytes, Monocytes, Neutrophils and White Blood Cell (WBC) Count at the Indicated Time Points | WBC, Change from Baseline at Week 32 | -0.40 10^9 cells/liter (10^9/L) | — |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Lymphocytes, Monocytes, Neutrophils and White Blood Cell (WBC) Count at the Indicated Time Points | WBC, Change from Baseline at Week 48 | -0.30 10^9 cells/liter (10^9/L) | — |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Lymphocytes, Monocytes, Neutrophils and White Blood Cell (WBC) Count at the Indicated Time Points | L,Change from Baseline at Week 4 | -0.11 10^9 cells/liter (10^9/L) | Standard Deviation 0.261 |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Lymphocytes, Monocytes, Neutrophils and White Blood Cell (WBC) Count at the Indicated Time Points | WBC, Baseline | 4.20 10^9 cells/liter (10^9/L) | Standard Deviation 2.239 |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Lymphocytes, Monocytes, Neutrophils and White Blood Cell (WBC) Count at the Indicated Time Points | L,Change from Baseline at Week 8 | -0.04 10^9 cells/liter (10^9/L) | Standard Deviation 0.251 |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Lymphocytes, Monocytes, Neutrophils and White Blood Cell (WBC) Count at the Indicated Time Points | L, Change from Baseline at Week 12 | -0.10 10^9 cells/liter (10^9/L) | Standard Deviation 0.283 |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Lymphocytes, Monocytes, Neutrophils and White Blood Cell (WBC) Count at the Indicated Time Points | L, Change from Baseline at Week 16 | 0.01 10^9 cells/liter (10^9/L) | Standard Deviation 0.254 |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Lymphocytes, Monocytes, Neutrophils and White Blood Cell (WBC) Count at the Indicated Time Points | L, Change From Baseline at Week 24 | 0.20 10^9 cells/liter (10^9/L) | — |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Lymphocytes, Monocytes, Neutrophils and White Blood Cell (WBC) Count at the Indicated Time Points | L, Change from Baseline at Week 32 | -0.50 10^9 cells/liter (10^9/L) | — |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Lymphocytes, Monocytes, Neutrophils and White Blood Cell (WBC) Count at the Indicated Time Points | L, Change from Baseline at Week 48 | -0.40 10^9 cells/liter (10^9/L) | — |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Lymphocytes, Monocytes, Neutrophils and White Blood Cell (WBC) Count at the Indicated Time Points | M, Baseline | 0.39 10^9 cells/liter (10^9/L) | Standard Deviation 0.121 |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Lymphocytes, Monocytes, Neutrophils and White Blood Cell (WBC) Count at the Indicated Time Points | M,Change from Baseline at Week 4 | -0.06 10^9 cells/liter (10^9/L) | Standard Deviation 0.172 |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Lymphocytes, Monocytes, Neutrophils and White Blood Cell (WBC) Count at the Indicated Time Points | M,Change from Baseline at Week 8 | -0.03 10^9 cells/liter (10^9/L) | Standard Deviation 0.138 |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Lymphocytes, Monocytes, Neutrophils and White Blood Cell (WBC) Count at the Indicated Time Points | M,Change from Baseline at Week 12 | -0.03 10^9 cells/liter (10^9/L) | Standard Deviation 0.138 |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Lymphocytes, Monocytes, Neutrophils and White Blood Cell (WBC) Count at the Indicated Time Points | M,Change from Baseline at Week 16 | -0.07 10^9 cells/liter (10^9/L) | Standard Deviation 0.16 |
| Cohort II: INO-3112: Salvage Therapy | Change From Baseline in Lymphocytes, Monocytes, Neutrophils and White Blood Cell (WBC) Count at the Indicated Time Points | L, Baseline | 0.70 10^9 cells/liter (10^9/L) | Standard Deviation 0.4 |
| Cohort II: INO-3112: Salvage Therapy | Change From Baseline in Lymphocytes, Monocytes, Neutrophils and White Blood Cell (WBC) Count at the Indicated Time Points | L,Change from Baseline at Week 4 | 0.00 10^9 cells/liter (10^9/L) | Standard Deviation 0.2 |
| Cohort II: INO-3112: Salvage Therapy | Change From Baseline in Lymphocytes, Monocytes, Neutrophils and White Blood Cell (WBC) Count at the Indicated Time Points | M,Change from Baseline at Week 16 | 0.10 10^9 cells/liter (10^9/L) | — |
| Cohort II: INO-3112: Salvage Therapy | Change From Baseline in Lymphocytes, Monocytes, Neutrophils and White Blood Cell (WBC) Count at the Indicated Time Points | L,Change from Baseline at Week 8 | -0.10 10^9 cells/liter (10^9/L) | Standard Deviation 0.141 |
| Cohort II: INO-3112: Salvage Therapy | Change From Baseline in Lymphocytes, Monocytes, Neutrophils and White Blood Cell (WBC) Count at the Indicated Time Points | N,Change from Baseline at Week 12 | 0.10 10^9 cells/liter (10^9/L) | — |
| Cohort II: INO-3112: Salvage Therapy | Change From Baseline in Lymphocytes, Monocytes, Neutrophils and White Blood Cell (WBC) Count at the Indicated Time Points | L, Change from Baseline at Week 12 | -0.20 10^9 cells/liter (10^9/L) | — |
| Cohort II: INO-3112: Salvage Therapy | Change From Baseline in Lymphocytes, Monocytes, Neutrophils and White Blood Cell (WBC) Count at the Indicated Time Points | WBC, Change from Baseline at Week 16 | 1.40 10^9 cells/liter (10^9/L) | — |
| Cohort II: INO-3112: Salvage Therapy | Change From Baseline in Lymphocytes, Monocytes, Neutrophils and White Blood Cell (WBC) Count at the Indicated Time Points | L, Change from Baseline at Week 16 | -0.20 10^9 cells/liter (10^9/L) | — |
| Cohort II: INO-3112: Salvage Therapy | Change From Baseline in Lymphocytes, Monocytes, Neutrophils and White Blood Cell (WBC) Count at the Indicated Time Points | N,Change from Baseline at Week 16 | 0.10 10^9 cells/liter (10^9/L) | — |
| Cohort II: INO-3112: Salvage Therapy | Change From Baseline in Lymphocytes, Monocytes, Neutrophils and White Blood Cell (WBC) Count at the Indicated Time Points | WBC, Change from Baseline at Week 4 | 0.40 10^9 cells/liter (10^9/L) | Standard Deviation 1.114 |
| Cohort II: INO-3112: Salvage Therapy | Change From Baseline in Lymphocytes, Monocytes, Neutrophils and White Blood Cell (WBC) Count at the Indicated Time Points | N, Baseline | 4.03 10^9 cells/liter (10^9/L) | Standard Deviation 0.551 |
| Cohort II: INO-3112: Salvage Therapy | Change From Baseline in Lymphocytes, Monocytes, Neutrophils and White Blood Cell (WBC) Count at the Indicated Time Points | WBC, Change from Baseline at Week 12 | 0.40 10^9 cells/liter (10^9/L) | — |
| Cohort II: INO-3112: Salvage Therapy | Change From Baseline in Lymphocytes, Monocytes, Neutrophils and White Blood Cell (WBC) Count at the Indicated Time Points | M, Baseline | 0.30 10^9 cells/liter (10^9/L) | Standard Deviation 0.1 |
| Cohort II: INO-3112: Salvage Therapy | Change From Baseline in Lymphocytes, Monocytes, Neutrophils and White Blood Cell (WBC) Count at the Indicated Time Points | N,Change from Baseline at Week 4 | 0.37 10^9 cells/liter (10^9/L) | Standard Deviation 1.266 |
| Cohort II: INO-3112: Salvage Therapy | Change From Baseline in Lymphocytes, Monocytes, Neutrophils and White Blood Cell (WBC) Count at the Indicated Time Points | M,Change from Baseline at Week 4 | 0.07 10^9 cells/liter (10^9/L) | Standard Deviation 0.153 |
| Cohort II: INO-3112: Salvage Therapy | Change From Baseline in Lymphocytes, Monocytes, Neutrophils and White Blood Cell (WBC) Count at the Indicated Time Points | WBC, Change from Baseline at Week 8 | 0.85 10^9 cells/liter (10^9/L) | Standard Deviation 0.212 |
| Cohort II: INO-3112: Salvage Therapy | Change From Baseline in Lymphocytes, Monocytes, Neutrophils and White Blood Cell (WBC) Count at the Indicated Time Points | M,Change from Baseline at Week 8 | 0.05 10^9 cells/liter (10^9/L) | Standard Deviation 0.212 |
| Cohort II: INO-3112: Salvage Therapy | Change From Baseline in Lymphocytes, Monocytes, Neutrophils and White Blood Cell (WBC) Count at the Indicated Time Points | N,Change from Baseline at Week 8 | 0.85 10^9 cells/liter (10^9/L) | Standard Deviation 0.212 |
| Cohort II: INO-3112: Salvage Therapy | Change From Baseline in Lymphocytes, Monocytes, Neutrophils and White Blood Cell (WBC) Count at the Indicated Time Points | M,Change from Baseline at Week 12 | 0.10 10^9 cells/liter (10^9/L) | — |
| Cohort II: INO-3112: Salvage Therapy | Change From Baseline in Lymphocytes, Monocytes, Neutrophils and White Blood Cell (WBC) Count at the Indicated Time Points | WBC, Baseline | 5.30 10^9 cells/liter (10^9/L) | Standard Deviation 0.721 |
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.
Time frame: Baseline and Weeks 4,8,12,16,24,32 and 48
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Platelet Count at the Indicated Time Points | Platelet Count, Change from Baseline at Week 48 | -73.00 10^9 cells/liter (10^9/L) | — |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Platelet Count at the Indicated Time Points | Platelet Count, Change from Baseline at Week 12 | -41.00 10^9 cells/liter (10^9/L) | Standard Deviation 61.563 |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Platelet Count at the Indicated Time Points | Platelet Count, Change from Baseline at Week 16 | -32.86 10^9 cells/liter (10^9/L) | Standard Deviation 49.911 |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Platelet Count at the Indicated Time Points | Platelet Count, Change From Baseline at Week 24 | -17.00 10^9 cells/liter (10^9/L) | — |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Platelet Count at the Indicated Time Points | Platelet Count, Change from Baseline at Week 32 | -68.00 10^9 cells/liter (10^9/L) | — |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Platelet Count at the Indicated Time Points | Platelet Count, Baseline | 259.86 10^9 cells/liter (10^9/L) | Standard Deviation 46.674 |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Platelet Count at the Indicated Time Points | Platelet Count, Change from Baseline at Week 4 | -45.29 10^9 cells/liter (10^9/L) | Standard Deviation 55.479 |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Platelet Count at the Indicated Time Points | Platelet Count, Change from Baseline at Week 8 | -40.57 10^9 cells/liter (10^9/L) | Standard Deviation 39.327 |
| Cohort II: INO-3112: Salvage Therapy | Change From Baseline in Platelet Count at the Indicated Time Points | Platelet Count, Baseline | 271.33 10^9 cells/liter (10^9/L) | Standard Deviation 73.704 |
| Cohort II: INO-3112: Salvage Therapy | Change From Baseline in Platelet Count at the Indicated Time Points | Platelet Count, Change from Baseline at Week 16 | 2.00 10^9 cells/liter (10^9/L) | — |
| Cohort II: INO-3112: Salvage Therapy | Change From Baseline in Platelet Count at the Indicated Time Points | Platelet Count, Change from Baseline at Week 4 | 26.00 10^9 cells/liter (10^9/L) | Standard Deviation 48.754 |
| Cohort II: INO-3112: Salvage Therapy | Change From Baseline in Platelet Count at the Indicated Time Points | Platelet Count, Change from Baseline at Week 12 | 37.00 10^9 cells/liter (10^9/L) | — |
| Cohort II: INO-3112: Salvage Therapy | Change From Baseline in Platelet Count at the Indicated Time Points | Platelet Count, Change from Baseline at Week 8 | 93.00 10^9 cells/liter (10^9/L) | Standard Deviation 84.853 |
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.
Time frame: Baseline and Weeks 4 and 8
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Red Blood Cell (RBC) Count at the Indicated Time Points | RBC Count, Baseline | 3.34 10^12 cells/liter | Standard Deviation 0.382 |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Red Blood Cell (RBC) Count at the Indicated Time Points | RBC Count, Change from Baseline at Week 4 | 0.07 10^12 cells/liter | Standard Deviation 0.355 |
| Cohort I: INO-3112: Curative Intent | Change From Baseline in Red Blood Cell (RBC) Count at the Indicated Time Points | RBC Count, Change from Baseline at Week 8 | 0.23 10^12 cells/liter | Standard Deviation 0.386 |
| Cohort II: INO-3112: Salvage Therapy | Change From Baseline in Red Blood Cell (RBC) Count at the Indicated Time Points | RBC Count, Baseline | 3.97 10^12 cells/liter | Standard Deviation 0.586 |
| Cohort II: INO-3112: Salvage Therapy | Change From Baseline in Red Blood Cell (RBC) Count at the Indicated Time Points | RBC Count, Change from Baseline at Week 4 | -0.23 10^12 cells/liter | Standard Deviation 0.351 |
| Cohort II: INO-3112: Salvage Therapy | Change From Baseline in Red Blood Cell (RBC) Count at the Indicated Time Points | RBC Count, Change from Baseline at Week 8 | -0.55 10^12 cells/liter | Standard Deviation 0.778 |
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.
Time frame: Up to 36 weeks
Population: Safety population included all participants who received at least one dose of study treatment plus EP.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort I: INO-3112: Curative Intent | Percentage of Participants With at Least 1 Treatment Emergent Adverse Event (TEAE) | 100 percentage of participants |
| Cohort II: INO-3112: Salvage Therapy | Percentage of Participants With at Least 1 Treatment Emergent Adverse Event (TEAE) | 100 percentage of participants |
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.
Time frame: Up to 36 weeks
Population: Safety population included all participants who received at least one dose of study treatment plus EP.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort I: INO-3112: Curative Intent | Percentage of Participants With Grade 3 or Higher TEAEs Graded Per Common Terminology Criteria for Adverse Events, Version 4.03 (CTCAE, v 4.03) | Anaemia | 0 percentage of participants |
| Cohort I: INO-3112: Curative Intent | Percentage of Participants With Grade 3 or Higher TEAEs Graded Per Common Terminology Criteria for Adverse Events, Version 4.03 (CTCAE, v 4.03) | Disseminated Intravascular Coagulation | 0 percentage of participants |
| Cohort I: INO-3112: Curative Intent | Percentage of Participants With Grade 3 or Higher TEAEs Graded Per Common Terminology Criteria for Adverse Events, Version 4.03 (CTCAE, v 4.03) | Abdominal Pain | 14.3 percentage of participants |
| Cohort I: INO-3112: Curative Intent | Percentage of Participants With Grade 3 or Higher TEAEs Graded Per Common Terminology Criteria for Adverse Events, Version 4.03 (CTCAE, v 4.03) | Intestinal Perforation | 0 percentage of participants |
| Cohort I: INO-3112: Curative Intent | Percentage of Participants With Grade 3 or Higher TEAEs Graded Per Common Terminology Criteria for Adverse Events, Version 4.03 (CTCAE, v 4.03) | Pneumonia | 14.3 percentage of participants |
| Cohort I: INO-3112: Curative Intent | Percentage of Participants With Grade 3 or Higher TEAEs Graded Per Common Terminology Criteria for Adverse Events, Version 4.03 (CTCAE, v 4.03) | Pathological Fracture | 0 percentage of participants |
| Cohort II: INO-3112: Salvage Therapy | Percentage of Participants With Grade 3 or Higher TEAEs Graded Per Common Terminology Criteria for Adverse Events, Version 4.03 (CTCAE, v 4.03) | Pneumonia | 0 percentage of participants |
| Cohort II: INO-3112: Salvage Therapy | Percentage of Participants With Grade 3 or Higher TEAEs Graded Per Common Terminology Criteria for Adverse Events, Version 4.03 (CTCAE, v 4.03) | Anaemia | 33.3 percentage of participants |
| Cohort II: INO-3112: Salvage Therapy | Percentage of Participants With Grade 3 or Higher TEAEs Graded Per Common Terminology Criteria for Adverse Events, Version 4.03 (CTCAE, v 4.03) | Intestinal Perforation | 33.3 percentage of participants |
| Cohort II: INO-3112: Salvage Therapy | Percentage of Participants With Grade 3 or Higher TEAEs Graded Per Common Terminology Criteria for Adverse Events, Version 4.03 (CTCAE, v 4.03) | Disseminated Intravascular Coagulation | 33.3 percentage of participants |
| Cohort II: INO-3112: Salvage Therapy | Percentage of Participants With Grade 3 or Higher TEAEs Graded Per Common Terminology Criteria for Adverse Events, Version 4.03 (CTCAE, v 4.03) | Pathological Fracture | 33.3 percentage of participants |
| Cohort II: INO-3112: Salvage Therapy | Percentage of Participants With Grade 3 or Higher TEAEs Graded Per Common Terminology Criteria for Adverse Events, Version 4.03 (CTCAE, v 4.03) | Abdominal Pain | 0 percentage of participants |
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.
Time frame: Up to 36 weeks
Population: Safety population included all participants who received at least one dose of study treatment plus EP.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort I: INO-3112: Curative Intent | Percentage of Participants With Injection Site Reactions | Injection Site Bruising | 28.6 percentage of participants |
| Cohort I: INO-3112: Curative Intent | Percentage of Participants With Injection Site Reactions | Injection Site Discolouration | 0 percentage of participants |
| Cohort I: INO-3112: Curative Intent | Percentage of Participants With Injection Site Reactions | Injection Site Erythema | 14.3 percentage of participants |
| Cohort I: INO-3112: Curative Intent | Percentage of Participants With Injection Site Reactions | Injection Site Haemorrhage | 14.3 percentage of participants |
| Cohort I: INO-3112: Curative Intent | Percentage of Participants With Injection Site Reactions | Injection Site Pain | 14.3 percentage of participants |
| Cohort I: INO-3112: Curative Intent | Percentage of Participants With Injection Site Reactions | Injection Site Swelling | 14.3 percentage of participants |
| Cohort II: INO-3112: Salvage Therapy | Percentage of Participants With Injection Site Reactions | Injection Site Pain | 66.7 percentage of participants |
| Cohort II: INO-3112: Salvage Therapy | Percentage of Participants With Injection Site Reactions | Injection Site Bruising | 33.3 percentage of participants |
| Cohort II: INO-3112: Salvage Therapy | Percentage of Participants With Injection Site Reactions | Injection Site Haemorrhage | 0 percentage of participants |
| Cohort II: INO-3112: Salvage Therapy | Percentage of Participants With Injection Site Reactions | Injection Site Discolouration | 33.3 percentage of participants |
| Cohort II: INO-3112: Salvage Therapy | Percentage of Participants With Injection Site Reactions | Injection Site Swelling | 33.3 percentage of participants |
| Cohort II: INO-3112: Salvage Therapy | Percentage of Participants With Injection Site Reactions | Injection Site Erythema | 0 percentage of participants |
Primary
Rates of Acute Gastrointestinal, Genitourinary, or Other Chemoradiation Side Effects Above the Expected, Graded Per Acute Radiation Morbidity Scoring Criteria
Time frame: Up to 36 weeks
Population: 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.
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).
Time frame: Baseline and Weeks 2, 4, 6, 8, 10,12,14,16, 24, 32, 36, 40 and 48
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort I: INO-3112: Curative Intent | 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) | Increase from Baseline at Week 48 | 248.8 SFU/10^6 PBMC | Standard Deviation 351.79 |
| Cohort I: INO-3112: Curative Intent | 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) | Increase from Baseline at Week 12 | 353.3 SFU/10^6 PBMC | Standard Deviation 472.3 |
| Cohort I: INO-3112: Curative Intent | 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) | Increase from Baseline at Week 14 | 27.5 SFU/10^6 PBMC | Standard Deviation 8.24 |
| Cohort I: INO-3112: Curative Intent | 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) | Increase from Baseline at Week 16 | 310.3 SFU/10^6 PBMC | Standard Deviation 460 |
| Cohort I: INO-3112: Curative Intent | 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) | Increase from Baseline at Week 24 | 244.2 SFU/10^6 PBMC | Standard Deviation 324.77 |
| Cohort I: INO-3112: Curative Intent | 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) | Increase from Baseline at Week 32 | 121.9 SFU/10^6 PBMC | Standard Deviation 133.43 |
| Cohort I: INO-3112: Curative Intent | 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) | Increase from Baseline at Week 36 | 6.7 SFU/10^6 PBMC | — |
| Cohort I: INO-3112: Curative Intent | 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) | Increase from Baseline at Week 40 | 246.3 SFU/10^6 PBMC | Standard Deviation 341.18 |
| Cohort I: INO-3112: Curative Intent | 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 | 8.6 SFU/10^6 PBMC | Standard Deviation 6.03 |
| Cohort I: INO-3112: Curative Intent | 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) | Increase from Baseline at Week 4 | 26.4 SFU/10^6 PBMC | Standard Deviation 29.84 |
| Cohort I: INO-3112: Curative Intent | 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) | Increase from Baseline at Week 6 | 20.0 SFU/10^6 PBMC | — |
| Cohort I: INO-3112: Curative Intent | 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) | Increase from Baseline at Week 8 | 68.3 SFU/10^6 PBMC | Standard Deviation 49.5 |
| Cohort I: INO-3112: Curative Intent | 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) | Increase from Baseline at Week 10 | 50.0 SFU/10^6 PBMC | Standard Deviation 21.21 |
| Cohort II: INO-3112: Salvage Therapy | 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 | 6.7 SFU/10^6 PBMC | Standard Deviation 2.89 |
| Cohort II: INO-3112: Salvage Therapy | 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) | Increase from Baseline at Week 2 | 1.7 SFU/10^6 PBMC | Standard Deviation 2.35 |
| Cohort II: INO-3112: Salvage Therapy | 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) | Increase from Baseline at Week 16 | 53.3 SFU/10^6 PBMC | — |
| Cohort II: INO-3112: Salvage Therapy | 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) | Increase from Baseline at Week 4 | 2.5 SFU/10^6 PBMC | Standard Deviation 3.54 |
| Cohort II: INO-3112: Salvage Therapy | 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) | Increase from Baseline at Week 32 | 10.0 SFU/10^6 PBMC | — |
| Cohort II: INO-3112: Salvage Therapy | 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) | Increase from Baseline at Week 6 | 24.2 SFU/10^6 PBMC | Standard Deviation 12.96 |
| Cohort II: INO-3112: Salvage Therapy | 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) | Increase from Baseline at Week 12 | 6.7 SFU/10^6 PBMC | — |
| Cohort II: INO-3112: Salvage Therapy | 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) | Increase from Baseline at Week 8 | 0.0 SFU/10^6 PBMC | Standard Deviation 0 |
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.
Time frame: Baseline and Weeks 2, 4, 6, 8, 10,12,14,16, 24, 32, 36, 40 and 48
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort I: INO-3112: Curative Intent | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-18, Week 12 | 0.8 log titer | Standard Deviation 1.75 |
| Cohort I: INO-3112: Curative Intent | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-16, Week 12 | 0.8 log titer | Standard Deviation 1.75 |
| Cohort I: INO-3112: Curative Intent | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-16, Week 14 | 2.0 log titer | Standard Deviation 2.77 |
| Cohort I: INO-3112: Curative Intent | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-16, Week 16 | 1.4 log titer | Standard Deviation 2.44 |
| Cohort I: INO-3112: Curative Intent | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-16, Week 24 | 3.0 log titer | Standard Deviation 2.36 |
| Cohort I: INO-3112: Curative Intent | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-16, Week 32 | 1.7 log titer | Standard Deviation 2.59 |
| Cohort I: INO-3112: Curative Intent | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-16, Week 36 | 0.0 log titer | Standard Deviation 0 |
| Cohort I: INO-3112: Curative Intent | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-16, Week 40 | 3.3 log titer | Standard Deviation 2.89 |
| Cohort I: INO-3112: Curative Intent | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-16, Week 48 | 3.7 log titer | Standard Deviation 3.26 |
| Cohort I: INO-3112: Curative Intent | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-18, Baseline | 0.0 log titer | Standard Deviation 0 |
| Cohort I: INO-3112: Curative Intent | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-18, Week 2 | 3.1 log titer | Standard Deviation 4.32 |
| Cohort I: INO-3112: Curative Intent | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-18, Week 4 | 0.7 log titer | Standard Deviation 1.6 |
| Cohort I: INO-3112: Curative Intent | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-18, Week 6 | 0.0 log titer | Standard Deviation 0 |
| Cohort I: INO-3112: Curative Intent | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-18, Week 8 | 0.6 log titer | Standard Deviation 1.48 |
| Cohort I: INO-3112: Curative Intent | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-18, Week 10 | 1.3 log titer | Standard Deviation 2.26 |
| Cohort I: INO-3112: Curative Intent | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-16 ,Baseline | 0.0 log titer | Standard Deviation 0 |
| Cohort I: INO-3112: Curative Intent | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-18, Week 14 | 0.0 log titer | Standard Deviation 0 |
| Cohort I: INO-3112: Curative Intent | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-18, Week 16 | 1.4 log titer | Standard Deviation 2.53 |
| Cohort I: INO-3112: Curative Intent | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-18, Week 24 | 0.7 log titer | Standard Deviation 1.6 |
| Cohort I: INO-3112: Curative Intent | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-18, Week 32 | 1.3 log titer | Standard Deviation 2.02 |
| Cohort I: INO-3112: Curative Intent | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-18, Week 36 | 1.5 log titer | Standard Deviation 3.05 |
| Cohort I: INO-3112: Curative Intent | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-18, Week 40 | 1.3 log titer | Standard Deviation 2.26 |
| Cohort I: INO-3112: Curative Intent | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-18, Week 48 | 0.0 log titer | Standard Deviation 0 |
| Cohort I: INO-3112: Curative Intent | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-16, Week 2 | 2.5 log titer | Standard Deviation 3.54 |
| Cohort I: INO-3112: Curative Intent | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-16, Week 4 | 0.7 log titer | Standard Deviation 1.6 |
| Cohort I: INO-3112: Curative Intent | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-16, Week 6 | 2.5 log titer | Standard Deviation 3.54 |
| Cohort I: INO-3112: Curative Intent | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-16, Week 8 | 0.6 log titer | Standard Deviation 1.48 |
| Cohort I: INO-3112: Curative Intent | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-16, Week 10 | 0.0 log titer | Standard Deviation 0 |
| Cohort II: INO-3112: Salvage Therapy | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-16 ,Baseline | 0.0 log titer | Standard Deviation 0 |
| Cohort II: INO-3112: Salvage Therapy | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-18, Week 8 | 0.0 log titer | Standard Deviation 0 |
| Cohort II: INO-3112: Salvage Therapy | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-16, Week 2 | 0.0 log titer | Standard Deviation 0 |
| Cohort II: INO-3112: Salvage Therapy | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-18, Week 16 | 6.1 log titer | — |
| Cohort II: INO-3112: Salvage Therapy | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-16, Week 4 | 0.0 log titer | Standard Deviation 0 |
| Cohort II: INO-3112: Salvage Therapy | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-18, Week 10 | 0.0 log titer | — |
| Cohort II: INO-3112: Salvage Therapy | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-16, Week 6 | 0.0 log titer | Standard Deviation 0 |
| Cohort II: INO-3112: Salvage Therapy | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-18, Baseline | 0.0 log titer | Standard Deviation 0 |
| Cohort II: INO-3112: Salvage Therapy | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-16, Week 8 | 0.0 log titer | Standard Deviation 0 |
| Cohort II: INO-3112: Salvage Therapy | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-18, Week 32 | 0.0 log titer | — |
| Cohort II: INO-3112: Salvage Therapy | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-16, Week 10 | 0.00 log titer | — |
| Cohort II: INO-3112: Salvage Therapy | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-18, Week 2 | 0.0 log titer | Standard Deviation 0 |
| Cohort II: INO-3112: Salvage Therapy | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-16, Week 12 | 0.0 log titer | — |
| Cohort II: INO-3112: Salvage Therapy | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-18, Week 12 | 6.1 log titer | — |
| Cohort II: INO-3112: Salvage Therapy | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-18, Week 4 | 0.0 log titer | Standard Deviation 0 |
| Cohort II: INO-3112: Salvage Therapy | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-16, Week 16 | 0.0 log titer | — |
| Cohort II: INO-3112: Salvage Therapy | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-18, Week 24 | 0.0 log titer | — |
| Cohort II: INO-3112: Salvage Therapy | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-16, Week 24 | 0.0 log titer | — |
| Cohort II: INO-3112: Salvage Therapy | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-18, Week 6 | 0.0 log titer | Standard Deviation 0 |
| Cohort II: INO-3112: Salvage Therapy | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-16, Week 32 | 0.0 log titer | — |
| Cohort II: INO-3112: Salvage Therapy | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-18, Week 36 | 0.0 log titer | — |
| Cohort II: INO-3112: Salvage Therapy | E6 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by Enzyme-linked Immunosorbent Assay (ELISA) | HPV-16, Week 36 | 0.0 log titer | — |
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.
Time frame: Baseline and Weeks 2, 4, 6, 8, 10, 12, 14, 16, 24, 32, 36, 40 and 48
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort I: INO-3112: Curative Intent | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-18, Week 12 | 2.2 log titer | Standard Deviation 3.26 |
| Cohort I: INO-3112: Curative Intent | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-16, Week 12 | 2.0 log titer | Standard Deviation 2.85 |
| Cohort I: INO-3112: Curative Intent | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-16, Week 14 | 3.1 log titer | Standard Deviation 4.32 |
| Cohort I: INO-3112: Curative Intent | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-16, Week 16 | 2.1 log titer | Standard Deviation 2.75 |
| Cohort I: INO-3112: Curative Intent | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-16, Week 24 | 2.7 log titer | Standard Deviation 3.13 |
| Cohort I: INO-3112: Curative Intent | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-16, Week 32 | 2.1 log titer | Standard Deviation 2.38 |
| Cohort I: INO-3112: Curative Intent | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-16, Week 36 | 1.6 log titer | Standard Deviation 2.14 |
| Cohort I: INO-3112: Curative Intent | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-16, Week 40 | 0.0 log titer | Standard Deviation 0 |
| Cohort I: INO-3112: Curative Intent | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-16, Week 48 | 0.0 log titer | Standard Deviation 0 |
| Cohort I: INO-3112: Curative Intent | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-18, Baseline | 0.0 log titer | Standard Deviation 0 |
| Cohort I: INO-3112: Curative Intent | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-18, Week 2 | 1.7 log titer | Standard Deviation 2.89 |
| Cohort I: INO-3112: Curative Intent | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-18, Week 4 | 0.8 log titer | Standard Deviation 2.05 |
| Cohort I: INO-3112: Curative Intent | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-18, Week 6 | 5.0 log titer | Standard Deviation 1.55 |
| Cohort I: INO-3112: Curative Intent | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-18, Week 8 | 2.4 log titer | Standard Deviation 3.72 |
| Cohort I: INO-3112: Curative Intent | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-18, Week 10 | 1.3 log titer | Standard Deviation 2.26 |
| Cohort I: INO-3112: Curative Intent | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-16, Baseline | 0.0 log titer | Standard Deviation 0 |
| Cohort I: INO-3112: Curative Intent | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-18, Week 14 | 2.0 log titer | Standard Deviation 2.77 |
| Cohort I: INO-3112: Curative Intent | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-18, Week 16 | 3.5 log titer | Standard Deviation 3.56 |
| Cohort I: INO-3112: Curative Intent | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-18, Week 24 | 1.2 log titer | Standard Deviation 2.94 |
| Cohort I: INO-3112: Curative Intent | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-18, Week 32 | 1.9 log titer | Standard Deviation 3.05 |
| Cohort I: INO-3112: Curative Intent | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-18, Week 36 | 0.0 log titer | Standard Deviation 0 |
| Cohort I: INO-3112: Curative Intent | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-18, Week 40 | 5.2 log titer | Standard Deviation 4.51 |
| Cohort I: INO-3112: Curative Intent | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-18, Week 48 | 3.6 log titer | Standard Deviation 5.1 |
| Cohort I: INO-3112: Curative Intent | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-16, Week 2 | 0.0 log titer | Standard Deviation 0 |
| Cohort I: INO-3112: Curative Intent | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-16, Week 4 | 0.7 log titer | Standard Deviation 1.6 |
| Cohort I: INO-3112: Curative Intent | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-16, Week 6 | 0.0 log titer | Standard Deviation 0 |
| Cohort I: INO-3112: Curative Intent | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-16, Week 8 | 0.8 log titer | Standard Deviation 2.05 |
| Cohort I: INO-3112: Curative Intent | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-16, Week 10 | 3.3 log titer | Standard Deviation 3.09 |
| Cohort II: INO-3112: Salvage Therapy | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-16, Baseline | 0.0 log titer | Standard Deviation 0 |
| Cohort II: INO-3112: Salvage Therapy | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-18, Week 8 | 0.0 log titer | Standard Deviation 0 |
| Cohort II: INO-3112: Salvage Therapy | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-16, Week 2 | 2.0 log titer | Standard Deviation 2.77 |
| Cohort II: INO-3112: Salvage Therapy | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-18, Week 16 | 7.2 log titer | — |
| Cohort II: INO-3112: Salvage Therapy | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-16, Week 4 | 0.0 log titer | Standard Deviation 0 |
| Cohort II: INO-3112: Salvage Therapy | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-18, Week 10 | 0.0 log titer | — |
| Cohort II: INO-3112: Salvage Therapy | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-16, Week 6 | 0.0 log titer | Standard Deviation 0 |
| Cohort II: INO-3112: Salvage Therapy | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-18, Baseline | 0.0 log titer | Standard Deviation 0 |
| Cohort II: INO-3112: Salvage Therapy | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-16, Week 8 | 3.6 log titer | Standard Deviation 5.1 |
| Cohort II: INO-3112: Salvage Therapy | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-18, Week 32 | 8.3 log titer | — |
| Cohort II: INO-3112: Salvage Therapy | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-16, Week 10 | 7.2 log titer | — |
| Cohort II: INO-3112: Salvage Therapy | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-18, Week 2 | 0.0 log titer | Standard Deviation 0 |
| Cohort II: INO-3112: Salvage Therapy | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-16, Week 12 | 7.2 log titer | — |
| Cohort II: INO-3112: Salvage Therapy | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-18, Week 12 | 7.2 log titer | — |
| Cohort II: INO-3112: Salvage Therapy | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-18, Week 4 | 0.0 log titer | Standard Deviation 0 |
| Cohort II: INO-3112: Salvage Therapy | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-16, Week 16 | 7.2 log titer | — |
| Cohort II: INO-3112: Salvage Therapy | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-18, Week 24 | 8.3 log titer | — |
| Cohort II: INO-3112: Salvage Therapy | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-16, Week 24 | 7.2 log titer | — |
| Cohort II: INO-3112: Salvage Therapy | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-18, Week 6 | 0.0 log titer | Standard Deviation 0 |
| Cohort II: INO-3112: Salvage Therapy | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-16, Week 32 | 7.2 log titer | — |
| Cohort II: INO-3112: Salvage Therapy | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-18, Week 36 | 8.3 log titer | — |
| Cohort II: INO-3112: Salvage Therapy | E7 Antigen Specific Anti-HPV-16/18 Antibody Titers Assessed by ELISA | HPV-16, Week 36 | 0.0 log titer | — |