Non-metastatic Breast Cancer
Conditions
Keywords
HSP-130 Phase 1-2 Study in patients with Breast cancer
Brief summary
This is a study of how one or more injections of HSP-130 under the skin effect the white blood cell counts and drug levels in women with breast cancer that has not spread to distant sites in the body (non-metastatic). This will be studied in women before breast surgery or while receiving chemotherapy. Safety will also be studied. Additionally, the purpose of this study is to evaluate the effects and safety of single and multiple doses of HSP-130 in subjects with non-metastatic breast cancer. This study will determine the dose to move forward for future clinical trials.
Detailed description
This is an open-label, sequential enrollment study characterizing the pharmacodynamic (PD), pharmacokinetic (PK) and safety of HSP-130 in subjects with non-metastatic breast cancer who have not previously received chemotherapy at any point prior to enrollment in this study (ZIN-130-1504). The purpose of this study is to evaluate the effects and safety of single and multiple doses of HSP-130 in subjects with non-metastatic breast cancer. This study will determine the dose to move forward for future clinical trials. There are two aspects of the study. In the initial part of the study, 6 subjects will be sequentially enrolled to receive HSP-130 treatment (3 mg , or 6 mg by subcutaneous injection) during the period between biopsy and definitive surgery. This will determine whether 3 mg and 6 mg have similar or different effects on the PD variables (absolute neutrophil counts and CD34+ cell counts). This part of the study is referred to as Cycle 0 since study subjects will receive no chemotherapy while receiving HSP-130 until the effect of HSP-130 on the PD variables is known. A total of 12 subjects may be enrolled in Cycle 0. The objective of Cycle 1-4 is to determine the dose to be taken forward to Phase 3 clinical trials. Cycles 1-4 subjects will receive HSP-130 after their definitive breast surgery at the time they receive TAC chemotherapy (docetaxel, doxorubicin, and cyclophosphamide). Subjects will receive up to 4 cycles of every 3 week TAC chemotherapy with HSP-130 given on Day 2 of the chemotherapy regimen. * If the 3 mg dose is found to be inferior (potentially subtherapeutic) to the 6 mg dose in Cycle 0, only the 6 mg dose will be studied in Cycles 1-4 (n=12), when subjects receive concomitant chemotherapy. * If the 3 mg dose is found to be comparable to the PD results obtained in Cycle 0 with 6 mg, the 3 mg dose (n=12) will also be studied in women receiving TAC chemotherapy. Data from the HSP-130 6 mg regimen (plus 3 mg, as appropriate) will be analysed, discussed with the FDA and determination if a dose greater than 6 mg is appropriate to study (e.g., 12 mg). If all three doses are studied, a total enrollment of up to 36 subjects is projected for Cycles 1-4.
Interventions
DRUGHSP-130
Dosage will vary per each cohort: (Five independent cohorts) Cycle 0 Regimen A - 3 mg Cycle 0 Regimen B - 6 mg Cycles 1-4 Regimen B - 6 mg Cycles 1-4 Regimen A (Potential)- 3 mg Cycles 1-4 Regimen C (Conditional)- 12 mg
Sponsors
Hospira, now a wholly owned subsidiary of Pfizer
Pfizer
Study design
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* A subject will be eligible for study participation if all of the following criteria are met at Screening: 1. Is informed, has been given ample time and opportunity to read about participation in the study and has signed and dated the written informed consent form approved by an Independent Ethics committee (IEC) prior to any study related activities 2. Females ≥ 18 years 3. Histologically confirmed and documented invasive breast cancer 4. Breast cancer without evidence of distant metastases (Stage 4) based on staging work-up 5. Chemotherapy naive, who have not received chemotherapy in the neoadjuvant setting and who are candidates for chemotherapy in the adjuvant setting of taxane/cyclophosphamide-based regimen, e.g., TAC, as background chemotherapy 6. Zubrod/WHO/ECOG performance status ≤ 2 7. Adequate bone marrow, hepatic, and renal function reserve as evidenced by: 1. Hemoglobin ≥ 10 mg/dl 2. ANC ≥ 1.5 x 10\^9/L 3. Platelet count of ≥ 100 x 10\^9/L 4. Total bilirubin ≤ 2 mg/dl 5. Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤ 3 x the upper limit of normal (ULN) of the reference lab 6. Serum creatinine of ≤ 1.5 x ULN for reference lab or estimated glomerular filtration rate (eGFR) of ≥ 60 mg/min 8. Body mass index (BMI) of 19 to 40 kg/m\^2 , inclusive 9. Subjects of childbearing potential, and their partners, agree to pregnancy prevention throughout the duration of the study (through the Follow-up Visit). Specific type of pregnancy prevention should be discussed with, and acceptable to, the treating oncologist in the context of the tumoral hormone receptor status. Subjects and their partners must agree to use of an effective method of contraception, to avoid impregnation of females throughout the course of the study Medically acceptable forms of birth control can include, with approval of the treating physician: 1. Barrier methods (condom or diaphragm with spermicide) 2. Intrauterine device (IUD) 3. Hormone contraceptives (such as oral \[pill\], injection, skin patch, implant, cervical ring) 4. Subjects using oral contraceptives must be on a stable regimen for at least 3 months prior to Screening. Sexually active subjects must use contraception while on HSP-130 from admission to the final Follow-up Visit 10. Able to understand verbal or written instructions and comply with all study requirements, to communicate effectively with study personnel and is available for the planned duration of the study
Exclusion criteria
* A subject will NOT be eligible for study participation if any of the following criteria are met at Screening: 1. Previous G-CSF exposure, including filgrastim, lenograstim, pegfilgrastim, lipegfilgrastim, granulocyte/macrophage colony stimulating growth factor (GM-CSF), or any other branded or biosimilar G-CSF 2. Prior autologous stem cell harvest of any type 3. Drug sensitivity, allergic reaction, or known hypersensitivity or idiosyncratic reaction to E. coli - derived proteins, filgrastim, other G-CSFs, or pegylated agents 4. Known hypersensitivity to docetaxel, polysorbate 80, or doxorubicin 5. For subjects receiving doxorubicin, no concurrent use of inhibitors and inducers of CYP3A4, CYP2D6, and/or P-gp or with trastuzumab due to increased risk of cardiac dysfunction 6. Chemotherapy other than that included in this study (taxane/cyclophosphamide-based regimen, e.g., TAC or TC) or neoadjuvant chemotherapy; or known immunosuppressive agents including chronic oral corticosteroid use, or radiation therapy within 4 weeks of first dose of HSP-130, prior bone marrow or stem cell transplantation, or malignancy within 5 years 7. Known HER2 + ( overexpressing breast cancer) 8. Known triple negative (estrogen receptor-negative, progesterone receptor-negative and HER2-negative) breast cancer 9. ≥ Grade 2 underlying neuropathy 10. Current diagnosis of active tuberculosis or other severe infection, such as sepsis, abscesses or opportunistic infections 11. Treatment with systemically active antibiotics within 72 hours before chemotherapy 12. Known infection with HIV 13. Known sickle cell disease 14. Known severe persistent drug-induced myelosuppression 15. New York Heart Association (NYHA) class III or IV heart failure, severe uncontrolled cardiac disease (unstable angina, clinically significant ECG abnormalities) or MI within the previous 6 months before the first administration of HSP-130 16. Any malignancy other than breast cancer, with exception of adequately treated squamous or basal cell carcinoma of the skin or cervical carcinoma in situ, within 5 years before the first administration of the HSP-130 17. Current or recent treatment (within 30 days before the first administration of the HSP-130) with any other investigational medicinal product 18. Pregnancy or lactation; Subjects planning to be pregnant or to breastfeed before, during, or within 12 months after administration of the HSP-130 are not permitted to enroll in the study 19. Received a live, live-attenuated, or non-live vaccine within 4 weeks before the first administration of the HSP-130 20. Patient has evidence of any other coexisting disease or medical or psychological condition, metabolic dysfunction, physical examination finding or clinical lab finding giving reasonable suspicion of a disease or condition that contraindicated the use of an HSP-130, or patient is high risk for treatment complication
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Effect Curve for Absolute Neutrophil Count (AUECANC): Cycle 0 | Cycle 0: Predose (0 hour), 48, 96, 144, 192, 240 and 312 hours post-dose | Absolute neutrophil count (ANC) is a measure of the number of neutrophil granulocytes (also known as polymorphonuclear cells, PMN's, polys, granulocytes, segmented neutrophils or segs) present in the blood. |
| Maximum Observed Serum Concentration (Cmax): Cycle 1 and Cycle 4 | Cycle 1 and 4: Predose (0 hour), 6, 12, 24, 48, 96, 144, 192, 240 and 312 hours post-dose | — |
| Area Under the Serum Concentration Time Curve From Time of Dose Administration to Time of Last Measurable Concentration (AUCt): Cycle 1 and Cycle 4 | Cycle 1 and 4: Predose (0 hour), 6, 12, 24, 48, 96, 144, 192, 240 and 312 hours post-dose | AUC0-t= Area under the serum concentration of HSP-130 versus time curve from the time of dose administration to time of last quantifiable concentration (0-t). |
| Duration of Severe Neutropenia (DSN): Cycle 1 | Cycle 1: Predose (0 hour), 48, 96, 144, 192, 240 and 312 hours post-dose | Severe Neutropenia was defined as grade 4 neutropenia in which the ANC was \< 0.5 x10\^9 per liter. DSN was defined as the days with grade 4 neutropenia (ANC \< 0.5 x10\^9/L). |
| Maximum Observed Serum Concentration (Cmax): Cycle 0 | Cycle 0: Predose (0 hour), 6, 12, 24, 48, 96, 144, 192, 240 and 312 hours post-dose | — |
| Area Under the Serum Concentration Time Curve From Time of Dose Administration to Time Infinity (AUCinf): Cycle 0 | Cycle 0: Predose (0 hour), 6, 12, 24, 48, 96, 144, 192, 240 and 312 hours post-dose | AUCinf = Area under the serum concentration of HSP-130 versus time curve (AUC) from the time of dose administration to extrapolated infinite time (0-inf). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Effect Curve for Absolute Neutrophil Count From Time of Dose Administration to Time Infinity (AUEC_ANC Inf): Cycle 1 and Cycle 4 | Cycle 1 and 4: Predose (0 hour), 48, 96, 144, 192, 240 and 312 hours post-dose | Absolute neutrophil count (ANC) is a measure of the number of neutrophil granulocytes (also known as polymorphonuclear cells, PMN's, polys, granulocytes, segmented neutrophils or segs) present in the blood. |
| Time to ANC Recovery: Cycle 1 and Cycle 4 | Cycle 1 and 4: Predose (0 hour), 48, 96, 144, 192, 240 and 312 hours post-dose | Time to ANC recovery was defined as the time from documentation of the first day with ANC greater than equal to (\>=) 2.0 x10\^9/L after any day with ANC \<2.0 x10\^9/L. |
| Area Under the Serum Concentration Time Curve From Time of Dose Administration to Time Infinity (AUCinf): Cycle 1 and Cycle 4 | Cycle 1 and 4: Predose (0 hour), 6, 12, 24, 48, 96, 144, 192, 240 and 312 hours post-dose | AUC0-inf = Area under the serum concentration versus time curve (AUC) from the time of dose administration to extrapolated infinite time (0-inf). |
| Time To Achieve Maximum Serum Concentration (Tmax): Cycle 1 and Cycle 4 | Cycle 1 and 4: Predose (0 hour), 6, 12, 24, 48, 96, 144, 192, 240 and 312 hours post-dose | — |
| Elimination Half-Life (t1/2): Cycle 1 and Cycle 4 | Cycle 1 and 4: Predose (0 hour), 6, 12, 24, 48, 96, 144, 192, 240 and 312 hours post-dose | t1/2 is the time taken for plasma concentration of a drug to reduce by 50% of its initial value. |
| Elimination Rate Constant (λz): Cycle 1 and Cycle 4 | Cycle 1 and 4: Predose (0 hour), 6, 12, 24, 48, 96, 144, 192, 240 and 312 hours post-dose | Elimination rate constant was defined as the rate at which the drug was removed from the body. |
| Apparent Clearance (CL/F): Cycle 1 and Cycle 4 | Cycle 1 and 4: Predose (0 hour), 6, 12, 24, 48, 96, 144, 192, 240 and 312 hours post-dose | CL/F was defined as a quantitative measure of the rate at which a drug substance is removed from the body. |
| Protein-Content Corrected Area Under the Serum Concentration Time Curve From Time of Dose Administration to Time of Last Measurable Concentration (AUCt): Cycle 1 and Cycle 4 | Cycle 1 and 4: Predose (0 hour), 6, 12, 24, 48, 96, 144, 192, 240 and 312 hours post-dose | The protein-content correction was conducted for AUCt parameter: Protein-content corrected AUCt= Nominal Protein-content AUCt / (Actual protein concentration/10.0 mg/mL). |
| Protein-Content Corrected Area Under the Serum Concentration Time Curve From Time of Dose Administration to Time Infinity (AUCinf): Cycle 1 and Cycle 4 | Cycle 1 and 4: Predose (0 hour), 6, 12, 24, 48, 96, 144, 192, 240 and 312 hours post-dose | The protein-content correction was conducted for AUCinf parameter: Protein-content corrected AUCinf = Nominal Protein-content AUCinf / (Actual protein concentration/10.0 mg/mL). |
| Protein-Content Corrected Maximum Observed Serum Concentration (Cmax): Cycle 1 and Cycle 4 | Cycle 1 and 4: Predose (0 hour), 6, 12, 24, 48, 96, 144, 192, 240 and 312 hours post-dose | The protein-content correction was conducted for Cmax parameter: Protein-content corrected Cmax = Nominal Protein-content Cmax / (Actual protein concentration/10.0 mg/mL). |
| Maximum Effect for Absolute Neutrophil Count (ANC_Emax): Cycle 0 | Cycle 0: Predose (0 hour), 48, 96, 144, 192, 240 and 312 hours post-dose | ANC was a measure of the number of neutrophil granulocytes (also known as polymorphonuclear cells, PMN's, polys, granulocytes, segmented neutrophils or segs) present in the blood. |
| Time of Maximum Effect for Absolute Neutrophil Count (ANC_Tmax): Cycle 0 | Cycle 0: Predose (0 hour), 48, 96, 144, 192, 240 and 312 hours post-dose | ANC was a measure of the number of neutrophil granulocytes (also known as polymorphonuclear cells, PMN's, polys, granulocytes, segmented neutrophils or segs) present in the blood. |
| Area Under the Effect Curve for CD34+ (AUECCD34+): Cycle 0 | Cycle 0: Predose (0 hour), 48, 96, 144, 192, 240 and 312 hours post-dose | — |
| Maximum Effect for CD34+ Count (CD34+_Emax): Cycle 0 | Cycle 0: Predose (0 hour), 48, 96, 144, 192, 240 and 312 hours post-dose | — |
| Time of Maximum Effect for CD34+ Count (CD34+ Tmax): Cycle 0 | Cycle 0: Predose (0 hour), 48, 96, 144, 192, 240 and 312 hours post-dose | — |
| Area Under the Effect Curve for Absolute Neutrophil Count From Time of Dose Administration to Time Infinity (AUEC_ANC Inf): Cycle 0 | Cycle 0: Predose (0 hour), 48, 96, 144, 192, 240 and 312 hours post-dose | ANC is a measure of the number of neutrophil granulocytes (also known as polymorphonuclear cells, PMN's, polys, granulocytes, segmented neutrophils or segs) present in the blood. |
| Area Under the Effect Curve From Time of Dose Administration to Time Infinity for CD34 + (AUEC_CD34+ Inf): Cycle 0 | Cycle 0: Predose (0 hour), 48, 96, 144, 192, 240 and 312 hours post-dose | — |
| Area Under the Serum Concentration Time Curve From the Time of Dose Administration to the Time of Last Measurable Concentration (AUCt): Cycle 0 | Cycle 0: Predose (0 hour), 6, 12, 24, 48, 96, 144, 192, 240 and 312 hours post-dose | AUC0-t= Area under the serum concentration of HSP-130 versus time curve from the time of dose administration to time of last quantifiable concentration (0-t). |
| Time To Achieve Maximum Serum Concentration (Tmax): Cycle 0 | Cycle 0: Predose (0 hour), 6, 12, 24, 48, 96, 144, 192, 240 and 312 hours post-dose | — |
| Elimination Half-Life (t1/2): Cycle 0 | Cycle 0: Predose (0 hour), 6, 12, 24, 48, 96, 144, 192, 240 and 312 hours post-dose | t1/2 is the time taken for plasma concentration of HSP 130 to reduce by 50 percent (%) of its initial value. |
| Elimination Rate Constant (λz): Cycle 0 | Cycle 0: Predose (0 hour), 6, 12, 24, 48, 96, 144, 192, 240 and 312 hours post-dose | Elimination rate constant was defined as the rate at which the drug was removed from the body. |
| Apparent Clearance (CL/F): Cycle 0 | Cycle 0: Predose (0 hour), 6, 12, 24, 48, 96, 144, 192, 240 and 312 hours post-dose | Clearance of a drug was defined as the rate at which a drug was metabolized or eliminated by normal biological processes. |
| Protein-Content Corrected Area Under the Serum Concentration Time Curve From Time of Dose Administration to Time Infinity (AUCinf): Cycle 0 | Cycle 0: Predose (0 hour), 6, 12, 24, 48, 96, 144, 192, 240 and 312 hours post-dose | The protein-content correction was conducted for AUCinf parameter: Protein-content corrected AUCinf = Nominal Protein-content AUCinf / (Actual protein concentration/10.0 mg/mL). |
| Protein-Content Corrected Area Under the Serum Concentration Time Curve From Time of Dose Administration to Time of Last Measurable Concentration (AUCt): Cycle 0 | Cycle 0: Predose (0 hour), 6, 12, 24, 48, 96, 144, 192, 240 and 312 hours post-dose | The protein-content correction was conducted for AUCt parameter: Protein-content corrected AUCt= Nominal Protein-content AUCt / (Actual protein concentration/10.0 mg/mL). |
| Protein-Content Corrected Maximum Observed Serum Concentration (Cmax): Cycle 0 | Cycle 0: Predose (0 hour), 6, 12, 24, 48, 96, 144, 192, 240 and 312 hours post-dose | The protein-content correction was conducted for Cmax parameter: Protein-content corrected Cmax = Nominal Protein-content Cmax / (Actual protein concentration/10.0 mg/mL). |
| Duration of Severe Neutropenia (DSN): Cycle 4 | Cycle 4: Predose (0 hour), 48, 96, 144, 192, 240 and 312 hours post-dose | Severe Neutropenia was defined as grade 4 neutropenia in which the ANC was \< 0.5 x10\^9/L. DSN was defined as the days with grade 4 neutropenia (ANC \< 0.5 x10\^9/L). |
| Absolute Neutrophil Count Nadir Concentration: Cycle 1 and Cycle 4 | Cycle 1 and 4: Predose (0 hour), 48, 96, 144, 192, 240, and 312 hours post-dose | Nadir was defined as the lowest count for ANC concentration reported after first dose of study treatment. |
| Time of ANC Nadir Concentration: Cycle 1 and Cycle 4 | Cycle 1 and 4: Predose (0 hour), 48, 96, 144, 192, 240, and 312 hours post-dose | Time of ANC Nadir (in hours) was defined as the time from the first dose of study treatment on Day 2 of Cycle 1 and 4 to the time the lowest value was recorded. |
| Area Under the Effect Curve (AUEC_ANCt): Cycle 1 and Cycle 4 | Cycle 1 and 4: Predose (0 hour), 48, 96, 144, 192, 240, and 312 hours post-dose | ANC is a measure of the number of neutrophil granulocytes (also known as polymorphonuclear cells, PMN's, polys, granulocytes, segmented neutrophils or segs) present in the blood. |
| Incidence of Febrile Neutropenia: Cycle 1 and Cycle 4 | Cycle 1 and 4: Predose (0 hour), 48, 96, 144, 192, 240 and 312 hours post-dose | Febrile Neutropenia was defined as tympanic or axillary body temperature greater than (\>) 38.5 °C for \>1 hour and ANC less than (\<) 1.0 \*10\^9/L. |
| Incidence of Severe Neutropenia: Cycle 1 and Cycle 4 | Cycle 1 and 4: Predose (0 hour), 48, 96, 144, 192, 240, and 312 hours post-dose | Severe Neutropenia was defined as grade 4 neutropenia in which the ANC was \< 0.5 x10\^9/L. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Duration of Exposure to Study Drug Medication | Baseline up to approximately Day 94 | — |
| Number of Participants With Positive Anti-pegfilgrastim (Anti-drug) Antibodies | Baseline up to approximately Day 94 | — |
| Number of Participants With Clinically Significant Physical Examination Abnormalities | Baseline up to approximately Day 94 | Physical examination included physical assessment of the spleen. Clinically significant abnormality was based on investigator's discretion. |
| Number of Participants With Clinically Significant Vital Sign Abnormalities | Baseline up to approximately Day 94 | Vital sign assessment included body temperature (tympanic or axillary), heart rate (sitting), blood pressure (sitting systolic and diastolic), and respiratory rate. Clinically significant abnormality was based upon investigator's discretion. |
| Number of Participants With Laboratory Abnormalities | Baseline up to approximately Day 94 | Criteria: hematology (hemoglobin, hematocrit, platelet count, white blood cell count, neutrophils); chemistry (alkaline phosphatase, glucose, lactate dehydrogenase, alanine aminotransferase, aspartate aminotransferase, albumin, creatinine and gamma-glutamyl transpeptidase, blood urea nitrogen, total protein, phosphate, and uric acid); urinalysis. The clinical laboratory results and patterns observed were consistent with the known therapeutic response and the safety profile for the US and EU approved pegylated filgrastim (Neulasta). |
| Number of Participants With Treatment-Emergent Adverse Events (AEs) of Special Interest | Baseline up to approximately Day 94 | AEs of Special Interest (AESI) included Potential Allergic Reactions, Splenomegaly, Splenic Rupture, Acute Respiratory Distress Syndrome, Alveolar Hemorrhage, Hemoptysis, Leukocytosis, Thrombocytopenia, Capillary Leak Syndrome, Cytokine Release Syndrome, Cutaneous Vasculitis and Glomerulonephritis. |
| Number of Participants With At Least 1 Concomitant Medication | Baseline up to approximately Day 94 | — |
| Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Baseline up to approximately Day 94 | An AE was any untoward medical occurrence in participants who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment Emergent Adverse Event (TEAE) was adverse event that started or worsened in severity after the HSP-130 administration up to and including 30 days post HSP-130 administration (up to Day 94). AEs included both serious and non-serious. |
| Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities | Baseline up to approximately Day 94 | Clinically significant abnormality was based upon investigator's discretion. |
Countries
Hungary, Spain
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cycle 0: HSP-130 3mg Participants who had not received background chemotherapy treatment in the study were administered a single dose of 3 mg of HSP-130 SC at Day 1 of Cycle 0. Participants were followed approximately 30 days after last dose of study treatment. | 6 |
| Cycles 0: HSP-130 6mg Participants who had not received background chemotherapy treatment in the study were administered a single dose of 6 mg of HSP-130 SC at Day 1 of Cycle 0. Participants were followed approximately 30 days after last dose of study treatment. | 6 |
| Cycles 1-4: HSP-130 6mg Participants in Cycles 1-4 received background chemotherapy treatment at Day 1 and were administered a single dose of 6 mg of HSP-130 SC at Day 2 of Cycles 1-4 (each cycle was approximately 3 weeks if there were no chemotherapy treatment delays). Participants were followed approximately 30 days after last dose of study treatment. | 13 |
| Total | 25 |
Baseline characteristics
| Characteristic | Cycle 0: HSP-130 3mg | Cycles 0: HSP-130 6mg | Cycles 1-4: HSP-130 6mg | Total |
|---|---|---|---|---|
| Age, Continuous | 66.8 years STANDARD_DEVIATION 8.89 | 60.8 years STANDARD_DEVIATION 13.6 | 55.1 years STANDARD_DEVIATION 8.95 | 59.3 years STANDARD_DEVIATION 10.93 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 5 Participants | 10 Participants | 21 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 3 Participants | 4 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 6 Participants | 13 Participants | 24 Participants |
| Sex: Female, Male Female | 6 Participants | 6 Participants | 13 Participants | 25 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 13 |
| other Total, other adverse events | 6 / 6 | 6 / 6 | 13 / 13 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 2 / 13 |
Outcome results
Primary
Area Under the Effect Curve for Absolute Neutrophil Count (AUECANC): Cycle 0
Absolute neutrophil count (ANC) is a measure of the number of neutrophil granulocytes (also known as polymorphonuclear cells, PMN's, polys, granulocytes, segmented neutrophils or segs) present in the blood.
Time frame: Cycle 0: Predose (0 hour), 48, 96, 144, 192, 240 and 312 hours post-dose
Population: FAS included all participants who received at least 1 dose of study medication. This outcome measure was not planned to be analyzed for Cycles 1-4: HSP-130 6mg arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cycle 0: HSP-130 3mg | Area Under the Effect Curve for Absolute Neutrophil Count (AUECANC): Cycle 0 | 3900.482 hour*10^9 Neutrophils per Liter | Standard Deviation 683.687 |
| Cycles 0: HSP-130 6mg | Area Under the Effect Curve for Absolute Neutrophil Count (AUECANC): Cycle 0 | 5880.985 hour*10^9 Neutrophils per Liter | Standard Deviation 1287.2887 |
Primary
Area Under the Serum Concentration Time Curve From Time of Dose Administration to Time Infinity (AUCinf): Cycle 0
AUCinf = Area under the serum concentration of HSP-130 versus time curve (AUC) from the time of dose administration to extrapolated infinite time (0-inf).
Time frame: Cycle 0: Predose (0 hour), 6, 12, 24, 48, 96, 144, 192, 240 and 312 hours post-dose
Population: FAS included all participants who received at least 1 dose of study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cycle 0: HSP-130 3mg | Area Under the Serum Concentration Time Curve From Time of Dose Administration to Time Infinity (AUCinf): Cycle 0 | 1425862.2 hour*picogram per milliliter (h*pg/mL) | Standard Deviation 949518.8 |
| Cycles 0: HSP-130 6mg | Area Under the Serum Concentration Time Curve From Time of Dose Administration to Time Infinity (AUCinf): Cycle 0 | 5689476.1 hour*picogram per milliliter (h*pg/mL) | Standard Deviation 3757035.5 |
Primary
Area Under the Serum Concentration Time Curve From Time of Dose Administration to Time of Last Measurable Concentration (AUCt): Cycle 1 and Cycle 4
AUC0-t= Area under the serum concentration of HSP-130 versus time curve from the time of dose administration to time of last quantifiable concentration (0-t).
Time frame: Cycle 1 and 4: Predose (0 hour), 6, 12, 24, 48, 96, 144, 192, 240 and 312 hours post-dose
Population: FAS included all participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cycle 0: HSP-130 3mg | Area Under the Serum Concentration Time Curve From Time of Dose Administration to Time of Last Measurable Concentration (AUCt): Cycle 1 and Cycle 4 | Cycle 1 | 10084193.7 h*pg/mL | Standard Deviation 14047222.7 |
| Cycle 0: HSP-130 3mg | Area Under the Serum Concentration Time Curve From Time of Dose Administration to Time of Last Measurable Concentration (AUCt): Cycle 1 and Cycle 4 | Cycle 4 | 6017621.6 h*pg/mL | Standard Deviation 5920395.4 |
Primary
Duration of Severe Neutropenia (DSN): Cycle 1
Severe Neutropenia was defined as grade 4 neutropenia in which the ANC was \< 0.5 x10\^9 per liter. DSN was defined as the days with grade 4 neutropenia (ANC \< 0.5 x10\^9/L).
Time frame: Cycle 1: Predose (0 hour), 48, 96, 144, 192, 240 and 312 hours post-dose
Population: FAS included all participants who received at least 1 dose of study medication. This outcome measure was not planned to be analyzed for Cycle 0: HSP-130 3mg and Cycle 0: HSP-130 6mg arms. Here, 'Overall number of participants analyzed' signifies number of participants evaluable for the specified outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cycle 0: HSP-130 3mg | Duration of Severe Neutropenia (DSN): Cycle 1 | 0.667 days | Standard Deviation 0.9847 |
Primary
Maximum Observed Serum Concentration (Cmax): Cycle 0
Time frame: Cycle 0: Predose (0 hour), 6, 12, 24, 48, 96, 144, 192, 240 and 312 hours post-dose
Population: FAS included all participants who received at least 1 dose of study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cycle 0: HSP-130 3mg | Maximum Observed Serum Concentration (Cmax): Cycle 0 | 38026.7 picogram per milliliter (pg/mL) | Standard Deviation 28821.7 |
| Cycles 0: HSP-130 6mg | Maximum Observed Serum Concentration (Cmax): Cycle 0 | 155766.7 picogram per milliliter (pg/mL) | Standard Deviation 99051.8 |
Primary
Maximum Observed Serum Concentration (Cmax): Cycle 1 and Cycle 4
Time frame: Cycle 1 and 4: Predose (0 hour), 6, 12, 24, 48, 96, 144, 192, 240 and 312 hours post-dose
Population: FAS included all participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cycle 0: HSP-130 3mg | Maximum Observed Serum Concentration (Cmax): Cycle 1 and Cycle 4 | Cycle 1 | 118130.8 pg/mL | Standard Deviation 119028.6 |
| Cycle 0: HSP-130 3mg | Maximum Observed Serum Concentration (Cmax): Cycle 1 and Cycle 4 | Cycle 4 | 95200.0 pg/mL | Standard Deviation 93544.1 |
Secondary
Absolute Neutrophil Count Nadir Concentration: Cycle 1 and Cycle 4
Nadir was defined as the lowest count for ANC concentration reported after first dose of study treatment.
Time frame: Cycle 1 and 4: Predose (0 hour), 48, 96, 144, 192, 240, and 312 hours post-dose
Population: FAS included all participants who received at least 1 dose of study medication. This outcome measure was not planned to be analyzed for Cycle 0: HSP-130 3mg and Cycle 0: HSP-130 6mg arms.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cycle 0: HSP-130 3mg | Absolute Neutrophil Count Nadir Concentration: Cycle 1 and Cycle 4 | Cycle 1 | 1.132 *10^9 Neutrophils per Liter | Standard Deviation 1.148 |
| Cycle 0: HSP-130 3mg | Absolute Neutrophil Count Nadir Concentration: Cycle 1 and Cycle 4 | Cycle 4 | 1.623 *10^9 Neutrophils per Liter | Standard Deviation 1.8364 |
Secondary
Apparent Clearance (CL/F): Cycle 0
Clearance of a drug was defined as the rate at which a drug was metabolized or eliminated by normal biological processes.
Time frame: Cycle 0: Predose (0 hour), 6, 12, 24, 48, 96, 144, 192, 240 and 312 hours post-dose
Population: FAS included all participants who received at least 1 dose of study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cycle 0: HSP-130 3mg | Apparent Clearance (CL/F): Cycle 0 | 4235.6 milliliter per hour (mL/h) | Standard Deviation 4714.4 |
| Cycles 0: HSP-130 6mg | Apparent Clearance (CL/F): Cycle 0 | 1655.9 milliliter per hour (mL/h) | Standard Deviation 1242.6 |
Secondary
Apparent Clearance (CL/F): Cycle 1 and Cycle 4
CL/F was defined as a quantitative measure of the rate at which a drug substance is removed from the body.
Time frame: Cycle 1 and 4: Predose (0 hour), 6, 12, 24, 48, 96, 144, 192, 240 and 312 hours post-dose
Population: FAS included all participants who received at least 1 dose of study medication. Here 'number analyzed' signifies number of participants evaluable for this outcome measure at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cycle 0: HSP-130 3mg | Apparent Clearance (CL/F): Cycle 1 and Cycle 4 | Cycle 1 | 1326.8 mL/h | Standard Deviation 1010.2 |
| Cycle 0: HSP-130 3mg | Apparent Clearance (CL/F): Cycle 1 and Cycle 4 | Cycle 4 | 2342.8 mL/h | Standard Deviation 2043.8 |
Secondary
Area Under the Effect Curve (AUEC_ANCt): Cycle 1 and Cycle 4
ANC is a measure of the number of neutrophil granulocytes (also known as polymorphonuclear cells, PMN's, polys, granulocytes, segmented neutrophils or segs) present in the blood.
Time frame: Cycle 1 and 4: Predose (0 hour), 48, 96, 144, 192, 240, and 312 hours post-dose
Population: FAS included all participants who received at least 1 dose of study medication. This outcome measure was not planned to be analyzed for Cycle 0: HSP-130 3mg and Cycle 0: HSP-130 6mg arms.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cycle 0: HSP-130 3mg | Area Under the Effect Curve (AUEC_ANCt): Cycle 1 and Cycle 4 | Cycle 1 | 2540.285 hour*10^9 Neutrophils per Liter | Standard Deviation 854.2237 |
| Cycle 0: HSP-130 3mg | Area Under the Effect Curve (AUEC_ANCt): Cycle 1 and Cycle 4 | Cycle 4 | 3186.542 hour*10^9 Neutrophils per Liter | Standard Deviation 1362.0079 |
Secondary
Area Under the Effect Curve for Absolute Neutrophil Count From Time of Dose Administration to Time Infinity (AUEC_ANC Inf): Cycle 0
ANC is a measure of the number of neutrophil granulocytes (also known as polymorphonuclear cells, PMN's, polys, granulocytes, segmented neutrophils or segs) present in the blood.
Time frame: Cycle 0: Predose (0 hour), 48, 96, 144, 192, 240 and 312 hours post-dose
Population: FAS included all participants who received at least 1 dose of study medication. Here, 'Overall number of participants analyzed' signifies number of participants evaluable for the specified outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cycle 0: HSP-130 3mg | Area Under the Effect Curve for Absolute Neutrophil Count From Time of Dose Administration to Time Infinity (AUEC_ANC Inf): Cycle 0 | 5254.288 hour*10^9 Neutrophils per Liter | Standard Deviation 1699.7088 |
| Cycles 0: HSP-130 6mg | Area Under the Effect Curve for Absolute Neutrophil Count From Time of Dose Administration to Time Infinity (AUEC_ANC Inf): Cycle 0 | 6576.165 hour*10^9 Neutrophils per Liter | Standard Deviation 1821.9919 |
Secondary
Area Under the Effect Curve for Absolute Neutrophil Count From Time of Dose Administration to Time Infinity (AUEC_ANC Inf): Cycle 1 and Cycle 4
Absolute neutrophil count (ANC) is a measure of the number of neutrophil granulocytes (also known as polymorphonuclear cells, PMN's, polys, granulocytes, segmented neutrophils or segs) present in the blood.
Time frame: Cycle 1 and 4: Predose (0 hour), 48, 96, 144, 192, 240 and 312 hours post-dose
Population: FAS included all participants who received at least 1 dose of study medication. Here, number analyzed field signifies that the number of participants were evaluable at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cycle 0: HSP-130 3mg | Area Under the Effect Curve for Absolute Neutrophil Count From Time of Dose Administration to Time Infinity (AUEC_ANC Inf): Cycle 1 and Cycle 4 | Cycle 1 | 5636.963 hour*10^9 Neutrophils per Liter | Standard Deviation 1974.1635 |
| Cycle 0: HSP-130 3mg | Area Under the Effect Curve for Absolute Neutrophil Count From Time of Dose Administration to Time Infinity (AUEC_ANC Inf): Cycle 1 and Cycle 4 | Cycle 4 | 12399.370 hour*10^9 Neutrophils per Liter | Standard Deviation 18345.3366 |
Secondary
Area Under the Effect Curve for CD34+ (AUECCD34+): Cycle 0
Time frame: Cycle 0: Predose (0 hour), 48, 96, 144, 192, 240 and 312 hours post-dose
Population: FAS included all participants who received at least 1 dose of study medication. This outcome measure was not planned to be analyzed for Cycles 1-4: HSP-130 6mg arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cycle 0: HSP-130 3mg | Area Under the Effect Curve for CD34+ (AUECCD34+): Cycle 0 | 1749.523 hour*cells per microliter (h*cells/ mcL) | Standard Deviation 1022.3037 |
| Cycles 0: HSP-130 6mg | Area Under the Effect Curve for CD34+ (AUECCD34+): Cycle 0 | 2752.198 hour*cells per microliter (h*cells/ mcL) | Standard Deviation 2152.8794 |
Secondary
Area Under the Effect Curve From Time of Dose Administration to Time Infinity for CD34 + (AUEC_CD34+ Inf): Cycle 0
Time frame: Cycle 0: Predose (0 hour), 48, 96, 144, 192, 240 and 312 hours post-dose
Population: FAS included all participants who received at least 1 dose of study medication. This outcome measure was not planned to be analyzed for Cycles 1-4: HSP-130 6mg arm. Here Overall number of participants analyzed signifies number of participants evaluable for the specified outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cycle 0: HSP-130 3mg | Area Under the Effect Curve From Time of Dose Administration to Time Infinity for CD34 + (AUEC_CD34+ Inf): Cycle 0 | 1835.221 hour*cells per microliter (h*cells/mcL) | Standard Deviation 1036.6473 |
| Cycles 0: HSP-130 6mg | Area Under the Effect Curve From Time of Dose Administration to Time Infinity for CD34 + (AUEC_CD34+ Inf): Cycle 0 | 3159.470 hour*cells per microliter (h*cells/mcL) | Standard Deviation 2197.4774 |
Secondary
Area Under the Serum Concentration Time Curve From the Time of Dose Administration to the Time of Last Measurable Concentration (AUCt): Cycle 0
AUC0-t= Area under the serum concentration of HSP-130 versus time curve from the time of dose administration to time of last quantifiable concentration (0-t).
Time frame: Cycle 0: Predose (0 hour), 6, 12, 24, 48, 96, 144, 192, 240 and 312 hours post-dose
Population: FAS included all participants who received at least 1 dose of study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cycle 0: HSP-130 3mg | Area Under the Serum Concentration Time Curve From the Time of Dose Administration to the Time of Last Measurable Concentration (AUCt): Cycle 0 | 1410202.6 h*pg/mL | Standard Deviation 948443.5 |
| Cycles 0: HSP-130 6mg | Area Under the Serum Concentration Time Curve From the Time of Dose Administration to the Time of Last Measurable Concentration (AUCt): Cycle 0 | 5677700.3 h*pg/mL | Standard Deviation 3756049.2 |
Secondary
Area Under the Serum Concentration Time Curve From Time of Dose Administration to Time Infinity (AUCinf): Cycle 1 and Cycle 4
AUC0-inf = Area under the serum concentration versus time curve (AUC) from the time of dose administration to extrapolated infinite time (0-inf).
Time frame: Cycle 1 and 4: Predose (0 hour), 6, 12, 24, 48, 96, 144, 192, 240 and 312 hours post-dose
Population: FAS included all participants who received at least 1 dose of study medication. Here, 'number analyzed' field signifies that the number of participants were evaluable at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cycle 0: HSP-130 3mg | Area Under the Serum Concentration Time Curve From Time of Dose Administration to Time Infinity (AUCinf): Cycle 1 and Cycle 4 | Cycle 1 | 10093213.5 h*pg/mL | Standard Deviation 14047936.2 |
| Cycle 0: HSP-130 3mg | Area Under the Serum Concentration Time Curve From Time of Dose Administration to Time Infinity (AUCinf): Cycle 1 and Cycle 4 | Cycle 4 | 6425013.3 h*pg/mL | Standard Deviation 6000938.3 |
Secondary
Duration of Severe Neutropenia (DSN): Cycle 4
Severe Neutropenia was defined as grade 4 neutropenia in which the ANC was \< 0.5 x10\^9/L. DSN was defined as the days with grade 4 neutropenia (ANC \< 0.5 x10\^9/L).
Time frame: Cycle 4: Predose (0 hour), 48, 96, 144, 192, 240 and 312 hours post-dose
Population: FAS included all participants who received at least 1 dose of study medication. This outcome measure was not planned to be analyzed for Cycle 0: HSP-130 3mg and Cycle 0: HSP-130 6mg arms. Here, 'Overall number of participants analyzed signifies number of participants evaluable for the specified outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cycle 0: HSP-130 3mg | Duration of Severe Neutropenia (DSN): Cycle 4 | 0.667 days | Standard Deviation 0.9847 |
Secondary
Elimination Half-Life (t1/2): Cycle 0
t1/2 is the time taken for plasma concentration of HSP 130 to reduce by 50 percent (%) of its initial value.
Time frame: Cycle 0: Predose (0 hour), 6, 12, 24, 48, 96, 144, 192, 240 and 312 hours post-dose
Population: FAS included all participants who received at least 1 dose of study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cycle 0: HSP-130 3mg | Elimination Half-Life (t1/2): Cycle 0 | 50.0 hour | Standard Deviation 15.5 |
| Cycles 0: HSP-130 6mg | Elimination Half-Life (t1/2): Cycle 0 | 48.8 hour | Standard Deviation 12.5 |
Secondary
Elimination Half-Life (t1/2): Cycle 1 and Cycle 4
t1/2 is the time taken for plasma concentration of a drug to reduce by 50% of its initial value.
Time frame: Cycle 1 and 4: Predose (0 hour), 6, 12, 24, 48, 96, 144, 192, 240 and 312 hours post-dose
Population: FAS included all participants who received at least 1 dose of study medication. Here 'number analyzed' signifies number of participants evaluable for this outcome measure at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cycle 0: HSP-130 3mg | Elimination Half-Life (t1/2): Cycle 1 and Cycle 4 | Cycle 1 | 30.7 hour | Standard Deviation 10.8 |
| Cycle 0: HSP-130 3mg | Elimination Half-Life (t1/2): Cycle 1 and Cycle 4 | Cycle 4 | 29.5 hour | Standard Deviation 9.5 |
Secondary
Elimination Rate Constant (λz): Cycle 0
Elimination rate constant was defined as the rate at which the drug was removed from the body.
Time frame: Cycle 0: Predose (0 hour), 6, 12, 24, 48, 96, 144, 192, 240 and 312 hours post-dose
Population: FAS included all participants who received at least 1 dose of study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cycle 0: HSP-130 3mg | Elimination Rate Constant (λz): Cycle 0 | 0.015 per hour | Standard Deviation 0.0051 |
| Cycles 0: HSP-130 6mg | Elimination Rate Constant (λz): Cycle 0 | 0.015 per hour | Standard Deviation 0.0041 |
Secondary
Elimination Rate Constant (λz): Cycle 1 and Cycle 4
Elimination rate constant was defined as the rate at which the drug was removed from the body.
Time frame: Cycle 1 and 4: Predose (0 hour), 6, 12, 24, 48, 96, 144, 192, 240 and 312 hours post-dose
Population: FAS included all participants who received at least 1 dose of study medication. Here, 'number analyzed' signifies number of participants evaluable for this outcome measure at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cycle 0: HSP-130 3mg | Elimination Rate Constant (λz): Cycle 1 and Cycle 4 | Cycle 1 | 0.026 per hour | Standard Deviation 0.0099 |
| Cycle 0: HSP-130 3mg | Elimination Rate Constant (λz): Cycle 1 and Cycle 4 | Cycle 4 | 0.025 per hour | Standard Deviation 0.006 |
Secondary
Incidence of Febrile Neutropenia: Cycle 1 and Cycle 4
Febrile Neutropenia was defined as tympanic or axillary body temperature greater than (\>) 38.5 °C for \>1 hour and ANC less than (\<) 1.0 \*10\^9/L.
Time frame: Cycle 1 and 4: Predose (0 hour), 48, 96, 144, 192, 240 and 312 hours post-dose
Population: FAS included all participants who received at least 1 dose of study medication. This outcome measure was not planned to be analyzed for Cycle 0: HSP-130 3mg and Cycle 0: HSP-130 6mg arms.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cycle 0: HSP-130 3mg | Incidence of Febrile Neutropenia: Cycle 1 and Cycle 4 | Cycle 1 | 1 participants |
| Cycle 0: HSP-130 3mg | Incidence of Febrile Neutropenia: Cycle 1 and Cycle 4 | Cycle 4 | 0 participants |
Secondary
Incidence of Severe Neutropenia: Cycle 1 and Cycle 4
Severe Neutropenia was defined as grade 4 neutropenia in which the ANC was \< 0.5 x10\^9/L.
Time frame: Cycle 1 and 4: Predose (0 hour), 48, 96, 144, 192, 240, and 312 hours post-dose
Population: FAS included all participants who received at least 1 dose of study medication. This outcome measure was not planned to be analyzed for Cycle 0: HSP-130 3mg and Cycle 0: HSP-130 6mg arms.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cycle 0: HSP-130 3mg | Incidence of Severe Neutropenia: Cycle 1 and Cycle 4 | Cycle 1 | 5 participants |
| Cycle 0: HSP-130 3mg | Incidence of Severe Neutropenia: Cycle 1 and Cycle 4 | Cycle 4 | 5 participants |
Secondary
Maximum Effect for Absolute Neutrophil Count (ANC_Emax): Cycle 0
ANC was a measure of the number of neutrophil granulocytes (also known as polymorphonuclear cells, PMN's, polys, granulocytes, segmented neutrophils or segs) present in the blood.
Time frame: Cycle 0: Predose (0 hour), 48, 96, 144, 192, 240 and 312 hours post-dose
Population: FAS included all participants who received at least 1 dose of study medication. This outcome measure was not planned to be analyzed for Cycles 1-4: HSP-130 6mg arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cycle 0: HSP-130 3mg | Maximum Effect for Absolute Neutrophil Count (ANC_Emax): Cycle 0 | 24.512 *10^9 Neutrophils per Liter | Standard Deviation 6.071 |
| Cycles 0: HSP-130 6mg | Maximum Effect for Absolute Neutrophil Count (ANC_Emax): Cycle 0 | 43.257 *10^9 Neutrophils per Liter | Standard Deviation 5.5683 |
Secondary
Maximum Effect for CD34+ Count (CD34+_Emax): Cycle 0
Time frame: Cycle 0: Predose (0 hour), 48, 96, 144, 192, 240 and 312 hours post-dose
Population: FAS included all participants who received at least 1 dose of study medication. This outcome measure was not planned to be analyzed for Cycles 1-4: HSP-130 6mg arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cycle 0: HSP-130 3mg | Maximum Effect for CD34+ Count (CD34+_Emax): Cycle 0 | 13.970 cells per microliter (cells/mcL) | Standard Deviation 6.8536 |
| Cycles 0: HSP-130 6mg | Maximum Effect for CD34+ Count (CD34+_Emax): Cycle 0 | 27.343 cells per microliter (cells/mcL) | Standard Deviation 18.4805 |
Secondary
Protein-Content Corrected Area Under the Serum Concentration Time Curve From Time of Dose Administration to Time Infinity (AUCinf): Cycle 0
The protein-content correction was conducted for AUCinf parameter: Protein-content corrected AUCinf = Nominal Protein-content AUCinf / (Actual protein concentration/10.0 mg/mL).
Time frame: Cycle 0: Predose (0 hour), 6, 12, 24, 48, 96, 144, 192, 240 and 312 hours post-dose
Population: FAS included all participants who received at least 1 dose of study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cycle 0: HSP-130 3mg | Protein-Content Corrected Area Under the Serum Concentration Time Curve From Time of Dose Administration to Time Infinity (AUCinf): Cycle 0 | 1440264.8 h*pg/mL | Standard Deviation 959109.9 |
| Cycles 0: HSP-130 6mg | Protein-Content Corrected Area Under the Serum Concentration Time Curve From Time of Dose Administration to Time Infinity (AUCinf): Cycle 0 | 5689476.1 h*pg/mL | Standard Deviation 3757035.5 |
Secondary
Protein-Content Corrected Area Under the Serum Concentration Time Curve From Time of Dose Administration to Time Infinity (AUCinf): Cycle 1 and Cycle 4
The protein-content correction was conducted for AUCinf parameter: Protein-content corrected AUCinf = Nominal Protein-content AUCinf / (Actual protein concentration/10.0 mg/mL).
Time frame: Cycle 1 and 4: Predose (0 hour), 6, 12, 24, 48, 96, 144, 192, 240 and 312 hours post-dose
Population: FAS included all participants who received at least 1 dose of study medication. Here 'number analyzed' signifies number of participants evaluable at the specified timepoints only.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cycle 0: HSP-130 3mg | Protein-Content Corrected Area Under the Serum Concentration Time Curve From Time of Dose Administration to Time Infinity (AUCinf): Cycle 1 and Cycle 4 | Cycle 1 | 10096698.3 h*pg/mL | Standard Deviation 14046434.6 |
| Cycle 0: HSP-130 3mg | Protein-Content Corrected Area Under the Serum Concentration Time Curve From Time of Dose Administration to Time Infinity (AUCinf): Cycle 1 and Cycle 4 | Cycle 4 | 6454443.8 h*pg/mL | Standard Deviation 6037499.6 |
Secondary
Protein-Content Corrected Area Under the Serum Concentration Time Curve From Time of Dose Administration to Time of Last Measurable Concentration (AUCt): Cycle 0
The protein-content correction was conducted for AUCt parameter: Protein-content corrected AUCt= Nominal Protein-content AUCt / (Actual protein concentration/10.0 mg/mL).
Time frame: Cycle 0: Predose (0 hour), 6, 12, 24, 48, 96, 144, 192, 240 and 312 hours post-dose
Population: FAS included all participants who received at least 1 dose of study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cycle 0: HSP-130 3mg | Protein-Content Corrected Area Under the Serum Concentration Time Curve From Time of Dose Administration to Time of Last Measurable Concentration (AUCt): Cycle 0 | 1424447.1 h*pg/mL | Standard Deviation 958023.7 |
| Cycles 0: HSP-130 6mg | Protein-Content Corrected Area Under the Serum Concentration Time Curve From Time of Dose Administration to Time of Last Measurable Concentration (AUCt): Cycle 0 | 5677700.3 h*pg/mL | Standard Deviation 3756049.2 |
Secondary
Protein-Content Corrected Area Under the Serum Concentration Time Curve From Time of Dose Administration to Time of Last Measurable Concentration (AUCt): Cycle 1 and Cycle 4
The protein-content correction was conducted for AUCt parameter: Protein-content corrected AUCt= Nominal Protein-content AUCt / (Actual protein concentration/10.0 mg/mL).
Time frame: Cycle 1 and 4: Predose (0 hour), 6, 12, 24, 48, 96, 144, 192, 240 and 312 hours post-dose
Population: FAS included all participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cycle 0: HSP-130 3mg | Protein-Content Corrected Area Under the Serum Concentration Time Curve From Time of Dose Administration to Time of Last Measurable Concentration (AUCt): Cycle 1 and Cycle 4 | Cycle 1 | 10087666.8 h*pg/mL | Standard Deviation 14045724.4 |
| Cycle 0: HSP-130 3mg | Protein-Content Corrected Area Under the Serum Concentration Time Curve From Time of Dose Administration to Time of Last Measurable Concentration (AUCt): Cycle 1 and Cycle 4 | Cycle 4 | 6045733.4 h*pg/mL | Standard Deviation 5955438.5 |
Secondary
Protein-Content Corrected Maximum Observed Serum Concentration (Cmax): Cycle 0
The protein-content correction was conducted for Cmax parameter: Protein-content corrected Cmax = Nominal Protein-content Cmax / (Actual protein concentration/10.0 mg/mL).
Time frame: Cycle 0: Predose (0 hour), 6, 12, 24, 48, 96, 144, 192, 240 and 312 hours post-dose
Population: FAS included all participants who received at least 1 dose of study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cycle 0: HSP-130 3mg | Protein-Content Corrected Maximum Observed Serum Concentration (Cmax): Cycle 0 | 38410.8 pg/mL | Standard Deviation 29112.8 |
| Cycles 0: HSP-130 6mg | Protein-Content Corrected Maximum Observed Serum Concentration (Cmax): Cycle 0 | 155766.7 pg/mL | Standard Deviation 99051.8 |
Secondary
Protein-Content Corrected Maximum Observed Serum Concentration (Cmax): Cycle 1 and Cycle 4
The protein-content correction was conducted for Cmax parameter: Protein-content corrected Cmax = Nominal Protein-content Cmax / (Actual protein concentration/10.0 mg/mL).
Time frame: Cycle 1 and 4: Predose (0 hour), 6, 12, 24, 48, 96, 144, 192, 240 and 312 hours post-dose
Population: FAS included all participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cycle 0: HSP-130 3mg | Protein-Content Corrected Maximum Observed Serum Concentration (Cmax): Cycle 1 and Cycle 4 | Cycle 1 | 118173.0 pg/mL | Standard Deviation 119004.2 |
| Cycle 0: HSP-130 3mg | Protein-Content Corrected Maximum Observed Serum Concentration (Cmax): Cycle 1 and Cycle 4 | Cycle 4 | 95670.1 pg/mL | Standard Deviation 94209.4 |
Secondary
Time of ANC Nadir Concentration: Cycle 1 and Cycle 4
Time of ANC Nadir (in hours) was defined as the time from the first dose of study treatment on Day 2 of Cycle 1 and 4 to the time the lowest value was recorded.
Time frame: Cycle 1 and 4: Predose (0 hour), 48, 96, 144, 192, 240, and 312 hours post-dose
Population: FAS included all participants who received at least 1 dose of study medication. This outcome measure was not planned to be analyzed for Cycle 0: HSP-130 3mg and Cycle 0: HSP-130 6mg arms.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cycle 0: HSP-130 3mg | Time of ANC Nadir Concentration: Cycle 1 and Cycle 4 | Cycle 1 | 129.231 hour | Standard Deviation 23.0585 |
| Cycle 0: HSP-130 3mg | Time of ANC Nadir Concentration: Cycle 1 and Cycle 4 | Cycle 4 | 142.154 hour | Standard Deviation 65.3323 |
Secondary
Time of Maximum Effect for Absolute Neutrophil Count (ANC_Tmax): Cycle 0
ANC was a measure of the number of neutrophil granulocytes (also known as polymorphonuclear cells, PMN's, polys, granulocytes, segmented neutrophils or segs) present in the blood.
Time frame: Cycle 0: Predose (0 hour), 48, 96, 144, 192, 240 and 312 hours post-dose
Population: FAS included all participants who received at least 1 dose of study medication. This outcome measure was not planned to be analyzed for Cycles 1-4: HSP-130 6mg arm.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cycle 0: HSP-130 3mg | Time of Maximum Effect for Absolute Neutrophil Count (ANC_Tmax): Cycle 0 | 71.950 hour |
| Cycles 0: HSP-130 6mg | Time of Maximum Effect for Absolute Neutrophil Count (ANC_Tmax): Cycle 0 | 47.800 hour |
Secondary
Time of Maximum Effect for CD34+ Count (CD34+ Tmax): Cycle 0
Time frame: Cycle 0: Predose (0 hour), 48, 96, 144, 192, 240 and 312 hours post-dose
Population: FAS included all participants who received at least 1 dose of study medication. This outcome measure was not planned to be analyzed for Cycles 1-4: HSP-130 6mg arm.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cycle 0: HSP-130 3mg | Time of Maximum Effect for CD34+ Count (CD34+ Tmax): Cycle 0 | 96.000 hour |
| Cycles 0: HSP-130 6mg | Time of Maximum Effect for CD34+ Count (CD34+ Tmax): Cycle 0 | 96.600 hour |
Secondary
Time To Achieve Maximum Serum Concentration (Tmax): Cycle 0
Time frame: Cycle 0: Predose (0 hour), 6, 12, 24, 48, 96, 144, 192, 240 and 312 hours post-dose
Population: FAS included all participants who received at least 1 dose of study medication.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cycle 0: HSP-130 3mg | Time To Achieve Maximum Serum Concentration (Tmax): Cycle 0 | 12.0 hour |
| Cycles 0: HSP-130 6mg | Time To Achieve Maximum Serum Concentration (Tmax): Cycle 0 | 23.5 hour |
Secondary
Time To Achieve Maximum Serum Concentration (Tmax): Cycle 1 and Cycle 4
Time frame: Cycle 1 and 4: Predose (0 hour), 6, 12, 24, 48, 96, 144, 192, 240 and 312 hours post-dose
Population: FAS included all participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cycle 0: HSP-130 3mg | Time To Achieve Maximum Serum Concentration (Tmax): Cycle 1 and Cycle 4 | Cycle 1 | 24.1 hour |
| Cycle 0: HSP-130 3mg | Time To Achieve Maximum Serum Concentration (Tmax): Cycle 1 and Cycle 4 | Cycle 4 | 23.5 hour |
Secondary
Time to ANC Recovery: Cycle 1 and Cycle 4
Time to ANC recovery was defined as the time from documentation of the first day with ANC greater than equal to (\>=) 2.0 x10\^9/L after any day with ANC \<2.0 x10\^9/L.
Time frame: Cycle 1 and 4: Predose (0 hour), 48, 96, 144, 192, 240 and 312 hours post-dose
Population: FAS included all participants who received at least 1 dose of study medication. This outcome measure was not planned to be analyzed for Cycle 0: HSP-130 3mg and Cycle 0: HSP-130 6mg arms.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cycle 0: HSP-130 3mg | Time to ANC Recovery: Cycle 1 and Cycle 4 | Cycle 1 | 2.615 days | Standard Deviation 1.7097 |
| Cycle 0: HSP-130 3mg | Time to ANC Recovery: Cycle 1 and Cycle 4 | Cycle 4 | 2.000 days | Standard Deviation 1.633 |
Other Pre-specified
Duration of Exposure to Study Drug Medication
Time frame: Baseline up to approximately Day 94
Population: Safety analysis set included all participants who received at least 1 dose of study medication.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cycle 0: HSP-130 3mg | Duration of Exposure to Study Drug Medication | 3.00 days |
| Cycles 0: HSP-130 6mg | Duration of Exposure to Study Drug Medication | 6.00 days |
| Cycles 1-4: HSP-130 6mg | Duration of Exposure to Study Drug Medication | 24.0 days |
Other Pre-specified
Number of Participants With At Least 1 Concomitant Medication
Time frame: Baseline up to approximately Day 94
Population: Safety analysis set included all participants who received at least 1 dose of study medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cycle 0: HSP-130 3mg | Number of Participants With At Least 1 Concomitant Medication | 6 Participants |
| Cycles 0: HSP-130 6mg | Number of Participants With At Least 1 Concomitant Medication | 6 Participants |
| Cycles 1-4: HSP-130 6mg | Number of Participants With At Least 1 Concomitant Medication | 13 Participants |
Other Pre-specified
Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities
Clinically significant abnormality was based upon investigator's discretion.
Time frame: Baseline up to approximately Day 94
Population: Safety analysis set included all participants who received at least 1 dose of study medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cycle 0: HSP-130 3mg | Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities | 0 Participants |
| Cycles 0: HSP-130 6mg | Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities | 0 Participants |
| Cycles 1-4: HSP-130 6mg | Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities | 0 Participants |
Other Pre-specified
Number of Participants With Clinically Significant Physical Examination Abnormalities
Physical examination included physical assessment of the spleen. Clinically significant abnormality was based on investigator's discretion.
Time frame: Baseline up to approximately Day 94
Population: Safety analysis set included all participants who received at least 1 dose of study medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cycle 0: HSP-130 3mg | Number of Participants With Clinically Significant Physical Examination Abnormalities | 0 Participants |
| Cycles 0: HSP-130 6mg | Number of Participants With Clinically Significant Physical Examination Abnormalities | 0 Participants |
| Cycles 1-4: HSP-130 6mg | Number of Participants With Clinically Significant Physical Examination Abnormalities | 0 Participants |
Other Pre-specified
Number of Participants With Clinically Significant Vital Sign Abnormalities
Vital sign assessment included body temperature (tympanic or axillary), heart rate (sitting), blood pressure (sitting systolic and diastolic), and respiratory rate. Clinically significant abnormality was based upon investigator's discretion.
Time frame: Baseline up to approximately Day 94
Population: Safety analysis set included all participants who received at least 1 dose of study medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cycle 0: HSP-130 3mg | Number of Participants With Clinically Significant Vital Sign Abnormalities | 0 Participants |
| Cycles 0: HSP-130 6mg | Number of Participants With Clinically Significant Vital Sign Abnormalities | 0 Participants |
| Cycles 1-4: HSP-130 6mg | Number of Participants With Clinically Significant Vital Sign Abnormalities | 0 Participants |
Other Pre-specified
Number of Participants With Laboratory Abnormalities
Criteria: hematology (hemoglobin, hematocrit, platelet count, white blood cell count, neutrophils); chemistry (alkaline phosphatase, glucose, lactate dehydrogenase, alanine aminotransferase, aspartate aminotransferase, albumin, creatinine and gamma-glutamyl transpeptidase, blood urea nitrogen, total protein, phosphate, and uric acid); urinalysis. The clinical laboratory results and patterns observed were consistent with the known therapeutic response and the safety profile for the US and EU approved pegylated filgrastim (Neulasta).
Time frame: Baseline up to approximately Day 94
Population: Safety analysis set included all participants who received at least 1 dose of study medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cycle 0: HSP-130 3mg | Number of Participants With Laboratory Abnormalities | 6 Participants |
| Cycles 0: HSP-130 6mg | Number of Participants With Laboratory Abnormalities | 6 Participants |
| Cycles 1-4: HSP-130 6mg | Number of Participants With Laboratory Abnormalities | 13 Participants |
Other Pre-specified
Number of Participants With Positive Anti-pegfilgrastim (Anti-drug) Antibodies
Time frame: Baseline up to approximately Day 94
Population: Safety analysis set included all participants who received at least 1 dose of study medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cycle 0: HSP-130 3mg | Number of Participants With Positive Anti-pegfilgrastim (Anti-drug) Antibodies | 0 Participants |
| Cycles 0: HSP-130 6mg | Number of Participants With Positive Anti-pegfilgrastim (Anti-drug) Antibodies | 0 Participants |
| Cycles 1-4: HSP-130 6mg | Number of Participants With Positive Anti-pegfilgrastim (Anti-drug) Antibodies | 0 Participants |
Other Pre-specified
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE was any untoward medical occurrence in participants who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment Emergent Adverse Event (TEAE) was adverse event that started or worsened in severity after the HSP-130 administration up to and including 30 days post HSP-130 administration (up to Day 94). AEs included both serious and non-serious.
Time frame: Baseline up to approximately Day 94
Population: Safety analysis set included all participants who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cycle 0: HSP-130 3mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 6 Participants |
| Cycle 0: HSP-130 3mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| Cycles 0: HSP-130 6mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 6 Participants |
| Cycles 0: HSP-130 6mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| Cycles 1-4: HSP-130 6mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 13 Participants |
| Cycles 1-4: HSP-130 6mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 2 Participants |
Other Pre-specified
Number of Participants With Treatment-Emergent Adverse Events (AEs) of Special Interest
AEs of Special Interest (AESI) included Potential Allergic Reactions, Splenomegaly, Splenic Rupture, Acute Respiratory Distress Syndrome, Alveolar Hemorrhage, Hemoptysis, Leukocytosis, Thrombocytopenia, Capillary Leak Syndrome, Cytokine Release Syndrome, Cutaneous Vasculitis and Glomerulonephritis.
Time frame: Baseline up to approximately Day 94
Population: Safety analysis set included all participants who received at least 1 dose of study medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cycle 0: HSP-130 3mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) of Special Interest | 0 Participants |
| Cycles 0: HSP-130 6mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) of Special Interest | 2 Participants |
| Cycles 1-4: HSP-130 6mg | Number of Participants With Treatment-Emergent Adverse Events (AEs) of Special Interest | 2 Participants |