Study of Subcutaneously Administered Peginesatide in Anemic Cancer Patients Receiving Chemotherapy

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety, pharmacodynamics (PD), and pharmacokinetics (PK) of multiple subcutaneously administered injections of peginesatide in anemic cancer participants receiving chemotherapy.

Detailed Description
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This was a Phase 2, open-label, multi-center, sequential dose finding study with up to 6 treatment cohorts receiving chemotherapy with 15 participants per cohort. The primary objective of this study was to determine the dose of peginesatide administered every 3 weeks (Q3W) by subcutaneous injection associated with a hemoglobin increase of ≥ 1 g/dL in ≥ 50% of anemic cancer participants receiving chemotherapy at 9 weeks following the first dose.

Official Title
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A Phase 2, Open-Label, Multi-Center Dose Escalation Study of the Safety, Pharmacodynamics, and Pharmacokinetics of Subcutaneously Administered Peginesatide in Anemic Cancer Patients Receiving Chemotherapy

Conditions
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Chemotherapy Induced Anemia, Cancer

Intervention / Treatment
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* Drug: peginesatide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant is informed of the investigational nature of this study and has given written, witnessed informed consent in accordance with institutional, local, and national guidelines Males or females ≥ 18 and ≤ 80 years of age; pre-menopausal females (with the exception of those who are surgically sterile) must have a negative pregnancy test at screening; those who are sexually active must practice a highly effective method of birth control for at least 2 weeks prior to study start, and must be willing to continue practicing birth control for at least 4 weeks after the last dose of study drug. A highly effective method of birth control is defined as one that results in a low failure rate (i.e., less than 1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, some IUDs, sexual abstinence (only acceptable if practiced as a life-style and not acceptable if one who is sexually active practices abstinence only for the duration of study) or vasectomized partner Participants with histologically confirmed solid tumor malignancy or lymphoma who are scheduled to receive at least 9 weeks of cyclic myelosuppressive chemotherapy while on study Hemoglobin value of ≥ 8 and < 11 g/dL within 1 week prior to administration of study drug. ECOG Performance Status of 0-2 One reticulocyte hemoglobin content (CHr) > 29 picograms within 4 weeks prior to study drug administration. One transferrin saturation ≥ 15% within 4 weeks prior to study drug administration. One serum or red cell folate level above the lower limit of normal within 4 weeks prior to study drug administration One vitamin B12 level above the lower limit of normal within 4 weeks prior to study drug administration One absolute neutrophil count ≥ 1.0 x 10^9/L within 1 week prior to administration of study drug One platelet count ≥ 75 x 10^9/L within 1 week prior to administration of study drug Life expectancy > 6 months. Exclusion Criteria: Treatment with any erythropoiesis stimulating agent (ESA) in the past 90 days History of failure to respond to ESA treatment Known antibodies to other ESAs or history of pure red cell aplasia (PRCA) Acute or chronic leukemia, myelodysplastic syndrome (MDS), or multiple myeloma Any previous or planned radiotherapy to more than 50% of either the pelvis or spine Known intolerance to parenteral iron supplementation Red blood cell transfusion within 4 weeks prior to study drug administration Known hemoglobinopathy (e.g., homozygous sickle-cell disease, thalassemia of all types, etc.) Known hemolysis History of pulmonary embolism or deep venous thrombosis (DVT) in the previous 2 years or current therapeutic doses of anticoagulants Known blood loss as a cause of anemia Uncontrolled, or symptomatic inflammatory disease (e.g., rheumatoid arthritis, systemic lupus erythematosus, etc.) Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 times the upper limit of normal; AST or ALT > 5 times the upper limit of normal if liver metastases are present. Creatinine > 175 micromoles per liter (µmol/L) History of bone marrow or peripheral blood cell transplantation Pyrexia/fever of ≥ 39 °C within 48 hours prior to study drug administration Poorly controlled hypertension, per the Investigator's judgment, within 4 weeks prior to study drug administration (e.g., systolic ≥ 170 mm Hg or diastolic ≥ 100 mm Hg on repeat readings) Epileptic seizure in the 6 months prior to study drug administration Advanced chronic congestive heart failure - New York Heart Association Class IV High likelihood of early withdrawal or interruption of the study Anticipated elective surgery during the study period History of multiple drug allergies Exposure to any investigational agent within 1 month prior to administration of study drug or planned receipt during the study period.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Peginesatide starting dose of 0.1 milligram per kilogram (mg/kg) administered subcutaneously (SC) once every 3 weeks (Q3W) for a total of 4 doses. | Drug: peginesatide<br> <br> * Other names: AF37702 Injection;|
| Experimental: Cohort 2<br>Peginesatide starting dose of 0.15 mg/kg administered SC Q3W for a total of 4 doses. | Drug: peginesatide<br> <br> * Other names: AF37702 Injection;|
| Experimental: Cohort 3<br>Peginesatide starting dose of 0.2 mg/kg administered SC Q3W for a total of 4 doses. | Drug: peginesatide<br> <br> * Other names: AF37702 Injection;|
| Experimental: Cohort 4<br>Peginesatide starting dose of 0.05 mg/kg administered SC Q3W for a total of 4 doses. | Drug: peginesatide<br> <br> * Other names: AF37702 Injection;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants with a hemoglobin increase of ≥ 1 gram per deciliter (g/dL) at 9 weeks following Dose 1 |  | Week 9 post Dose 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events and serious adverse events |  | 13 Weeks | 
| Time to achieve hemoglobin increase ≥ 1 g/dL from baseline |  | Baseline to Week 13 | 
| Proportion of participants with a hemoglobin response |  | 13 Weeks | 
| Pharmacokinetic parameters |  | 13 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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anemia, EPO, CIA, cancer, chemotherapy, chemotherapy induced anemia, hemoglobin, Hb, Hgb, erythropoietin, erythropoiesis stimulating agent, ESA, Hematide, Omontys, peginesatide, red blood cell, red blood cell production