A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study Investigating the Efficacy and Safety of BGE-117 in Moderately to Severely Anemic Older Individuals After Major Hip Surgery
Trial Snapshot
- Phase
- Phase 2
- Status
- Withdrawn
- Sponsor
- BioAge Labs, Inc.
- Locations
- 1
- Primary Endpoint
- Time to 2.0 g/dL Increase in Hemoglobin Level
Study Overview
Brief Summary
The purpose of this study is to explore the safety and tolerability of BGE-117 and gain information on the effectiveness of different doses when given to patients 65 years or older with moderate to severe anemia following major hip surgery. BGE-117 is given once daily in a capsule by mouth for up to 12 weeks. Patients are also given oral iron supplements. Anemia following surgery has been associated with decreases in patient functioning. This study will measure improvement of anemia, as well as various patient functioning.
Detailed Description
BGE-117 is being investigated to determine whether it is an effective treatment for moderate to severe anemia in older individuals (65 years of age or older) after major hip surgery. Currently, there are limited treatment options for postoperative anemia, in this patient population, available in the USA, Australia, or New Zealand. The increased risk of morbidity, mortality, and poor quality of life in the population of older individuals with postoperative anemia highlights the unmet medical need for a therapeutic agent that can alleviate physical and functional deficits in these patients. Study BGE-117-203 will be the first clinical study conducted in older patients with postoperative anemia. The study will collect important safety, efficacy, and dosing information across this population of patients to provide key data for designing further clinical studies in the development programs for BGE-117.
The study will enroll 2 populations of patients requiring hip surgery:
- older individuals who are scheduled for elective unilateral or bilateral hip surgery (total or partial hip replacement or revision of a previous replacement)
- older individuals with an acute hip fracture requiring surgical repair or replacement (usually performed within 48 hours after the fracture event)
These individuals must also meet the inclusion criterion for a hemoglobin level of ≤ 10 g/dL and ≥ 7.0 g/dL from postoperative Day 1 to postoperative Day 7.
The total planned enrollment for the study is approximately 192 subjects. The first 96 subjects who are enrolled will be randomized in a 1:2:1 ratio to 1 of 3 treatment groups:
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 65 Years to — (Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Alert and able to voluntarily provide written, signed, and dated informed consent
- •≥ 65 years of age at the time of completing informed consent
- •Major hip surgery, that has occurred within the previous 7 days or is scheduled to occur within the next 7 days, defined as:
- •Unilateral or bilateral total or partial hip arthroplasty or revision OR
- •Hip fracture repair surgery scheduled or performed within 48 hours after hospital admission (either fracture repair or total or partial hip replacement)
- •Postoperative anemia defined as a hemoglobin level ≤ 10.0 g/dL and ≥ 7.0 g/dL from postoperative Day 1 to postoperative Day 7
- •For hip fracture subjects only: score between 1 and 5 on the Clinical Frailty Scale (CFS) at baseline before fracture
- •Estimated glomerular filtration rate (eGFR) of ≥ 60 mL/min/m2 as measured by the Modification of Diet in Renal Disease (MDRD) method
- •Current or planned perioperative use of mechanical or chemical antithrombotic prophylaxis in accordance with local standard of care
Exclusion Criteria
- •Any current unstable medical condition that the investigator considers would put the subject at unacceptable risk, affect study compliance, or prevent the understanding of the study's objectives or investigational procedures or possible consequences; for example, increased risk of falls that is judged to be clinically significant, clinically significant autonomic dysfunction, active infections requiring antimicrobial treatment
- •History of thromboembolic disease in the previous 6 months
- •Other medically significant injuries (e.g., head injuries, internal bleeding, or other as judged by the study investigator) that occur concurrently with hip fractures that complicate endpoint assessments, subject safety, and/or study conduct
- •History of seizures within the previous 2 years
- •History of coagulation disorder (e.g., Factor V Leiden, idiopathic thrombocytopenic purpura) or use of concomitant medications that increase the risk of thromboembolic events (TEEs) as judged by the study investigator
- •Class III or IV heart failure, as defined by the New York Heart Association (NYHA) functional classification system
- •QTcF > 500 msec or QTcF > 530 msec in subjects with bundle branch block. A triplicate electrocardiogram (ECG) should be performed if the initial ECG indicates prolonged QTc interval using the automated or manually calculated QTcF value.
- •Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels ≥ 3 × the upper limit of normal (ULN) (Historical standard-of-care laboratory results may be used to confirm eligibility if collected within 14 days before informed consent)
- •Bilirubin level > 1.5 × ULN (isolated bilirubin level > 1.5 × ULN is acceptable if bilirubin is fractionated and direct bilirubin is < 35%) (Historical standard of care laboratory results may be used to confirm eligibility if collected within 14 days before informed consent)
- •Recent or planned administration of an erythropoietin stimulating agent (ESA) or a HIF-PHI within 12 weeks of informed consent
- •History of malignant hypertension or current uncontrolled hypertension (average systolic blood pressure ≥ 160 mmHg and/or average diastolic blood pressure ≥ 100 mmHg based on 3 readings). Blood pressure should be measured after 5 minutes of unattended rest, with 2 repeated readings 1 to 2 minutes apart
- •History of diabetic retinopathy
- •History or diagnosis of any of the following:
- •Anemia due to pernicious anemia, thalassemia, sickle cell anemia, sickle trait, or myelodysplastic syndromes
- •Bone-marrow hypoplasia or pure red cell aplasia
- •Androgen deprivation therapy within the previous 12 months or radiation treatment for prostate cancer
- •Myocardial infarction, acute coronary syndrome, stroke, transient ischemic attack, or prothrombotic arrhythmia or condition (e.g., untreated/uncontrolled atrial fibrillation) within 6 months before informed consent or during the Screening Period
- •Active malignancy and/or receiving anti cancer treatment within 12 weeks of informed consent (squamous cell or basal cell carcinoma of the skin are excluded from this criterion). Subjects who have planned initiation of cancer therapies during the study period (such as, but not limited to, chemotherapy, radiotherapy) are excluded.
- •Planned intravenous (IV) iron therapy scheduled to start after informed consent and to continue during the expected time of participation in the study
- •Presence of acute kidney injury (AKI) based upon the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines:
- •Increase in serum creatinine by ≥ 0.3 mg/dL (≥ 26.5 µmol/L) within 48 hours, or
- •Increase in serum creatinine to ≥ 1.5 times the value at baseline, which is known or presumed to have occurred within the previous 7 days
- •Chronic bleeding condition such as active gastrointestinal (GI) bleeding
- •Inability or unwillingness to adhere to protocol specified visits, procedures, and contraception requirements
- •Receipt of an investigational drug or device within 30 days before informed consent
- •Previously screened for or enrolled in the BGE-117-203 study
- •Known allergy to or intolerance of BGE-117, or other components of the IP (BGE-117 or matching placebo)
- •Known allergy to ferrous sulfate preparations
Arms & Interventions
BGE-117 4mg
BGE-117 4mg, Capsules, Oral-administered Once Per Day up to 12 weeks Ferrous sulfate 325mg, Tablets, Oral-administered 3 Times Per Week up to 12 weeks
Intervention: BGE-117, 4mg (Drug)
BGE-117 4mg
BGE-117 4mg, Capsules, Oral-administered Once Per Day up to 12 weeks Ferrous sulfate 325mg, Tablets, Oral-administered 3 Times Per Week up to 12 weeks
Intervention: Ferrous Sulfate (Dietary Supplement)
BGE-117 8mg
BGE-117 8mg, Capsules, Oral-administered Once Per Day up to 12 weeks Ferrous sulfate 325mg, Tablets, Oral-administered 3 Times Per Week up to 12 weeks
Intervention: BGE-117, 4mg (Drug)
BGE-117 8mg
BGE-117 8mg, Capsules, Oral-administered Once Per Day up to 12 weeks Ferrous sulfate 325mg, Tablets, Oral-administered 3 Times Per Week up to 12 weeks
Intervention: Ferrous Sulfate (Dietary Supplement)
BGE-117 16mg
BGE-117 16mg, Capsules, Oral-administered Once Per Day up to 12 weeks Ferrous sulfate 325mg, Tablets, Oral-administered 3 Times Per Week up to 12 weeks
Intervention: BGE-117, 4mg (Drug)
BGE-117 16mg
BGE-117 16mg, Capsules, Oral-administered Once Per Day up to 12 weeks Ferrous sulfate 325mg, Tablets, Oral-administered 3 Times Per Week up to 12 weeks
Intervention: Ferrous Sulfate (Dietary Supplement)
BGE-117 16mg
BGE-117 16mg, Capsules, Oral-administered Once Per Day up to 12 weeks Ferrous sulfate 325mg, Tablets, Oral-administered 3 Times Per Week up to 12 weeks
Intervention: BGE-117, 12mg (Drug)
Placebo
Matching Placebo Capsules, Oral-administered Once Per Day up to 12 weeks Ferrous sulfate 325mg, Tablets, Oral-administered 3 Times Per Week up to 12 weeks
Intervention: Ferrous Sulfate (Dietary Supplement)
Placebo
Matching Placebo Capsules, Oral-administered Once Per Day up to 12 weeks Ferrous sulfate 325mg, Tablets, Oral-administered 3 Times Per Week up to 12 weeks
Intervention: Matching Placebo (Other)
Outcomes
Primary Outcomes
Time to 2.0 g/dL Increase in Hemoglobin Level
Time Frame: Up to Day 85
The time to a 2.0 g/dL increase in hemoglobin level over the postoperative baseline hemoglobin level. The primary comparison is the high-dose group compared to placebo. Note: Baseline hemoglobin level is the postoperative hemoglobin level most recently obtained before the start of investigational product administration.
Secondary Outcomes
- Hemoglobin Response as a Function of Clinical Outcome Assessment(Up to Day 85)
- Time to 3.0 g/dL Increase in Hemoglobin Level(Up to Day 85)
- Hemoglobin Level Return to Baseline for Elective Hip Replacement(Day 8, 15, 22, 29, 36, 43, 57, and 85)
- Change in Ambulation Status(First Dose to Day 85 and Follow-up (Up to Day 183))
- Mean Dose at End of Study(Day 85)
- Disposition after Hospital Discharge(Up to Day 85)
- Hemoglobin Response as a Function of Iron Status and Hepcidin(Up to Day 85)
- Hemoglobin Level from Nadir Hemoglobin(Day 8, 15, 22, 29, 36, 43, 57, and 85)
- Time to 1.0 g/dL Increase in Hemoglobin Level(Up to Day 85)
- 3.0 g/dL Improvement in Hemoglobin Level(Day 8, 15, 22, 29, 36, 43, 57, and 85)
- Analysis of Pharmacokinetic Parameters to Develop a Population Pharmacokinetic Model for BGE-117 (AUC(0-24)/Dose)(Day 1, 43, and 85)
- Analysis of Pharmacokinetic Parameters to Develop a Population Pharmacokinetic Model for BGE-117 (Clearance)(Day 1, 43, and 85)
- Analysis of Pharmacokinetic Parameters to Develop a Population Pharmacokinetic Model for BGE-117 (Half-Life)(Day 1, 43, and 85)
- Hemoglobin Level from Baseline(Day 8, 15, 22, 29, 36, 43, 57, and 85)
- 1.0 g/dL Improvement in Hemoglobin Level(Day 8, 15, 22, 29, 36, 43, 57, and 85)
- 2.0 g/dL Improvement in Hemoglobin Level(Day 8, 15, 22, 29, 36, 43, 57, and 85)
- All-Cause Mortality(First Dose to Day 85 and Follow-up (Up to Day 183))
- Hospital Readmission - Any Cause(First Dose to Day 85 and Follow-up (Up to Day 183))
- Hospital Readmission - Surgery-Related(First Dose to Day 85 and Follow-up (Up to Day 183))
- Surgical Complications(First Dose to Day 85 and Follow-up (Up to Day 183))
- Surgical Complications by Clavien-Dindo Classification(First Dose to Day 85 and Follow-up (Up to Day 183))
- Days Alive and At Home (DAH)(Day 60)
- Quality of Recovery-15 (QoR-15) Questionnaire(Day 8, 15, 22, and 29)
- Visual Analog Scale for Pain (VAS-Pain)(Up to Day 15)
- Subjects Requiring a Dose Decrease(Up to Day 85)
- European Quality of Life Five Day (EQ-5D-5L) Questionnaire(Day 15, 43, and 85)
- Timed Up and Go (TUG) Test(Day 15, 43, and 85)
- Safety Analyses (Treatment-Emergent Adverse Events) - Number of Events(First Dose to Day 85 and Follow-up (Up to Day 183))
- Safety Analyses (Adverse Events) - Individual Summary(First Dose to Day 85 and Follow-up (Up to Day 183))
- Analysis of Pharmacokinetic Parameters to Develop a Population Pharmacokinetic Model for BGE-117 (Volume of Distribution)(Day 1, 43, and 85)
- 6-minute Walk Test (6MWT) Distance(Day 15, 43, and 85)
- Safety Analyses (Treatment-Emergent Adverse Events) - Incidence(First Dose to Day 85 and Follow-up (Up to Day 183))
- Safety Analyses (Quantitative Safety Data) - Vital Signs(First Dose to Day 85 and Follow-up (Up to Day 183))
- Safety Analyses (Quantitative Safety Data) - Wells Score for DVT(First Dose to Day 85 and Follow-up (Up to Day 183))
- Safety Analyses (Quantitative Safety Data) - Electrocardiogram (ECG)(First Dose to Day 85 and Follow-up (Up to Day 183))
- World Health Organization Disability Assessment Schedule (WHODAS) Questionnaire(Day 29, 57, and 85)
- Safety Analyses (Treatment-Emergent Adverse Events) - Percentage(First Dose to Day 85 and Follow-up (Up to Day 183))
- Safety Analyses (Quantitative Safety Data) - Clinical Laboratory Tests(First Dose to Day 85 and Follow-up (Up to Day 183))