Study to Evaluate Efficacy and Safety of BGE-117 in the Treatment of Anemia of Aging

Study Overview
=================
Brief Summary
-----------------
The primary objectives of this study to evaluate the safety, tolerability and efficacy of BGE-117 in the treatment of anemia of aging in participants ≥ 65 years of age.

Detailed Description
-----------------
This is a randomized, placebo-controlled, multicenter, double- blind study of BGE-117 administered PO in participants ≥ 65 years of age for the treatment of anemia of aging. Anemia of aging accounts for approximately one-third of anemia in patients over 65 years of age, defined as a suboptimal hemoglobin level due to different underlying characteristics. This study's planned size is 160 evaluable subjects (80 subjects randomized to BGE-117 and 80 subjects randomized to placebo). After signing informed consent, participants may be Pre-screened for hemoglobin using HemoCue, and subsequently will be screened for study eligibility. Screening will include full physical examination, vital signs, safety and study-related laboratory evaluation, ophthalmic exam, ECG, Wells score for DVT, and clinical outcome assessment. If confirmed that the participant qualifies for this protocol according to listed inclusion and exclusion criteria, participants will be randomized to BGE-117 or placebo, PO, once per day, for a treatment period duration of approximately 12 weeks. Dose adjustments for study medication during the treatment period are made according to a dosing algorithm to achieve and maintain hemoglobin (Hb) within the target range (12.5-13.0 g/dL). Study procedures and assessments are performed at various timepoints during the treatment period per the schedule outlined in the study protocol. Participants will undergo follow-up assessments for approximately 4 weeks after administration of the last dose.

Official Title
-----------------
A Phase 2a, 12-Week, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate Efficacy and Safety of BGE-117 in the Treatment of Anemia of Aging

Conditions
-----------------
Anemia

Intervention / Treatment
-----------------
* Drug: BGE-117
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Ability to voluntarily provide written, signed, and dated informed consent to participate in the study An understanding, ability, and willingness to fully comply with study procedures and restrictions Is 65 years of age or older at the time of Screening (Visit 1) Anemia of Aging defined as a hemoglobin level in the range of ≥ 9.0 g/dL to ≤ 11.5 g/dL (≥ 90 g/L to ≤ 115 g/L) as determined by central laboratory measurement. (Note: For subjects with newly diagnosed anemia, appropriate investigations for the cause of the anemia should be completed according to standard-of-care under the direction of the subject's primary care physician. Weight at Screening (Visit 1) is ≥ 40.0 kg Exclusion Criteria: 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 previous12 months or radiation treatment for prostate cancer Thyroid-stimulating hormone (TSH) <0.1 mIU/L or >10.0 mIU/L Folic acid and Vitamin B12 levels less than the lower limit of normal range eGFR as measured by Modification of Diet in Renal Disease (MDRD) <30.0 mL/m/1.73 m2 Myocardial infarction, acute coronary syndrome, stroke, transient ischemic attack, or pro thrombotic arrhythmia or condition (e.g., untreated atrial fibrillation) within 6 months before Screening or during the Screening (Visit 1). Cancer diagnosis with active or uncertain disease (i.e. active malignancy), or are receiving active treatment within 12 weeks before Screening (Visit 1) (squamous cell or basal cell carcinoma of the skin are excluded from this criterion) Suspected or history of hematologic malignancy. Remote or childhood hematologic malignancies may be permitted as judged by the investigator. Age-related clonal changes in hematopoiesis (e.g., clonal hematopoiesis of indeterminate potential (CHIP), clonal cytopenia of undetermined significance (CCUS)) are permitted as judged by the investigator. Intravenous (IV) iron within 12 weeks before Screening (Visit 1) or during the Screening Period or Treatment Period. Rescue therapy with IV iron is permitted during the Follow-up Period if the subject's hemoglobin is below their baseline level. Note: oral iron supplementation is permitted. The subject must have started treatment with oral iron supplements at least 4 weeks before Screening. The same dose and dosing regimen should be maintained throughout the Screening Period and Treatment Period. Erythropoieisis-stimulating agent (ESA) treatment within 12 weeks before Screening (Visit 1) or during the Screening Period or Treatment Period. Rescue therapy with ESA is permitted during the Follow-up Period if the subject's hemoglobin level is below baseline. History of uncontrolled hypertension including: Difficult-to-control hypertension (unless approved by the investigator and the Medical Monitor) Malignant hypertension (unless approved by the investigator and the Medical Monitor) Systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 95 mmHg (confirmed by repeated measurement) within 2 weeks before randomization. Note: Subjects being treated for hypertension should have been on a stable medication and dosing regimen for at least 8 weeks before randomization Subjects may be rescreened after their blood pressure is controlled Evidence of gastrointestinal bleeding within 12 weeks before Screening (Visit 1), as judged by the investigator Blood or plasma donation within 8 weeks before Screening (Visit 1) or at any time during the study period. Class III 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 Note: This evaluation will be done only at Screening (Visit 1); ECG and corresponding intervals and overall interpretation can be mechanically or manually read by an appropriately designated and trained personnel. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≥ 3 × the upper limit of normal (ULN) Bilirubin > 1.5 × ULN (isolated bilirubin > 1.5 × ULN is acceptable if bilirubin is fractionated and direct bilirubin is < 35%) Note: Bilirubin increases associated with Gilbert's syndrome are permitted. A reported average intake of alcohol of ≥ 80 g/day (i.e., equivalent of 6 cans of beer or 5 shots of hard liquor) Increase in hemoglobin level to the target range (12.5-13.0 g/dL) would pose an unacceptable medical risk to the subject, as judged by the investigator History of severe allergic or anaphylactic reactions or hypersensitivity to excipients in the investigational product Use of another investigational agent within 30 days or 5 half-lives of the investigational agent; whichever is longer Prior randomization in the current study (BGE-117-201) 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. This includes: Current, unstable active liver or biliary disease (generally defined by the onset of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal/gastric varices, persistent jaundice, or cirrhosis) Note: Stable liver disease (including asymptomatic gallstones, asymptomatic chronic hepatitis B, chronic hepatitis C, or Gilbert's syndrome) is acceptable if the subject otherwise meets entry criteria and the investigator and Sponsor approve entry into the study. Current or relevant history of a medical condition that may require inpatient treatment or make the subject unlikely to complete the study Unable or unwilling to adhere to the contraception requirements specified in the protocol

Ages Eligible for Study
-----------------
Minimum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BGE-117<br>BGE-117 Capsules (4mg or 12mg) to be taken by mouth once a day for 84 days. | Drug: BGE-117<br>* Active Treatment<br>|
| Placebo Comparator: Placebo<br>Placebo Capsules to be taken by mouth once a day for 84 days. | Other: Placebo<br>* Placebo<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hemoglobin | Change in Hemoglobin compared to baseline | Day 85 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-Fatigue) Score | Improvement in FACIT-Fatigue Score compared to baseline. The FACIT-Fatigue assessment is a 13-item questionnaire that assesses self-reported fatigue and its impact on daily activities and function. The scale is scored from 0 (Not at all) to 4 (Very Much). A lower score is considered improvement and a better outcome. | Day 29, 57, 85 and Follow-up (up to 120 days) | 
| Hemoglobin | Change in Hemoglobin compared to baseline | Day 29, 57, and Follow-up (up to 120 days) | 
| Short Physical Performance Battery (SPPB) Score | Change in SPPB Score compared to baseline. The SPPB assessment consists of a Balance Test, a Gait Speed Test, and a Chair Stand Test. Each of the three tests is scored from 0 to 4 points with a composite score from 0 to 12 points. A higher score is considered a better outcome. | Day 29, 57, 85, and Follow-up (up to 120 days) | 
| 6-minute Walk Test (6MWT) Distance | Change in 6MWT Distance compared to baseline. Increased distance is considered a better outcome. | Day 29, 57, 85, and Follow-up (up to 120 days) | 
| 36-Item Short Form Survey Instrument (SF-36) | Change in SF-36 compared to baseline. The SF-36 is a general health status questionnaire to assess patient perception of health in several domains, including physical functioning, role physical, bodily pain, vitality, social functioning, role emotional, mental health, and general health over the past 7 days. Each of the categories is scored from 0 to 100. A higher score is considered a better outcome. | Day 29, 57, 85, and Follow-up (Up to 120 days) | 
| BGE-117 Starting Dose Evaluation | Evaluate the starting dose of BGE-117 in the treatment of anemia of aging for subjects with eGFR ≥ 60 mL/min/1.73 m2 and subjects with eGFR ≥ 30 and < 60 mL/min/ 1.73 m2 | First dose to Day 85 | 
| Grip Strength | Evaluate the change in grip strength measures using the Jamar Hand Dynamometer grip strength test. | Day 29, 57, 85, and Follow-up (Up to 120 days) | 
| Clinical Global Impression (CGI) Measures | Change in CGI measures compared to baseline. The CGI is a questionnaire-based instrument to assess subjects' progress and treatment response over time. The study will collect the CGI-Change of Condition to measure change in energy level and CGI-Therapeutic Efficacy to assess perceived therapeutic efficacy of treatment. A lower score is considered a better outcome. | Day 29, 57, 85, and Follow-up (Up to 120 days) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
BGE-117, Anemia, BioAge