A Double-blind, Placebo-controlled, Randomized INTerventional Clinical Trial (SARA-INT)

Safety and Efficacy of BIO-101 175 mg b.i.d. and 350 mg b.i.d. 26-week Oral Administration to Patients Suffering From Age-related SARcopenia, Including Sarcopenic Obesity, Aged ≥65 Years and at Risk of Mobility Disability

The main objective of the study is to evaluate the effect of two daily doses of BIO101 versus placebo on mobility function as measured by gait speed using the 400MW test. The absolute change from baseline in meters/second observed in each treatment group at 6 Month was compared to the placebo group. Due to the Covid pandemic >50% of data at endpoint was missing, which may have affected the ability of the study to deliver the expected results. Additionally, although the planned duration of treatment was 6 months, it was extended up to 9 months for some participants as a result of the pandemic.

The aim of this phase 2 double-blind, placebo-controlled, randomized interventional clinical trial (SARA-INT) is to evaluate the safety and efficacy of BIO-101 175 mg b.i.d. and 350 mg b.i.d. 9 months oral administration to participants suffering from age-related sarcopenia, including sarcopenic obesity, aged ≥65 years and at risk of mobility disability. There are 3-arms (2 doses versus placebo). This comparative clinical trial evaluated the effects up to 9 month treatment duration, based on the hypothesis that physical function of sarcopenic, older participants with an initial degree of mobility disability (SPPB) may be improved by BIO101.

Included participants were randomized in a 1:1:1 ratio, to one of the 3 arms of treatment in a blinded manner. The randomization was stratified by gender and by center. Based on absence of long-term toxicology data, the investigational drug exposure was initially capped at 6 months.

Inclusion Criteria:

1. Provision of signed and dated informed consent form
2. Stated willingness to comply with all study procedures and availability for the duration of the study
3. Male or female, aged ≥ 65 years and living in the community, reporting loss of physical function over the last 6-12 months
4. Short Physical Performance Battery (SPPB) score ≤ 8
5. ALM/BMI < 0.789 in men and 0.512 in women, or ALM < 19.75kg in men and <15.02kg in women, as measured by DEXA scan
6. Ability to take oral medication and be willing to adhere to the study intervention regimen.
7. Agreement to adhere to Lifestyle Considerations throughout study duration
8. In the US, women and members of minority groups must be included in accordance with the NIH Policy on Inclusion of Women and Minorities as Participants In Research Involving Human participants.

Exclusion Criteria:

1. Current use of anabolic drugs (e.g. testosterone); current use of Erythropoietin; current use of corticosteroid agents (except local administration route, like eye drops or dermatologic formulations)

2. Non-menopaused women (however ongoing replacement hormonal treatment is not an exclusion criterion)

3. Known allergic reactions to components of the investigational drug.

4. Treatment with another investigational drug or other intervention within three months

5. Unable to understand and perform the functional tests, as judged by the Investigator

6. Inability to perform the 400MW test within 15 minutes

7. Clinical conditions:

   1. Current diagnosis of major psychiatric disorders.
   2. Alcohol abuse or dependence
   3. Severe arthritis
   4. Cancer requiring active treatment (cancer treated with chemotherapy, or radiotherapy and currently on remission is not an exclusion criterion)
   5. Lung disease requiring regular use of supplemental oxygen
   6. Inflammatory conditions requiring regular use of oral or parenteral corticosteroid agents
   7. Severe cardiovascular disease (including New York Heart Association [NYHA] class III or IV congestive heart failure, clinically significant valvular disease, history of cardiac arrest, presence of an implantable defibrillator, or uncontrolled angina)
   8. Parkinson's disease or other progressive neurological disorder
   9. Renal disease requiring dialysis, or known renal insufficiency (moderate or severe reduction in GFR≤30 ml/min/1.73 m2)
   10. Chest pain, severe shortness of breath, or occurrence of other safety concerns during the baseline functional tests 400-meter walk test or 6MWT
   11. History or active signs or symptoms of gallbladder/biliary disease (e.g. previous episodes of cholestasis/biliary tract obstruction, cholelithiasis, cholecystitis, etc.). Of note, history of cholecystectomy and no active biliary signs or symptoms, is not an exclusion criterion.

8. Current physical/rehabilitation therapy (except for passive physical therapy. However, this should not be initiated the week before an evaluation visit and once started, it should be maintained over the study duration).