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

Study Overview

• Status: Completed
• Conditions: Muscle Weakness; Sarcopenia; Gait Disorders in Old Age
• Intervention / Treatment: Drug: Placebo; Drug: BIO101

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 233
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Bruxelles, Belgium, 1090
    • Vrije Universiteit Brussel
  • Leuven, Belgium, 3000
    • Universitaire Ziekenhuizen (UZ) Leuven - Gasthuisberg - Centrum voor metabole botziekten
  • Liège, Belgium, 4020
    • Université de Liège
• United States
  • California
    • Banning, California, United States, 92221
      • Advanced Clinical Research
    • Garden Grove, California, United States, 92844
      • SC Clinical Research, Inc
    • San Diego, California, United States, 92123
      • California Research Foundation
  • Florida
    • Gainesville, Florida, United States, 32611
      • Institut On Aging
    • Jacksonville, Florida, United States, 32209
      • Jax-Ascent University of Florida
    • Miami Lakes, Florida, United States, 33014
      • Panax Clinical Research
    • Plant City, Florida, United States, 33563
      • Clinical Research of Central Florida
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70808
      • Pennington Biomedical Research Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Jean Mayer USDA Human Nutrition research Center on Aging Tufts University
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
      • New Mexico Clinical Research & Osteoporosis Center
  • New York
    • New York, New York, United States, 10032
      • Columbia University
  • North Carolina
    • Wilmington, North Carolina, United States, 28401
      • PMJ Research of Wilmington
    • Winston-Salem, North Carolina, United States, 27101
      • Bowman Gray Center for Medical Education-of- Wake Forest School of Medicine
  • Oklahoma
    • Yukon, Oklahoma, United States, 73099
      • Tekton Research
  • Texas
    • Austin, Texas, United States, 78745
      • Tekton Research
    • Houston, Texas, United States, 77030
      • Medical Center
    • San Antonio, Texas, United States, 78229
      • Science Advancing Medicine Clinical Research Center
    • San Antonio, Texas, United States, 78245
      • The University of Texas Health Science Center at San Antonio
  • Utah
    • West Jordan, Utah, United States, 84088
      • Advanced Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: No

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo was taken orally, two capsules twice daily (BID), 12 hours apart, up to 9 months.	Drug: Placebo; Oral capsules
Experimental: 175mg BIO101; BIO101 was taken orally, two capsules BID, 12 hours apart, up to 9 months.	Drug: BIO101; Oral capsules; Other Names: 20 hydroxyecdysone (20E)
Experimental: 350mg BIO101; BIO101 was taken orally, two capsules BID, 12 hours apart, up to 9 months.	Drug: BIO101; Oral capsules; Other Names: 20 hydroxyecdysone (20E)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to 6 Months in Gait Speed for 400 Meter Walking (MW) Test	Gait speed was measured using the 400 MW test, which measured how long it took the participant to walk a distance of 400 meters. Missing data imputed using adjusted Bayesian Multiple Imputation (MI) methods for Non-Completers who failed to perform the Test feasibility and Multiple Imputation for participants who without data on on-Site visit. Data up to 9 months was used where 6 months data were unavailable for participants enrolled during the COVID-19 pandemic.	Baseline and 6 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to 6 Months in Short Form-36 (SF-36) 10 Item Physical Function Domain (PF-10) Sub-score	The Physical Function Domain (PF-10) of the SF-36 assesses an individual's perceived physical functioning and limitations in various activities. It consists of ten items that ask about a person's ability to perform different physical activities and tasks. Scores on the PF-10 range from 0 to 100 where 100 indicates no physical limitations. Missing data imputed using adjusted Bayesian MI methods. Data up to 9 month was used where 6 month data were unavailable for participants enrolled during the COVID-19 pandemic.	Baseline and 6 Months
Change From Baseline to 6 Months in Handgrip Strength Test	Handgrip strength was a commonly used measure of upper body skeletal muscle function and had been widely used as a general indicator of frailty with predictive validity for both mortality and functional limitations. Participants were instructed to stand upright and with the dynamometer beside them but not against their body. Strength was measured three times for both hands. The highest value of all 3 attempts was kept for further analysis. Grip strength was measured in the dominant hand using a hydraulic grip strength dynamometer. Data up to month 9 was used where 6 month data were unavailable for participants enrolled during the COVID-19 pandemic.	Baseline and 6 Months
Change From Baseline to 6 Months in Appendicular Lean Body Mass (ALM) Based on Dual-energy X-ray Absorptiometry (DEXA) Measurements	DEXA scans provided accurate measurements of body composition, recording fat and lean mass distribution throughout the entire body. Foundation of National Health Institute (FNIH) project report recommended ALM alone was used to measure gender-specific low muscle mass. Data up to month 9 was used where 6 month data were unavailable for participants enrolled during the COVID-19 pandemic.	Baseline and 6 Months
Rate of Response for Completing 400 MW Test After 6 Months	A responder was defined as an improvement (increase) of 0.1 m/s or more in 400MW gait speed test compared to baseline. A non-responder was defined as a participant that was not a responder. Participants with a missing value at the visit and/or missing baseline value were considered as non-responders. Data up to month 9 was used where 6 month data were unavailable for participants enrolled during the COVID-19 pandemic.	Baseline and 6 Months
Change From Baseline to 6 Months in Muscle Strength Based on Knee Extension	Isometric knee extension torque was measured with a knee extension dynamometer chair. The participants were positioned in an upright position, with straps to affix the hips to the chair and the ankle to a force or torque transducer at the knee angle of 90°. Lever arm length was recorded as the distance between the knee axis of rotation and the middle of the pad. Knee extension was measured using the maximum peak torque measurement Newton meter (Nm) for 60°/s, 90°/s and 180°/s for the tested leg (either right or left). The Knee extension torque was obtained either directly or by multiplying recorded peak force with the lever arm length. The assay with the highest torque output was taken for analyses. Data up to month 9 was used where 6 month data were unavailable for participants enrolled during the COVID-19 pandemic.	Baseline and 6 Months
Change From Baseline to 6 Months in Time for Five Chair Stands as Part of the Short Physical Performance Battery (SPPB) Assessment	The SPPB was a series of tests designed to examine physical movements. The chair stands tests involved standing from a chair a number of times to test leg strength. Each performance measures were assigned a score ranging from 0 to 4, with 4 indicating the highest level of performance and 0 the inability to complete the test. The time to complete the task was recorded. The time required to perform five chair stands was scored as follows: ≥ 16.70 sec = 1; 13.70 to 16.69 sec = 2; 11.20 to 13.69 sec = 3; ≤ 11.19 = 4. A score of 0 was assigned to participants unable to perform the task. A summary score ranging from 0 (worst performers) to 12 (best performers) was calculated by adding sub scores from the chair stands test. Data up to month 9 was used where 6 month data were unavailable for participants enrolled during the COVID-19 pandemic.	Baseline and 6 Months
Change From Baseline to 6 Months in Distance in the 6-Minute Walk Test (6MWT)	The 6MWT was a test for functional exercise capacity and involved measuring the distance a participant could cover within the allotted time of 6 minutes. Data up to month 9 was used where 6 month data were unavailable for participants enrolled during the COVID-19 pandemic.	Baseline and 6 Months
Change From Baseline to 6 Months in Pepper Assessment Tool for Disability (PAT-D) for Obese Participants	The PAT-D was a disability questionnaire which asked respondents how much difficulty they had with a range of activities with functioning. PAT-D scores range from 1 (worst) to 5 (best). Data up to month 9 was used where 6 month data were unavailable for participants enrolled during the COVID-19 pandemic.	Baseline and 6 Months
Change From Baseline to 6 Months in SPPB Total Score	The SPPB was a series of tests designed to examine physical movements. Results of the SPPB included total gait speed score, total balance test score, and total chair stand score. The first tests examined balance (without the assistance of a cane or walker) with the feet in three different orientations, the second test examined gait speed, and the third tests involved standing from a Chair a number of times to test leg strength. A score of 0 was assigned to participants unable to perform the task. A summary score ranging from 0 (worst performers) to 12 (best performers) was calculated by adding sub scores from the walking speed, chair stands and balance tests. Data up to month 9 was used where 6 month data were unavailable for participants enrolled during the COVID-19 pandemic.	Baseline and 6 Months
Change From Baseline to 6 Months in Sarcopenia Quality of Life (SarQoL) Auto-Evaluation Questionnaire	The SarQoL was a sarcopenia-specific, self-administered, quality of life questionnaire designed for community-dwelling elderly study participants aged 65 years and older. The questionnaire contained 22 questions, which took approximately 10 minutes to complete. The questionnaire covered 7 domains: physical and mental health; locomotion; body composition; functionality; activities of daily living; leisure activities; and fears. Most questions are answered on a 4 point Likert scale. The total scoring of the SarQoL questionnaire ranges from 0 (worst imaginable health) to 100 (best imaginable health). A higher score reflected a higher quality of life. Data up to month 9 was used where 6 month data were unavailable for participants enrolled during the COVID-19 pandemic.	Baseline and 6 Months
Change From Baseline to 6 Months in Stair Climb Power Test (SCPT)	The SCPT measured the ability to ascend and descend stairs and tests lower body strength and balance and measures time (in seconds) taken to ascend and descend a flight of stairs (10 steps with a 20 cm step height; a handrail was recommended). Step heights should have been suitable (between 16 and 20 cm). Data up to month 9 was used where 6 month data were unavailable for participants enrolled during the COVID-19 pandemic.	Baseline and 6 Months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biomarkers	Biomarkers specific to Sarcopenia, to the Renin Angiotensin System	Change from Baseline Biomarkers to measurement at 6 months
Actimetry	The continuous physical activity of the volunteers will be recorded using a specific device during the 6-month study period.	Change from actimetry at Month 0 to measurement at 6 months

Collaborators and Investigators

• Sponsor: Biophytis
• Investigators: Study Director: Rob Van Maanen, Biophytis

Study record dates

Study Major Dates

• Study Start (Actual): February 7, 2017
• Primary Completion (Actual): April 26, 2020
• Study Completion (Actual): April 26, 2020

Study Registration Dates

• First Submitted: February 13, 2018
• First Submitted That Met QC Criteria: February 26, 2018
• First Posted (Actual): March 2, 2018

Study Record Updates

• Last Update Posted (Actual): October 1, 2024
• Last Update Submitted That Met QC Criteria: September 5, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: Sarcopenia; Short Physical Performance Battery; Sarcopenic Obesity; 6-minute walking distance; 400 meters walking test; BIO101; Appendicular lean mass
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Manifestations; Pathological Conditions, Anatomical; Muscular Atrophy; Atrophy; Muscle Weakness; Sarcopenia
• Other Study ID Numbers: BIO101-CL03

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No