Clinical trial NCT03452488: A Double-blind, Placebo-controlled, Randomized INTerventional Clinical Trial (SARA-INT)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Sarcopenia
Gait Disorders in Old Age
Muscle Weakness
Keywords: Sarcopenia
Sarcopenic Obesity
6-minute walking distance
400 meters walking test
BIO101
Short Physical Performance Battery
Appendicular lean mass
Lead sponsor: Biophytis
Sponsor class: INDUSTRY
First posted: 2018-03-02
Enrollment: 233
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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).

Primary outcomes:
measure: Change From Baseline to 6 Months in Gait Speed for 400 Meter Walking (MW) Test
timeFrame: Baseline and 6 Months
Secondary outcomes:
measure: Change From Baseline to 6 Months in Short Form-36 (SF-36) 10 Item Physical Function Domain (PF-10) Sub-score
timeFrame: Baseline and 6 Months
measure: Change From Baseline to 6 Months in Handgrip Strength Test
timeFrame: Baseline and 6 Months
measure: Change From Baseline to 6 Months in Appendicular Lean Body Mass (ALM) Based on Dual-energy X-ray Absorptiometry (DEXA) Measurements
timeFrame: Baseline and 6 Months
measure: Rate of Response for Completing 400 MW Test After 6 Months
timeFrame: Baseline and 6 Months
measure: Change From Baseline to 6 Months in Muscle Strength Based on Knee Extension
timeFrame: Baseline and 6 Months
measure: Change From Baseline to 6 Months in Time for Five Chair Stands as Part of the Short Physical Performance Battery (SPPB) Assessment
timeFrame: Baseline and 6 Months
measure: Change From Baseline to 6 Months in Distance in the 6-Minute Walk Test (6MWT)
timeFrame: Baseline and 6 Months
measure: Change From Baseline to 6 Months in Pepper Assessment Tool for Disability (PAT-D) for Obese Participants
timeFrame: Baseline and 6 Months
measure: Change From Baseline to 6 Months in SPPB Total Score
timeFrame: Baseline and 6 Months
measure: Change From Baseline to 6 Months in Sarcopenia Quality of Life (SarQoL) Auto-Evaluation Questionnaire
timeFrame: Baseline and 6 Months
measure: Change From Baseline to 6 Months in Stair Climb Power Test (SCPT)
timeFrame: Baseline and 6 Months
Other outcomes:
Locations:
city: Banning
country: United States
facility: Advanced Clinical Research
state: California
city: Garden Grove
country: United States
facility: SC Clinical Research, Inc
state: California
city: San Diego
country: United States
facility: California Research Foundation
state: California
city: Gainesville
country: United States
facility: Institut On Aging
state: Florida
city: Jacksonville
country: United States
facility: Jax-Ascent University of Florida
state: Florida
city: Miami Lakes
country: United States
facility: PANAX Clinical Research
state: Florida
city: Plant City
country: United States
facility: Clinical Research of Central Florida
state: Florida
city: Baton Rouge
country: United States
facility: Pennington Biomedical Research Center
state: Louisiana
city: Boston
country: United States
facility: Jean Mayer USDA Human Nutrition research Center on Aging Tufts University
state: Massachusetts
city: Albuquerque
country: United States
facility: New Mexico Clinical Research & Osteoporosis Center
state: New Mexico
city: New York
country: United States
facility: Columbia University
state: New York
city: Wilmington
country: United States
facility: PMJ Research of Wilmington
state: North Carolina
city: Winston-Salem
country: United States
facility: Bowman Gray Center for Medical Education-of- Wake Forest School of Medicine
state: North Carolina
city: Yukon
country: United States
facility: Tekton Research
state: Oklahoma
city: Austin
country: United States
facility: Tekton Research
state: Texas
city: Houston
country: United States
facility: Medical Center
state: Texas
city: San Antonio
country: United States
facility: Science Advancing Medicine Clinical Research Center
state: Texas
city: San Antonio
country: United States
facility: The University of Texas Health Science Center at San Antonio
state: Texas
city: West Jordan
country: United States
facility: Advanced Clinical Research
state: Utah
city: Bruxelles
country: Belgium
facility: Vrije Universiteit Brussel
city: Leuven
country: Belgium
facility: Universitaire Ziekenhuizen (UZ) Leuven - Gasthuisberg - Centrum voor metabole botziekten
city: Liège
country: Belgium
facility: Université de Liège
Study officials:
affiliation: Biophytis
name: Rob Van Maanen
role: STUDY_DIRECTOR
References: