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

Sponsor

Biophytis (Industry)

Overall Status

Completed

CT.gov ID

NCT03452488

Collaborator

(none)

233

Enrollment

Locations

Arms

31.9

Actual Duration (Months)

10.6

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

SARA-INT is a phase 2 interventional study performed in Europe and USA aimed to evaluate the clinical benefits, safety and tolerability of the investigational drug BIO101 administered orally for a six-month (26 weeks) duration to older patients, community dwelling men and women aged ≥65 years, suffering from age-related sarcopenia (including sarcopenic obesity), and at risk of mobility disability.

The double-blind, placebo controlled clinical trial will collect and analyse data on physical performance and body composition and will specifically focus on the change of one functional measurement, the gait speed measured during the 400MW test plus the change of a highly standardised patient reported outcome (PRO), the physical function domain PF-10 at the SF-36 auto-evaluation questionnaire, in order to estimate the efficacy of BIO101 administered over 26 weeks, in preventing mobility disability in the target population.

Condition or Disease	Intervention/Treatment	Phase
Sarcopenia Gait Disorders in Old Age Muscle Weakness	Drug: BIO101 Drug: Placebo oral capsule	Phase 2

Detailed Description

SARA-INT is a three- arm interventional, phase 2, randomized, double blind placebo controlled clinical trial. It will be conducted in the EU (Belgium, France and Italy) and in the US.

334 community dwelling older adults (men or women≥65 years) reporting loss of physical function and considered at risk of mobility disability, will be selected to perform SPPB (Short Physical Performance Battery)1 tests. Those with SPPB scores ≤ 8 will be selected to perform body composition analysis with DEXA Scan. (DEXA Scans performed no more than 8 weeks before the date of randomization will be acceptable and in that case should not be repeated up to the end of the study visit). Participants with ALM/BMI < 0.789 in men and < 0.512 in women, or ALM <19.75kg in men and <15.02kg in women corresponding to the operational definition of sarcopenia according to the criteria of FNIH, will be definitively included and randomized if other inclusion/exclusion criteria are also satisfied.

The overarching objective of SARA-INT clinical trial is to evaluate the efficacy and safety of BIO101 26-week oral administration on the prevention of mobility disability in at-risk, community dwelling older adults (≥65 years) reporting loss of physical function over the previous year, and in particular:

To estimate treatment effect improvement on physical function after six-month treatment versus placebo in the target population.
To estimate treatment effect on decrease of risk of mobility disability after six-month treatment versus placebo in the target population.

The primary objective of SARA-INT is to evaluate the effects of two daily doses of BIO101 versus placebo on mobility function as measured by the gait speed during the 400MW test

The first key secondary objective is to evaluate the effect of BIO101 on physical function from the patient's perspective using an adapted patient reported outcome (PRO).

The second key objective is to assess on a simplified function test, i.e. raising from a chair, a minimal clinically significant benefit on mobility.

SARA-INT other secondary objectives are: To assess changes in body composition and specifically on appendicular lean body mass, which is an expression of sarcopenia; To estimate the change of 400MW test as a dichotomous variable, for possible use in further studies; To estimate the effect on muscular strength; To assess the overall change on SPPB as cumulative expression of a physically frail status; To estimate the effect on a sarcopenia specific PRO, in view of future studies.

SARA-INT exploratory objectives are:

To compare plasma and/or urinary levels of putative biomarkers of sarcopenia and of drug activity, and calculate their correlation with physical function changes over the study duration.
To compare change from baseline of the estimated cumulative daily activity as continuously recorded via a connected wearable actimeter device.

A selection of physical activity indexes (by actimetry) will be described and a correlation with primary and key secondary outcome will be tested.

The study plan is divided in a) screening and randomization phase; and b) treatment and evaluation phase and c) post-treatment follow-up. The recruitment is estimated to last 24 months. The investigational phase will comprise three main visits, the inclusion visit, the 3-month evaluation and the 6-month final evaluation visit, plus an intermediate visit after 1-month focused on safety assessment. Telephone interviews will be conducted at 5 months and 6 weeks after the end of treatment.

Study Design

Study Type:

Interventional

Actual Enrollment :

233 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Parallel assignmentParallel assignment

Masking:

Double (Participant, Investigator)

Masking Description:

Each treatment kit will show a preprinted kit number affixed on the primary, secondary and tertiary container. The kit number will be assigned via the eCRF after a patient is qualified and is randomised. Nor the Investigator and his staff, either the Sponsor will be aware of the treatment that corresponds to the kit number. The assigned treatment cannot be retrieved from the system, unless a specific unblinding procedure is engaged by the investigator when this is judged necessary by the responsible physician of the investigator center in the context of a severe or serious adverse event.

Primary Purpose:

Treatment

Official Title:

Safety and Efficacy of BIO-101 Oral Administration to Patients Suffering From Age-related SARcopenia, Including Sarcopenic Obesity, Aged ≥65 Years and at Risk of Mobility Disability (SARA-INT)

Actual Study Start Date :

May 24, 2018

Actual Primary Completion Date :

Dec 30, 2020

Actual Study Completion Date :

Jan 20, 2021

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Arm 1 - Placebo oral capsule 4 capsules taken twice a day: in the morning and in the evening with the meal approximately at 12-hour distance for 26 weeks. Component : Microcrystalline cellulose, Colloidal anhydrous silica	Drug: Placebo oral capsule Oral capsules containing Microcrystalline cellulose, Colloidal anhydrous silica
Experimental: Arm 2 - BIO101 - Half daily dose 350 mg 4 capsules taken twice a day (2 placebo and 2 experimental study drug) in the morning and in the evening with the meal approximately at 12-hour distance for 26 weeks. Study Drug Component : 251 mg per capsule including 175 mg of active principle 20-hydroxyecdysone (20E) containing also the following compendial excipients: colloidal silica, microcrystalline cellulose and magnesium stearate.	Drug: BIO101 Oral capsules containing the BIO101 active principle is 20-hydroxyecdysone (20E) at 97%. Component : 251 mg per capsule including 175 mg of active principle 20E containing also the following compendial excipients: colloidal silica, microcrystalline cellulose and magnesium stearate. Drug: Placebo oral capsule Oral capsules containing Microcrystalline cellulose, Colloidal anhydrous silica
Experimental: Arm 3 - BIO101 - Full daily dose 700 mg 4 capsules taken twice a day (4 experimental study drug) in the morning and in the evening with the meal approximately at 12-hour distance for 26 weeks. Study Drug Component : 251 mg per capsule including 175 mg of active principle 20E containing also the following compendial excipients: colloidal silica, microcrystalline cellulose and magnesium stearate.	Drug: BIO101 Oral capsules containing the BIO101 active principle is 20-hydroxyecdysone (20E) at 97%. Component : 251 mg per capsule including 175 mg of active principle 20E containing also the following compendial excipients: colloidal silica, microcrystalline cellulose and magnesium stearate.

Arm

Intervention/Treatment

Placebo Comparator: Arm 1 - Placebo oral capsule

4 capsules taken twice a day: in the morning and in the evening with the meal approximately at 12-hour distance for 26 weeks. Component : Microcrystalline cellulose, Colloidal anhydrous silica

Drug: Placebo oral capsule

Oral capsules containing Microcrystalline cellulose, Colloidal anhydrous silica

Experimental: Arm 2 - BIO101 - Half daily dose 350 mg

4 capsules taken twice a day (2 placebo and 2 experimental study drug) in the morning and in the evening with the meal approximately at 12-hour distance for 26 weeks. Study Drug Component : 251 mg per capsule including 175 mg of active principle 20-hydroxyecdysone (20E) containing also the following compendial excipients: colloidal silica, microcrystalline cellulose and magnesium stearate.

Drug: BIO101

Oral capsules containing the BIO101 active principle is 20-hydroxyecdysone (20E) at 97%. Component : 251 mg per capsule including 175 mg of active principle 20E containing also the following compendial excipients: colloidal silica, microcrystalline cellulose and magnesium stearate.

Drug: Placebo oral capsule

Oral capsules containing Microcrystalline cellulose, Colloidal anhydrous silica

Experimental: Arm 3 - BIO101 - Full daily dose 700 mg

4 capsules taken twice a day (4 experimental study drug) in the morning and in the evening with the meal approximately at 12-hour distance for 26 weeks. Study Drug Component : 251 mg per capsule including 175 mg of active principle 20E containing also the following compendial excipients: colloidal silica, microcrystalline cellulose and magnesium stearate.

Drug: BIO101

Outcome Measures

Primary Outcome Measures

Gait speed measured during the 400MW test. [The change from baseline to month 6 will be compared between groups of treatment (each dose versus placebo).]
The 400MWT is a measure of how long it takes a participant to walk a distance of 400 m. it is express in m/s

Secondary Outcome Measures

PF-10 subscore of the SF-36 [The change from baseline to month 6 will be compared between groups of treatment (each dose versus placebo)]
Electronically self administrated or filling a paper booklet Patient Reported Outcome SF-36 will be assessed through a SF-36 questionnaire. The physical function score (PF-10), role limitations due to physical problems.
Appendicular Lean Body Mass [The change from baseline to month 6 will be compared between groups of treatment (each dose versus placebo)]
Body composition especially Lean Body Mass in kg measured using DEXA. This will allow definition of the appendicular Lean Body mass
Body Fat Mass [The change from baseline to month 6 will be compared between groups of treatment (each dose versus placebo)]
Body composition especially Fat Mass will be measured in kg. This will allow definition of the body Fat mass
400MW test rate of success to complete the test [The change from baseline to month 6 will be compared between groups of treatment (each dose versus placebo)]
The 400MW rate of success is the ability to complete the test at all (yes/no).
handgrip test [Change from Baseline Grip Strength to measurement at 6 months]
The grip strength will be measured using the appropriate dynamometer. Strength in kg will be measured 3 times for both hands and the highest value will be kept for further analysis.
Knee extension test [Change from Baseline Knee extension to measurement at 6 months]
The knee extension in kg measurement will be performed using isokinetic dynamometer.
Stair Climb Power Test [Change from Baseline Stair Climb Power Test to measurement at 6 months]
The ability to ascend and descend stairs (9 stairs of 20 cm height) will be assessed in a specific period of time
SPPB [Change from Baseline SPPB to measurement at 6 months]
Physical performance tests corresponding to standing balance, walking speed and chair stand will be assessed
Patient Reported Outcomes : SarQoL: Sarcopenia Quality of Life [The change from baseline to month 6 will be compared between groups of treatment (each dose versus placebo)]
Electronically self administrated or filling a paper booklet Patient Reported Outcome SarQoL will be assessed through the SarQoL. The SarQoL® is composed of 22 questions including in total 55 items rated on a 4-point Likert scale. The questionnaire is scored, through a scoring algorithm, on 100 points, with higher scores reflecting a better quality of life.

Other Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

65 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Provision of signed and dated informed consent form
Stated willingness to comply with all study procedures and availability for the duration of the study
Male or female, aged ≥ 65 years and living in the community, reporting loss of physical function over the last 6-12 months
Short Physical Performance Battery (SPPB) score ≤ 8
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
Ability to take oral medication and be willing to adhere to the study intervention regimen.
Agreement to adhere to Lifestyle Considerations throughout study duration
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 Subjects.

Exclusion Criteria:

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)
Non-menopausal women (however ongoing replacement hormonal treatment is not an exclusion criterion)
Known allergic reactions to components of the investigational drug (i.e. stemmacantha carthamoides leaves and roots).
Febrile illness within 7 days
Treatment with another investigational drug or other intervention within three months
Unable to understand and perform the functional tests, as judged by the Investigator
Inability to perform the 400MW test within 15 minutes
Clinical conditions:
Current diagnosis of major psychiatric disorders.
Alcohol abuse or dependence
Severe arthritis
Cancer requiring active treatment (cancer treated with chemotherapy, or radiotherapy and currently on remission is not an exclusion criterion)
Lung disease requiring regular use of supplemental oxygen
Inflammatory conditions requiring regular use of oral or parenteral corticosteroid agents
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)
Parkinson's disease or other progressive neurological disorder
Renal disease requiring dialysis, or known renal insufficiency (moderate or severe reduction in GFR≤30 ml/min/1.73 m2)
Chest pain, severe shortness of breath, or occurrence of other safety concerns during the baseline functional tests 400-meter walk test or 6MWT
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.
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).

Contacts and Locations

Locations

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