E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10063024 |
E.1.2 | Term | Sarcopenia |
E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of the study is to evaluate the effect of multiple doses of REGN1033 administered SC for 12 weeks on total lean body mass measured by DEXA in patients with sarcopenia. |
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E.2.2 | Secondary objectives of the trial |
- To assess the safety and tolerability of REGN1033 administered SC for 12 weeks in patients with sarcopenia
- To assess the effects of REGN1033 administered SC for 12 weeks on measures of strength and function |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Optional Genomics Sub-Study |
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E.3 | Principal inclusion criteria |
1. Men and women aged 70 years and older (all women participating in the study must be postmenopausal)
2. Are capable, in the investigator's opinion, of completing the study per protocol and have no significant health issues or conditions (including but not limited to severe arthritis of the major lower extremity joints and symptom-limited ambulation) that would impact the capability to get an accurate measurement of study endpoints
3. Appendicular lean mass relative to height squared: ≤7.23 kg/m² (men); ≤5.67 kg/m² (women)
4. 4M gait speed <1.0 m/s (>4s to travel 4 meters at normal walking pace)
5. BMI between 18.5 kg/m² and 37 kg/m², inclusive
6. Ability to follow a physical activity and walking program (involving activity such as walking starting with 5 to 10 minutes on most days of the week, and progressing to 30 minutes on most days of the week).
7. Willing and able to comply with clinic visits and study-related procedures (with the exception of the stair climb test, see protocol section 6.3.2.3).
8. Provide signed informed consent
9. Able to understand and complete study-related questionnaires |
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E.4 | Principal exclusion criteria |
1. Hospitalization or immobilization with a duration of >48 hours within the month prior to screening
2. Having had a surgical procedure within 1 month prior to screening that required general anesthesia and was associated with loss of ambulation for at least 3 days, or a planned surgical procedure requiring general anesthesia within the next 6 months
3. Participate in muscle strengthening training involving major muscle groups of arms and legs for at least 20 minutes 3 times per week AND regular exercise consisting of an average of approximately 3.5 hours per week or 30 minutes or more per day of at least moderate physical activity which increases heart rate and breathing rate.
4. Chronic medications introduced within 2 weeks prior to screening
5. Weight loss of >10% body weight within 6 months prior to screening
6. Respiratory disease (eg, severe chronic obstructive pulmonary disease) that requires oxygen treatment
7. Cancer requiring treatment currently or in the past 3 years (except primary nonmelanoma skin cancer or in situ cervical cancer), or any weight loss attributed to cancer within the last year (per the investigator’s assessment)
8. Neurological conditions that are causing impaired muscle function or mobility (may include stroke with residual paresis, paralysis, neuropathy, Parkinson disease, or multiple sclerosis)
9. MMSE score of <24
10. Active or inadequately treated Major Depressive Disorder within 3 months prior to screening
11. Cardiovascular conditions such as New York Heart Association class III or IV heart failure, cardiomyopathy, intermittent claudication, myocardial infarction, or acute coronary syndrome within 6 months prior to screening; symptomatic ventricular cardiac arrhythmia (note: sinus dysrhythmia, asymptomatic block or well controlled atrial fibrillation with normal resting ventricular rate are not exclusion criteria)
12. Abnormal echocardiogram findings at screening that are clinically significant, which may include but are not limited to:
- Cardiomyopathy
- Left ventricular ejection fraction <50%
- Moderate or severe diastolic dysfunction, grade II/III
- Aortic stenosis
- Valvular disease with hemodynamic significance
- Left ventricular wall thickness ≥1.4 cm (men) and ≥1.3 cm (women)
13. Uncontrolled diabetes defined as hemoglobin A1C (HbA1C) >9% at screening (1 retest allowed)
14. Diastolic blood pressure >100 mm Hg or systolic blood pressure >170 mm Hg (average of 1 reading at visit 1 and 1 reading at visit 2)
15. Alanine aminotransferase (ALT) >3x the upper limit of normal (1 retest allowed)
16. Reduced renal function defined as estimated glomerular filtration rate <30 mL/min/1.73 m² (1 retest allowed)
17. Creatine phosphokinase >5 x the upper limit of normal (1 repeat lab is allowed)
18. Use of any prescription or over-the-counter agents known to influence muscle mass or performance within 1 year prior to screening. These may include but are not limited to anabolic steroids, chronic systemic corticosteroids, insulin-like growth factor-1 (IGF-1), growth hormone (GH), replacement androgen therapy, and anti-androgen therapy.
19. Participation in any clinical trial of small molecule drugs within 30 days prior to screening or biologics within 3 months prior to screening
20. Participation within 6 months prior to screening in clinical trials of interventions that are intended to influence muscle mass or performance
21. History of human immunodeficiency virus infection
22. Positive test for hepatitis B surface antigen and/or hepatitis C antibody at the screening visit
23. History of hypersensitivity to doxycycline or other tetracycline antibiotics (REGN1033 drug product may contain trace amount of doxycycline from the production process)
24. Men* sexually active with their female partners of childbearing potential** who are unwilling to practice adequate contraception during the study (adequate contraceptive measures include stable use of oral contraceptives or other prescription pharmaceutical contraceptives; intrauterine device; condom plus contraceptive sponge, foam, or jelly, or diaphragm plus contraceptive sponge, foam, or jelly)
25. Hemoglobin <10 g/dL (1 retest is allowed)
*Contraception is not required for men with documented vasectomy.
**Women with bilateral tubal ligation or hysterectomy, or women who are postmenopausal (amenorrheic for at least 12 months) are not to be considered of childbearing potential. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint in the study is the percent change in total lean body mass. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
The secondary endpoints are:
TEAEs from baseline to the end of the study
Changes from baseline in:
- Appendicular lean mass by DEXA
- Maximal leg press strength (1-RM)
- Maximal chest press strength (1-RM)
- 4M gait speed
- SPPB and SPPB subscores
- Distance walked in the 6MWT
- Regional and total fat mass by DEXA
- Unloaded and loaded stair climb power
- Hand grip strength by handheld dynamometer |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The secondary endpoints will be evaluated from the timepoint of baseline estimation to the end of the study. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 9 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
France |
Netherlands |
Spain |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |