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 | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10020100 |
E.1.2 | Term | Hip fracture |
E.1.2 | System Organ Class | 10022117 - Injury, poisoning and procedural complications |
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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 this study is to determine the efficacy of VK5211 after 12 weeks of treatment by mean placebo-corrected percentage change in total body less head (TBLH) lean body mass assessed by whole body DXA scan. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are:
• To assess the safety and tolerability of VK5211 after 12 weeks of treatment by comparing overall adverse events, vital signs, 12-lead ECG data, physical examinations, and hematology/chemistry/urinalysis data to placebo.
• To determine the efficacy of VK5211 after 12 weeks of treatment by mean placebo-corrected change in:
o Hip bone mineral density (BMD) assessed by DXA
o Total lean body mass
o Appendicular lean body mass
o Bone turnover markers (s-CTX and s-PINP)
• To assess plasma concentration of VK5211 near Tmax and at trough levels in relation to total lean body mass.
The exploratory objectives of this study are to determine the efficacy of VK5211 compared to placebo after 12 weeks of treatment by:
• Physical Performance Assessments
o 6MWT and BORG Scale
o Grip Strength
o SPPB
• Patient Reported Outcomes
o Pre- and Post-fracture PADLs/IADLs
o SF-36 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Each subject must meet the following criteria to be eligible for the study (subjects may be rescreened for failure of inclusion/exclusion criteria after consultation with medical monitor):
1. Males or females ≥65 years old who experienced a hip fracture (occurring 3-11 weeks prior) with no residual surgical issues will be eligible for participation.
2. Subjects must be willing and able to sign informed consent.
3. Blood pressure within the following parameters: systolic blood pressure (SBP) <180 mmHg and diastolic blood pressure (DBP) < 100 mmHg) with a heart rate of 45 to 90 bpm measured at Screening after resting for 5 minutes in the seated position.
4. MMSE score ≥ 20.
5. Ability to walk 4 meters at Screening with or without a cane or walker with a gait speed of ≤ 0.8 m/s.
6. Suitable for participation in the study in the opinion of the Investigator. |
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E.4 | Principal exclusion criteria |
Subjects who meet any of the following criteria must be excluded from the study:
1. Clinically significant new illness in the 1 month prior to Screening. (The qualifying hip fracture does not count as a significant illness).
2. Cognitive impairment as indicated by a score of < 20 on the MMSE performed at Screening or as determined by Investigator judgment if 20 or higher.
3. Pathological fracture (e.g. fracture due to Paget’s disease of bone, malignancy, etc.). Fracture due to postmenopausal osteoporosis is not considered pathological for this trial.
4. Glycosylated hemoglobin (HbA1c) > 9.5 % at Screening.
5. Presence of hardware in the contralateral hip.
6. Previous participation in any clinical study with an investigational drug, biologic, or device within 4 weeks prior to Screening.
7. Previous participation in a VK5211 or LGD-4033 study.
8. Use of antibody-based therapy for bone disease within 6 months prior to Screening. Subjects taking antibody-based therapy may be weaned off and re-screened on a case-bycase basis pending evaluation by the Sponsor.
9. Use of the following medications within 30 days prior to Screening or during the study:
• Hormone replacement therapy with estrogen agonists or SERMs (vaginal estrogens are permitted).
• Teriperatide (Forteo) is excluded;[supplemental Vitamin D3 and/or Calcium is permitted].
• Initiation of ANY new bone active therapy after Screening for duration of the study and follow up period (examples include IV and oral bisphosphonates, Denosumab, Teriperatide, etc.)
10. History of severe allergies (i.e., anyone with a known history of anaphylaxis to medication[s] or allergens).
11. Subject who has donated any blood, or had significant blood loss not associated with the qualifying hip fracture within 56 days prior to dosing.
12. Subject who has donated plasma within 7 days prior to dosing.
13. History of regular smoking or tobacco use within 3 months prior to Screening.
14. Not suitable to participate in the study in the opinion of the Investigator including an existing physical or mental condition that may prevent compliance with the protocol.
15. Not suitable to participate in the study in the opinion of the Investigator on the basis of clinically significant laboratory values.
16. ECG will be performed at Screening. Subjects with QTcF interval >450 msec (or >500 msec in the presence of a bundle branch block or paced ventricular rhythm) or any other exclusionary cardiac conditions noted previously on the locally read ECG are excluded from study participation. Other abnormal findings on the ECG should be carefully
considered and any subject excluded who, in the judgment of the PI, may not safely complete treatment in this study.
17. History of active or uncontrolled heart failure or hypertension within 3 months of Screening.
18. Symptoms of acute or unstable coronary artery disease within 6 months of Screening.
19. History of cerebrovascular disease within 1 year of Screening.
20. History of epilepsy or any other seizure disorder within 1 year of Screening.
21. History of unexplained or untreated syncope in the past 12 months.
22. History of organ transplantation.
23. Positive history of human immunodeficiency virus, or acute/active hepatitis B, or hepatitis C.
24. Malignancy within 5 years of Screening (with the exception of previously treated basal cell carcinoma and squamous cell skin carcinoma in-situ).
25. History (within 2 years prior to Screening) of alcohol or drug/solvent abuse.
26. Documented sensitivity to any of the ingredients in the Investigational Product (IP) formulation. |
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E.5 End points |
E.5.1 | Primary end point(s) |
To determine the efficacy of VK5211 after 12 weeks of treatment by mean placebo-corrected percentage change in total body less head (TBLH) lean body mass assessed by whole body DXA scan. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
DXA Scan at baseline, Visit 4 (approx. 12 weeks) and Visit 5 (approx. 24 weeks). |
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E.5.2 | Secondary end point(s) |
Secondary endpoints:
• To assess the safety and tolerability of VK5211 after 12 weeks of treatment by comparing overall adverse events, vital signs, 12-lead ECG data, physical examinations, and hematology/chemistry/urinalysis data to placebo.
• To determine the efficacy of VK5211 after 12 weeks of treatment by mean placebo-corrected change in:
o Hip bone mineral density (BMD) assessed by DXA
o Total lean body mass
o Appendicular lean body mass
o Bone turnover markers (s-CTX and s-PINP)
• To assess plasma concentration of VK5211 near Tmax and at trough levels in relation to total lean body mass.
The exploratory objectives of this study are to determine the efficacy of VK5211 compared to placebo after 12 weeks of treatment by:
• Physical Performance Assessments
o 6MWT and BORG Scale
o Grip Strength
o SPPB
• Patient Reported Outcomes
o Pre- and Post-fracture PADLs/IADLs
o SF-36 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary endpoints:
• assessment of safety and tolerability of VK5211:
- adverse events and vital signs: at randomization, Visit1-Visit5
- 12-lead ECG: at randomization, Visit 4 and Visit 5
- physical examinations: Visit 2, Visit 4 and Visit 5
- hematology/chemistry/urinalysis: randomization, Visit 2-5
• efficacy of VK5211 after 12 weeks of treatment by mean placebo-corrected change in:
o Hip bone mineral density (BMD), total lean body mass, appendicular lean body mass assessed by DXA at randomization, Visit 4 and Visit 5
o Bone turnover markers (s-CTX and s-PINP): at randomization, Visit 2-5
• assessment of plasma concentration of VK5211 near Tmax and at trough levels in relation to total lean body mass: Visit 2-5
Exploratory efficacy analysis:
- at randomization, Visit 2-5 |
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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 | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
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 |
Hungary |
Romania |
Serbia |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
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 | 1 |
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 | 8 |
E.8.9.2 | In all countries concerned by the trial days | 15 |