Bone Loss, Chronic Spinal Paralysis, Osteopenia, Osteoporosis, Osteoporosis, Spinal Cord Injuries
Conditions
Keywords
Spinal Cord Injury, Osteoporosis, Romosozumab (Evenity), Alendronate (Fosamax), Bone Diseases, Metabolic Bone Diseases, Anabolic Treatment, Bisphosphonate, Bone Density, Spinal Cord Diseases, Romosozumab, Alendronate, Physiological Effects of Drugs
Brief summary
This two-year open-label pilot clinical trial will evaluate the efficacy and safety of romosozumab to treat bone loss in females with chronic spinal cord injury (SCI) and osteoporosis (OP). Participants will receive monthly injections of romosozumab during the first 12 months of the study. During the second year, participants will take oral alendronate tablets on a weekly basis.
Detailed description
This is a single-site, singe-arm, open-label pilot study to evaluate safety and efficacy of a sequential drug treatment (12 months of romosozumab injections followed by 12 months with alendronate tablets) to treat bone loss in women with chronic SCI and OP. During the first year, participants will receive monthly subcutaneous injections of romosozumab 210 mg. This drug works by increasing bone formation and is FDA-approved for treating OP in post-menopausal women at high risk of fracture or those who did not benefit from using other available OP treatments. During the second year, participants will take weekly oral alendronate 70 mg. Alendronate is FDA-approved for the treatment of osteopenia and the treatment of OP in post-menopausal women and men as well as for the prevention and treatment of glucocorticoid-induced OP. In this study, it will be used to help maintain any increases in bone mass gained from the year of treatment with romosozumab. Twelve participants will receive the study drug treatment, take daily supplements (calcium and vitamin D), and return to the research site for study visits over the course of two years. Computerized tomography (CT) imaging, dual-energy X-ray absorptiometry (DXA) imaging, and serum bone markers will be collected at various time points.
Interventions
DRUGRomosozumab
Year 1 study drug
DRUGAlendronate
Year 2 study drug
Sponsors
Amgen
Northwestern University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥18 years * Female sex * SCI 6 or more months prior to enrollment * Non-ambulatory status (Walking Index for Spinal Cord Injury II score of 3 or less) * Osteoporosis by DXA defined as a t-score of -2.5 at any skeletal site (lumbar spine, total hip, or femoral neck) or a t-score of -2.0 plus a history of a fragility fracture * Good general health, as determined by the study investigator * Able to understand and agree to informed consent in English * Able and willing to complete all the study visits * Females of childbearing potential must be willing and able to use an effective method of contraception or practice abstinence throughout the course of the study and up to 90 days after the last use of study drug. * Vitamin D 25-hydroxy levels ≥ 20 ng/ml (subjects may be repleted and retested prior to baseline) * Normal serum calcium levels (based on current local laboratory normal range) * No known endocrinopathies (diabetes type 1 or 2, treated thyroid conditions can be included) * Normal serum thyroid stimulating hormone and/or T4 levels (based on current local laboratory normal ranges) * Able to take oral medication sitting upright for at least 30 minutes
Exclusion criteria
* Have Paget's disease of the bone * Have abnormal laboratory values that in the judgement of the investigator would put the participant at increased risk of treatment * Any active gastrointestinal condition that results in malabsorption * Abnormalities of the esophagus which delay emptying such as stricture or achalasia * Known hypersensitivity to romosozumab or alendronate * Increased risk of aspiration * Osteonecrosis of the jaw (ONJ) or risk factor for ONJ, such as invasive dental procedures (e.g., tooth extraction, dental implants, oral surgery in the past 6 months), poor oral hygiene, periodontal and/or pre-existing dental disease, or planned invasive dental procedure over the next two years * Heterotopic ossification of the knee region that interferes with CT analysis * History of bone metastasis and skeletal malignancies * History of alcoholism or drug abuse within the 2 years prior to study screening, which in the opinion of the investigator may affect subject's health and/or study commitment * Other medical conditions that in the opinion of the investigator would preclude the subject from completing the study * Currently being prescribed anticonvulsants at a dose or frequency that is determined to interfere with bone metabolism as determined by the investigator * Currently being prescribed glucocorticoids, other than inhaled glucocorticoids * Current or use during past 5 years of any bone-active agents, including any FDA approved treatment (e.g., teriparatide, abaloparatide, denosumab, any bisphosphonate (oral or IV), raloxifene, bazedoxifene, hormone therapy (estrogen and estrogen/progestin) and calcitonin) as well as any strontium-containing compounds. * Pregnant, planning to become pregnant, or lactating * Any history of stroke or cardiovascular disease other than controlled hypertension * Renal insufficiency (calculated creatinine clearance less than 35 ml/min) * Any other neurological impairment that may impair ambulation or muscle function
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Integral vBMC at the Knee (Distal Femur) | Baseline - 12 months | Change from baseline to the Month 12 visit in volumetric bone mineral content (vBMC) obtained via CT (three-dimensional) imaging of the knee. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in BMD at the Total Hip and Femoral Neck | Baseline - 12 months | Change from baseline to the Month 12 visit in bone mineral density (BMD) obtained via DXA (two-dimensional) imaging of the total hip. |
| Change in vBMC at the Hip | Baseline - 12 months | Change from baseline to the Month 12 visit in volumetric bone mineral content (vBMC) obtained via CT imaging of the hip. |
| Change in Serum Bone Biomarkers (CTX and P1NP) | Baseline - 12 months | Change from baseline to the Month 12 visit in serum levels of CTX and P1NP. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Open-label Romosozumab Participants received monthly subcutaneous injections of romosozumab (210 mg) for 12 months. | 12 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Year 2: Alendronate | Lost to Follow-up | 1 |
| Year 2: Alendronate | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Open-label Romosozumab |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants |
| Age, Continuous | 45.4 years STANDARD_DEVIATION 8.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 10 Participants |
| Region of Enrollment United States | 12 Participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 12 / 12 | 9 / 12 |
| serious Total, serious adverse events | 0 / 12 | 2 / 12 |
Outcome results
Primary
Change in Integral vBMC at the Knee (Distal Femur)
Change from baseline to the Month 12 visit in volumetric bone mineral content (vBMC) obtained via CT (three-dimensional) imaging of the knee.
Time frame: Baseline - 12 months
Population: Females with Chronic SCI
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Females With Chronic SCI | Change in Integral vBMC at the Knee (Distal Femur) | -0.78 g |
Secondary
Change in BMD at the Total Hip and Femoral Neck
Change from baseline to the Month 12 visit in bone mineral density (BMD) obtained via DXA (two-dimensional) imaging of the total hip.
Time frame: Baseline - 12 months
Population: Females with Chronic SCI
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Females With Chronic SCI | Change in BMD at the Total Hip and Femoral Neck | Total Hip | 0.023 g/cm^2 |
| Females With Chronic SCI | Change in BMD at the Total Hip and Femoral Neck | Femoral Neck | 0.033 g/cm^2 |
Secondary
Change in Serum Bone Biomarkers (CTX and P1NP)
Change from baseline to the Month 12 visit in serum levels of CTX and P1NP.
Time frame: Baseline - 12 months
Population: Females with chronic SCI
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Females With Chronic SCI | Change in Serum Bone Biomarkers (CTX and P1NP) | CTX | -0.0093 ng/mL |
| Females With Chronic SCI | Change in Serum Bone Biomarkers (CTX and P1NP) | P1NP | -18.25 ng/mL |
Secondary
Change in vBMC at the Hip
Change from baseline to the Month 12 visit in volumetric bone mineral content (vBMC) obtained via CT imaging of the hip.
Time frame: Baseline - 12 months
Population: Females with Chronic SCI
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Females With Chronic SCI | Change in vBMC at the Hip | 0.063 g |