Clinical trial NCT04708886: Romosozumab in Women With Chronic SCI
Official title: Effects of Romosozumab on Bone Health in Women With Spinal Cord Injury and Osteoporosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Osteoporosis
Bone Loss
Osteopenia, Osteoporosis
Spinal Cord Injuries
Chronic Spinal Paralysis
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
Lead sponsor: Northwestern University
Sponsor class: OTHER
Collaborators: name: Amgen
First posted: 2021-01-14
Enrollment: 12
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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 baseline, 3 months, 6 months, 12 months, and 24 months.

Eligibility criteria: 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

Primary outcomes:
measure: Change in knee integral vBMC
timeFrame: Baseline - 12 months
Secondary outcomes:
measure: Change in hip BMD
timeFrame: Baseline - 12 months
measure: Change in hip vBMC
timeFrame: Baseline - 12 months
Other outcomes:
measure: Change in BMC and BMD at regions of interest around the knee
timeFrame: Baseline - 12 months
measure: Change in serum bone markers
timeFrame: Baseline - 12 months
Locations:
city: Chicago
country: United States
facility: Northwestern University Feinberg School of Medicine
state: Illinois
Study officials:
affiliation: Northwestern University
name: Thomas J Schnitzer, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Cosman F, Crittenden DB, Adachi JD, Binkley N, Czerwinski E, Ferrari S, Hofbauer LC, Lau E, Lewiecki EM, Miyauchi A, Zerbini CA, Milmont CE, Chen L, Maddox J, Meisner PD, Libanati C, Grauer A. Romosozumab Treatment in Postmenopausal Women with Osteoporosis. N Engl J Med. 2016 Oct 20;375(16):1532-1543. doi: 10.1056/NEJMoa1607948. Epub 2016 Sep 18.
citation: Saag KG, Petersen J, Brandi ML, Karaplis AC, Lorentzon M, Thomas T, Maddox J, Fan M, Meisner PD, Grauer A. Romosozumab or Alendronate for Fracture Prevention in Women with Osteoporosis. N Engl J Med. 2017 Oct 12;377(15):1417-1427. doi: 10.1056/NEJMoa1708322. Epub 2017 Sep 11.
citation: Keaveny TM, Crittenden DB, Bolognese MA, Genant HK, Engelke K, Oliveri B, Brown JP, Langdahl BL, Yan C, Grauer A, Libanati C. Greater Gains in Spine and Hip Strength for Romosozumab Compared With Teriparatide in Postmenopausal Women With Low Bone Mass. J Bone Miner Res. 2017 Sep;32(9):1956-1962. doi: 10.1002/jbmr.3176. Epub 2017 Jun 26.