Safety and Efficacy of Abaloparatide-SC in Men With Osteoporosis (ATOM)

Study Overview
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Brief Summary
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A 12-month study to measure the efficacy and safety of abaloparatide in men with osteoporosis.

Detailed Description
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The primary objective of this prospective controlled study is to evaluate the efficacy and the safety of abaloparatide 80 micrograms (mcg) per day administered subcutaneously (SC) compared to placebo in men with osteoporosis. Efficacy was primarily assessed by the change in bone mineral density (BMD) over 12 months.

Official Title
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A Randomized, Double-blind, Placebo-controlled, Phase 3 Multicenter Study to Evaluate the Safety and Efficacy of Abaloparatide-SC for the Treatment of Men With Osteoporosis

Conditions
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Osteoporosis, Osteoporosis, Age-Related, Osteoporosis Localized to Spine, Age Related Osteoporosis, Osteoporosis Senile, Osteoporosis of Vertebrae

Intervention / Treatment
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* Drug: Abaloparatide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria Healthy ambulatory male from 40 to 85 years of age (inclusive) with primary osteoporosis or osteoporosis associated with hypogonadism. The participant has a BMD T-score based on female or male reference range (depending on date of enrollment) as assessed by the central imaging vendor of ≤ -2.5 at the lumbar spine (L1-L4) or hip (femoral neck or total hip) by dual energy X-ray absorptiometry (DXA) or ≤ -1.5 and with radiologic evidence of vertebral fracture or a documented history of low-trauma nonvertebral fracture sustained in the past 5 years. Men older than 65 years may be enrolled if they have a BMD T-score ≤ -2.0 even if they do not meet the fracture criteria. Normal medical history, physical examination, including vital signs, and body mass index. Hypogonadal participants whose doses of androgens have been stable for at least twelve months before randomization are eligible and may continue therapy during the study. Laboratory tests within the normal range including serum calcium (albumin-corrected), parathyroid hormone, serum phosphorus and alkaline phosphatase, and thyroid stimulating hormone values. Key Exclusion Criteria Presence of abnormalities of the lumbar spine that would prohibit assessment of spinal BMD, defined as having at least 2 radiologically evaluable vertebrae within L1-L4. A BMD T-score of ≤-3.5 at the total hip, femoral neck, or lumbar spine based on female or male reference range (depending on date of enrollment). Unevaluable hip BMD or participants who have undergone bilateral hip replacement. Fragility fracture within the prior twelve months. History of severe vertebral fracture or >2 moderate vertebral fractures. History of bone disorders (for example, Paget's disease) other than osteoporosis. participant with clinical signs of hypogonadism present at screening who plan to initiate testosterone replacement. History of prior external beam or implant radiation therapy involving the skeleton other than radioiodine. History of chronic or recurrent renal, hepatic, pulmonary, allergic, cardiovascular, gastrointestinal, endocrine, central nervous system, hematologic or metabolic diseases, or immunologic, emotional and/or psychiatric disturbances to a degree that would interfere with the interpretation of study data or compromise the safety of the participant. History of Cushing's disease, growth hormone deficiency or excess, hyperthyroidism, hypo- or hyperparathyroidism or malabsorptive syndromes within the past year.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants will be randomized in a 2:1 treatment ratio (abaloparatide:placebo).
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Abaloparatide<br>Participants self-administered daily doses of abaloparatide 80 mcg SC using a single-participant, multiple-use, prefilled injection pen that delivers 30 doses. Participants received a new injection pen every 30 days. | Drug: Abaloparatide<br>* Abaloparatide is a synthetic peptide that is a potent and selective activator of the parathyroid hormone 1 receptor signaling pathway.<br>* Other names: abaloparatide-SC;|
| Placebo Comparator: Placebo<br>Participants self-administered daily doses of placebo SC using a single-participant, multiple-use, prefilled injection pen that delivers 30 doses. Participants received a new injection pen every 30 days. | Drug: Placebo<br>* Abaloparatide-matched placebo.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Lumbar Spine BMD at Month 12 | Lumbar Spine BMD was assessed by DXA scans evaluated by a central imaging laboratory. Lumbar spine scans included L1 through L4. Positive changes from baseline indicate improvement in bone health. | Baseline, Month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Total Hip BMD at Month 12 | Total hip BMD was assessed by DXA scans evaluated by a central imaging laboratory. Positive changes from baseline indicate improvement in bone health. | Baseline, Month 12 | 
| Percent Change From Baseline in Femoral Neck BMD at Month 12 | Femoral neck BMD was assessed by DXA scans evaluated by a central imaging laboratory. Positive changes from baseline indicate improvement in bone health. | Baseline, Month 12 | 
| Percent Change From Baseline in Lumbar Spine BMD at Month 6 | Lumbar Spine BMD was assessed by DXA scans evaluated by a central imaging laboratory. Lumbar spine scans included L1 through L4. Positive changes from baseline indicate improvement in bone health. | Baseline, Month 6 | 
| Percent Change in Total Hip BMD From Baseline at Month 6 | Total hip BMD was assessed by DXA scans evaluated by a central imaging laboratory. Positive changes from baseline indicate improvement in bone health. | Baseline, Month 6 | 
| Percent Change From Baseline in Femoral Neck BMD at Month 6 | Femoral neck BMD was assessed by DXA scans evaluated by a central imaging laboratory. Positive changes from baseline indicate improvement in bone health. | Baseline, Month 6 | 
| Percent Change From Baseline in Ultra-Distal Radius BMD at Month 12 | Ultra-distal radius BMD was assessed by DXA scans. Positive changes from baseline indicate improvement in bone health. | Baseline, Month 12 | 
| Percent Change From Baseline in Distal One-third Radius BMD at Month 12 | Distal one-third radius BMD was assessed by DXA scans. Positive changes from baseline indicate improvement in bone health. | Baseline, Month 12 | 
| Percent Change From Baseline in Serum Procollagen Type I N-terminal Propeptide (s-PINP) at Month 12 | Blood samples were taken to measure s-PINP, a bone formation marker. s-PINP concentrations reflect the rate of skeletal new bone formation. Increases in s-PINP indicate anabolic biologic response in the bone. | Baseline, Month 12 | 
| Percent Change From Baseline in Serum Carboxy-terminal Cross-linking Telopeptide of Type I Collagen (s-CTX) at Month 12 | Blood samples were taken to measure s-CTX. Elevated levels of s-CTX indicate increased bone resorption (bone loss). | Baseline, Month 12 | 
| Number of Participants With New Clinical Fractures | Radiological evaluations were performed to identify any new clinical fractures (occurring after the screening visit). | Baseline through Month 12 | 
| Percent of Participants With Change in Disease Status | The percentage of participants converting from the categories of osteoporosis to osteopenia or from osteopenia to normal at End of Treatment (Month 12) was assessed. Osteoporosis was defined as lumbar spine or total hip BMD T-score ≤ -2.5. Osteopenia was defined as one of the following: Lumbar spine > -2.5 and total hip BMD T-score > -2.5 and < -1.0 Lumbar spine > -2.5 and < -1.0 and total hip BMD T-score > -2.5 Normal was defined as lumbar spine and total hip BMD T-score ≥ -1.0. | Baseline through Month 12 | 
| Percent of Participants Experiencing BMD Gains From Baseline of > 0%, > 3%, and > 6% at the Lumbar Spine, Femoral Neck, and Total Hip | Lumbar spine, femoral neck, and total hip BMD were assessed by DXA scans evaluated by a central imaging laboratory. | Month 12 | 
| Percent Change From Baseline in Total Hip Volumetric BMD as Measured by Quantitative Computed Tomography (QCT) at Month 12 | QCT scans were evaluated by a central imaging laboratory. | Baseline, Month 12 | 
| Percent Change From Baseline in Femoral Neck Volumetric BMD as Measured by QCT at Month 12 | QCT scans were evaluated by a central imaging laboratory. | Baseline, Month 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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male osteoporosis, BA058, abaloparatide, abaloparatide-SC, osteoporosis, TYMLOS®, fracture, bone loss