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

• ClinicalTrials.gov Identifier: NCT03512262
• Recruitment Status: Completed
• First Posted: April 30, 2018
• Results First Posted: April 7, 2023
• Last Update Posted: April 7, 2023
• Sponsor: Radius Health, Inc.
• Information provided by (Responsible Party): Radius Health, Inc.

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Osteoporosis; Osteoporosis, Age-Related; Osteoporosis Localized to Spine; Age Related Osteoporosis; Osteoporosis Senile; Osteoporosis of Vertebrae	Drug: Abaloparatide; Drug: Placebo	Phase 3

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 228 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Participants will be randomized in a 2:1 treatment ratio (abaloparatide:placebo).
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Treatment will be blinded to participants, investigators, outcome Assessor and care provider throughout the study except in a medical emergency where the identity of study medication is necessary to appropriately treat the participant.
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: May 3, 2018
• Actual Primary Completion Date: August 17, 2021
• Actual Study Completion Date: September 8, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Abaloparatide; 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; Abaloparatide is a synthetic peptide that is a potent and selective activator of the parathyroid hormone 1 receptor signaling pathway.; Other Names: TYMLOS®; BA058; abaloparatide-SC
Placebo Comparator: Placebo; 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; Abaloparatide-matched placebo.

Outcome Measures

Primary Outcome Measures :

1. Percent Change From Baseline in Lumbar Spine BMD at Month 12 [ Time Frame: Baseline, 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.

Secondary Outcome Measures :

1. Percent Change From Baseline in Total Hip BMD at Month 12 [ Time Frame: Baseline, 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.
2. Percent Change From Baseline in Femoral Neck BMD at Month 12 [ Time Frame: Baseline, 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.
3. Percent Change From Baseline in Lumbar Spine BMD at Month 6 [ Time Frame: Baseline, 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.
4. Percent Change in Total Hip BMD From Baseline at Month 6 [ Time Frame: Baseline, 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.
5. Percent Change From Baseline in Femoral Neck BMD at Month 6 [ Time Frame: Baseline, 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.
6. Percent Change From Baseline in Ultra-Distal Radius BMD at Month 12 [ Time Frame: Baseline, Month 12 ]
   Ultra-distal radius BMD was assessed by DXA scans. Positive changes from baseline indicate improvement in bone health.
7. Percent Change From Baseline in Distal One-third Radius BMD at Month 12 [ Time Frame: Baseline, Month 12 ]
   Distal one-third radius BMD was assessed by DXA scans. Positive changes from baseline indicate improvement in bone health.
8. Percent Change From Baseline in Serum Procollagen Type I N-terminal Propeptide (s-PINP) at Month 12 [ Time Frame: Baseline, 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.
9. Percent Change From Baseline in Serum Carboxy-terminal Cross-linking Telopeptide of Type I Collagen (s-CTX) at Month 12 [ Time Frame: Baseline, Month 12 ]
   Blood samples were taken to measure s-CTX. Elevated levels of s-CTX indicate increased bone resorption (bone loss).
10. Number of Participants With New Clinical Fractures [ Time Frame: Baseline through Month 12 ]
    Radiological evaluations were performed to identify any new clinical fractures (occurring after the screening visit).
11. Percent of Participants With Change in Disease Status [ Time Frame: Baseline through Month 12 ]

    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.
12. Percent of Participants Experiencing BMD Gains From Baseline of > 0%, > 3%, and > 6% at the Lumbar Spine, Femoral Neck, and Total Hip [ Time Frame: Month 12 ]
    Lumbar spine, femoral neck, and total hip BMD were assessed by DXA scans evaluated by a central imaging laboratory.
13. Percent Change From Baseline in Total Hip Volumetric BMD as Measured by Quantitative Computed Tomography (QCT) at Month 12 [ Time Frame: Baseline, Month 12 ]
    QCT scans were evaluated by a central imaging laboratory.
14. Percent Change From Baseline in Femoral Neck Volumetric BMD as Measured by QCT at Month 12 [ Time Frame: Baseline, Month 12 ]
    QCT scans were evaluated by a central imaging laboratory.

Eligibility Criteria

• Ages Eligible for Study: 40 Years to 85 Years (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, Alabama

University of Alabama at Birmingham

Birmingham, Alabama, United States, 35294

United States, California

Marin Endocrine Care & Research, Inc.

Greenbrae, California, United States, 94904

Alta California Medical Group

Simi Valley, California, United States, 93065

Diablo Clinical Research, Inc.

Walnut Creek, California, United States, 94598

United States, Colorado

Panorama Orthopedics & Spine Center

Golden, Colorado, United States, 80401

United States, District of Columbia

MedStar Georgetown-MedStar Georgetown Transplant Institute University Hospital (MGUH)

Washington, District of Columbia, United States, 20007

United States, Florida

Indago Research & Health Center, Inc.

Hialeah, Florida, United States, 33012

Baptist Diabetes Associates, Pa

Miami, Florida, United States, 33156

United States, Georgia

Center For Advanced Research & Education

Gainesville, Georgia, United States, 30501

Meridian Clinical Research

Savannah, Georgia, United States, 31406

United States, Illinois

Northwestern University

Chicago, Illinois, United States, 60611

The University of Chicago

Chicago, Illinois, United States, 60637

United States, New Mexico

New Mexico Clinical Research & Osteoporosis Center, Inc.

Albuquerque, New Mexico, United States, 87106

United States, New York

SUNY Upstate Medical University

Syracuse, New York, United States, 13210

United States, North Carolina

PMG Research of Cary, LLC

Cary, North Carolina, United States, 27518

PMG Research of Wilmington, LLC

Wilmington, North Carolina, United States, 28401

United States, Ohio

Ohio State University Medical Center

Columbus, Ohio, United States, 43210

United States, Pennsylvania

Altoona Center For Clinical Research

Duncansville, Pennsylvania, United States, 16635

United States, Texas

Centex Studies, Inc.

Houston, Texas, United States, 77058

Centex Studies, Inc

McAllen, Texas, United States, 78504

United States, Virginia

Hunter Holmes McGuire VA Medical Center

Richmond, Virginia, United States, 23249

United States, Wisconsin

University of Wisconsin Osteoporosis Clinical Research Program

Madison, Wisconsin, United States, 53705

Italy

Azienda Ospedaliera Universitaria Senese-Policlincio Santa Maria Alle Scotte

Siena, Toscana, Italy, 53100

Azienda ospedaliera universitaria Careggi

Florence, Tuscany, Italy, 50139

Azienda ospedaliera universitaria integrata di verona(AOUI)

Verona, Italy, 37134

Poland

Krakowskie Centrum Medyczne Sp. z o.o.

Kraków, Malopolskie, Poland, 31-501

Synexus Polska Sp. z o.o. Oddzial w Warszawie

Warszawa, Mazowieckie, Poland, 01-192

Zdrowie Osteo-Medic s.c. Lidia I Artur Racewicz, Agnieszka I Jerzy Supronik

Białystok, Podlaskie, Poland, 15-351

ClinicMed Daniluk, Nowak Sp.j.

Białystok, Poland, 15-879

ETG Siedlce

Siedlce, Poland, 08-110

Lubelskie Centrum Diagnostyczne

Swidnik, Poland, 21-040

NZOZ Nasz Lekarz

Toruń, Poland, 87100

Synexus Polska Sp z o.o Oddzial we Wroclawiu

Wrocław, Poland, 50-381

Centrum Leczenia Osteoporozy Klinika Zdrowej Kosci

Łódź, Poland, 90-558

Sponsors and Collaborators

Radius Health, Inc.

  Study Documents (Full-Text)

Documents provided by Radius Health, Inc.:

Study Protocol  [PDF] March 30, 2021

Statistical Analysis Plan  [PDF] August 25, 2021

More Information

Publications:

Rizzoli R, Bonjour JP, Ferrari SL. Osteoporosis, genetics and hormones. J Mol Endocrinol. 2001 Apr;26(2):79-94. doi: 10.1677/jme.0.0260079.

Mannstadt M, Juppner H, Gardella TJ. Receptors for PTH and PTHrP: their biological importance and functional properties. Am J Physiol. 1999 Nov;277(5):F665-75. doi: 10.1152/ajprenal.1999.277.5.F665.

Dempster DW, Cosman F, Parisien M, Shen V, Lindsay R. Anabolic actions of parathyroid hormone on bone. Endocr Rev. 1993 Dec;14(6):690-709. doi: 10.1210/edrv-14-6-690. No abstract available. Erratum In: Endocr Rev 1994 Apr;15(2):261.

• Responsible Party: Radius Health, Inc.
• ClinicalTrials.gov Identifier: NCT03512262
• Other Study ID Numbers: BA058-05-019; ATOM ( Other Identifier: Radius Health, Inc. )
• First Posted: April 30, 2018
• Results First Posted: April 7, 2023
• Last Update Posted: April 7, 2023
• Last Verified: April 2023

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Radius Health, Inc.:

BA058; abaloparatide; abaloparatide-SC; osteoporosis; male osteoporosis; TYMLOS®; fracture; bone loss

Additional relevant MeSH terms:

Osteoporosis; Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Abaloparatide; Parathyroid Hormone-Related Protein; Bone Density Conservation Agents; Physiological Effects of Drugs; Calcium-Regulating Hormones and Agents