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

Osteoporosis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03512262
• Other study ID #: BA058-05-019
• Secondary ID: ATOM
• Status: Completed
• Phase: Phase 3
• Start date: May 3, 2018
• Est. completion date: September 8, 2021

Study information

• Verified date: April 2023
• Source: Radius Health, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 228
• Est. completion date: September 8, 2021
• Est. primary completion date: August 17, 2021
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 40 Years to 85 Years

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• Abaloparatide
Abaloparatide is a synthetic peptide that is a potent and selective activator of the parathyroid hormone 1 receptor signaling pathway.
• Placebo
Abaloparatide-matched placebo.

Locations

Country	Name	City	State
Italy	Azienda ospedaliera universitaria Careggi	Florence	Tuscany
Italy	Azienda Ospedaliera Universitaria Senese-Policlincio Santa Maria Alle Scotte	Siena	Toscana
Italy	Azienda ospedaliera universitaria integrata di verona(AOUI)	Verona
Poland	ClinicMed Daniluk, Nowak Sp.j.	Bialystok
Poland	Zdrowie Osteo-Medic s.c. Lidia I Artur Racewicz, Agnieszka I Jerzy Supronik	Bialystok	Podlaskie
Poland	Krakowskie Centrum Medyczne Sp. z o.o.	Kraków	Malopolskie
Poland	Centrum Leczenia Osteoporozy Klinika Zdrowej Kosci	Lódz
Poland	ETG Siedlce	Siedlce
Poland	Lubelskie Centrum Diagnostyczne	Swidnik
Poland	NZOZ Nasz Lekarz	Torun
Poland	Synexus Polska Sp. z o.o. Oddzial w Warszawie	Warszawa	Mazowieckie
Poland	Synexus Polska Sp z o.o Oddzial we Wroclawiu	Wroclaw
United States	New Mexico Clinical Research & Osteoporosis Center, Inc.	Albuquerque	New Mexico
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	PMG Research of Cary, LLC	Cary	North Carolina
United States	Northwestern University	Chicago	Illinois
United States	The University of Chicago	Chicago	Illinois
United States	Ohio State University Medical Center	Columbus	Ohio
United States	Altoona Center For Clinical Research	Duncansville	Pennsylvania
United States	Center For Advanced Research & Education	Gainesville	Georgia
United States	Panorama Orthopedics & Spine Center	Golden	Colorado
United States	Marin Endocrine Care & Research, Inc.	Greenbrae	California
United States	Indago Research & Health Center, Inc.	Hialeah	Florida
United States	Centex Studies, Inc.	Houston	Texas
United States	University of Wisconsin Osteoporosis Clinical Research Program	Madison	Wisconsin
United States	Centex Studies, Inc	McAllen	Texas
United States	Baptist Diabetes Associates, Pa	Miami	Florida
United States	Hunter Holmes McGuire VA Medical Center	Richmond	Virginia
United States	Meridian Clinical Research	Savannah	Georgia
United States	Alta California Medical Group	Simi Valley	California
United States	SUNY Upstate Medical University	Syracuse	New York
United States	Diablo Clinical Research, Inc.	Walnut Creek	California
United States	MedStar Georgetown-MedStar Georgetown Transplant Institute University Hospital (MGUH)	Washington	District of Columbia
United States	PMG Research of Wilmington, LLC	Wilmington	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Radius Health, Inc.

Countries where clinical trial is conducted

United States,  Italy,  Poland, 

References & Publications (3)

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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