Early Effects of Abaloparatide on Tissue-Based Indices of Bone Formation and Resorption

Phase 3

Completed

• Conditions: Osteoporosis; Osteoporosis, Postmenopausal; Osteoporosis Vertebral; Osteoporosis Risk; Osteoporosis Fracture; Osteoporosis Localized to Spine; Osteoporosis, Age-Related; Osteoporosis Senile; Osteoporosis of Vertebrae
• Interventions: Drug: Abaloparatide

• Registration Number: NCT03710889
• Lead Sponsor: Radius Health, Inc.

Brief Summary

The objective of this study is to measure the early effects of abaloparatide on tissue-based bone formation using samples obtained by transiliac crest bone biopsy after quadruple fluorochrome labeling.

Detailed Description

This was an open-label, single-arm study of postmenopausal women with osteoporosis treated with 80 micrograms (μg) abaloparatide for 3 months. Transiliac bone biopsies were taken at 3 months after quadruple fluorochrome labeling. The treatment duration of 3 months was determined to be the optimal time when biochemical markers of bone turnover peak and are predictive of subsequent changes in bone mineral density (BMD).

The main study was conducted for a 3-month treatment period with a 1-month follow up. A sub-study was conducted at 1 site to collect peripheral quantitative computed tomography (pQCT) data. Study treatment for participants in the sub-study was extended for an additional 3 months of study drug administration for a total of 6 months of treatment.

Study Timeline

• Study Start: 2018-09-20
• Study First Submitted: 2018-10-15
• Study First Submitted QC: 2018-10-17
• Study First Posted: 2018-10-18
• Primary Completion: 2020-07-15
• Study Completion: 2020-07-15
• Results First Submitted: 2021-09-05
• Status Verified: 2021-10
• Results First Submitted QC: 2021-10-12
• Last Update Submitted: 2021-10-12
• Results First Posted: 2021-10-15
• Last Update Posted: 2021-10-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 23

Inclusion Criteria

Not provided

Exclusion Criteria

Participants with any of the following characteristics are not eligible to participate in the study:

1. Presence of abnormalities of the lumbar spine that would prohibit assessment of lumbar spine BMD, defined as having at least 2 radiologically evaluable vertebrae within L1-L4.
2. Unevaluable hip BMD or participants who have undergone bilateral hip replacement (unilateral hip replacement is acceptable).
3. History of bone disorders (for example, Paget's disease) other than postmenopausal osteoporosis.
4. Clinically significant abnormality of serum hemoglobin, hematocrit, white blood cells (WBC) and platelets, coagulation, or usual serum chemistry: electrolytes, renal function, liver function and serum proteins.
5. Unexplained elevation of serum alkaline phosphatase.
6. History of radiotherapy (radiation therapy), other than radioiodine.
7. History of bleeding disorder that would preclude a bone biopsy, in the opinion of the Investigator.
8. 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.
9. History of Cushing's disease, hyperthyroidism, hypo- or hyperparathyroidism, or malabsorptive syndromes within the past year.
10. History of significantly impaired renal function (serum creatinine > 177 micromoles [µmol]/L or >2.0 milligrams [mg]/deciliter [dL]). If the serum creatinine is >1.5 and ≤ 2.0 mg/dL, the calculated creatinine clearance (Cockcroft-Gault) must be ≥ 30 mL/minute (min).
11. History of any cancer within the past 5 years (other than basal cell or squamous cell cancer of the skin).
12. History of osteosarcoma at any time or a history of hereditary disorders which could predispose the participant to osteosarcoma.
13. History of nephrolithiasis or urolithiasis within the past 5 years.
14. Participant known to be positive for hepatitis B, hepatitis C, or human immunodeficiency virus infection (HIV-1 or HIV-2). Testing is not required in the absence of clinical signs and symptoms suggestive of HIV infection or acute or chronic hepatitis.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Abaloparatide	Abaloparatide	Participants self-administered a single daily dose of 80 micrograms (µg) of abaloparatide subcutaneously (SC) during the treatment period. Participants were instructed to use a new injection pen after each 30-day period.

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Mineralizing Surface/Bone Surface (MS/BS) in the Cancellous Envelope at Month 3	Baseline (Day 1), Month 3	Change in dynamic histomorphometry indices was assessed in the cancellous envelope.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Bone Formation Rate/Bone Surface (BFR/BS) in the Cancellous Envelope at Month 3	Baseline (Day 1), Month 3	Change in dynamic histomorphometry indices was assessed in the cancellous envelope. BFR/BS was reported as cubic millimeter/square millimeter/year (mm\^3/mm\^2/year).
Change in Serum Carboxy-Terminal Cross-Linking Telopeptide of Type I Collagen (s-CTX) From Baseline at Month 1 and Month 3	Baseline (Day 1), Months 1 and 3	Blood samples were taken to measure efficacy-related markers of bone metabolism at Day 1, Month 1, and Month 3.
Change in Serum Procollagen Type I N-terminal Propeptide (s-P1NP) From Baseline at Month 1 and Month 3	Baseline (Day 1), Months 1 and 3	Blood samples were taken to measure efficacy related markers of bone metabolism at Day 1, Month 1, and Month 3.

Trial Locations

Locations (4)

Panorama Orthopedics & Spine Center; 🇺🇸 Golden, Colorado, United States

Center for Advanced Research & Education; 🇺🇸 Gainesville, Georgia, United States

Harvard Medical School; 🇺🇸 Boston, Massachusetts, United States

Henry Ford Health System; 🇺🇸 Detroit, Michigan, United States