Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Phase II Trial of Abaloparatide vs. Placebo in Post-Menopausal Women Receiving Initial Spinal Fusion Surgery

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03841058
Recruitment Status : Suspended (Due to COVID-19.)
First Posted : February 15, 2019
Last Update Posted : April 22, 2020
Sponsor:
Information provided by (Responsible Party):
Hospital for Special Surgery, New York

Brief Summary:
This is a prospective randomized, double-blinded, placebo-controlled, phase 2, 12-month pilot to study the efficacy of abaloparatide in postmenopausal women needing lumbar spinal fusion surgery. Seventy-two women with low bone mass who are scheduled to undergo spinal fusion surgery will be randomized 2:1 in a blinded fashion to receive either 80 mcg of abaloparatide subcutaneously (SC) every day or an identical-appearing placebo SC for 6 months. Outcomes include surgical outcome at one year, pain, and fusion bone mass volume (FBMV) as a marker of bone union at 6 months and 1 year.

Condition or disease Intervention/treatment Phase
Spinal Fusion Drug: Abaloparatide Drug: Placebo Phase 2

Detailed Description:

This is a prospective randomized, double-blinded, placebo-controlled, phase 2, 12-month pilot to study the efficacy of abaloparatide in postmenopausal women needing lumbar spinal fusion surgery. Seventy-two women with low bone mass who are scheduled to undergo spinal fusion surgery will be randomized 2:1 in a blinded fashion to receive either 80 mcg of abaloparatide subcutaneously (SC) every day or an identical-appearing placebo SC for 6 months. This study has 3 objectives:

  1. In this pilot study we will evaluate surgical outcomes at one year and the primary outcome will be fusion based on CT exam with categories of Fusion/ Indeterminate/ Not fused and this will be compared between groups receiving 6 months of abaloparatide vs. placebo. Secondary outcomes for surgical success will be evidence of pedicle screw loosening, adjacent segment fracture and proximal junctional kyphosis. This data will be used to determine effect sizes and variance to power the next larger clinical trial.
  2. To determine if abaloparatide/Tymlos versus placebo leads to a faster reduction in pain as assessed by both the Numeric Rating Scale (NRS) and the Oswestry Disability Index (ODI) for low back pain at 6 months.
  3. As an exploratory proof of concept objective we will determine if abaloparatide/Tymlos versus placebo results in greater fusion bone mass volume (FBMV) as a marker of bone union at 6 months and 1 year to see whether at one year post lumbar spinal fusion surgery, greater FBMV is associated with improved spinal surgery outcomes including: enhanced bone union, reduced pedicle screw loosening, adjacent segment fracture and proximal junctional kyphosis. This would serve as evidence that FBMV can be used as an early validated marker of fusion surgery success.

All analyses will be two-sided and the alpha level will be set at 0.05. FBMV, pain and function will be compared by drug (Abaloparatide vs. placebo) at 6 months. Compliance will be considered as taking 80% of the study drug. For the primary analysis we will evaluate bone union and reduced pedicle screw loosening, adjacent segment fracture, and proximal junctional kyphosis as dichotomous variables at 12 months using logistic regression and comparing the placebo group to the abaloparatide group. We will also evaluate FBMV as a continuous variable and evaluate differences in this outcome between abaloparatide and placebo groups at 6 months as an exploratory outcome variable. We will determine if FBMV differs in those with or without markers of surgical success for validity of FBMV, regardless of prior treatment group. In addition, these data will be used to determine effect sizes and variance to power the next larger clinical trial.

We will evaluate NRS and ODI score by using repeated measures of these variables over time by treatment group and evaluate NRS at 6 months in the placebo versus abaloparatide group. Comorbidity, age, prior fracture, prior use of bisphosphonates and other covariates will be evaluated, via multivariable regression, as to whether they lead to a change in the estimate of effect in order to be considered for inclusion in the models.

If abaloparatide can improve outcomes following lumbar spine fusion surgery, this pilot study could lead to the requisite two year trial that may have an impact on the treatment of fusion surgery patients.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 72 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomized controlled trial
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Placebo will be used that will be identical to active drug in appearance
Primary Purpose: Treatment
Official Title: Phase II Trial of Abaloparatide vs. Placebo in Post-Menopausal Women Receiving Initial Spinal Fusion Surgery
Actual Study Start Date : December 19, 2018
Estimated Primary Completion Date : September 2021
Estimated Study Completion Date : September 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Abaloparatide
Abaloparatide 80 mcg dose administered subcutaneously with a pen once daily for 6 months
Drug: Abaloparatide
80 mcg delivered SC by a pen
Other Name: Tymlos

Placebo Comparator: Placebo
Placebo administered subcutaneously with a pen once daily for 6 months
Drug: Placebo
A pen to deliver a SC dose of placebo
Other Name: placebo pen




Primary Outcome Measures :
  1. Difference in measure of fusion mass bridging from transverse process to transverse process [ Time Frame: one year ]
    CT assessment of fusion mass using a qualitative five-point scale to assess fusion quality (1 = unfused, 2 = partial unilateral fusion, 3 = partial bilateral fusion, 4 = complete unilateral fusion, 5 = complete bilateral fusion)

  2. Difference in incidence of adverse surgical outcomes [ Time Frame: one year ]
    Adverse outcomes include pedicle screw loosening, adjacent segment fracture and proximal junctional kyphosis will be evaluated on CT images


Secondary Outcome Measures :
  1. Pain assessed by the Numeric Rating Scale [ Time Frame: 6 months ]
    Numeric Rating Scale (NRS) from 0 to 10 with higher scores indicating more pain.

  2. Pain assessed by the Oswestry Disability Index [ Time Frame: 6 months ]
    Oswestry Disability Index for low back pain with a score of 0 to 50 points or 0 to 100%. Higher scores indicate more pain.


Other Outcome Measures:
  1. CT evaluation of Fusion bone mass volume [ Time Frame: 6 months and 1 year ]
    fusion bone mass volume (FBMV) as a marker of bone union will be assessed on CT images



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   50 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Postmenopausal women (defined as >12 months since last menstrual cycle)
  • Age of 50 years or older,
  • Requiring posterolateral lumbar spine fusion surgery (L1-2; L2-3; L3-4; L4-5, L5-S1) with single or multi-level fusion for degenerative conditions of the lumbar spine (including lumbar degenerative disk disease, severe instability, high grade spondylolisthesis, deformity, degenerative scoliosis, pseudoarthrosis, and spinal stenosis) under the care of spine surgeons at the Hospital for Special Surgery.

Exclusion Criteria:

  1. Hypersensitivity to abaloparatide
  2. Patients with increased risk of osteosarcoma: Paget's disease, prior radiation therapy
  3. Patients with active hypercalcemia or current diagnosis of hyperparathyroidism
  4. History of multiple renal calculi or renal calculus within 2 years
  5. Unexplained elevations in alkaline phosphatase
  6. Evidence of metastatic cancer or multiple myeloma.
  7. Patients unwilling to take placebo or abaloparatide.
  8. Patients whose surgery is for a revision to a prior lumbar spinal fusion surgery
  9. Chronic oral steroids (>= 7.5 mg prednisone/d currently and for more than 1 month) for an inflammatory comorbid diagnosis
  10. Patients who cannot understand and sign the informed consent
  11. Patients who are unable to meet the proposed follow-up schedule
  12. Patients with >1 year of prior cumulative treatment with Forteo and/or Tymlos, or any use of Forteo or Tymlos within the 6 months prior to enrollment.
  13. Patients who have received bisphosphonate treatment of >1 year in past 5 years
  14. Patients who are current smokers
  15. Non-English speakers

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03841058


Locations
Layout table for location information
United States, New York
Hospital for Special Surgery
New York, New York, United States, 10021
Sponsors and Collaborators
Hospital for Special Surgery, New York
Investigators
Layout table for investigator information
Principal Investigator: Emily Stein, MD Hospital for Special Surgery, New York
Layout table for additonal information
Responsible Party: Hospital for Special Surgery, New York
ClinicalTrials.gov Identifier: NCT03841058    
Other Study ID Numbers: 2018-0287
First Posted: February 15, 2019    Key Record Dates
Last Update Posted: April 22, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Hospital for Special Surgery, New York:
abalopartide
pain
surgical outcome
Additional relevant MeSH terms:
Layout table for MeSH terms
Abaloparatide
Bone Density Conservation Agents
Physiological Effects of Drugs