Phase II Trial of Abaloparatide vs. Placebo in Post-Menopausal Women Receiving Initial Spinal Fusion Surgery
Abaloparatide vs. Placebo in Postmenopausal Women Receiving Initial Spinal Fusion Surgery
Sponsors
Source
Hospital for Special Surgery, New York
Oversight Info
Has Dmc
Yes
Is Fda Regulated Drug
Yes
Is Fda Regulated Device
No
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.
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 the investigators will evaluate surgical outcomes at one year
(enhanced bone union, reduced pedicle screw loosening, adjacent segment fracture and
proximal junctional kyphosis) and compare the impact of 6 months of abaloparatide vs.
placebo on surgical success, these 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 for
low back pain at 6 months.
3. As an exploratory proof of concept objective the investigators 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. The investigators
will 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. The
investigators 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 determine if FBMV differs in those exhibiting each of these outcomes
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. The
investigators 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.
Overall Status
Not yet recruiting
Start Date
2019-05-01
Completion Date
2021-05-01
Primary Completion Date
2021-05-01
Phase
Phase 2
Study Type
Interventional
Primary Outcome
Measure |
Time Frame |
|
Difference in measure of fusion mass bridging from transverse process to transverse process |
one year |
|
Difference in incidence of adverse surgical outcomes |
one year |
Secondary Outcome
Measure |
Time Frame |
|
Pain assessed by the Numeric Rating Scale |
6 months |
|
Pain assessed by the Oswestry Disability Index |
6 months |
Enrollment
72
Condition
Intervention
Intervention Type
Drug
Intervention Name
Description
80 mcg delivered SC by a pen
Arm Group Label
Abaloparatide
Other Name
Tymlos
Intervention Type
Drug
Intervention Name
Description
A pen to deliver a SC dose of placebo
Arm Group Label
Placebo
Other Name
placebo pen
Eligibility
Criteria
Inclusion Criteria:
- Postmenopausal women with low bone mass (BMD t-score <-1.0 and >-2.5 at spine, hip or
wrist (low BMD) and without prior fragility fracture)
- 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:
- Hypersensitivity to abaloparatide
- Patients with increased risk of osteosarcoma: Paget's disease, prior radiation therapy
*Patients with active hypercalcemia or current hyperparathyroidism
- History of multiple renal calculi or renal calculus within 2 years
- Unexplained elevations in alkaline phosphatase
- Evidence of metastatic cancer or multiple myeloma.
- Patients unable to complete the mini mental state exam (MMSE <18)
- Patients unwilling to take placebo or abaloparatide.
- Patients with 4 or more epidurals given in the preceding 12 months
- Patients whose surgery is for a revision to a prior spinal surgery
- Chronic oral steroids (> 7.5 mg prednisone/d) for an inflammatory comorbid diagnosis
- Previous lumbar surgery, transforaminal lumbar interbody fusion (with removal of a
unilateral facet joint)
- Spondylolisthesis, with >50% slippage
- Patients who cannot understand and sign the informed consent
- Patients who are unable to meet the proposed follow-up schedule
- Patients with a history of gout or hyperuricemia
- Patients with >1 year of prior treatment with Forteo or any use within the 6 months
prior to enrollment.
- Patients cannot have taken oral bisphosphonate treatment in past 1 year or IV
bisphosphonates in the past 2 years
- Non-English speakers
Gender
Female
Minimum Age
50 Years
Maximum Age
N/A
Healthy Volunteers
No
Verification Date
2019-02-01
Lastchanged Date
N/A
Firstreceived Date
N/A
Responsible Party
Responsible Party Type
Sponsor
Keywords
Has Expanded Access
No
Number Of Arms
2
Arm Group
Arm Group Label
Abaloparatide
Arm Group Type
Active Comparator
Description
Abaloparatide 80 mcg dose administered subcutaneously with a pen once daily for 6 months
Arm Group Label
Placebo
Arm Group Type
Placebo Comparator
Description
Placebo administered subcutaneously with a pen once daily for 6 months
Firstreceived Results Date
N/A
Other Outcome
Measure
CT evaluation of Fusion bone mass volume
Time Frame
6 months and 1 year
Description
fusion bone mass volume (FBMV) as a marker of bone union will be assessed on CT images
Patient Data
Sharing Ipd
No
Firstreceived Results Disposition Date
N/A
Study Design Info
Allocation
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Randomized controlled trial
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description
Placebo will be used that will be identical to active drug in appearance
Study First Submitted
February 6, 2019
Study First Submitted Qc
February 12, 2019
Study First Posted
February 15, 2019
Last Update Submitted
February 12, 2019
Last Update Submitted Qc
February 12, 2019
Last Update Posted
February 15, 2019
ClinicalTrials.gov processed this data on February 15, 2019
Conditions
Conditions usually refer to a disease, disorder, syndrome, illness, or injury. In ClinicalTrials.gov,
conditions include any health issue worth studying, such as lifespan, quality of life, health risks, etc.
Interventions
Interventions refer to the drug, vaccine, procedure, device, or other potential treatment being studied.
Interventions can also include less intrusive possibilities such as surveys, education, and interviews.
Study Phase
Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions
that study is seeking to answer:
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.