Effect of Abaloparatide on Lumbar Disc Degeneration

The investigators will perform a randomized, double blind, placebo controlled
proof-of-concept Phase 2 clinical trial of the effect of abaloparatide for the treatment of
lumbar degenerative disc disease. Adults with clinically significant lumbar degenerative disc
disease who meet inclusion and exclusion criteria and sign informed consent with be
randomized in a 2:1 ratio to study drug:placebo.

The study team physicians will review pertinent laboratory data, medication history, and
problem lists in the potential research participant's medical record to ensure eligibility
for the study. The investigators will also contact the potential research participants by
telephone to explain the study in further detail and elicit information not available in the
medical record that would affect the potential participant's eligibility to participate in
the study.

Potential research participants who meet the study criteria and are interested in
participating in the study will have an appointment arranged at the Johns Hopkins Orthopedic
Clinic. At the study visit, a study team physician and research coordinator will review the
study and consent the research participants.

Research participants who provide informed consent will have age, sex, and ethnicity
recorded, undergo a focused history and physical exam, and have any necessary blood samples
collected for inclusion/exclusion criteria. The focused history will include the age of onset
of symptoms, age at diagnosis of degenerative disc disease, mechanism of injury, treatments
utilized, and the research participant's current perception of his or her disease control.
The focused physical exam will include inspection and palpation of the affected sites to
assess for pain and mobility of the spine. Research participants will be asked to rate
current pain attributed to degenerative disc disease on a Likert scale pain level and asked
to fill out the Oswestry Disability Index (ODI) and Patient-Reported Outcomes Measurement
Information System (PROMIS-29) and have spinal x-rays and an MRI of the lumbar spine
obtained.

One hundred nine people who meet the study criteria and provide informed consent will be
randomly assigned to 2 groups (abaloparatide:placebo) in a 2:1 fashion (n=73 abaloparatide;
36 placebo).

Participants will be taught how to self-administer a injection of the study drug.
Participants and the study doctor will not know if the participant is receiving abaloparatide
or placebo as the study drug. Participants will inject the study drug daily for 3 months.

Blood and urine samples will be collected 2 weeks after study initiation to evaluate clinical
safety.

Physical exams, health questionnaires, and MRI scans will be performed at 3-, 6-, and
12-month follow-up visits.

The trial will be blinded for all the investigators acquiring and analyzing the data.

Inclusion Criteria:

- Symptomatic moderate to severe discogenic low back pain as defined by centralized
chronic low back pain with a discogenic character (i.e. increases with activity,
worsened with sitting or standing, or requires frequent change of positions) and has
been present for 6+ months

- Identifiable change in disc morphology as defined by MRI consistent with early
degenerative disc disease as defined by both Modified Pfirrmann (MRI) score of 2-3
(Graded 1-8, where 1= hydrated healthy disc, 8 = dark, dehydrated disc) and Modic
Grade II change or less

- Single- or two-level DDD at lumbar spine

- < 30% vertebral body height loss

- Oswestry disability index score > 30

- Failed > 3 months of appropriate non-operative care (i.e. pain medication, local drug
injections, physical therapy)

- Predominant back pain with or without leg pain

- Able and willing to comply with follow-up schedule

- Willing to give written informed consent

Exclusion Criteria:

- Presence of objective motor deficit

- Symptomatic compressive pathology due to stenosis or disc herniation

- Any spondylolisthesis

- Any spondylolysis

- Scoliosis > 20 degrees

- Spinal tumor

- Previous thoracic or lumbar fusion

- Current or prior fracture at T10-S1

- Arachnoiditis

- Current or prior use of PTHrP (abaloparatide) or PTH (teriparatide) analog

- Diagnosis of osteoporosis or osteopenia that is not well controlled on anti-resorptive
therapy and anticipated to require use of an anabolic agent, such as abaloparatide or
teriparatide.

- Evidence of metabolic bone disease as evidenced by abnormalities in calcium, intact
parathyroid hormone, phosphorus or alkaline phosphatase in blood or elevated spot
urine calcium to creatinine ratio.

- History of or current osteosarcoma or cancer metastatic to the bone

- History of or current Paget's disease of bone

- History of or current nephrolithiasis

- History of or current multiple myeloma

- History of focal radiation to any bone

- Current Pregnancy or breastfeeding

- Current use of medications that increase risk of hypercalcemia, such as thiazide
diuretics

- Diagnosis of psychotic disorder

- Participation in another study on investigational drug

- Inability to provide informed consent