Safety and Tolerability of Intravenous LLP2A-Alendronate for Osteopenia Secondary to Glucocorticoids
Condition: Osteopenia; Osteoporosis; Osteonecrosis
MeSH terms: Osteoporosis; Bone Diseases, Metabolic; Osteonecrosis
Study type: Interventional
Phase: Phase 1

Summary: 
      A Phase 1 Randomized, Double-Blind, Placebo-Controlled Single and Multiple Ascending Dose
      Study of the Safety and Tolerability of Intravenous LLP2A-Alendronate in Adult Men and Women
      with Osteopenia Secondary to Corticosteroids
    

Detailed description: 
      The study is designed to evaluate safety and tolerability of LLP2A-Ale beginning with a
      single ascending dose (SAD) cohort followed by multiple ascending dose (MAD) cohorts with
      matching placebo in each cohort. The population in this study includes patients with low bone
      density (osteopenia with a T score ≤ -1.0) in the femoral neck, total hip or lumbosacral
      spine who are taking Corticosteroids. Up to 59 patients will be enrolled, 32 in the SAD and
      27 in the MAD.

      LLP2A-Ale is a novel anabolic agent. It appears that LLP2A-Ale may have utility in a variety
      of conditions where new bone formation is required. Non-traumatic osteonecrosis (ON) has been
      selected as the first indication for LLP2A-Ale because of the high unmet need, absence of
      treatments besides surgical joint replacement, and the clear need to attract and stimulate
      differentiation of stem cells into the region of necrotic bone. However, osteonecrosis is a
      rare, sporadic disease. Therefore, the Phase 1 study is being performed in people at risk for
      osteonecrosis, as a population representative of people with osteonecrosis, who will be the
      participants in any subsequent Phase 2 and 3 studies.

      Non-traumatic ON may also be caused by a variety of underlying medical conditions.
      Glucocorticoid use, alcohol, and smoking contribute to up to 80% of cases of nontraumatic ON.
      The relationship to GC is the strongest in people receiving relatively long term therapy,
      with risk increasing with cumulative exposure over three or more months. Vasculitis from
      autoimmune diseases predisposes to ON and ON is particularly associated with Systemic Lupus
      Erythematous (SLE), possibly due to coexistence of vasculitis and chronic GC treatment. In
      different series, symptomatic ON is reported in about 5-30% of SLE patients. Because many
      foci of ON are asymptomatic, rates based on MRI surveillance are higher, in the range of 30 -
      50%, and often are multifocal. Because of the particularly high incidence of ON in SLE we
      anticipate that SLE patients will be a significant component of the population in later
      trials. Therefore investigators in this Phase 1 trial include rheumatologists in order to
      increase the likelihood of inclusion of lupus patients in this first study.
    

Intervention name(s): LLP2A-ALENDRONATE; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): A small molecule, LLP2A-Ale that directs endogenous mesenchymal stem cells (MSCs), the cells that have the potential to grow bone tissue, to the bone surface to form new bone. Single administration of LLP2A-Ale given intravenously over 120 minutes.; Placebo, one time single administration given intravenously over 120 minutes.
Other intervention name(s): LLP2A-Ale
Intervention MeSH terms: Alendronate
Allocation: Randomized
Intervention model: Sequential Assignment
Intervention model description: Randomized, Double-Blind, Placebo-Controlled Single and Multiple Ascending Dose Study
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: Glucocorticoids