Safety and Tolerability of Intravenous LLP2A-Alendronate for Osteopenia Secondary to Glucocorticoids
|Osteopenia Osteoporosis Osteonecrosis||Drug: LLP2A-ALENDRONATE Drug: Placebo||Phase 1|
|Study Design:||Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:
Randomized, Double-Blind, Placebo-Controlled Single and Multiple Ascending Dose StudyMasking: Participant, Care Provider, Investigator
Primary Purpose: Treatment
|Official Title:||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 Glucocorticoids|
- Dose limiting Adverse events [ Time Frame: Duration of the Study, average of 4 years ]Incidence of dose limiting or intolerable treatment related adverse events (AEs) including A serious drug-related adverse event in ≥ 1 subject receiving LLP2A-Ale and/or Severe drug related adverse events in ≥ 2 subjects receiving LLP2A-Ale
- Severe infusion reactions [ Time Frame: Duration of the study, average of 4 years ]Fever, myalgia, nausea/vomit, headache, flu like symptoms in ≥ 2 subjects receiving LLP2A-Ale
- Grade 2 elevated creatinine [ Time Frame: Duration of the study, average of 4 years ]serum creatinine greater than 1.5 - 3.0 x baseline; greater than 1.5 - 3.0 x upper limit of normal (CTCAE v4.0) in ≥ 1 patient.
|Actual Study Start Date:||October 14, 2016|
|Estimated Study Completion Date:||June 2020|
|Estimated Primary Completion Date:||January 2020 (Final data collection date for primary outcome measure)|
50, 150, 400 or 750 μg/kg or placebo given as a one time intravenous administration over 120 minutes.
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.
Other Name: LLP2A-Ale
Placebo Comparator: Placebo
placebo given as a one time intravenous administration over 120 minutes.
Placebo, one time single administration given intravenously over 120 minutes.
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 50 patients will be enrolled, 32 in the SAD and 18 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT03197623
|Contact: Christy Pifer, BSfirstname.lastname@example.org|
|Contact: Center for Musculoskeletal Health||916-734-4534||CMHClinicalTrials@ucdmc.ucdavis.edu|
|United States, California|
|West Coast Clinical Trials (WCCT)||Recruiting|
|Cypress, California, United States, 92626|
|Contact: Kacie Hale, BS 714-252-0700 email@example.com|
|Principal Investigator: Bonnie Bock, MD|
|Diablo Clinical Research||Recruiting|
|Walnut Creek, California, United States, 94598|
|Contact: Lana Norman 925-930-7267 lnorman@Diabloclinical.com|
|Contact: Ava Paulazzo (925) 930-7267 apaulazzo@Diabloclinical.com|
|Principal Investigator: Mark Christiansen, MD|
|United States, Pennsylvania|
|Altoona Center for Clinical Research||Recruiting|
|Duncansville, Pennsylvania, United States, 16635|
|Contact: Lisa Claycomb 814-696-7053 firstname.lastname@example.org|
|Principal Investigator: Alan Kivitz, MD|
|United States, Texas|
|Metroplex Clinical Research Center||Recruiting|
|Dallas, Texas, United States, 75231|
|Contact: Michael Johnson 214-879-6737 email@example.com|
|Principal Investigator: Roy Fleischmann, MD|
|Principal Investigator:||Nancy E Lane, MD||UC Davis Health|
|Study Director:||Nancy E Lane, MD||UC Davis Health|