Safety and Tolerability of Intravenous LLP2A-Alendronate for Osteopenia Secondary to Glucocorticoids
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|ClinicalTrials.gov Identifier: NCT03197623|
Recruitment Status : Completed
First Posted : June 23, 2017
Last Update Posted : August 6, 2021
|Condition or disease||Intervention/treatment||Phase|
|Osteopenia Osteoporosis Osteonecrosis||Drug: LLP2A-ALENDRONATE Drug: Placebo||Phase 1|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||58 participants|
|Intervention Model:||Sequential Assignment|
|Intervention Model Description:||Randomized, Double-Blind, Placebo-Controlled Single and Multiple Ascending Dose Study|
|Masking:||Triple (Participant, Care Provider, Investigator)|
|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|
|Actual Study Start Date :||October 14, 2016|
|Actual Primary Completion Date :||March 15, 2021|
|Actual Study Completion Date :||March 31, 2021|
50, 150, 400, 750 or 1200 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.
- 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.
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): NCT03197623
|United States, California|
|West Coast Clinical Trials (WCCT)|
|Cypress, California, United States, 92626|
|Diablo Clinical Research|
|Walnut Creek, California, United States, 94598|
|United States, Pennsylvania|
|Altoona Center for Clinical Research|
|Duncansville, Pennsylvania, United States, 16635|
|United States, Texas|
|Metroplex Clinical Research Center|
|Dallas, Texas, United States, 75231|
|Principal Investigator:||Nancy E Lane, MD||UC Davis Health|
|Study Director:||Nancy E Lane, MD||UC Davis Health|