Summary

for people ages 20-75 (full criteria)
at Walnut Creek, California and other locations
study started
estimated completion
Nancy E Lane, MD

Description

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.

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

Details

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.

Keywords

Osteopenia Osteoporosis Osteonecrosis Glucocorticoids Bone Diseases, Metabolic Alendronate LLP2A-ALENDRONATE

Eligibility

You can join if…

Open to people ages 20-75

Subjects must meet all of the following criteria to be included in the study.

  1. 20 - 75 years old
  2. Receiving 5 - 40 mg/day prednisone, or equivalent of another GC (methylprednisolone 4 mg/day, or prednisone 10 mg every other day) for a minimum of 4 consecutive weeks prior to enrollment
  3. Anticipated to continue to receive at least 5 mg/day prednisone or equivalent throughout study participation
  4. T score ≤ -1.0 in the femoral neck, total hip or lumbosacral spine.
  5. Must be ambulatory and able to attend all appointments
  6. Women of child-bearing potential (i.e., non-postmenopausal women or women who are not surgically sterile) must agree to use one of the following methods of birth control for the duration of the clinical trial: systemic hormonal contraceptive (oral, injected, transdermal), intrauterine device, double barrier (e.g., cervical cap or diaphragm with condom or spermicide). Men with female partners must agree to use double barrier contraception, unless their partner is using systemic hormonal contraceptives or has an intrauterine device.
  7. In the opinion of the investigator, the concurrent medical conditions of the study subject are stable.

You CAN'T join if...

Subjects who meet any of the following criteria will be excluded from the study:

  1. Weight greater than the limit of the DXA table at the clinical site
  2. History of bone disease (besides osteopenia), skeletal injury at sites of DXA/QCT examination, skeletal radiation, or conditions that interfere with the ability to have an accurate DXA/QCT scan at any site
  3. History or concurrent conditions that might place the patient at increased risk, such as renal insufficiency (CKD 4 or 5), glomerulonephritis, atypical infections due to impaired immunity, hypersensitivity to multiple IV medications
  4. History of or concurrent presence of medical conditions which might interfere with ability to participate for the duration of the study, such as clinically significant cardiovascular disease, uncontrollable hypertension, uncontrolled asthma, symptomatic pulmonary fibrosis, recent GI bleeding requiring transfusion, psychosis, substance abuse or hospital admission within 6 months of enrollment (except for elective procedures)
  5. Prior use or current need for prohibited concomitant medications (Section 5.10)
  6. Rheumatic disease with clinically significant renal or central nervous system involvement
  7. History of deep vein thrombosis (DVT) or taking any prophylaxis/treatment within the last 5 years
  8. History of clinically significant atrial fibrillation and/or taking medications for its treatment and prevention
  9. Unable or unwilling to comply with restrictions on alcohol, smoking
  10. . Previous hypersensitivity to alendronate.
  11. . Any of the following on Screening laboratory tests:
  12. Total calcium values outside the normal range (corrected if albumin < lower limit of normal (LLN))
  13. Phosphate level < LLN
  14. 25-hydroxyvitamin D (25-OH Vitamin D) below 10ng/mL
  15. TSH > upper limit of normal (ULN)
  16. Hepatic enzymes (ALT, AST, GGT) > 1.5 X ULN
  17. Creatinine clearance (eGFR)< 35 mL/min/1.73 m2 using the Modification of Diet in Renal Disease (MDRD) formula
  18. Hemoglobin < 10 g/dL
  19. Positive serology for HIV, Hepatitis B or C
  20. Positive pregnancy test
  21. Prolonged QTc interval (> 450 ms) (QTcF (Fredericia) of > 450 msec for men, > 470 msec for women)
  22. Any other clinically significant laboratory value as judged by the investigator

Locations

  • Diablo Clinical Research accepting new patients
    Walnut Creek California 94598 United States
  • West Coast Clinical Trials (WCCT) accepting new patients
    Cypress California 92626 United States

Lead Scientist

  • Nancy E Lane, MD
    Professor, General Medicine, Geriatrics, and Bioethics. Authored (or co-authored) 161 research publications

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Nancy E. Lane, MD
Links
Sign up for this study
ID
NCT03197623
Phase
Phase 1
Study Type
Interventional
Last Updated