This site became the new ClinicalTrials.gov on June 19th. Learn more.
Show more
ClinicalTrials.gov Menu IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu IMPORTANT: Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu
Give us feedback
Trial record 1 of 1 for:    NCT03197623
Previous Study | Return to List | Next Study

Safety and Tolerability of Intravenous LLP2A-Alendronate for Osteopenia Secondary to Glucocorticoids

This study is currently recruiting participants.
See Contacts and Locations
Verified June 2017 by Nancy E. Lane, MD, University of California, Davis
Sponsor:
Collaborator:
California Institute for Regenerative Medicine
Information provided by (Responsible Party):
Nancy E. Lane, MD, University of California, Davis
ClinicalTrials.gov Identifier:
NCT03197623
First received: April 19, 2017
Last updated: June 21, 2017
Last verified: June 2017
  Purpose
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.

Condition Intervention Phase
Osteopenia Osteoporosis Osteonecrosis Drug: LLP2A-ALENDRONATE Drug: Placebo Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:
Randomized, Double-Blind, Placebo-Controlled Single and Multiple Ascending Dose Study
Masking: 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

Resource links provided by NLM:


Further study details as provided by Nancy E. Lane, MD, University of California, Davis:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 50
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)
Arms Assigned Interventions
Experimental: LLP2A-ALENDRONATE
50, 150, 400 or 750 μg/kg or placebo given as a one time intravenous administration over 120 minutes.
Drug: LLP2A-ALENDRONATE
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.
Drug: Placebo
Placebo, one time single administration given intravenously over 120 minutes.

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 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.

  Eligibility

Ages Eligible for Study:   20 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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.

Exclusion Criteria:

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:

    • Total calcium values outside the normal range (corrected if albumin < lower limit of normal (LLN))
    • Phosphate level < LLN
    • 25-hydroxyvitamin D (25-OH Vitamin D) below 10ng/mL
    • TSH > upper limit of normal (ULN)
    • Hepatic enzymes (ALT, AST, GGT) > 1.5 X ULN
    • Creatinine clearance (eGFR)< 35 mL/min/1.73 m2 using the Modification of Diet in Renal Disease (MDRD) formula
    • Hemoglobin < 10 g/dL
    • Positive serology for HIV, Hepatitis B or C
    • Positive pregnancy test
    • Prolonged QTc interval (> 450 ms) (QTcF (Fredericia) of > 450 msec for men, > 470 msec for women)
    • Any other clinically significant laboratory value as judged by the investigator
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT03197623

Contacts
Contact: Christy Pifer, BS 916-734-4536 capifer@ucdavis.edu
Contact: Center for Musculoskeletal Health 916-734-4534 CMHClinicalTrials@ucdmc.ucdavis.edu

Locations
United States, California
West Coast Clinical Trials (WCCT) Recruiting
Cypress, California, United States, 92626
Contact: Kacie Hale, BS    714-252-0700    kacie.hale@wcct.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    altoonaresearch@gmail.com   
Principal Investigator: Alan Kivitz, MD         
United States, Texas
Metroplex Clinical Research Center Recruiting
Dallas, Texas, United States, 75231
Contact: Michael Johnson    214-879-6737    mjohnson@mcrcdallas.com   
Principal Investigator: Roy Fleischmann, MD         
Sponsors and Collaborators
Nancy E. Lane, MD
California Institute for Regenerative Medicine
Investigators
Principal Investigator: Nancy E Lane, MD UC Davis Health
Study Director: Nancy E Lane, MD UC Davis Health
  More Information

Responsible Party: Nancy E. Lane, MD, Professor, University of California, Davis
ClinicalTrials.gov Identifier: NCT03197623     History of Changes
Other Study ID Numbers: 20161825
LLP2A-001 ( Other Identifier: UC Davis )
Study First Received: April 19, 2017
Last Updated: June 21, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Nancy E. Lane, MD, University of California, Davis:
Glucocorticoids

Additional relevant MeSH terms:
Osteoporosis
Bone Diseases, Metabolic
Osteonecrosis
Bone Diseases
Musculoskeletal Diseases
Necrosis
Pathologic Processes
Glucocorticoids
Alendronate
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Bone Density Conservation Agents

ClinicalTrials.gov processed this record on July 26, 2017