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

NCT03197623 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: 20161825LLP2A-001
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 4

Brief 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

Conditions

Osteopenia; Osteoporosis; Osteonecrosis

Keywords

Glucocorticoids

Outcome Measures

Primary Outcomes (1)

• Dose limiting Adverse events

  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

  Duration of the Study, average of 4 years

Secondary Outcomes (2)

• Severe infusion reactions

  Duration of the study, average of 4 years

• Grade 2 elevated creatinine

  Duration of the study, average of 4 years

Study Arms (2)

LLP2A-ALENDRONATE

EXPERIMENTAL

50, 150, 400, 750 or 1200 μg/kg or placebo given as a one time intravenous administration over 120 minutes.

Drug: LLP2A-ALENDRONATE

Placebo

PLACEBO COMPARATOR

Placebo given as a one time intravenous administration over 120 minutes.

Drug: Placebo

Interventions

LLP2A-ALENDRONATE DRUG

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.

Also known as: LLP2A-Ale

LLP2A-ALENDRONATE

Placebo DRUG

Placebo, one time single administration given intravenously over 120 minutes.

Placebo

Eligibility Criteria

• Age: 20 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must meet all of the following criteria to be included in the study.
• years old
• 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
• Anticipated to continue to receive at least 5 mg/day prednisone or equivalent throughout study participation
• T score ≤ -1.0 in the femoral neck or total hip or lumbosacral spine. Only one result from one of these locations that is ≤ -1.0 is required. For screening DXA, a DXA completed within 6 months of screening may be used; otherwise DXA must be completed within 4 weeks of screening visit.
• Must be ambulatory and able to attend all appointments
• Women 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.
• In the opinion of the investigator, the concurrent medical conditions of the study subject are stable
• Subject undergoing PET/CT scans must have the ability to lay motionless for up to 30-45 minutes
• Anticipated to continue to receive all chronic medications without dose changes throughout study participation
• Subjects undergoing PET/CT scans must have the ability to lay motionless for up to 30-45 minutes

You may not qualify if:

• Subjects who meet any of the following criteria will be excluded from the study:
• Weight greater than the limit of the DXA table at the clinical site
• History or concurrent conditions that might place the subject at increased risk, such as renal insufficiency (CKD 4 or 5), glomerulonephritis, atypical infections due to impaired immunity, hypersensitivity to multiple IV medications
• 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)
• Prior use or current need for prohibited concomitant medications
• Rheumatic disease with clinically significant renal or central nervous system involvement
• History of deep vein thrombosis (DVT) along with taking any prophylaxis/treatment that occurred within the last 5 years
• History of clinically significant atrial fibrillation and/or taking medications for its treatment and prevention
• Unable or unwilling to comply with restrictions on alcohol 9. Previous hypersensitivity to alendronate
• \. 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
• hydroxyvitamin D (25-OH Vitamin D) below 10ng/mL
• TSH \> upper limit of normal (ULN)
• Hepatic enzymes (ALT, AST, GGT) \> 1.5 X ULN

Sponsors & Collaborators

• Nancy E. Lane, MD: lead
• California Institute for Regenerative Medicine (CIRM): collaborator

Study Sites (4)

West Coast Clinical Trials (WCCT)

Cypress, California, 92626, United States

Location

Diablo Clinical Research

Walnut Creek, California, 94598, United States

Location

Altoona Center for Clinical Research

Duncansville, Pennsylvania, 16635, United States

Location

Metroplex Clinical Research Center

Dallas, Texas, 75231, United States

Location

MeSH Terms

Conditions

Bone Diseases, Metabolic; Osteoporosis; Osteonecrosis

Condition Hierarchy (Ancestors)

Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Necrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Nancy E Lane, MD

  UC Davis Health

  PRINCIPAL INVESTIGATOR

• Nancy E Lane, MD

  UC Davis Health

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Model Details: Randomized, Double-Blind, Placebo-Controlled Single and Multiple Ascending Dose Study

Study Record Dates

• First Submitted: April 19, 2017
• First Posted: June 23, 2017
• Study Start: October 14, 2016
• Primary Completion: March 15, 2021
• Study Completion: March 31, 2021
• Last Updated: August 6, 2021

Record last verified: 2021-08

Locations

US (4)