OsteopeniaPhase 1NCT03197623
Safety and Tolerability of Intravenous LLP2A-Alendronate for Osteopenia Secondary to Glucocorticoids
A Phase 1 study testing LLP2A-ALENDRONATE in people with Osteopenia and Osteoporosis, run by Nancy E. Lane, MD at 4 sites in United States.
Trial 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 Read more about this study
- Who is it for?
- Ages 20 to 85 years
- Conditions the study is for
- Osteopenia, Osteoporosis, Osteonecrosis
- What is being tested?
- LLP2A-ALENDRONATE
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 58 participants
- Where
- 4 sitesUnited States
- Study dates
- 14 Oct 2016to 31 Mar 2021
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects must meet all of the following criteria to be included in the study.
- 20 - 85 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
Show all 11Show fewer
- 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
Who cannot join
- 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
Show all 21Show fewer
- 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
- 10. 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 (eGRF) <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 (QTcF (Fredericia) of > 450 msec for men, > 470 msec for women)
- Any other clinically significant laboratory value as judged by the investigator 11. Subject cannot enroll in MAD part of study until after 60 days of completing SAD part of study 12. Subjects undergoing PET/CT scans must not be breast-feeding 13. History of hypersensitivity to fluoride
Trial locations and contacts
4 sites in 1 country.
United States4 sites
West Coast Clinical Trials (WCCT)
Cypress, California, 92626
Metroplex Clinical Research Center
Dallas, Texas, 75231
Altoona Center for Clinical Research
Duncansville, Pennsylvania, 16635
Diablo Clinical Research
Walnut Creek, California, 94598
About this study
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
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
Read the 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 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.
- Conditions
- Osteopenia, Osteoporosis, Osteonecrosis
- Being tested
- LLP2A-ALENDRONATE, Placebo
- Keywords
- Glucocorticoids
- Medical subject headings
- Bone Diseases, Metabolic, Osteoporosis, Osteonecrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LLP2A-ALENDRONATEDrug
Also called LLP2A-Ale
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.
PlaceboDrug
Placebo, one time single administration given intravenously over 120 minutes.
| Study group | Role | What they receive |
|---|---|---|
| LLP2A-ALENDRONATE | Experimental | 50, 150, 400, 750 or 1200 μg/kg or placebo given as a one time intravenous administration over 120 minutes. Receives: Drug: LLP2A-ALENDRONATE |
| Placebo | Placebo comparator | Placebo given as a one time intravenous administration over 120 minutes. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Duration of the Study, average of 4 years
Secondary outcomes (2)
Severe infusion reactions
Fever, myalgia, nausea/vomit, headache, flu like symptoms in ≥ 2 subjects receiving LLP2A-Ale
Measured: Duration of the study, average of 4 years
Grade 2 elevated creatinine
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.
Measured: Duration of the study, average of 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jun 2017
- Study start14 Oct 2016
- Primary completion15 Mar 2021
- Study completion31 Mar 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for OsteopeniaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Model description
- Randomized, Double-Blind, Placebo-Controlled Single and Multiple Ascending Dose Study
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 58 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nancy E. Lane, MD
- Sponsor type
- University, hospital or other
- Collaborators
- California Institute for Regenerative Medicine (CIRM)
- Responsible party
- Sponsor-investigator, Nancy E. Lane, MD, University of California, Davis
- Investigators
- Nancy E Lane, MD, Principal investigator, UC Davis HealthNancy E Lane, MD, Study director, UC Davis Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03197623
- Sponsor's protocol ID
- 20161825
- Other IDs
- LLP2A-001
- Status last verified
- Aug 2021
- First submitted
- 19 Apr 2017
- Last updated
- 6 Aug 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 6 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03197623
- Acronym / sponsor ID
- 20161825
- Conditions
- Osteopenia, Osteoporosis, Osteonecrosis
- Keywords
- Glucocorticoids
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 58 participants (actual)
- Lead sponsor
- Nancy E. Lane, MDUniversity, hospital or other
- Collaborators
- California Institute for Regenerative Medicine (CIRM)
- Study start
- 14 Oct 2016 (actual)
- Primary completion
- 15 Mar 2021 (actual)
- Study completion
- 31 Mar 2021 (actual)
- First posted
- 23 Jun 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- Randomized, Double-Blind, Placebo-Controlled Single and Multiple Ascending Dose Study
| Arm | Type | Receives |
|---|---|---|
| LLP2A-ALENDRONATE | Experimental | Drug: LLP2A-ALENDRONATE50, 150, 400, 750 or 1200 μg/kg or placebo given as a one time intravenous administration over 120 minutes. |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo given as a one time intravenous administration over 120 minutes. |
Who may qualify
- Ages
- 20 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Subjects must meet all of the following criteria to be included in the study.
- 20 - 85 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.
Key exclusion criteria (21 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LLP2A-ALENDRONATEAlso: LLP2A-AleA 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. | Drug | LLP2A-ALENDRONATE |
| PlaceboPlacebo, one time single administration given intravenously over 120 minutes. | Drug | Placebo |
Primary outcome
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
2 secondary outcomes
Severe infusion reactions
Time frame: Duration of the study, average of 4 years
Grade 2 elevated creatinine
Time frame: Duration of the study, average of 4 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Aug 2021.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nancy E Lane, MD principal investigator
UC Davis Health
Nancy E Lane, MD study director
UC Davis Health
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing LLP2A-ALENDRONATE in people with Osteopenia and Osteoporosis, run by Nancy E. Lane, MD at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose limiting Adverse events (time frame: Duration of the Study, average of 4 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Aug 2021.