Primary Osteoarthritis Patients Scheduled for Total Knee Replacement SurgeryPhase 1NCT02491281
First-in-human Single Ascending Dose Study of LNA043 in Patients Scheduled for Total Knee Replacement
A Phase 1 study testing LNA043 in people with Primary Osteoarthritis Patients Scheduled for Total Knee Replacement Surgery, run by Novartis Pharmaceuticals at 1 site in United States.
Trial summary
This study is designed to evaluate the safety and tolerability of ascending single doses of LNA043 given intra-articularly into the human knee joint prior to its removal at total knee replacement surgery. Read more about this study
- Who is it for?
- Ages 50 to 75 years
- Conditions the study is for
- Primary Osteoarthritis Patients Scheduled for Total Knee Replacement Surgery
- What is being tested?
- LNA043
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 28 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Nov 2015to 6 Mar 2018
- 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 50 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male and female patients age 50 to 75 years of age inclusive, and in good health as determined by past medical history, physical examination, vital signs, electrocardiogram, and laboratory tests at screening
- Patients diagnosed with primary osteoarthritis of the knee assessed locally for whom a total knee replacement is planned
- General health status acceptable for total knee replacement surgery in the opinion of the investigator
- Stable medications within 3 months prior to enrollment (such as appropriate pain medication, antibiotics prophylaxis) and standard of care
Who cannot join
- Presence of inflammatory arthropathy (including but not limited to rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, gout), active acute or chronic infection, or systemic cartilage disorder
- Prior cartilage repair surgery, e.g. microfracture, autologous cartilage implantation (ACI) or else, at the same knee
- Any surgical therapy or local treatment i.a. into the knee (viscosupplementation) to the knee within 2 months prior to enrollment
- BMI > 40; presence of uncontrolled diabetes or hyperthyroidism
- Large effusion in the knee to be replaced, more than (>)1 cm fluid in the suprapatellar space at the midline
- Corticosteroid use by any route except topical and nasal in the 3 months prior to enrollment
Show all 9Show fewer
- History of malignancy of any organ system (other than localized basal cell carcinoma of the skin or in-situ cervical cancer), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases
- Pregnant or nursing (lactating) women
- Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized, Placebo Controlled, Double-blind First-in-human Single Ascending Dose Study of LNA043 in Primary Osteoarthritis Patients Scheduled for Total Knee Replacement
This study is designed to evaluate the safety and tolerability of ascending single doses of LNA043 given intra-articularly into the human knee joint prior to its removal at total knee replacement surgery. In addition, this will help to establish the presence of LNA043 within the articular cartilage, assess pharmacokinetics and immunogenicity, and will allow exploration of biomarkers of hyaline cartilage repair.
- Being tested
- LNA043, Placebo
- Keywords
- Primary Osteoarthritis, Total Knee Replacement, cartilage
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LNA043Drug
ascending single dose on Day 1; 1 to 4 week(s) prior total knee replacement surgery
PlaceboDrug
ascending single dose on Day 1; 1 to 4 week(s) prior total knee replacement surgery
| Study group | Role | What they receive |
|---|---|---|
| LNA043 | Experimental | LNA043 given intra-articularly Receives: Drug: LNA043 |
| Placebo | Placebo comparator | Placebo given intra-articularly Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety endpoints (including number of adverse events CTC-AE, physical exam, vital signs, ECG, safety laboratory and pain measured using KOOS)
Safety and tolerability of LNA043 after one intra-articular injection into the knee of osteoarthritis patients scheduled for total knee replacement
Measured: Up to and including 7 days post-dose
Secondary outcomes (4)
Immunohistochemical staining for LNA043 in knee cartilage
Joint presence and persistence of LNA043 within the cartilage of the knee
Measured: 1 up to 4 weeks post-dose
Concentration of LNA043 in serum and synovial fluid
LNA043 pharmacokinetics in serum and concentration in synovial fluid to determine local and systemic exposure
Measured: Pre-dose, Day 1, Day 4, Day 8, and Day 36
Concentration of ANGPTL in serum and synovial fluid
ANGPTL levels in serum and the synovial fluid
Measured: Pre-dose, Day 1, Day 4, Day 8, and Day 36
Presence of anti-LNA043
Immunogenicity in serum
Measured: Pre-dose, Day 8, and Day 36
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jul 2015 (estimated)
- Study start16 Nov 2015
- Primary completion7 Feb 2018
- Study completion6 Mar 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Primary Osteoarthritis Patients Scheduled for Total Knee Replacement SurgeryStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- 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
- Other
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02491281
- Sponsor's protocol ID
- CLNA043X2101
- Status last verified
- Aug 2018
- First submitted
- 23 Jun 2015
- Last updated
- 11 Dec 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Publications
Gerwin N, Scotti C, Halleux C, Fornaro M, Elliott J, Zhang Y, Johnson K, Shi J, Walter S, Li Y, Jacobi C, Laplanche N, Belaud M, Paul J, Glowacki G, Peters T, Wharton KA Jr, Vostiar I, Polus F, Kramer I, Guth S, Seroutou A, Choudhury S, Laurent D, Gimbel J, Goldhahn J, Schieker M, Brachat S, Roubenoff R, Kneissel M. Angiopoietin-like 3-derivative LNA043 for cartilage regeneration in osteoarthritis: a randomized phase 1 trial. Nat Med. 2022 Dec;28(12):2633-2645. doi: 10.1038/s41591-022-02059-9. Epub 2022 Dec 1.
PubMed 36456835
Study at a glance
From the registry record, last updated by the sponsor on 11 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Placebo Controlled, Double-blind First-in-human Single Ascending Dose Study of LNA043 in Primary Osteoarthritis Patients Scheduled for Total Knee Replacement
- ClinicalTrials.gov ID
- NCT02491281
- Acronym / sponsor ID
- CLNA043X2101
- Keywords
- Primary Osteoarthritis, Total Knee Replacement, cartilage
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 16 Nov 2015 (actual)
- Primary completion
- 7 Feb 2018 (actual)
- Study completion
- 6 Mar 2018 (actual)
- First posted
- 8 Jul 2015 (estimated)
- 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.
This study is designed to evaluate the safety and tolerability of ascending single doses of LNA043 given intra-articularly into the human knee joint prior to its removal at total knee replacement surgery. In addition, this will help to establish the presence of LNA043 within the articular cartilage, assess pharmacokinetics and immunogenicity, and will allow exploration of biomarkers of hyaline cartilage repair.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| LNA043 | Experimental | Drug: LNA043LNA043 given intra-articularly |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo given intra-articularly |
Who may qualify
- Ages
- 50 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Male and female patients age 50 to 75 years of age inclusive, and in good health as determined by past medical history, physical examination, vital signs, electrocardiogram, and laboratory tests at screening
- Patients diagnosed with primary osteoarthritis of the knee assessed locally for whom a total knee replacement is planned
- General health status acceptable for total knee replacement surgery in the opinion of the investigator
- Stable medications within 3 months prior to enrollment (such as appropriate pain medication, antibiotics prophylaxis) and standard of care
Key exclusion criteria (9 listed)
- Presence of inflammatory arthropathy (including but not limited to rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, gout), active acute or chronic infection, or systemic cartilage disorder
- Prior cartilage repair surgery, e.g. microfracture, autologous cartilage implantation (ACI) or else, at the same knee
- Any surgical therapy or local treatment i.a. into the knee (viscosupplementation) to the knee within 2 months prior to enrollment
- BMI > 40; presence of uncontrolled diabetes or hyperthyroidism
- Large effusion in the knee to be replaced, more than (>)1 cm fluid in the suprapatellar space at the midline
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 |
|---|---|---|
| LNA043ascending single dose on Day 1; 1 to 4 week(s) prior total knee replacement surgery | Drug | LNA043 |
| Placeboascending single dose on Day 1; 1 to 4 week(s) prior total knee replacement surgery | Drug | Placebo |
Primary outcome
Safety endpoints (including number of adverse events CTC-AE, physical exam, vital signs, ECG, safety laboratory and pain measured using KOOS)
Time frame: Up to and including 7 days post-dose
Safety and tolerability of LNA043 after one intra-articular injection into the knee of osteoarthritis patients scheduled for total knee replacement
4 secondary outcomes
Immunohistochemical staining for LNA043 in knee cartilage
Time frame: 1 up to 4 weeks post-dose
Concentration of LNA043 in serum and synovial fluid
Time frame: Pre-dose, Day 1, Day 4, Day 8, and Day 36
Concentration of ANGPTL in serum and synovial fluid
Time frame: Pre-dose, Day 1, Day 4, Day 8, and Day 36
Presence of anti-LNA043
Time frame: Pre-dose, Day 8, and Day 36
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 11 Dec 2020.
- Derived from this study: PubMed 36456835Gerwin N, Scotti C, Halleux C, Fornaro M, Elliott J, Zhang Y, Johnson K, Shi J, Walter S, Li Y, Jacobi C, Laplanche N, Belaud M, Paul J, Glowacki G, Peters T, Wharton KA Jr, Vostiar I, Polus F, Kramer I, Guth S, Seroutou A, Choudhury S, Laurent D, Gimbel J, Goldhahn J, Schieker M, Brachat S, Roubenoff R, Kneissel M. Angiopoietin-like 3-derivative LNA043 for cartilage regeneration in osteoarthritis: a randomized phase 1 trial. Nat Med. 2022 Dec;28(12):2633-2645. doi: 10.1038/s41591-022-02059-9. Epub 2022 Dec 1.
- A Plain Language Trial Summary is available on novartisclinicatrials.comLink provided by the sponsor.
- Results for CLNA043X2101 can be found on the Novartis Clinical Trial Results WebsiteLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided. Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing LNA043 in people with Primary Osteoarthritis Patients Scheduled for Total Knee Replacement Surgery, run by Novartis Pharmaceuticals at 1 site 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 4 inclusion and 9 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 11 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
Safety endpoints (including number of adverse events CTC-AE, physical exam, vital signs, ECG, safety laboratory and pain measured using KOOS) (time frame: Up to and including 7 days post-dose). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02491281, which also lists 1 linked publication.
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 11 Dec 2020.