First-in-human Single Ascending Dose Study of LNA043 in Patients Scheduled for Total Knee Replacement

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02491281
• Collaborator: (none)
• Enrollment: 28
• Location: 1
• Arms: 2
• Actual Duration (Months): 27.6
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief 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. 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.

Condition or Disease	Intervention/Treatment	Phase
Primary Osteoarthritis Patients Scheduled for Total Knee Replacement Surgery	Drug: LNA043; Drug: Placebo	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 28 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Other
• 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
• Actual Study Start Date: Nov 16, 2015
• Actual Primary Completion Date: Feb 7, 2018
• Actual Study Completion Date: Mar 6, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LNA043 LNA043 given intra-articularly	Drug: LNA043; ascending single dose on Day 1; 1 to 4 week(s) prior total knee replacement surgery
Placebo Comparator: Placebo Placebo given intra-articularly	Drug: Placebo; ascending single dose on Day 1; 1 to 4 week(s) prior total knee replacement surgery

Outcome Measures

Primary Outcome Measures

1. Safety endpoints (including number of adverse events CTC-AE, physical exam, vital signs, ECG, safety laboratory and pain measured using KOOS) [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

Secondary Outcome Measures

1. Immunohistochemical staining for LNA043 in knee cartilage [1 up to 4 weeks post-dose]

   Joint presence and persistence of LNA043 within the cartilage of the knee

2. Concentration of LNA043 in serum and synovial fluid [Pre-dose, Day 1, Day 4, Day 8, and Day 36]

   LNA043 pharmacokinetics in serum and concentration in synovial fluid to determine local and systemic exposure

3. Concentration of ANGPTL in serum and synovial fluid [Pre-dose, Day 1, Day 4, Day 8, and Day 36]

   ANGPTL levels in serum and the synovial fluid

4. Presence of anti-LNA043 [Pre-dose, Day 8, and Day 36]

   Immunogenicity in serum

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Key Inclusion Criteria:

• 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:

• 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

• 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Phoenix	Arizona	United States	85053

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• A Plain Language Trial Summary is available on novartisclinicatrials.com
• Results for CLNA043X2101 can be found on the Novartis Clinical Trial Results Website

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT02491281
• Other Study ID Numbers: CLNA043X2101
• First Posted: Jul 8, 2015
• Last Update Posted: Dec 11, 2020
• Last Verified: Aug 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Undecided
• 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 Novartis Pharmaceuticals: Primary Osteoarthritis, Total Knee Replacement, cartilage
• Additional relevant MeSH terms: Osteoarthritis

Study Results

No Results Posted as of Dec 11, 2020