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A Safety, Tolerability, Pharmacokinetics (PK) and Target Engagement Study in Healthy Volunteers and Subjects With Osteoarthritis (OA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03485365
Recruitment Status : Suspended (Due to the COVID-19 pandemic, this study has temporarily suspended recruitment activities. Other elements of the study are ongoing.)
First Posted : April 2, 2018
Last Update Posted : May 6, 2020
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Brief Summary:
This study is the first administration of GSK3858279 to humans. The purpose of this study to evaluate safety, tolerability, PK, target engagement and potential for efficacy of single intravenous (IV) and subcutaneous (SC) doses of GSK3858279 in healthy volunteers and subjects with osteoarthritis of the knee. The primary objective of the study is to evaluate the safety and tolerability of escalating doses of GSK3858279 in following single IV and single SC dosing in healthy volunteers in Part A. Single IV doses and a single SC dose will be investigated in separate cohorts of subjects in Part A. Part B will investigate the safety, tolerability, PK and target engagement in blood and potential for efficacy on pain of subjects with OA of the knee after a single IV dose. Subjects will be randomized in 3:1 ratio to receive GSK3858279 and placebo in sequential manner in Part A. In Part B, subjects will be randomized in parallel groups to receive either GSK3858279 or placebo. Approximately 48 healthy subjects will be enrolled amongst 6 cohorts in Part A and up to a maximum of 50 subjects will be enrolled in Part B of the study. The total study duration will be approximately 140 days for Part A and Part B.

Condition or disease Intervention/treatment Phase
Pain, Inflammatory Drug: GSK3858279 IV Drug: GSK3858279 SC Drug: Placebo matching GSK3858279 IV Drug: Placebo matching GSK3858279 SC Phase 1

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 98 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Subjects will be randomized in 3:1 ratio to receive GSK3858279 and placebo in sequential manner in Part A. In Part B, subjects will be randomized in parallel groups to receive either GSK3858279 or placebo.
Masking: Double (Participant, Investigator)
Masking Description: This will be a double blind study. Subjects and investigator will be masked.
Primary Purpose: Treatment
Official Title: A Two-part Phase I Randomized Double Blind (Sponsor Open) Placebo Controlled Study to Evaluate Safety, Tolerability, Pharmacokinetics, Target Engagement and Potential for Efficacy of Single Intravenous and Subcutaneous Doses of GSK3858279 in Healthy Volunteers and Participants With Osteoarthritis of the Knee
Actual Study Start Date : May 17, 2018
Estimated Primary Completion Date : December 22, 2021
Estimated Study Completion Date : December 22, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Osteoarthritis

Arm Intervention/treatment
Experimental: Part A: Cohort 1: GSK3858279
Eligible subjects will receive GSK3858279 up to a dose of 0.1 milligram/kilogram (mg/kg) via IV route.
Drug: GSK3858279 IV
GSK3858279 will be available as a brown to yellow solution for injection to be administered via IV route.

Placebo Comparator: Part A: Cohort 1: Placebo
Eligible subjects will receive placebo matching to GSK3858279 via IV route.
Drug: Placebo matching GSK3858279 IV
Placebo is 0.9 percent sodium chloride solution which will be administered via IV route.

Experimental: Part A: Cohort 2: GSK3858279
Eligible subjects will receive GSK3858279 up to a dose of 0.3 mg/kg via IV route.
Drug: GSK3858279 IV
GSK3858279 will be available as a brown to yellow solution for injection to be administered via IV route.

Placebo Comparator: Part A: Cohort 2: Placebo
Eligible subjects will receive placebo matching to GSK3858279 via IV route.
Drug: Placebo matching GSK3858279 IV
Placebo is 0.9 percent sodium chloride solution which will be administered via IV route.

Experimental: Part A: Cohort 3: GSK3858279
Eligible subjects will receive GSK3858279 up to a dose of 1 mg/kg via IV route.
Drug: GSK3858279 IV
GSK3858279 will be available as a brown to yellow solution for injection to be administered via IV route.

Placebo Comparator: Part A: Cohort 3: Placebo
Eligible subjects will receive placebo matching to GSK3858279 via IV route.
Drug: Placebo matching GSK3858279 IV
Placebo is 0.9 percent sodium chloride solution which will be administered via IV route.

Experimental: Part A: Cohort 4: GSK3858279
Eligible subjects will receive GSK3858279 up to a dose of 3 mg/kg via IV route.
Drug: GSK3858279 IV
GSK3858279 will be available as a brown to yellow solution for injection to be administered via IV route.

Placebo Comparator: Part A: Cohort 4: Placebo
Eligible subjects will receive placebo matching to GSK3858279 via IV route.
Drug: Placebo matching GSK3858279 IV
Placebo is 0.9 percent sodium chloride solution which will be administered via IV route.

Experimental: Part A: Cohort 5: GSK3858279
Eligible subjects will receive GSK3858279 up to a dose of 10 mg/kg via IV route.
Drug: GSK3858279 IV
GSK3858279 will be available as a brown to yellow solution for injection to be administered via IV route.

Placebo Comparator: Part A: Cohort 5: Placebo
Eligible subjects will receive placebo matching to GSK3858279 via IV route.
Drug: Placebo matching GSK3858279 IV
Placebo is 0.9 percent sodium chloride solution which will be administered via IV route.

Experimental: Part A: Cohort 6: GSK3858279
Eligible subjects will receive GSK3858279 between 1 mg/kg and 3 mg/kg via SC route.
Drug: GSK3858279 SC
GSK3858279 will be available as a brown to yellow solution for injection to be administered via SC route.

Placebo Comparator: Part A: Cohort 6: Placebo
Eligible subjects will receive placebo matching to GSK3858279 via SC route.
Drug: Placebo matching GSK3858279 SC
Placebo is 0.9 percent sodium chloride solution which will be administered via SC route.

Experimental: Part B: GSK3858279
Eligible subjects will receive GSK3858279 one or two dose levels, up to 10 mg/kg, to be determined based on data from Part A) via IV route.
Drug: GSK3858279 IV
GSK3858279 will be available as a brown to yellow solution for injection to be administered via IV route.

Placebo Comparator: Part B: Placebo
Eligible subjects will receive placebo matching to GSK3858279 via IV route.
Drug: Placebo matching GSK3858279 IV
Placebo is 0.9 percent sodium chloride solution which will be administered via IV route.




Primary Outcome Measures :
  1. Part A: Number of subjects with adverse events (AE) and serious adverse events (SAE) [ Time Frame: Up to 140 days ]
    AE is any untoward medical occurrence in a subject or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant.

  2. Part B: Number of subjects with AE and SAE [ Time Frame: Up to 140 days ]
    AE is any untoward medical occurrence in a subject or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant.

  3. Part A: Number of subjects with abnormal hematology parameters [ Time Frame: Up to 140 days ]
    Hematology parameters will be assessed including platelet count, red blood cell (RBC) count, hemoglobin, hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), percent reticulocytes; white blood cell (WBC) count, neutrophils, lymphocytes, monocytes, eosinophils and basophils.

  4. Part B: Number of subjects having abnormal hematology parameters [ Time Frame: Up to 140 days ]
    Hematology parameters which will be assessed include platelet count, RBC count, hemoglobin, hematocrit, MCV, MCH, percent reticulocytes; WBC count, neutrophils, lymphocytes, monocytes, eosinophils and basophils.

  5. Part A: Number of subjects having abnormal clinical chemistry parameters [ Time Frame: Up to 140 days ]
    Clinical chemistry parameters will be assessed including blood urea nitrogen, potassium, aspartate aminotransferase (AST), total and direct bilirubin, creatinine, sodium, alanine aminotransferase (ALT), total protein, glucose (non-fasting), calcium, alkaline phosphatase and cardiac troponin T.

  6. Part B: Number of subjects having abnormal clinical chemistry parameters [ Time Frame: Up to 140 days ]
    Clinical chemistry parameters will be assessed including blood urea nitrogen, potassium, AST, total and direct bilirubin, creatinine, ALT, total protein, glucose (non-fasting), calcium, alkaline phosphatase and cardiac troponin T.

  7. Part A: Number of subjects having abnormal urinalysis parameters [ Time Frame: Up to 140 days ]
    Urinalysis parameters will be assessed including specific gravity, potential of hydrogen (pH), glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocyte esterase by dipstick. Microscopic examination will be performed if blood or protein is abnormal).

  8. Part B: Number of subjects having abnormal urinalysis [ Time Frame: Up to 140 days ]
    Urinalysis parameters will be assessed including specific gravity, pH, glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocyte esterase by dipstick. Microscopic examination will be performed if blood or protein is abnormal).

  9. Part A: Number of subjects having abnormal 12-lead electrocardiogram (ECG) findings [ Time Frame: Up to 140 days ]
    Triplicate or single 12-lead ECG will be obtained using an ECG machine.

  10. Part B: Number of subjects having abnormal 12-lead ECG findings [ Time Frame: Up to 140 days ]
    Triplicate or single 12-lead ECG will be obtained using an ECG machine .

  11. Part A: Number of subjects having abnormal temperature [ Time Frame: Up to 140 days ]
    Temperature which will be measured in a semi- supine position after 5 minutes rest.

  12. Part B: Number of subjects having abnormal temperature [ Time Frame: Up to 140 days ]
    Temperature which will be measured in a semi- supine position after 5 minutes rest.

  13. Part A: Number of subjects having abnormal pulse rate [ Time Frame: Up to 140 days ]
    Pulse rate will be measured in a semi-supine position.

  14. Part B: Number of subjects having abnormal pulse rate [ Time Frame: Up to 140 days ]
    Pulse rate will be measured in a semi-supine position.

  15. Part A: Number of subjects having abnormal blood pressure [ Time Frame: Up to 140 days ]
    Systolic and diastolic blood pressure will be assessed in a semi-supine position.

  16. Part B: Number of subjects having abnormal blood pressure [ Time Frame: Up to 140 days ]
    Systolic and diastolic blood pressure will be assessed in a semi-supine position.


Secondary Outcome Measures :
  1. Part A: Serum PK concentrations following a single IV dose of GSK3858279 [ Time Frame: Pre-dose, 2 , 4, 8, and 12 hours (h) post-dose on Day 1, 24 h post-dose on Day 2, 48 h post-dose on Day 3; Days 8, 15, 22, 29, 43, 57, 85, 112 and 140 ]
    Blood samples for PK analysis of GSK3858279 will be collected at the indicated time points.

  2. Part A: Serum PK concentration following single SC dose of GSK3858279 [ Time Frame: Pre-dose and 8 h post dose on Day 1, 24 h post-dose on Day 2, 48 h post-dose on Day 3; Days 8, 15, 22, 29,43, 57, 85, 112 and 140 ]
    Blood samples for PK analysis of GSK3858279 will be collected at the indicated time points.

  3. Part B: Serum PK concentration following single IV dose of GSK3858279 [ Time Frame: Pre-dose, 2 , 4, 8 h post-dose on Day 1, 24 h post-dose on Day 2, Days 8, 15, 29, 57, 85, 112 and 140 ]
    Blood samples for PK analysis of GSK3858279 will be collected at the indicated time points.

  4. Part A: Area under the time-concentration curve (AUC) from zero to 24 h (0-24) (AUC[0-24]) following a single IV dose of GSK3858279 [ Time Frame: Pre-dose, 2 , 4, 8, and 12 h post-dose on Day 1, 24 h post-dose on Day 2, 48 h post-dose on Day 3; Days 8, 15, 22, 29, 43, 57, 85, 112 and 140 ]
    Blood samples for PK analysis of GSK3858279 will be collected at the indicated time points.

  5. Part A: AUC from zero to time t (0-t) (AUC[0-t]) following a single IV dose of GSK3858279 [ Time Frame: Pre-dose, 2 , 4, 8, and 12 h post-dose on Day 1, 24 h post-dose on Day 2, 48 h post-dose on Day 3; Day 8, 15, 22, 29, 43, 57, 85, 112 and 140 ]
    Blood samples for PK analysis of GSK3858279 will be collected at the indicated time points.

  6. Part A: AUC from zero to infinity (0-infinity) (AUC[0-infinity]) following a single iv dose of GSK3858279 [ Time Frame: Pre-dose, 2 , 4, 8, and 12 h post-dose on Day 1, 24 h post-dose on Day 2, 48 h post-dose on Day 3; Days 8, 15, 22, 29, 43, 57, 85, 112 and 140 ]
    Blood samples for PK analysis of GSK3858279 will be collected at the indicated time points.

  7. Part A: (AUC[0-24]) following a single SC dose of GSK3858279 [ Time Frame: Pre-dose and 8 h post dose on Day 1, 24 h post-dose on Day 2, 48 h post-dose on Day 3; Days 8, 15, 22, 29,43, 57, 85, 112 and 140 ]
    Blood samples for PK analysis of GSK3858279 will be collected at the indicated time points.

  8. Part A: (AUC[0-t]) following a single SC dose of GSK3858279 [ Time Frame: Pre-dose and 8 h post dose on Day 1, 24 h post-dose on Day 2, 48 h post-dose on Day 3; Days 8, 15, 22, 29,43, 57, 85, 112 and 140 ]
    Blood samples for PK analysis of GSK3858279 will be collected at the indicated time points.

  9. Part A: (AUC[0-infinity]) following a single SC dose of GSK3858279 [ Time Frame: Pre-dose and 8 h post dose on Day 1, 24 h post-dose on Day 2, 48 h post-dose on Day 3; Days 8, 15, 22, 29,43, 57, 85, 112 and 140 ]
    Blood samples for PK analysis of GSK3858279 will be collected at the indicated time points.

  10. Part B: (AUC[0-24]) following a single IV dose of GSK3858279 [ Time Frame: Pre-dose, 2h, 4h, 8 h post-dose on Day 1, 24 h post-dose on Day 2, Days 8,15, 29, 57, 85, 112 and 140 ]
    Blood samples for PK analysis of GSK3858279 will be collected at the indicated time points.

  11. Part B: (AUC[0-t]) following a single IV dose of GSK3858279 [ Time Frame: Pre-dose, 2h , 4h, 8 h post-dose on Day 1, 24 h post-dose on Day 2, Days 8, 15, 29, 57, 85, 112 and 140 ]
    Blood samples for PK analysis of GSK3858279 will be collected at the indicated time points.

  12. Part B: (AUC[0-infinity]) following a single IV dose of GSK3858279 [ Time Frame: Pre-dose, 2h , 4, 8 h post-dose on Day 1, 24 h post-dose on Day 2, Days 8, 15, 29, 57, 85, 112 and 140 ]
    Blood samples for PK analysis of GSK3858279 will be collected at the indicated time points.

  13. Part A: Maximum concentration (Cmax) after a single IV dose of GSK3858279 [ Time Frame: Pre-dose, 2h , 4, 8, and 12 h post-dose on Day 1, 24 h post-dose on Day 2, 48 h post-dose on Day 3; Days 8, 15, 22, 29, 43, 57, 85, 112 and 140 ]
    Blood samples for PK analysis of GSK3858279 will be collected at the indicated time points.

  14. Part A: Cmax after single SC dose of GSK3858279 [ Time Frame: Pre-dose and 8 h post dose on Day 1, 24 h post-dose on Day 2, 48 h post-dose on Day 3; Days 8, 15, 22, 29,43, 57, 85, 112 and 140 ]
    Blood samples for PK analysis of GSK3858279 will be collected at the indicated time points.

  15. Part B: Cmax after single IV dose of GSK3858279 [ Time Frame: Pre-dose, 2 , 4, 8 h post-dose on Day 1, 24 h post-dose on Day 2, Days 8,15, 29, 57, 85, 112 and 140 ]
    Blood samples for PK analysis of GSK3858279 will be collected at the indicated time points.

  16. Part A: Half-life (t1/2) following a single IV dose of GSK3858279 [ Time Frame: Pre-dose, 2 , 4, 8, and 12 h post-dose on Day 1, 24 h post-dose on Day 2, 48 h post-dose on Day 3; Days 8, 15, 22, 29, 43, 57, 85, 112 and 140 ]
    Blood samples for PK analysis of GSK3858279 will be collected at the indicated time points.

  17. Part A: t1/2 following a single SC dose of GSK3858279 [ Time Frame: Pre-dose and 8 h post dose on Day 1, 24 h post-dose on Day 2, 48 h post-dose on Day 3; Days 8, 15, 22, 29,43, 57, 85, 112 and 140 ]
    Blood samples for PK analysis of GSK3858279 will be collected at the indicated time points.

  18. Part B: t1/2 following a single IV DOSE of GSK3858279 [ Time Frame: Pre-dose, 2 , 4, 8 h post-dose on Day 1, 24 h post-dose on Day 2, Days 8,15, 29, 57, 85, 112 and 140 ]
    Blood samples for PK analysis of GSK3858279 will be collected at the indicated time points.

  19. Part B: t1/2 following a single IV dose of GSK3858279 [ Time Frame: Pre-dose, 2 , 4, 8 h post-dose on Day 1, 24 h post-dose on Day 2, Days 8,15, 29,57, 85, 112 and 140 ]
    Blood samples for PK analysis of GSK3858279 will be collected at the indicated time points.

  20. Part A: Clearance (CL) following a single IV dose of GSK3858279 [ Time Frame: Pre-dose, 2 , 4, 8, and 12 h post-dose on Day 1, 24 h post-dose on Day 2, 48 h post-dose on Day 3; Days 8, 15, 22, 29, 43, 57, 85, 112 and 140 ]
    Blood samples for PK analysis of GSK3858279 will be collected at the indicated time points.

  21. Part A: CL following a single SC dose of GSK3858279 [ Time Frame: Pre-dose and 8 h post dose on Day 1, 24 h post-dose on Day 2, 48 h post-dose on Day 3; Days 8, 15, 22, 29,43, 57, 85, 112 and 140 ]
    Blood samples for PK analysis of GSK3858279 will be collected at the indicated time points.

  22. Part B: CL following a single IV dose of GSK3858279 [ Time Frame: Pre-dose, 2 , 4, 8 h post-dose on Day 1, 24 h post-dose on Day 2, Days 8,15,29,57,85, 112 and 140 ]
    Blood samples for PK analysis of GSK3858279 will be collected at the indicated time points.

  23. Part A: Volume of distribution (VSS) following a single IV dose of GSK3858279 [ Time Frame: Pre-dose, 2 , 4, 8, and 12 h post-dose on Day 1, 24 h post-dose on Day 2, 48 h post-dose on Day 3; Days 8, 15, 22, 29, 43, 57, 85, 112 and 140 ]
    Blood samples for PK analysis of GSK3858279 will be collected at the indicated time points.

  24. Part A: VSS following a single SC dose of GSK3858279 [ Time Frame: Pre-dose and 8 h post dose on Day 1, 24 h post-dose on Day 2, 48 h post-dose on Day 3; Days 8, 15, 22, 29,43, 57, 85, 112 and 140 ]
    Blood samples for PK analysis of GSK3858279 will be collected at the indicated time points.

  25. Part B: VSS following a single IV dose of GSK3858279 [ Time Frame: Pre-dose, 2 , 4, 8 h post-dose on Day 1, 24 h post-dose on Day 2, Days 8, 15, 29, 57, 85, 112 and 140 ]
    Blood samples for PK analysis of GSK3858279 will be collected at the indicated time points.

  26. Part A: Chemokine ligand 17 (CCL17) levels in serum following IV dose of GSK3858279 [ Time Frame: Pre-dose, 2 , 4, 8, and 12 h post-dose on Day 1, 24 h post-dose on Day 2, 48 h post-dose on Day 3; Days 8, 15, 22, 29, 43, 57, 85, 112 and 140 ]
    Blood samples will be collected for the evaluation of the free and total concentrations of CCL17 at the indicated time points.

  27. Part A: CCL17 levels in serum following SC dose of GSK3858279 [ Time Frame: Pre-dose and 8 h post dose on Day 1, 24 h post-dose on Day 2, 48 h post-dose on Day 3; Days 8, 15, 22, 29,43, 57, 85, 112 and 140 ]
    Blood samples will be collected for the evaluation of the free and total concentrations of CCL17 at the indicated time points.

  28. Part B: CCL17 levels in serum following IV dose of GSK3858279 [ Time Frame: Pre-dose, 2 , 4, 8 h post-dose on Day 1, 24 h post-dose on Day 2, Days 8, 15, 29, 57, 85, 112 and 140 ]
    Blood samples will be collected for the evaluation of the free and total concentrations of CCL17 at the indicated time points.

  29. Part B: Number of subjects with overall knee pain over past 24 h using numeric rating scale (NRS) [ Time Frame: Up to Day 43 ]
    The average knee pain in index knee will be assessed using a NRS, scoring pain on an 11-point scale, from 0 (no pain) to 10 (bad pain).

  30. Part B: Number of subjects with worst knee pain over past 24 h using NRS [ Time Frame: Up to Day 43 ]
    The worst knee pain in index knee, will be assessed using a NRS, scoring pain on an 11-point scale, from 0 (no pain) to 10 (bad pain).



Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

For Part A:

  • Subjects with 18 and 65 years of age inclusive, at the time of signing the informed consent.
  • Volunteers who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring.
  • Body weight within the range 50 to 100 kilogram (kg) and body mass index (BMI) within the range 18 to 32 kilogram per meter square (kg/m^2) (inclusive).
  • Male subjects are eligible to participate if they agree to the following for at least 28 weeks after the dose of study intervention: refrain from donating sperm plus either be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent or must agree to use contraception/barrier as detailed: agree to use a male condom and should also be advised of the benefit for a female partner to use a highly effective method of contraception as a condom may break or leak when having sexual intercourse with a woman of childbearing potential who is not currently pregnant.
  • A female subject is eligible to participate if she is of non-reproductive potential.
  • Capable of giving signed informed consent.

For Part B:

  • Age between 40 and 75 years of age inclusive, at the time of signing the informed consent.
  • Symptomatic mild to moderate OA of the index knee as defined by symptomatic for >=6 months with a clinical diagnosis of OA as per American College of Rheumatology (ACR) clinical diagnosis criteria.
  • Average of daily pain score >=4 and <=9 by 11 point NRS (0 to 10) in index knee over 7 days prior to dosing (Day-7 to Day-1). Data should be recorded on at least 5 of 7 occasions by the subject to obtain a valid Baseline value.
  • A subject must be willing and able to understand and participate in all scheduled evaluations and to complete all required tests and procedures including the use of subject diaries. This will be judged by the Investigator during the screening period.
  • Body weight within the range 50 to 100 kg and BMI within the range 19-35 kg/m^2 (inclusive)
  • Male subjects are eligible to participate if they agree to the following for at least 28 weeks after the dose of study intervention: refrain from donating sperm plus either be abstinent from heterosexual or homosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent or must agree to use contraception/barrier as detailed:) agree to use a male condom and should also be advised of the benefit for a female partner to use a highly effective method of contraception as a condom may break or leak when having sexual intercourse with a woman of childbearing potential who is not currently pregnant.
  • A female subject is eligible to participate if she is of non-reproductive potential.
  • Capable of giving signed informed consent.

Exclusion Criteria:

For Part A:

  • History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention; or interfering with the interpretation of data.
  • Personal or family history of cardiomyopathy.
  • Abnormal blood pressure at screening as determined by the investigator.
  • History of symptomatic herpes zoster.
  • Evidence of active or latent tuberculosis (TB) as documented by medical history, examination, and TB testing with a positive (not indeterminate) QuantiFERON test.
  • Significant allergies to humanized monoclonal antibodies as per principal investigator's and GlaxoSmithKline (GSK) medical monitor's judgments.
  • History or evidence of clinically significant multiple or severe drug allergies, intolerance to topical corticosteroids, or severe post-treatment hypersensitivity reactions (including, but not limited to, erythema multiforme major, linear immunoglobulin A (IgA) dermatosis, toxic epidermal necrolysis, and exfoliative dermatitis).
  • Lymphoma, leukemia, or any malignancy except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years.
  • ALT >1.5 times upper limit of normal (ULN).
  • Bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin <35 percent.
  • Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
  • Corrected QT (QTc) >450 milliseconds (msec).
  • History of Stevens Johnson Syndrome.
  • Known immunodeficiency.
  • Subjects with a chronic infection (example given [e.g.], osteomyelitis), who have been receiving treatment within three months prior to dosing or individuals with an active infection.
  • Previous or current history of bleeding diathesis.
  • Previous history of hypertrophic or keloid scarring.
  • Intended use of over-the-counter or prescription medication including herbal medications within 7 days prior to dosing until final follow-up visit.
  • Live vaccine(s), or plans to receive such vaccines within 1 month of screening until final follow-up visit.
  • Treatment with biologic agents (such as monoclonal antibodies including marketed drugs) within 3 months or 5 half-lives (whichever is longer) prior to dosing.
  • Treatment with antiplatelet or anticoagulant agents within 7 days of dosing.
  • Major surgery (as per investigator's judgment) within 3 months prior to dosing.
  • Participation in the study would result in loss of blood or blood products in excess of 500 milliliter (mL)within 3 months.
  • Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day.
  • Current enrolment or past participation in any other clinical study involving an investigational study intervention or any other type of medical research within the last 30 days, 5 half-lives or twice the duration of the biological product before dosing day in the current study.
  • Presence of Hepatitis B surface antigen (HBsAg) at screening.
  • Presence of the Hepatitis B core antibody (HBcAb) at screening.
  • Positive Hepatitis C antibody test result at screening.
  • Positive Hepatitis C ribonucleic acid (RNA) test result at screening or within 3 months prior to first dose of study intervention.
  • Abnormal clinically significant echocardiogram at screening, as assessed by the investigator.
  • Cardiac troponin levels out of normal range at screening.
  • Positive pre-study drug/alcohol screen.
  • Positive human immunodeficiency virus (HIV) antibody test.
  • Regular alcohol consumption within 6 months prior to the study defined as: an average weekly intake of >21 units for males and >14 units for females. One unit is equivalent to 8 gram (g) of alcohol: a half-pint (approximately 240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
  • Smokelyser levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
  • Regular use of known drugs of abuse.
  • Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates participation in the study.

For Part B:

  • Diagnosis of one or more of the following, as per medical records: a) Current inflammatory arthritis such as rheumatoid arthritis, autoimmune disorder affecting joints, seronegative spondyloarthritis, gout or pseudogout in any joint (defined as acute episodic attacks of swollen, painful joint in a subject with X-Ray chondrocalcinosis or calcium pyrophosphate dehydrate [CPPD] crystals). b) History of gout or pseudogout in any large joint. c) History or evidence of infectious arthritis, Paget's disease, ochronosis, Wilson's disease, primary osteochondromatosis, osteonecrosis and other causes of significant joint disease osteoarthritis as determined by the investigator. d) History of major trauma to the index joint. e) History of fibromyalgia. f) Current immunodeficiency diseases g) Current osteoporosis with symptomatic vertebral or hip fractures. h) Current regional pain syndromes caused by lumbar or cervical compressions with radiculopathy. i) History of significant medical illness in the opinion of the investigator would interfere with the study procedures and / or assessments. j) History of injury in the index knee within 6 months prior to signing informed consent. k) Significant pain in any joint other than the index knee or any referred pain that would impact ability to assess pain in index knee as per investigator's judgment (Pain in other locations should be less than pain in target knee).
  • Symptomatic herpes zoster within 3 months prior to screening.
  • Evidence of active or latent TB as documented by medical history, examination and TB testing: either a positive tuberculin skin test (TST; defined as a skin induration >5 millimeter (mm) at 48 to 72 h, regardless of Bacillus Calmette-Guerin (BCG) or other vaccination history) or a positive (not indeterminate) QuantiFERON test.
  • History of significant allergies to humanized monoclonal antibodies.
  • History or evidence of clinically significant multiple or severe drug allergies, intolerance to topical corticosteroids, or severe post-treatment hypersensitivity reactions (including, but not limited to, erythema multiforme major, linearIgA dermatosis, toxic epidermal necrolysis, and exfoliative dermatitis.
  • History of malignancy within the last 5 years, except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years.
  • Breast cancer within the past 10 years.
  • ALT >1.5 times the ULN.
  • Bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin <35 percent)
  • Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
  • QTc >450 msec or QTc >480 msec in subjects with bundle branch block.
  • History of any major cardiac or vascular event within the last 6 months, including and not limited to myocardial infarction, unstable angina, cerebrovascular event, peripheral arterial or venous thrombosis.
  • Current or history of renal disease, or estimated creatinine clearance <30 mL/minute/1.73/ m^2 or serum creatinine >1.5 times the ULN.
  • Planned surgical procedure over the duration of the study.
  • Previous or current history of bleeding diathesis.
  • History of Stevens Johnson Syndrome
  • Known immunodeficiency
  • Subjects with a chronic infection (e.g., osteomyelitis), who have been receiving treatment within three months prior to dosing or individuals with an active infection.
  • Live vaccine(s) within 1 month prior to screening, or plans to receive such vaccines during the study.
  • Treatment with biologic agents (such as monoclonal antibodies including marketed drugs) within 3 months or 5 half-lives (whichever is longer) prior to dosing.
  • Intra-articular therapy within 3 months prior to signing the informed consent.
  • Immunosuppressant's, including corticosteroids (parenteral within 3 months of screening; oral within 1 month of screening)
  • Opioid analgesics for the duration of the study.
  • Non-steroidal anti-inflammatory drugs (NSAIDs) from 24 h prior to first daily pain assessment at screening until last daily pain assessment (Day 42 visit).
  • Any topical analgesic or adjunctive treatment (e.g., TENS machine or acupuncture) from 24 h prior to first daily pain assessment at screening until last daily pain assessment (Day 42 visit).
  • Major surgery (as per investigator's judgment) within 3 months prior to dosing.
  • Participation in the study would result in loss of blood or blood products in excess of 500 mL within a 3-month period.
  • Exposure to more than 4 new chemical entities within 12 months prior to the dosing day.
  • Current enrolment or past participation within the last 6 months before signing of consent in this or any other clinical study involving an investigational study intervention.
  • Positive HIV antibody test.
  • Presence of HBsAg at screening.
  • Positive Hepatitis C antibody test result.
  • Positive Hepatitis C RNA test result at screening or within 3 months prior to first dose of study intervention.
  • Clinically significant abnormal ECG at screening, as assessed by the investigator.
  • Cardiac troponin levels out of normal range at screening.
  • A positive pre-study drug/alcohol screen at screening.
  • Regular alcohol consumption within 6 months prior to signing the informed consent defined as: an average weekly intake of >21 units for males and >14 units for females. One unit is equivalent to 8 g of alcohol: a half-pint (approximately 240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
  • Regular use of known drugs of abuse
  • Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates participation in the study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03485365


Locations
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United Kingdom
GSK Investigational Site
Cambridge, United Kingdom, CB2 2GG
Sponsors and Collaborators
GlaxoSmithKline
Investigators
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Study Director: GSK Clinical Trials GlaxoSmithKline
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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT03485365    
Other Study ID Numbers: 207804
2017-004809-41 ( EudraCT Number )
First Posted: April 2, 2018    Key Record Dates
Last Update Posted: May 6, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints of the study.
Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
URL: http://clinicalstudydatarequest.com

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by GlaxoSmithKline:
Pain
Osteoarthritis of the knee
Target engagement
GSK3858279
Pharmacokinetics
Sequential
Additional relevant MeSH terms:
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Osteoarthritis
Arthritis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases