Proof-of-concept Study to Assess the Efficacy, Tolerability and Safety of a Single Intraarticular Dose of GZ389988 Versus Placebo in Patients With Painful Osteoarthritis of the Knee

NCT02845271 | Completed Phase 2

• 3 other identifiers: ACT138302014-004805-34U1111-1163-0806
• Study Type: interventional
• Target: 104
• Locations: 1 country
• Sites: 2

Brief Summary

Primary Objective: To assess the efficacy of a single intraarticular dose of GZ389988 compared to placebo for relief of knee pain in patients with osteoarthritis (OA) of the knee. Secondary Objectives: To assess the safety and tolerability of a single intraarticular dose of GZ389988 in patients with painful OA of the knee. To assess the pharmacokinetic parameters of a single intraarticular dose of GZ389988 in patients with painful OA of the knee.

Conditions

Osteoarthritis

Outcome Measures

Primary Outcomes (1)

• Change from baseline in weekly mean score of Western Ontario and McMaster Universities Arthritis Index (WOMAC) A1 pain subscore (walking pain) collected daily in the target knee, as measured by the Visual Analogue Scale (VAS) 0-100

  Averaged over 4 weeks (up to Day 28)

Secondary Outcomes (13)

• Change from baseline in weekly mean score of WOMAC A1 pain sub-score (walking pain) collected daily in the target knee, as measured by the VAS 0-100

  Averaged over 12 weeks (up to Day 84)

• Change from baseline in weekly mean score of WOMAC A1 pain sub-score collected daily in the target knee

  Averaged over 1, 2, 3, 6, 8, and 10 weeks

• Change from baseline in weekly mean score of WOMAC A1 pain sub-score collected daily in the target knee

  At 1, 2, 3, 4, 6, 8, 10, and 12 weeks

• Change from baseline in weekly mean score of overall knee pain collected daily in the target knee

  At and averaged over 1, 2, 3, 4, 6, 8, 10, and 12 weeks

• Change from baseline in Patient Global Assessment (PGA) of disease status

  At and averaged over 1, 2, 3, 4, 6, 8, 10, and 12 weeks

Study Arms (2)

GZ389988

EXPERIMENTAL

Single intraarticular injection of GZ389988 in the knee joint

Drug: GZ389988; Drug: acetaminophen or paracetamol; Drug: fixed combination of paracetamol + codeine; Drug: fixed combination of paracetamol + tramadol hydrochloride

Placebo

PLACEBO COMPARATOR

Single intraarticular injection of placebo for GZ389988 in the knee joint

Drug: placebo; Drug: acetaminophen or paracetamol; Drug: fixed combination of paracetamol + codeine; Drug: fixed combination of paracetamol + tramadol hydrochloride

Interventions

placebo DRUG

Pharmaceutical form:solvent for parenteral use Route of administration: intraarticular

Placebo

GZ389988 DRUG

Pharmaceutical form:suspension for injection Route of administration: intraarticular

GZ389988

acetaminophen or paracetamol DRUG

Pharmaceutical form: tablet Route of administration: oral

GZ389988; Placebo

fixed combination of paracetamol + codeine DRUG

Pharmaceutical form: capsule Route of administration: oral

GZ389988; Placebo

fixed combination of paracetamol + tramadol hydrochloride DRUG

Pharmaceutical form: tablet Route of administration: oral

GZ389988; Placebo

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men or women 40 to 80 years of age.
• Diagnosis of primary knee osteoarthritis (OA), based upon the following:
• Fulfilling the American College of Rheumatology Clinical and Radiographic criteria for OA (at least knee pain and osteophytes), with
• X-ray evidence within the last 6 months for Kellgren and Lawrence classification II to IV.
• Western Ontario and McMaster Universities Arthritis Index (WOMAC) A1 Pain subscore (walking pain) over the last 48 hours ≥40 and ≤90 on VAS 0-100 in the target knee at screening with or without medication, and ≤30 on Visual Analogue Scale (VAS) 0-100 in the contralateral knee at screening with or without medication.
• WOMAC A1 pain subscore (walking pain) between 50 and 90 using the VAS 0-100, corresponding to moderate to severe pain in the target knee at baseline (from eDiary, average of at least 3 days in the time window between Day-5 and Day-1).
• Symptomatic for more than 6 months (if both symptomatic knees, at least for the most painful knee that will receive the study drug).
• Having given written informed consent prior to any procedure related to the study.
• Ambulatory with an active lifestyle and in good general health. (Assistive devices were allowed if used throughout a period of 3 months or more prior to screening, on the condition that they continue to be used throughout the study).
• A male who is sexually active must use a condom as part of a method of highly effective contraception (eg, condom + spermicide, and an additional contraceptive method used by the partner) during sexual intercourse with a women of childbearing potential for the duration of the study period up to the end-of-study visit and should not father a child in this period. Male patients also have to agree not to donate sperm for the duration of the study until the end-of-study visit.

You may not qualify if:

• Women of childbearing potential.
• Pregnant or breastfeeding women.
• Any uncontrolled, chronic condition or laboratory finding which, in the opinion of the Investigator, could potentially put the patient at increased risk.
• Patients with clinically significant or uncontrolled hepatic, gastrointestinal, cardiovascular, respiratory, neurological (including diabetic neuropathy), psychiatric, hematological, renal, or dermatological disease, or any other medical condition, such as symptomatic peripheral vascular disease of the study leg (prior or current), clinically significant venous or lymphatic stasis present in the study leg, that might interfere with the evaluation of investigational medicinal product (IMP) according to Investigator's medical judgment.
• Chondrocalcinosis.
• Fibromyalgia.
• Moderately severe or severe depression as indicated by Patient Health Questionnaire-9 (PHQ-9) total score at screening visit.
• Severe anxiety as indicated by Generalized Anxiety Disorder (GAD-7) score at screening visit.
• History or presence of drug or alcohol abuse (alcohol consumption \>40 grams per day).
• Any patient who, in the judgment of the Investigator, is likely to be noncompliant during the study, or unable to cooperate because of a language problem or poor mental development, or unable to use an electronic diary daily.
• Abnormal coagulation parameters: outside the range international normalized ratio (INR) 0.85-1.15, activated partial thromboplastin time \>33 seconds, platelets \<140 x 10\^9/L.
• Moderate to severe renal impairment.
• Underlying hepatobiliary disease and/or alanine aminotransferase (ALT) \>2 x upper limit of normal (ULN).
• High sensitivity C-reactive protein (hsCRP) \>2 x ULN.
• Hemoglobin \<10 g/dL, white blood cell count (WBC) \<3 x 10\^9/L.

Sponsors & Collaborators

• Genzyme, a Sanofi Company: lead

Study Sites (2)

Investigational Site Number 276001

Berlin, 14050, Germany

Location

Investigational Site Number 276002

Lübeck, 23538, Germany

Location

Related Publications (1)

• Krupka E, Jiang GL, Jan C. Efficacy and safety of intra-articular injection of tropomyosin receptor kinase A inhibitor in painful knee osteoarthritis: a randomized, double-blind and placebo-controlled study. Osteoarthritis Cartilage. 2019 Nov;27(11):1599-1607. doi: 10.1016/j.joca.2019.05.028. Epub 2019 Jul 25.

  PMID: 31351965 DERIVED

MeSH Terms

Conditions

Osteoarthritis

Interventions

Acetaminophen; Codeine; Tramadol

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Cyclohexanols; Hexanols; Fatty Alcohols; Alcohols; Dimethylamines; Methylamines; Lipids

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 19, 2016
• First Posted: July 27, 2016
• Study Start: July 21, 2016
• Primary Completion: June 28, 2017
• Study Completion: September 13, 2017
• Last Updated: April 13, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will share

Locations

DE (2)