First-in-human Study With Ascending Single Intra-articular Doses of GZ389988 in Patients With Painful Osteoarthritis of the Knee

NCT02424942 | Completed Phase 1

• 3 other identifiers: TDU138282014-004805-34U1111-1163-0806
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

Primary Objective: To assess the safety and tolerability of ascending single intraarticular doses of GZ389988 in patients with painful osteoarthritis (OA) of the knee. Secondary Objectives: To assess the pharmacokinetic (PK) parameters of ascending single intraarticular doses of GZ389988 in patients with painful OA of the knee. To obtain preliminary pharmacodynamic evaluation of ascending single intraarticular doses of GZ389988 in patients with painful OA of the knee.

Conditions

Osteoarthritis

Outcome Measures

Primary Outcomes (2)

• Proportion of patients with adverse events

  Up to Day 84 after single intraarticular dose of GZ389988

• Proportion of patients with serious adverse events

  12 additional weeks after day 84 (by phone calls)

Secondary Outcomes (13)

• Maximum plasma concentration (Cmax) of GZ389988 single dose intraarticular (IA)

  24 timepoints up to Day 84

• Area under the curve from time zero to last quantifiable concentration (AUClast) of single dose GZ389988 IA

  24 timepoints up to Day 84

• Area under the curve (AUC) of single dose GZ389988 IA

  24 timepoints up to Day 84

• Plasma elimination half-life (t1/2z) of single dose GZ389988 IA

  24 timepoints up to Day 84

• Time to peak plasma concentration (tmax) of single dose GZ389988 IA

  24 timepoints up to Day 84

Study Arms (2)

GZ389988

EXPERIMENTAL

Single intraarticular injection of GZ389988 in the knee joint

Drug: GZ389988

Placebo

PLACEBO COMPARATOR

Single intraarticular injection of placebo for GZ389988 in the knee joint

Drug: placebo

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

Eligibility Criteria

• Age: 40 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Men or women 40 to 60 years of age.
• Diagnosis of primary knee osteoarthritis, based upon the following:
• Fulfilling the American College of Rheumatology Clinical and Radiographic criteria for OA (at least knee pain and osteophytes),
• 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) between 50 and 90 using the 100-mm visual analog scale (VAS), corresponding to moderate to severe pain in the index knee, at both screening and baseline assessments at least 48 hours apart.
• 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 continued 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, dermatological disease, or any other medical condition that might interfere with the evaluation of the investigational medicinal product (IMP) according to Investigator's medical judgment.
• Chondrocalcinosis.
• Fibromyalgia.
• Major depression.
• 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.
• 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.
• Positive result on any of the following tests: hepatitis B surface (HBsAg) antigen, anti-hepatitis C virus (anti-HCV) antibodies, anti-human immunodeficiency virus 1 and 2 antibodies (anti-HIV1 and anti-HIV2 Ab).

Sponsors & Collaborators

• Genzyme, a Sanofi Company: lead

Study Sites (1)

Investigational Site Number 276001

Berlin, 14050, Germany

Location

MeSH Terms

Conditions

Osteoarthritis

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 10, 2015
• First Posted: April 23, 2015
• Study Start: April 1, 2015
• Primary Completion: July 1, 2016
• Study Completion: July 1, 2016
• Last Updated: August 17, 2016

Record last verified: 2016-08

Locations

DE (1)