NCT02205814

Brief Summary

This study is designed as a double-blind, randomised, placebo-controlled, four parallel arm, dose-finding study, to be conducted in approximately 26 sites, to evaluate the efficacy, safety, tolerability, and pharmacokinetics of single intra-articular (IA) injections of fasitibant in patients with symptomatic osteoarthritis (OA) of the knee. Approximately 400 male and female patients 40-80 years old, with BMI \< 30 kg/m² and with a clinical diagnosis of symptomatic primary osteoarthritis of the knee will be randomised to a total of 4 treatment arms. Each arm includes a single intra-articular injection of one of three dosages of fasitibant (low, intermediate and high dose) OR placebo. The randomisation ratio will be 1:1:1:1. The primary efficacy variable will be the change of the Western Ontario and McMaster Universities Visual Analogue Scale 3.1 A (WOMAC VA 3.1 A) (total pain) subscore from baseline up to 2 weeks after randomisation. Safety will be assessed by monitoring adverse events and clinical laboratory tests; local tolerability at the injection site will also be assessed. In addition, the population pharmacokinetics and the exposure-response relationship will be evaluated. The individual experimental clinical phase will last up to maximal 15 weeks encompassing 7 planned visits at site, including screening, randomisation, 4 follow-up visits and the End of study visit.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
436

participants targeted

Target at P75+ for phase_2 knee-osteoarthritis

Timeline
Completed

Started Apr 2014

Shorter than P25 for phase_2 knee-osteoarthritis

Geographic Reach
4 countries

25 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

April 1, 2014

Completed
3 months until next milestone

First Submitted

Initial submission to the registry

July 14, 2014

Completed
17 days until next milestone

First Posted

Study publicly available on registry

July 31, 2014

Completed
5 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2015

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2015

Completed
9 months until next milestone

Results Posted

Study results publicly available

September 16, 2015

Completed
Last Updated

November 3, 2015

Status Verified

October 1, 2015

Enrollment Period

9 months

First QC Date

July 14, 2014

Results QC Date

July 6, 2015

Last Update Submit

October 2, 2015

Conditions

Knee Osteoarthritis

Keywords

Osteoarthritis, KneeArthritisWOMACInjections, intra-articularFasitibantMEN 16132

Outcome Measures

Primary Outcomes (1)

  • Change in WOMAC A

    The validated Western Ontario and McMaster University questionnaire (WOMAC) was used to measure total knee pain choosing its visual analogue scale version (VAS). The WOMAC VA 3.1 A subscore (WOMAC A) ranges from 0 to 500 mm (summing up five VAS 0-100 mm) with higher scores indicating more pain.

    from baseline up to 2 weeks after randomisation

Secondary Outcomes (3)

  • Change in WOMAC INDEX

    from baseline up to 6 weeks after randomisation

  • Responder Rate According to OMERACT-OARSI Criteria

    from baseline up to 6 weeks after randomisation

  • Euro Quality of Life Questionnaire (EQ-5D-5L) Responder Rate

    from baseline up to 6 weeks after randomisation

Study Arms (4)

Fasitibant low dose

EXPERIMENTAL

Drug: solution for intra-articular injection

Drug: Fasitibant- low dose

Fasitibant intermediate dose

EXPERIMENTAL

Drug: solution for intra-articular injection

Drug: Fasitibant- intermediate dose

Fasitibant high dose

EXPERIMENTAL

Drug: solution for intra-articular injection

Drug: Fasitibant- high dose

PLACEBO

PLACEBO COMPARATOR

Drug: solution for intra-articular injection

Drug: Placebo comparator

Interventions

Fasitibant- low doseDRUG

Single intra-articular injection of low dose of fasitibant

Fasitibant low dose
Fasitibant- intermediate doseDRUG

Single intra-articular injection of intermediate dose of fasitibant

Fasitibant intermediate dose
Fasitibant- high doseDRUG

Single intra-articular injection of high dose of fasitibant

Fasitibant high dose
Placebo comparatorDRUG

Single intra-articular injection of placebo

PLACEBO

Eligibility Criteria

Age40 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Male or female patients aged 40 to 80 years with BMI \< 30 kg/m²
  • Patient with Kellgren-Lawrence Grade 2 to 3, symptomatic primary osteoarthritis at the index knee (ACR criteria), for which an IA treatment is indicated
  • Pain of moderate to severe intensity, even if treated with chronic doses of non steroidal antinflammatory drugs

You may not qualify if:

  • History of hypersensitivity/allergy to drugs including paracetamol and to disinfectants
  • Any pharmacological treatment of concomitant disease(s) started or changed during 4 weeks prior to randomisation, or likely to be changed during the course of the study
  • Use of systemic or topical corticosteroids \> 10 mg prednisolone equivalent per day, or immunosuppressant drugs
  • Current use of any pain or OA medication (e.g. NSAIDs, COX-2 inhibitors, analgesics, antidepressive agents), including topical treatments
  • Viscosupplementation to the target knee administered \< 4 months prior to randomisation and/or scheduled during the course of the study
  • Evidence of clinically significant hepatic disease or of moderate or severe renal insufficiency
  • Current use of any medications that are substrate of CYP3A4 and/or moderate or strong CYP3A4 inhibitors
  • Patients with any clinically relevant or unstable disease, or malignant neoplasms that, in the opinion of the Investigator, may pose the patient at risk, or confound the efficacy and safety results of the study
  • Patients with any clinically relevant abnormal safety laboratory test results, and/or abnormalities in vital signs, and/or ECG parameters
  • Pregnant and breastfeeding women
  • Any sign of significant immunodeficiency, systemic infection, knee infection or knee bursitis
  • Patients with bleeding diathesis or on therapy with anticoagulants

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (25)

Tucson Orthopaedic Institute

Tucson, Arizona, 85712, United States

Location

Colorado Orthopaedic Consultants

Englewood, Colorado, 80110, United States

Location

Avail Clinical Research, LLC

DeLand, Florida, 32720, United States

Location

Radiant Research

Columbus, Ohio, 43212, United States

Location

Columbus Clinical Research

Columbus, Ohio, 43213, United States

Location

Blair Orthopaedic Associates

Altoona, Pennsylvania, 16602, United States

Location

Tekton Research

Austin, Texas, 78745, United States

Location

Physicians Research Options, LLC

Draper, Utah, 84020, United States

Location

Spokan Joint Replacement Center

Spokane, Washington, 99218, United States

Location

Revmatologie s.r.o.

Brno, 638 00, Czechia

Location

Institute of Rheumatology, Charles University Faculty Hospital

Prague, 128 50, Czechia

Location

MEDICAL PLUS s.r.o

Uherské Hradiště, 686 01, Czechia

Location

Synexus Clinical Research GmbH, Research Centre Berlin

Berlin, 1262, Germany

Location

Synexus Clinical Research GmbH, Research Centre Bochum

Bochum, 44787, Germany

Location

Synexus Clinical Research GmbH, Research Centre Frankfurt

Frankfurt, 60596, Germany

Location

Clinical Research Hamburg GmbH

Hamburg, 22143, Germany

Location

Synexus Clinical Research GmbH, Research Centre Leipzig

Leipzig, 04103, Germany

Location

AmBeNet GmbH

Leipzig, 04107, Germany

Location

Dipartimento di Medicina Interna - SOD di Reumatologia Azienda - Ospedaliero Universitaria Careggi

Florence, Tuscany, 50139, Italy

Location

Azienda Ospedaliero-Universitaria S.Anna/ Unità Operativa Complessa e Sezione di Reumatologia/Dipartimento di Medicina Clinica e Sperimentale

Cona, 44124, Italy

Location

Ospedale Galateo U.O. di Reumatologia

Lecce, 73016, Italy

Location

Ospedale Fornaroli/Unità Complessa di Reumatologia

Magenta, 20013, Italy

Location

Ospedale Luigi Sacco, Azienda Ospedaliera, Polo Universitario/Unità Operativa Complessa di Reumatologia

Milan, 20157, Italy

Location

Azienda Ospedaliera di Perugia/Policlinico di Monteluce/Unità Operativa diagnosi e cura delle malattie reumatiche

Perugia, 06122, Italy

Location

Centro Ricerche Cliniche di Verona

Verona, 37134, Italy

Location

MeSH Terms

Conditions

Osteoarthritis, KneeArthritis

Interventions

(4-amino-5-(4-(4-(2,4-dichloro-3-(2,4-dimethyl-8-quinolyloxymethyl)phenylsulfonamido)tetrahydro-2H-4-pyranoylcarbonyl)piperazino)-5-oxopentyl)(trimethyl)ammonium

Condition Hierarchy (Ancestors)

OsteoarthritisJoint DiseasesMusculoskeletal DiseasesRheumatic Diseases

Results Point of Contact

Title
Angela Capriati, MD PhD - Corporate Director Clinical Research
Organization
MENARINI Group
acapriati@menarini-ricerche.it
+39 055 5680

Study Officials

  • Karel Pavelka, Professor

    Institute of Rheumatology, Charles University Faculty Hospital, Na Slupi 4, 128 50 Prague 2, Czech Republic

    STUDY CHAIR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 14, 2014

First Posted

July 31, 2014

Study Start

April 1, 2014

Primary Completion

January 1, 2015

Study Completion

January 1, 2015

Last Updated

November 3, 2015

Results First Posted

September 16, 2015

Record last verified: 2015-10

Locations

CZ(3)DE(6)US(9)IT(7)