Study of Safety, Efficacy of Fulranumab Adjunctive Use in OA of Hip or Knee, PAI3007

Randomized, 16-Week, Multi-Phase, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, and Efficacy of Fulranumab as Adjunctive Therapy in Subjects With Signs and Symptoms of Osteoarthritis of the Hip or Knee

The purpose of this study is to demonstrate the efficacy, safety, and tolerability of fulranumab as adjunctive therapy compared with placebo in participants with signs and symptoms of osteoarthritis of the hip or knee that are not adequately controlled by current pain therapy.

Study Overview

• Status: Completed
• Conditions: Pain; Osteoarthritis
• Intervention / Treatment: Drug: Placebo; Drug: Celecoxib 100 mg; Drug: Fulranumab 1 mg; Drug: Celecoxib 100 mg Matching Placebo; Drug: Fulranumab 3 mg

Detailed Description

This is a randomized (the study drug is assigned by chance), double-blind (neither physician nor participant knows the name of the assigned drug), placebo-controlled (an inactive substance is given to one group of participants while active drug is given to another group of participants to see if there is a difference in response), parallel-group (study drugs given to participants in all treatment groups during the same time period) to evaluate the efficacy (capacity of the investigational drug to produce an effect), safety, and tolerability of fulranumab administered as adjunctive therapy (in combination with other drug therapy) to participants with chronic moderate to severe pain and functional impairment from knee or hip osteoarthritis (OA) that is not adequately controlled by current pain therapy. The duration of participation in the study for an individual participant will be up to 67 weeks (includes a screening period of 3 weeks, a double-blind treatment period of 16 weeks, and a post-treatment follow-up period of up to 48 weeks). All participants will be randomly assigned in a 1:1:1 ratio to 1 of 3 treatments (placebo, fulranumab 1mg, fulranumab 3mg) and given a single injection subcutaneously (under the skin) once every 4 weeks for up to 16 weeks. In addition, participants may elect to receive adjunctive therapy (ie, double-blind supplemental oral analgesic medication or matching placebo) throughout the double-blind treatment period. Blood samples will be collected from each participant at time points during the study. Safety evaluations will include assessment of adverse events, physical examinations, laboratory tests and vital signs which will be monitored throughout the study.

• Study Type: Interventional
• Enrollment (Actual): 111
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Camperdown, Australia
  • Hobart, Australia
  • Kippa Ring, Australia
  • Kogarah, Australia
  • Maroochydore, Australia
  • Melbourne, Australia
  • Sherwood, Australia
• Canada
  • West Vancouver, Canada
  • British Columbia
    • Kamloops, British Columbia, Canada
    • Kelowna, British Columbia, Canada
  • Ontario
    • Toronto, Ontario, Canada
  • Quebec
    • Montreal, Quebec, Canada
• Czechia
  • Praha, Czechia
• Germany
  • Leipzig, Germany
• Hungary
  • Szekszard, Hungary
• Korea, Republic of
  • Anyang, Korea, Republic of
  • Jeju, Korea, Republic of
  • Seoul, Korea, Republic of
• Poland
  • Elblag, Poland
  • Katowice, Poland
  • Krakow, Poland
  • Torun, Poland
  • Warszaw, Poland
  • Warszawa, Poland
  • Wroclaw, Poland
• Spain
  • A Coruña, Spain
  • Santiago De Compostela, Spain
• Sweden
  • Lund, Sweden
  • Malmo, Sweden
• United Kingdom
  • Blackpool, United Kingdom
  • Cannock, United Kingdom
  • Mancheter, United Kingdom
  • Stourton, United Kingdom
• United States
  • Arizona
    • Glendale, Arizona, United States
    • Phoenix, Arizona, United States
    • Tucson, Arizona, United States
  • Arkansas
    • Little Rock, Arkansas, United States
  • California
    • Anaheim, California, United States
    • Garden Grove, California, United States
    • Los Angeles, California, United States
    • North Hollywood, California, United States
  • Colorado
    • Boulder, Colorado, United States
  • Florida
    • Coral Gables, Florida, United States
    • Miami, Florida, United States
    • Orlando, Florida, United States
    • Winter Park, Florida, United States
  • Georgia
    • Columbus, Georgia, United States
  • Illinois
    • Chicago, Illinois, United States
  • Kansas
    • Overland Park, Kansas, United States
  • Maryland
    • Elkridge, Maryland, United States
  • Michigan
    • Detroit, Michigan, United States
  • Missouri
    • Saint Louis, Missouri, United States
  • New York
    • Brooklyn, New York, United States
    • New York, New York, United States
  • Oklahoma
    • Norman, Oklahoma, United States
  • Tennessee
    • Knoxville, Tennessee, United States
    • Memphis, Tennessee, United States
    • Tullahoma, Tennessee, United States
  • Texas
    • Arlington, Texas, United States
    • Houston, Texas, United States
    • Lampasas, Texas, United States
    • Nassau Bay, Texas, United States
    • Sugar Land, Texas, United States
  • Virginia
    • Arlington, Virginia, United States
    • Charlottesville, Virginia, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Clinical diagnosis of osteoarthritis (OA) of hip or knee based on criteria defined by the American College of Rheumatology and radiographic evidence of OA (Kellgren-Lawrence class ≥2) of the study joint
• Scheduled joint replacement or planning to undergo a joint replacement surgery for the study joint
• Unsatisfactory response (inadequate efficacy or poor tolerability) on local standard of care that includes 3 medications from at least 2 of the following classes of analgesic medications (acetaminophen/paracetamol, NSAIDs, or opioid). For participants in the USA and Canada only: Unsatisfactory response (inadequate efficacy or poor tolerability) that includes all 3 classes of analgesic medications (acetaminophen/paracetamol, NSAIDs, and opioids other than codeine or codeine combination products)
• Moderate to severe pain and functional impairment based on the NRS, WOMAC pain and physical function subscales, and PGA
• During treatment and within 24 weeks after the last injection of study drug: if female of childbearing potential, is not pregnant, breast-feeding, or planning to become pregnant, or if male, will not father a child

Exclusion Criteria:

• Increased risk of osteonecrosis (ON) or rapidly progressive osteoarthritis (RPOA)
• Unstable or progressive neurologic disorders

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo; Participants will receive 4 subcutaneous (SC) injections (one injection every 4 weeks) of placebo during the double-blind treatment phase. In addition, participants may take adjunctive therapy with celecoxib 100 mg orally (by mouth) twice daily for up to 16 weeks.	Drug: Placebo; Placebo will be administered once every 4 weeks with or without adjunctive therapy for 16 weeks by subcutaneous (SC) injection (injection under the skin) into the thigh or abdomen.; Drug: Celecoxib 100 mg; Double-blind capsules taken twice daily for up to 16 weeks.
EXPERIMENTAL: Fulranumab 1 mg; Participants will receive 4 subcutaneous (SC) injections (one injection every 4 weeks) of fulranumab 1 mg during the double-blind treatment phase. In addition, participants may take adjunctive therapy with celecoxib placebo orally twice daily for up to 16 weeks.	Drug: Fulranumab 1 mg; Fulranumab will be administered once every 4 weeks with or without adjunctive therapy for up to 16 weeks by SC injection into the thigh or abdomen.; Drug: Celecoxib 100 mg Matching Placebo; Double-blind capsules taken twice daily for up to 16 weeks.
EXPERIMENTAL: Fulranumab 3 mg; Participants will receive 4 subcutaneous (SC) injections (one injection every 4 weeks) of fulranumab 3 mg during the double-blind treatment phase. In addition, participants may take adjunctive therapy with celecoxib placebo orally twice daily for up to 16 weeks.	Drug: Celecoxib 100 mg Matching Placebo; Double-blind capsules taken twice daily for up to 16 weeks.; Drug: Fulranumab 3 mg; Fulranumab will be administered once every 4 weeks with or without adjunctive therapy for up to 16 weeks by SC injection into the thigh or abdomen.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The number of participants with Adverse Events as a measure of safety and tolerability	Up to Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline to the end of Week 16 in Western Ontario and McMaster University Arthritis Index (WOMAC) pain subscale score	The WOMAC 3.1 is a multi-dimensional, osteoarthritis (OA) specific self-administered questionnaire using 24 questions with a 48-hour recall that are grouped into 3 subscales (pain, stiffness, and physical function) associated with hip or knee OA. Pain, stiffness, and physical function is rated on a scale of 0-10 (0 = less severe up to 10 = more severe).	Baseline, Week 16
Change from baseline to the end of Week 16 in Western Ontario and McMaster University Arthritis Index (WOMAC) physical function subscale score	See WOMAC 3.1 described above.	Baseline, Week 16

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC

Publications and helpful links

General Publications

• Kelly KM, Sanga P, Zaki N, Wang S, Haeussler J, Louie J, Thipphawong J. Safety and efficacy of fulranumab in osteoarthritis of the hip and knee: results from four early terminated phase III randomized studies. Curr Med Res Opin. 2019 Dec;35(12):2117-2127. doi: 10.1080/03007995.2019.1653068. Epub 2019 Sep 13.

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 25, 2015
• Primary Completion (ACTUAL): September 19, 2016
• Study Completion (ACTUAL): September 19, 2016

Study Registration Dates

• First Submitted: November 21, 2014
• First Submitted That Met QC Criteria: November 21, 2014
• First Posted (ESTIMATE): November 25, 2014

Study Record Updates

• Last Update Posted (ACTUAL): September 14, 2017
• Last Update Submitted That Met QC Criteria: September 6, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: Osteoarthritis; Celecoxib; Pain; Knee; Hip; Adjunctive therapy; Joint replacement surgery; Fulranumab; JNJ-42160443
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Immunologic Factors; Cyclooxygenase 2 Inhibitors; Celecoxib; Antibodies, Monoclonal
• Other Study ID Numbers: CR106249; 42160443PAI3007 (OTHER: Janssen Research & Development, LLC); 2014-003224-40 (EUDRACT_NUMBER)

Drug and device information, study documents

• Studies a U.S. FDA-regulated device product: No