Study of Efficacy, Safety of Fulranumab Adjunctive Use in OA of Hip or Knee, PAI3001

Sponsor

Janssen Research & Development, LLC (Industry)

Overall Status

Completed

CT.gov ID

NCT02336685

Collaborator

(none)

Enrollment

Locations

Arms

14.4

Actual Duration (Months)

1.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to demonstrate the efficacy, safety, and tolerability of fulranumab as adjunctive therapy compared with placebo in participants with chronic moderate to severe pain and functional impairment from knee or hip osteoarthritis that is not adequately controlled by current pain therapy.

Condition or Disease	Intervention/Treatment	Phase
Osteoarthritis Pain	Drug: Placebo Drug: Fulranumab 1 mg Drug: Fulranumab 3 mg Drug: Opioid	Phase 3

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. All participants will be allowed standard of care for OA pain during the double-blind treatment phase and must be taking an opioid at study entry and during the double-blind treatment phase. 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 Design

Study Type:

Interventional

Actual Enrollment :

79 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jul 7, 2015

Actual Primary Completion Date :

Sep 16, 2016

Actual Study Completion Date :

Sep 16, 2016

Arms and Interventions

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 to opioids as standard of care.	Drug: Placebo Placebo will be administered once every 4 weeks for 16 weeks by subcutaneous (SC) injection (injection under the skin) into the thigh or abdomen. Drug: Opioid Opioids will be administered as standard of care for osteoarthritis (OA) pain therapy during the double-blind treatment phase as per investigator discretion.
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 to opioids as standard of care.	Drug: Fulranumab 1 mg Fulranumab will be administered once every 4 weeks for up to 16 weeks by SC injection into the thigh or abdomen. Drug: Opioid Opioids will be administered as standard of care for osteoarthritis (OA) pain therapy during the double-blind treatment phase as per investigator discretion.
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 to opioids as standard of care.	Drug: Fulranumab 3 mg Fulranumab will be administered once every 4 weeks for up to 16 weeks by SC injection into the thigh or abdomen. Drug: Opioid Opioids will be administered as standard of care for osteoarthritis (OA) pain therapy during the double-blind treatment phase as per investigator discretion.

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 to opioids as standard of care.

Drug: Placebo

Placebo will be administered once every 4 weeks for 16 weeks by subcutaneous (SC) injection (injection under the skin) into the thigh or abdomen.

Drug: Opioid

Opioids will be administered as standard of care for osteoarthritis (OA) pain therapy during the double-blind treatment phase as per investigator discretion.

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 to opioids as standard of care.

Drug: Fulranumab 1 mg

Fulranumab will be administered once every 4 weeks for up to 16 weeks by SC injection into the thigh or abdomen.

Drug: Opioid

Opioids will be administered as standard of care for osteoarthritis (OA) pain therapy during the double-blind treatment phase as per investigator discretion.

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 to opioids as standard of care.

Drug: Fulranumab 3 mg

Fulranumab will be administered once every 4 weeks for up to 16 weeks by SC injection into the thigh or abdomen.

Drug: Opioid

Opioids will be administered as standard of care for osteoarthritis (OA) pain therapy during the double-blind treatment phase as per investigator discretion.

Outcome Measures

Primary Outcome Measures

Change from baseline to the end of Week 16 in Western Ontario and McMaster University Arthritis Index (WOMAC) pain subscale score [Baseline, Week 16]
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).
Change from baseline to the end of Week 16 in Western Ontario and McMaster University Arthritis Index (WOMAC) physical function subscale score [Baseline, Week 16]
See WOMAC 3.1 described above.
Change from baseline to the end of Week 16 in Patient Global Assessment (PGA) score [Baseline, Week 16]
The PGA is part of a comprehensive assessment of the impact of treatment for osteoarthritis that also includes pain and physical function. The PGA included in the present study indicates the perception of osteoarthritis in the study joint at the current time. Ratings are provided on an 11-point numerical rating scale from 0 ("Very Good") to 10 ("Very Bad").

Secondary Outcome Measures

Change from baseline to the end of Week 16 in Patient Global Assessment (PGA) score [Baseline, Week 16]
See PGA described above.
Change from baseline to the end of Week 16 in WOMAC Stiffness subscale score [Baseline, Week 16]
See WOMAC 3.1 described above.
Change from baseline to the end of Week 16 in daily numerical rating scale (NRS) score [Baseline, Week 16]
The numerical rating scale (NRS) uses an 11-point scale to assess OA pain ranging from 0 to 10 with high scores representing greater symptom severity (0=no pain and 10=pain as bad as you can imagine).
Change from baseline to the end of Week 16 in Medical Outcomes Study (MOS) Sleep subscale scores [Baseline, Week 16]
The MOS Sleep Scale (acute version) contains 12 items that address aspects of sleep. Six subscale scores may be calculated including: daytime somnolence, sleep disturbances, snoring, shortness of breath or headache upon awaking, adequacy of sleep and amount of sleep plus a summary index of sleep disturbances. A higher score indicates worse sleep in most domains, but the amount of sleep and adequacy of sleep are scored in the opposite direction. The primary subscale of interest in this study is daytime somnolence.
Change from baseline to the end of Week 16 in Short-Form-36 (SF-36) subscale scores [Baseline, Week 16]
The SF-36 is a self-administered, generic, 36-item questionnaire designed to cover 8 domains of functional health status and well-being, physical functioning, role limitations due to physical health problems, bodily pain, general health perceptions, vitality, social functioning, role limitations due to emotional problems, and mental health. Scoring yields 8 subscales based on the 8 domains covered in the questionnaire. These scales are scored from 0 to 100 with higher scores indicating better health.
Change from baseline to the end of Week 16 in EuroQol, 5 dimensions, 5 levels (EQ-5D-5L) scale score [Baseline, Week 16]
The EQ-5D is a self-administered, standardized measure of health status designed to provide a generic measure of health for clinical and economic appraisal that includes the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The EQ-5D 5 level (5L) version will be used in this study. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and unable or extreme problems. A unique health state is defined by combining 1 level from each of the 5 dimensions.
Change from baseline to the end of Week 16 in the percentage of participants who are responders based on WOMAC pain and physical function subscale scores and PGA scale scores [Baseline, Week 16]
Responders are defined as participants with percent improvement equal to and above the threshold values for WOMAC pain and physical function subscale scores and PGA scale scores, reported separately.
Change from baseline to the end of Week 16 in the percentage of participants who are responders based on OMERACT-OARSI, MCII, and PASS scale scores [Baseline, Week 16]
Responders are defined as participants with percent improvement equal to and above the threshold values for Outcome Measures in Rheumatology initiative/Osteoarthritis Research Society International (OMERACT-OARSI), Minimal Clinically Important Improvement (MCII), and the Patient Acceptable Symptom State (PASS) scale scores.
Change from baseline to the end of Week 16 in the percentage of participants who use rescue medication and other osteoarthritis (OA) analgesia [Baseline, Week 16]
Use of rescue medication (acetaminophen/paracetamol) and other OA pain medication will be recorded weekly during the study.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 99 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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
An unsatisfactory response (inadequate efficacy or poor tolerability) that includes all 3 classes of analgesic medications (acetaminophen/paracetamol, NSAIDs, and opioids) and receiving an opioid at study entry; For participants in the USA and Canada: An 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) and receiving an opioid (other than codeine or codeine combination products) at study entry
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

Contacts and Locations

Locations

	City	State	Country
1	Birmingham	Alabama	United States
2	Huntsville	Alabama	United States
3	Cerritos	California	United States
4	Denver	Colorado	United States
5	Stamford	Connecticut	United States
6	Lewes	Delaware	United States
7	Newark	Delaware	United States
8	Crystal River	Florida	United States
9	Fort Lauderdale	Florida	United States
10	Hialeah	Florida	United States
11	Opa-locka	Florida	United States
12	Port Orange	Florida	United States
13	Marietta	Georgia	United States
14	Woodstock	Georgia	United States
15	Chicago	Illinois	United States
16	Rockford	Illinois	United States
17	Prairie Village	Kansas	United States
18	Lake Charles	Louisiana	United States
19	New Orleans	Louisiana	United States
20	Frederick	Maryland	United States
21	Worcester	Massachusetts	United States
22	Las Vegas	Nevada	United States
23	Albuquerque	New Mexico	United States
24	Brooklyn	New York	United States
25	Lake Success	New York	United States
26	Oklahoma City	Oklahoma	United States
27	Downingtown	Pennsylvania	United States
28	Duncansville	Pennsylvania	United States
29	Philadelphia	Pennsylvania	United States
30	Wyomissing	Pennsylvania	United States
31	Jackson	Tennessee	United States
32	Austin	Texas	United States
33	Dallas	Texas	United States
34	Houston	Texas	United States
35	West Jordan	Utah	United States
36	Richmond	Virginia	United States
37	Burlington	Ontario	Canada
38	Sarnia	Ontario	Canada
39	Baja		Hungary
40	Szeged		Hungary
41	Canterbury		New Zealand
42	Newtown		New Zealand
43	Takapuna		New Zealand
44	Tauranga		New Zealand
45	Bialystok		Poland
46	Gdansk		Poland
47	Myslenice		Poland
48	Blackpool		United Kingdom
49	Cannock		United Kingdom
50	Greater Manchester		United Kingdom
51	Mancheter		United Kingdom
52	Matrix Park Buckshow Willage		United Kingdom
53	Stourton		United Kingdom