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

Sponsor

Janssen Research & Development, LLC (Industry)

Overall Status

Completed

CT.gov ID

NCT02301234

Collaborator

(none)

111

Enrollment

Locations

Arms

17.9

Actual Duration (Months)

1.7

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 signs and symptoms of osteoarthritis of the hip or knee that are 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: Celecoxib 100 mg Drug: Celecoxib 100 mg Matching Placebo	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. 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 Design

Study Type:

Interventional

Actual Enrollment :

111 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 Safety, Tolerability, and Efficacy of Fulranumab as Adjunctive Therapy in Subjects With Signs and Symptoms of Osteoarthritis of the Hip or Knee

Actual Study Start Date :

Mar 25, 2015

Actual Primary Completion Date :

Sep 19, 2016

Actual Study Completion Date :

Sep 19, 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, 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: 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. Drug: Celecoxib 100 mg Matching Placebo Double-blind capsules taken twice daily for up to 16 weeks.

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: 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.

Drug: Celecoxib 100 mg Matching Placebo

Double-blind capsules taken twice daily for up to 16 weeks.

Outcome Measures

Primary Outcome Measures

The number of participants with Adverse Events as a measure of safety and tolerability [Up to Week 52]

Secondary 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.

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
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

Contacts and Locations

Locations

	City	State	Country
1	Glendale	Arizona	United States
2	Phoenix	Arizona	United States
3	Tucson	Arizona	United States
4	Little Rock	Arkansas	United States
5	Anaheim	California	United States
6	Garden Grove	California	United States
7	Los Angeles	California	United States
8	North Hollywood	California	United States
9	Boulder	Colorado	United States
10	Coral Gables	Florida	United States
11	Miami	Florida	United States
12	Orlando	Florida	United States
13	Winter Park	Florida	United States
14	Columbus	Georgia	United States
15	Chicago	Illinois	United States
16	Overland Park	Kansas	United States
17	Elkridge	Maryland	United States
18	Detroit	Michigan	United States
19	Saint Louis	Missouri	United States
20	Brooklyn	New York	United States
21	New York	New York	United States
22	Norman	Oklahoma	United States
23	Knoxville	Tennessee	United States
24	Memphis	Tennessee	United States
25	Tullahoma	Tennessee	United States
26	Arlington	Texas	United States
27	Houston	Texas	United States
28	Lampasas	Texas	United States
29	Nassau Bay	Texas	United States
30	Sugar Land	Texas	United States
31	Arlington	Virginia	United States
32	Charlottesville	Virginia	United States
33	Camperdown		Australia
34	Hobart		Australia
35	Kippa Ring		Australia
36	Kogarah		Australia
37	Maroochydore		Australia
38	Melbourne		Australia
39	Sherwood		Australia
40	Kamloops	British Columbia	Canada
41	Kelowna	British Columbia	Canada
42	Toronto	Ontario	Canada
43	Montreal	Quebec	Canada
44	West Vancouver		Canada
45	Praha		Czechia
46	Leipzig		Germany
47	Szekszard		Hungary
48	Anyang		Korea, Republic of
49	Jeju		Korea, Republic of
50	Seoul		Korea, Republic of
51	Elblag		Poland
52	Katowice		Poland
53	Krakow		Poland
54	Torun		Poland
55	Warszawa		Poland
56	Warszaw		Poland
57	Wroclaw		Poland
58	A Coruña		Spain
59	Santiago De Compostela		Spain
60	Lund		Sweden
61	Malmo		Sweden
62	Blackpool		United Kingdom
63	Cannock		United Kingdom
64	Mancheter		United Kingdom
65	Stourton		United Kingdom