A Study to Evaluate the Efficacy and Safety of X0002 Spray in Subjects With Osteoarthritis

Osteoarthritis of the Knee Clinical Trial

Official title:

A Phase 2, Multicenter, Randomized, Double Blind, Placebo Controlled, Parallel Group, Dose Range Finding Study to Evaluate the Efficacy and Safety of X0002 Spray Versus Placebo in Subjects With Osteoarthritis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02067611
• Other study ID #: TF-X0002-21
• Status: Completed
• Phase: Phase 2
• First received: February 18, 2014
• Last updated: February 5, 2018
• Start date: February 2014
• Est. completion date: April 2016

Study information

• Verified date: February 2018
• Source: Techfields Pharma Co. Ltd
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a phase 2, multicenter, randomized, double blind (with dose), placebo controlled, parallel group, proof of concept, and dose range finding study to evaluate the efficacy, safety, and PK of X0002 spray in adult subjects with clinically symptomatic mild to moderate OA of the knee.

Objectives of the study:

1. To evaluate the efficacy of X0002 spray compared to placebo for relief of knee pain in subjects with osteoarthritis (OA) of the knee;

2. To assess the safety and tolerability of multiple doses of X0002 when administered as a topical spray.

Description:

This is a phase 2, multicenter, randomized, double blind (with dose), placebo controlled, parallel group, proof of concept, and dose range finding study to evaluate the efficacy, safety, and PK of X0002 spray in adult subjects with clinically symptomatic mild to moderate OA of the knee.

After a screening period of up to 3 weeks and radiographic evaluation of the target knee joint space, 225 subjects will be randomly assigned to 1 of 3 treatment groups in a 1:1:1 ratio with a 2:1 ratio of active:placebo within each treatment group in a 1:1:1 ratio with a 2:1 ratio of active:placebo within each treatment group (i.e., 2 subjects to active treatment and 1 subject to placebo):

Group A: low dose of X0002, twice daily (BID, approximately every 12 hours; n=50) or placebo (low dose), BID (approximately every 12 hours; n=25); Group B: middle dose of X0002, BID (approximately every 12 hours; n=50) or placebo , BID (approximately every 12 hours; n=25) ; Group C: High dose of X0002, BID (approximately every 12 hours; n=50) or placebo, BID (approximately every 12 hours; n=25) .

Safety and efficacy assessments will be performed at at 2, 4, 8, and 12 weeks of treatment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 216
• Est. completion date: April 2016
• Est. primary completion date: August 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 35 Years to 85 Years

Eligibility

Inclusion Criteria:

• A subject must be a male or female between 35 and 85 years of age, inclusive.

• A subject must have a body mass index (BMI) between 18.5 and 39.9 kg/m2, inclusive.

• A subject must have a diagnosis of idiopathic OA according to the American College of Rheumatology (ACR) clinical and radiographic criteria (knee pain, osteophytes, and at least one of the following: >50 years of age, morning stiffness lasting <30 minutes after getting up in the morning, or crepitus).

• A subject must have a Kellgren Lawrence Grade of 1 or 2 as determined by the Investigator or a local radiologist at Screening.

• A subject must have a history of clinically symptomatic mild to moderate OA of the knee for =6 months.

• A subject must have had knee pain while standing, walking, and/or on motion for at least 14 days during the month prior to Screening.

• A subject must have a knee pain score =40 mm and <90 mm on a 100 mm VAS (with or without analgesic medication) on at least 10 of the 14 days prior to randomization.

• A subject must be willing to discontinue any NSAIDs or other analgesic (eg, aspirin, acetaminophen) or potentially confounding concomitant treatments (eg, physiotherapy, acupuncture) starting 4 days before the administration of the first dose of study medication until completing participation in the study. (The use of =325 mg acetylsalicylic acid per day as cardiac prophylaxis is permitted.) The subject will be allowed to take rescue medication (acetaminophen) for pain during the study except during the 24 hours prior to Baseline (Day1), Week 2, Week 4, Week 8, Week 12/EOS, and Follow-up assessments.

• A subject must be willing to avoid unaccustomed physical activity (eg, starting a new weight lifting routine) for the duration of the study.

Exclusion Criteria:

• A subject who has secondary OA of the knee or OA of lower limb joints other than the knee that, in the opinion of the Investigator, could interfere with pain and functional assessments related to the knee

• A subject who has OA of the knee with a Kellgren Lawrence Grade =3 as determined by the Investigator or a local radiologist at Screening

• A subject who has a history of total or partial knee replacement, arthroplasty, or other knee surgery on either knee

• A subject who has had significant injury, as judged by the Investigator, involving the target knee within the 6 months before Screening.

• A subject who has skin lesions or wounds on or near the knees to be treated at Screening or on Day 1 prior to the first administration of study medication

• A subject who has used opiates or corticosteroids within 30 days before Screening or who requires treatment with chronic opiates or corticosteroids

• A subject who has had intra articular injections of corticosteroids, hyaluronic acid, or viscosupplements (eg, Synvisc®) to a knee to be treated within the 3 months before Screening.

• A subject who has a history of significant hypersensitivity, intolerance, or allergy to ibuprofen, any NSAIDs, aspirin, or acetaminophen

• A subject who has had an active peptic ulceration in the 12 months prior to Screening or a history of gastrointestinal (GI) bleeding within 5 years of Screening

• A subject who has used an anticoagulant (except aspirin up to 325 mg/day for cardiac prophylaxis) in the month prior to Screening

• A subject who has positive results on fecal occult blood testing at Screening or on Day 1 prior to the first administration of study medication

• A subject who has a history of chronic inflammatory disease (such as rheumatoid arthritis, psoriatic arthritis, gouty arthritis), fibromyalgia, conditions that may affect the target joint (eg, osteonecrosis, chondrocalcinosis), or asthma.

Related Conditions & MeSH terms

• Osteoarthritis
• Osteoarthritis of the Knee
• Osteoarthritis, Knee

Intervention

Drug:
• X0002
Parallel Assignment
• Placebo
Parallel Assignment

Locations

Country	Name	City	State
United States	New Mexico Clinical Research & Osteoporosis Center, Inc.	Albuquerque	New Mexico
United States	Heritage Valley Medical Group	Beaver	Pennsylvania
United States	Med Center	Carmichael	California
United States	Hightop Medical Research	Cincinnati	Ohio
United States	Columbus Regional Research Institute	Columbus	Georgia
United States	Clinical Research of South Florida	Coral Gables	Florida
United States	Avail Clinical Research, LLC	DeLand	Florida
United States	Altoona Center for Clinical Research	Duncansville	Pennsylvania
United States	Prestige Clinical Research, LLC	Franklin	Ohio
United States	Healthcare Research Network	Hazelwood	Missouri
United States	Health Awareness Inc.	Jupiter	Florida
United States	Suncoast Clinical Research, Inc	New Port Richey	Florida
United States	Health Research of Hampton Roads, Inc	Newport News	Virginia
United States	Clinical Trials Technology(CTT) Consultants, Inc.	Prairie Village	Kansas
United States	Sundance Clinical Research, LLC	Saint Louis	Missouri
United States	Quality Research Inc	San Antonio	Texas
United States	Encompass Clinical Research	Spring Valley	California
United States	Fiel Family & Sports Medicine/Clinical Research Advantage Inc	Tempe	Arizona
United States	New England Research Assoc.	Trumbull	Connecticut
United States	Diablo Clinical Research, Inc.	Walnut Creek	California

Sponsors (1)

Lead Sponsor	Collaborator
Lina Xu

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Subject's Global Assessment of Disease Status of the Target Knee at 2, 4, 8 and 12 Weeks of Treatment	Data for the exploratory efficacy endpoints will be summarized using descriptive statistics.; Safety analyses will be conducted on the SAS. Safety parameters will be listed and summarized using standard descriptive statistics, as appropriate. No formal statistical analyses are planned.	at 2, 4, 8, and 12 weeks of treatment
Other	Investigator's Global Assessment of Disease Status of the Target Knee at 2, 4, 8 and 12 Weeks of Treatment	Data for the exploratory efficacy endpoints will be summarized using descriptive statistics.; Safety analyses will be conducted on the SAS. Safety parameters will be listed and summarized using standard descriptive statistics, as appropriate. No formal statistical analyses are planned.	at 2, 4, 8, and 12 weeks of treatment
Other	Subject's Global Assessment of Response to Therapy of the Target Knee at 2, 4, 8 and 12 Weeks of Treatment	Data for the exploratory efficacy endpoints will be summarized using descriptive statistics.; Safety analyses will be conducted on the SAS. Safety parameters will be listed and summarized using standard descriptive statistics, as appropriate. No formal statistical analyses are planned.	at 2, 4, 8, and 12 weeks of treatment
Other	Investigator's Global Assessment of Response to Therapy of the Target Knee at 2, 4, 8 and 12 Weeks of Treatment	Data for the exploratory efficacy endpoints will be summarized using descriptive statistics.; Safety analyses will be conducted on the SAS. Safety parameters will be listed and summarized using standard descriptive statistics, as appropriate. No formal statistical analyses are planned.	at 2, 4, 8, and 12 weeks of treatment
Other	Change From Baseline Over Time in VAS Pain Scores for the Target Knee From Daily Diary Data.	Data for the exploratory efficacy endpoints will be summarized using descriptive statistics.; Safety analyses will be conducted on the SAS. Safety parameters will be listed and summarized using standard descriptive statistics, as appropriate. No formal statistical analyses are planned.	at 2, 4, 8, and 12 weeks of treatment
Other	Amount of Rescue Medication (Acetaminophen) Consumed Per Day for Target Knee Pain.	Data for the exploratory efficacy endpoints will be summarized using descriptive statistics.; Safety analyses will be conducted on the SAS. Safety parameters will be listed and summarized using standard descriptive statistics, as appropriate. No formal statistical analyses are planned.	at 2, 4, 8, and 12 weeks of treatment
Primary	To Evaluate the Efficacy of X0002 Spray Compared to Placebo for Relief of Knee Pain in Subjects With Osteoarthritis (OA) of the Knee	The Primary Efficacy Endpoint is change from Baseline in the WOMAC (VAS) pain subscale score for the target knee at 4 weeks of treatment, and will be analyzed using an analysis of covariance (ANCOVA). Treatment will be included as a fixed class effect and WOMAC Baseline pain subscale score as covariates. The primary comparisons of interest will be the difference between active Group A (low dose) and combined placebo, active Group B (middle dose) and combined placebo, and active Group C (high dose) and combined placebo.; Safety analyses will be conducted on the SAS. Safety parameters will be listed and summarized using standard descriptive statistics, as appropriate. No formal statistical analyses are planned.	4 weeks of treatment
Secondary	To Assess the Safety and Tolerability of Multiple Doses of X0002 When Administered as a Topical Spray	A sensitivity analysis will also be conducted on the Primary Efficacy Endpoint using an ANCOVA with treatment as a fixed class effect and WOMAC baseline pain subscale score as covariates, but the comparisons of interest will be the difference between the active and placebo subjects within each treatment group.; The Secondary Efficacy Endpoints, change from Baseline in the WOMAC subscale scores for pain, stiffness, and functional ability, and overall WOMAC score at 2, 8, and 12 weeks of treatment, will be by analyzed using the same methods as the for the Primary Efficacy Endpoint.; Safety analyses will be conducted on the SAS. Safety parameters will be listed and summarized using standard descriptive statistics, as appropriate. No formal statistical analyses are planned.	2, 8, and 12 weeks of treatment
Secondary	To Evaluate the Effect of X0002 Spray Compared to Placebo for the Relief of Joint Stiffness	A sensitivity analysis will also be conducted on the Primary Efficacy Endpoint using an ANCOVA with treatment as a fixed class effect and WOMAC baseline pain subscale score as covariates, but the comparisons of interest will be the difference between the active and placebo subjects within each treatment group.; The Secondary Efficacy Endpoints, change from Baseline in the WOMAC subscale scores for pain, stiffness, and functional ability, and overall WOMAC score at 2, 4, 8, and 12 weeks of treatment, will be by analyzed using the same methods as the for the Primary Efficacy Endpoint.; Safety analyses will be conducted on the SAS. Safety parameters will be listed and summarized using standard descriptive statistics, as appropriate. No formal statistical analyses are planned.	2, 4, 8, and 12 weeks of treatment
Secondary	To Assess the Effect of X0002 Spray Compared to Placebo on Difficulty Performing Daily Activities	A sensitivity analysis will also be conducted on the Primary Efficacy Endpoint using an ANCOVA with treatment as a fixed class effect and WOMAC baseline pain subscale score as covariates, but the comparisons of interest will be the difference between the active and placebo subjects within each treatment group.; The Secondary Efficacy Endpoints, change from Baseline in the WOMAC subscale scores for pain, stiffness, and functional ability, and overall WOMAC score at 2, 8, and 12 weeks of treatment, will be by analyzed using the same methods as the for the Primary Efficacy Endpoint.; Safety analyses will be conducted on the SAS. Safety parameters will be listed and summarized using standard descriptive statistics, as appropriate. No formal statistical analyses are planned.	at 2, 4, 8, and 12 weeks of treatment
Secondary	Characterize the Pharmacokinetics of X0002	Cmax, Tmax, AUCs, apparent terminal elimination rate constant, apparent terminal elimination half-life will be calculated.	at the Week 2, week 3, week 4 and Week 12