Evaluate Efficacy and Safety of X0002 in Treatment of Knee Osteoarthritis

NCT03691818 | Completed Phase 2

• 1 other identifier: TFR-X0002-201
• Study Type: interventional
• Target: 353
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a randomized, double-blind clinical trial in a Chinese population.

Conditions

KNEE OSTEOARTHRITIS

Outcome Measures

Primary Outcomes (1)

• Change of the Subject's Target OA Knee Compared to the Baseline as Assessed by WOMAC

  The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) has been used to assess subjects with OA of the hip or knee and consists of 24 questions in subscales measuring 3 concepts: pain, stiffness, and physical function. These questions measure the amount of pain, degree of difficulty in completing various day-to-day activities, and stiffness experienced in the hip or knee. Usually subject self-administered. A single question has 100 grades, where 0 = very good and 100 = very much worse. VAS (visual analog scale) scale is used for score record. 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.

  week 12

Secondary Outcomes (10)

• Incidence of Treatment-Emergent Adverse Events of X0002 Spray

  week 1 to week 14

• Relief of Knee Pain in Subjects With Osteoarthritis (OA) of the Knee as Evaluated by WOMAC Subscale

  week 2，4，8

• Relief of Joint Stiffness After Using X0002 Spray as Evaluated by WOMAC Subscale

  week 2，4，8, 12

• Difficulty Performing Daily Activities of OA Subjects as Assessed by WOMAC subscale

  week 2，4，8, 12

• Total Score of WOMAC Subscale as Estimated by Visual Analog Scale

  week 2，4，8, 12

Other Outcomes (2)

• Investigator's Global Assessment of Subjects' Disease Status and Therapy Effects at 2, 4, 8 and 12 Weeks of Treatment

  week 2，4，8, 12

• Change in the WOMAC Subscale Scores for Pain, Stiffness and Functional Ability of Target Knee

  week 14

Study Arms (9)

Low-dose test drug group

EXPERIMENTAL

X0002 Spray 1 Spray/time/Knee, 2 times/day; Ibuprofen Placebo Tab 400 mg/time, 3 times /day.

Drug: X0002 Spray; Drug: Ibuprofen Placebo Tab

Low-dose active drug control group

ACTIVE COMPARATOR

Ibuprofen Tablet 400 mg/time, 3 times /day; X0002 Placebo Spray 1 Spray/time/Knee, 2 times/day.

Drug: Ibuprofen Tablet; Drug: X0002 Placebo Spray

Low-dose placebo control group

PLACEBO COMPARATOR

Placebo Spray 1 Spray/time/Knee, 2 times/day; Ibuprofen Placebo Tab 400 mg/time, 3 times/day.

Drug: Ibuprofen Placebo Tab; Drug: X0002 Placebo Spray

Medium-dose test drug group

EXPERIMENTAL

X0002 Spray 2 Spray/time/Knee, 2 times/day; Ibuprofen Placebo Tab 400 mg/time, 3 times /day.

Drug: X0002 Spray; Drug: Ibuprofen Placebo Tab

Medium-dose active drug control group

ACTIVE COMPARATOR

X0002 Placebo Spray 2 Spray/time/Knee, 2 times/day; Ibuprofen Tablet 400 mg/time, 3 times /day.

Drug: Ibuprofen Tablet; Drug: X0002 Placebo Spray

Medium-dose placebo control group

PLACEBO COMPARATOR

X0002 Placebo Spray 2 Spray/time/Knee, 2 times/day; Ibuprofen Placebo Tab 400 mg/time, 3 times /day.

Drug: Ibuprofen Placebo Tab; Drug: X0002 Placebo Spray

High-dose test drug group

EXPERIMENTAL

X0002 Spray 4 Spray/time/Knee, 2 times/day; Ibuprofen Placebo Tab 400 mg/time, 3 times /day.

Drug: X0002 Spray; Drug: Ibuprofen Placebo Tab

High-dose active drug control group

ACTIVE COMPARATOR

X0002 Placebo Spray 4 Spray/time/Knee, 2 times/day; Ibuprofen Tablet 400 mg/time, 3 times /day.

Drug: Ibuprofen Tablet; Drug: X0002 Placebo Spray

High-dose placebo control group

PLACEBO COMPARATOR

X0002 Placebo Spray 4 Spray/time/Knee, 2 times/day; Placebo Tablet 400 mg/time, 3 times /day.

Drug: Ibuprofen Placebo Tab; Drug: X0002 Placebo Spray

Interventions

X0002 Spray DRUG

According to the different dose groups assigned, each knee joint was sprayed with 1, 2 or 4 sprays.

Also known as: Test drug

High-dose test drug group; Low-dose test drug group; Medium-dose test drug group

Ibuprofen Tablet DRUG

Ibuprofen Tab 400mg, tid.

Also known as: Active drug

High-dose active drug control group; Low-dose active drug control group; Medium-dose active drug control group

Ibuprofen Placebo Tab DRUG

Ibuprofen Placebo Tab 400mg, tid.

Also known as: Placebo Oral Tablet

High-dose placebo control group; High-dose test drug group; Low-dose placebo control group; Low-dose test drug group; Medium-dose placebo control group; Medium-dose test drug group

X0002 Placebo Spray DRUG

According to the different dose groups assigned, each knee joint was sprayed with 1, 2 or 4 sprays.

Also known as: Placebo Spray

High-dose active drug control group; High-dose placebo control group; Low-dose active drug control group; Low-dose placebo control group; Medium-dose active drug control group; Medium-dose placebo control group

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Ability to read and provide written, personally signed, and dated informed consent to participate in the study, in accordance with the GCP and applicable regulations, before completing any study related procedures.
• \. An understanding, ability, and willingness to fully comply with study procedures and restrictions.
• \. Subject must be a male or female between 40 and 75 years of age, inclusive.
• \. Female subjects must either not be of childbearing potential (defined as postmenopausal for at least 1 year or surgically sterile \[bilateral tubal ligation, bilateral oophorectomy, or hysterectomy\]) or be willing to practice at least 1 of the following medically acceptable methods of birth control: Hormonal methods such as oral, implantable, injectable, vaginal ring, or transdermal contraceptives for a minimum of 1 full cycle (based on the subjects usual menstrual cycle period) before study drug administration.
• Intrauterine device.
• Double-barrier method (condoms, sponge, or diaphragm with spermicidal jellies or cream).
• \. Subject must have a diagnosis of idiopathic OA according to the American College of Rheumatology clinical and radiographic criteria, and fulfillment of at least four of the 6 criteria: age of ≥50 years stiffness lasting \<30 minutes after getting up in the morning crepitus Bone tenderness Bone enlargement No joint fever
• \. Subject must have a history of clinically symptomatic OA of the knee for ≥6 months.
• \. Subject must have had knee pain while standing, walking, and/or in motion for at least 14 days during the month prior to screening.
• \. Subject must have a knee pain score ≥40 mm and \<90 mm on a 100 mm VAS (without analgesic medication) on at least 7 of the 10 days prior to randomization(according to the subject's diary card records).
• \. Subject must have a WOMAC pain average score of knee ≥40 mm and \<90 mm starting on the first screening visit.
• \. Subject must be willing to discontinue any NSAIDs or other analgesic (e.g. aspirin) or potentially confounding concomitant treatments (e.g. physiotherapy, acupuncture) starting on the first screening visit 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 the Second Screening Visit, Baseline (Day1), Week 2, Week 4, Week 8, Week 12, Week 14.
• \. Subject must be willing to discontinue applying any topical preparations containing Vitamin A acids \[including all trans-retinoic-acid (tretinoin), 13-cis-retinoic-acid (isotretinoin), 9-cis-retinoic-acid (alitretinoin), vitamin A (retinol), retinal, and their derivatives\] to the lower limbs starting on the first screening visit until completing participation in the study. (Topical preparations containing Vitamin A acids or retinol may be applied to areas of the skin above the waist, but should not be applied to areas of the skin exposed to study medication.) 12. Subject must be willing to avoid unaccustomed physical activity (e.g. starting a new weight lifting routine) for the duration of the study starting on the first screening visit.
• \. With the exception of OA of the knee, the subject must be in good general health with no clinically significant findings from medical history, vital signs, physical examination, ECG, and routine laboratory tests that could interfere with subject safety, or pain and functional assessments, as determined by the Investigator.

You may not qualify if:

• \. The subject had a history of trauma, and the injury affected the knee joint.
• \. 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.
• \. Subject who has a history of total or partial knee replacement, arthroplasty, or other knee surgery on either knee.
• \. Subject who has had significant injury, as estimated by the Investigator, involving the target knee within the 6 months before screening.
• \. 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.
• \. Subject who has used opiates or corticosteroids within 30 days before screening for the target knee or who requires treatment with chronic opiates or corticosteroids.
• \. Subject who has had intra articular injections of corticosteroids, hyaluronic acid, or viscosupplements (e.g. Synvisc®) to a knee to be treated within the 3 months before screening.
• \. Subject who has a history of significant hypersensitivity, intolerance, or allergy to ibuprofen, any NSAIDs, aspirin, or acetaminophen.
• \. Subject who has had an active peptic ulceration in the 6 months prior to screening or a history of gastrointestinal (GI) bleeding within 5 years of screening.
• \. Subject who has used an anticoagulant (except aspirin up to 325 mg/day for cardiac prophylaxis) in the month prior to Screening.
• \. Subject who has positive results on fecal occult blood testing at screening or on Day 1 prior to the first administration of study medication.
• \. Subject who has a history of chronic inflammatory disease (such as rheumatoid arthritis, psoriatic arthritis, gouty arthritis), fibromyalgia, or other conditions that may affect the target joint or the functional and pain assessments (e.g. osteonecrosis, chondrocalcinosis).
• \. Subject is an asthmatic requiring treatment with systemic corticosteroids. Asthmatic subjects using inhaled corticosteroids are eligible.
• \. Subject has any clinically significant unstable cardiac, respiratory, neurological, immunological, hematological, or renal disease, or any other condition that, in the investigators opinion, could compromise the subjects welfare, ability to communicate with the study staff, or otherwise contraindicate study participation.
• \. Subject has a significant renal or hepatic disease, as indicated by clinical laboratory assessment,defined as

Sponsors & Collaborators

• Tianjin XinChen-Techfields Pharma Co., LTD.: lead

Study Sites (1)

Chinese Academy of Medical Science & Peking Union Medical college Hospital

Beijing, Beijing Municipality, 100005, China

Location

MeSH Terms

Conditions

Osteoarthritis, Knee

Interventions

Drug Evaluation; Ibuprofen; Bulk Drugs

Condition Hierarchy (Ancestors)

Osteoarthritis; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Intervention Hierarchy (Ancestors)

Drug Development; Investigative Techniques; Evaluation Studies as Topic; Phenylpropionates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Pharmaceutical Preparations

Study Officials

• Zeng Xiaofeng

  lead institution

  PRINCIPAL INVESTIGATOR

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: September 3, 2018
• First Posted: October 2, 2018
• Study Start: July 16, 2018
• Primary Completion: October 21, 2019
• Study Completion: October 21, 2019
• Last Updated: January 13, 2020

Record last verified: 2019-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)