A PHASE 3 RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTICENTER STUDY OF THE ANALGESIC EFFICACY AND SAFETY OF THE SUBCUTANEOUS ADMINISTRATION OF TANEZUMAB IN SUBJECTS WITH OSTEOARTHRITIS OF THE HIP OR KNEE

• Register: EUCTR
• Last refreshed on: 24 January 2022
• Main ID: EUCTR2013-004508-21-DE
• Date of registration: 07/12/2015
• Prospective Registration: Yes
• Primary sponsor: Pfizer Inc, 235 East 42nd Street, New York, NY 10017
• Public title: A PHASE 3 RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTICENTER STUDY OF THE ANALGESIC EFFICACY AND SAFETY OF THE SUBCUTANEOUS ADMINISTRATION OF TANEZUMAB IN SUBJECTS WITH OSTEOARTHRITIS OF THE HIP OR KNEE
• Scientific title: A PHASE 3 RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTICENTER STUDY OF THE ANALGESIC EFFICACY AND SAFETY OF THE SUBCUTANEOUS ADMINISTRATION OF TANEZUMAB IN SUBJECTS WITH OSTEOARTHRITIS OF THE HIP OR KNEE
• Date of first enrolment: 19/04/2016
• Target sample size: 810
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-004508-21
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Austria, Bulgaria, Finland, France, Germany, Hungary, Italy, Japan, Poland, Portugal, Romania, Slovakia, Spain, Sweden, United Kingdom

Contacts

• Name: ClinicalTrials.gov call Center
• Affiliation: Pfizer Inc

• Name: ClinicalTrials.gov call Center
• Affiliation: Pfizer Inc

Key inclusion & exclusion criteria

Inclusion criteria:
- Evidence of a personally signed and dated informed consent document
indicating that the subject (or a legally acceptable representative) has
been informed of all pertinent aspects of the study.
- Male or female =18 years of age.
- A diagnosis of osteoarthritis of the hip or knee in the index joint based
on American College of Rheumatology criteria with x-ray confirmation (a
Kellgren-Lawrence 17 x-ray grade of =2 as diagnosed by the Central
Reader).
- Acetaminophen and oral NSAID therapy do not provide adequate pain
relief, or subject is unable to take NSAID; tramadol treatment has not
provided adequate pain relief or subject is unable to take tramadol;
opioid treatment has not provided adequate pain relief or subject is
unwilling to take opioids, or unable to take opioids.
- WOMAC Pain subscale Numerical Rating Scale (NRS) =5 in the index
joint at Screening.
- Subjects must be willing to discontinue all pain medications for
osteoarthritis except rescue medication (acetaminophen) and not use
prohibited pain medications throughout the duration of the study except
as permitted per protocol.
- Female subjects of childbearing potential and at risk for pregnancy
must agree to use 2 highly effective or acceptable methods of
contraception throughout the study and for 112 days (16 weeks) after
the last dose of assigned subcutaneous investigational product.
- Female subjects who are not of childbearing potential meet at least one
of the following criteria:
•Have undergone a documented hysterectomy and/or bilateral
oophorectomy;
•Have medically confirmed ovarian failure; or
•Achieved post-menopausal status defined as follows: cessation of
regular menses for at least 12 consecutive months with no alternative
pathological or physiological cause and have a serum follicle stimulating
hormone (FSH) level confirming the post-menopausal state.
- Subjects who are willing and able to comply with lifestyle guidelines,
scheduled visits, treatment plan, laboratory tests, and other study
procedures through the End of Study visit.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 510
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 300

Exclusion criteria:
- Subjects who are investigational site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the Investigator, or subjects who are Pfizer employees directly involved in the conduct of the trial.
- Body Mass Index (BMI) of >39 kg/m2.
History or radiographic evidence of other diseases that could confound efficacy assessments (e.g., rheumatoid arthritis).
History or radiographic evidence of orthopedic conditions that may increase the risk of, or confound assessment of joint safety conditions during the study.
- Planned surgical procedure during the duration of the study.
- Largely or wholly incapacitated, (eg, subject bedridden or confined to a wheelchair, permitting little or no self-care).
- Fibromyalgia, regional pain caused by lumbar or cervical compression with radiculopathy or other moderate to severe pain that may confound assessments or self-evaluation of the pain associated with osteoarthritis. Subjects with a present (current) history of sciatica are not eligible for participation. Subjects with a past history of sciatica who have been asymptomatic for at least one year and who have no evidence of radiculopathy or sciatic neuropathy on thorough neurologic examination are eligible for participation.
- Subjects with a past history of carpal tunnel syndrome (CTS) with signs or symptoms of CTS in the one year prior to Screening.
- Subjects considered unfit for surgery, defined as Grade >3 on the American Society of Anesthesiologists (ASA) physical classification system for surgery, or subjects who would not be willing to undergo joint replacement surgery if required.
- History of intolerance or hypersensitivity to acetaminophen (paracetamol) or any of its excipients or existence of a medical condition or use of concomitant medication for which the use of acetaminophen is contraindicated (refer to product labeling).
- Use of prohibited medications without the appropriate washout period (if applicable) prior to Screening or Initial Pain Assessment Period.
- Oral or intramuscular corticosteroids within 30 days prior to the Initial Pain Assessment Period.
- Intra-articular corticosteroid injection in the index joint within 12 weeks, or to any other joint within 30 days prior to the Initial Pain Assessment Period.
- Intra-articular hyaluronic acid injection in the index joint within 30 days (or within 18 weeks for long-acting formulations such as Synvisc) prior to the Initial Pain Assessment Period.
- History of cancer within 5 years prior to Screening, except for cutaneous basal cell or squamous cell cancer resolved by excision.
See the protocol for additional Exclusion Criteria.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Osteoarthritis of the hip or knee
MedDRA version: 20.0 Level: LLT Classification code 10023476 Term: Knee osteoarthritis System Organ Class: 100000004859
MedDRA version: 20.0 Level: LLT Classification code 10020108 Term: Hips osteoarthritis System Organ Class: 100000004859

Intervention(s)

Product Name: Tanezumab
Product Code: PF-04383119
Pharmaceutical Form: Solution for injection/infusion in pre-filled syringe
INN or Proposed INN: Tanezumab
CAS Number: 880266-57-9
Current Sponsor code: PF-04383119
Other descriptive name: RI624, RN624
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 2.5-
Pharmaceutical form of the placebo: Solution for injection in pre-filled syringe
Route of administration of the placebo: Subcutaneous use

Product Name: Tanezumab
Product Code: PF-04383119
Pharmaceutical Form: Solution for injection/infusion in pre-filled syringe
INN or Proposed INN: Tanezumab
CAS Number: 880266-57-9
Current Sponsor code: PF-04383119
Other descriptive name: RI624, RN624
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 5-
Pharmaceutical form of the placebo: Solution for injection in pre-filled syringe
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Timepoints are listed with the Endpoints.

Main Objective: •Demonstrate superior efficacy of tanezumab 5 mg and 2.5 mg administered subcutaneously (SC) every 8 weeks versus placebo at Week 24.

Primary end point(s): The co-primary efficacy endpoints are:
•Change from Baseline to Week 24 in the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) Pain subscale;
•Change from Baseline to Week 24 in the WOMAC Physical Function subscale;
•Change from Baseline to Week 24 in the Patient’s Global Assessment of Osteoarthritis.

Secondary Objective: •Evaluate the safety of tanezumab 2.5 mg SC and 5 mg SC.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Timepoints are listed with the Endpoints.

Secondary end point(s): Efficacy Measures
•WOMAC Pain subscale change from Baseline to Weeks 2, 4, 8, 12, 16, and 32.
•WOMAC Physical Function subscale change from Baseline to Weeks 2, 4, 8, 12, 16, and 32.
•Patient’s Global Assessment of Osteoarthritis (5 point Likert scale) change from Baseline to Weeks 2, 4, 8, 12, 16, and 32.
•Outcome Measures in Rheumatology – Osteoarthritis Research Society Initiative (OMERACT-OARSI) responder index at Weeks 2, 4, 8, 12, 16, 24, and 32.
•Cumulative distribution of percent change from Baseline in the WOMAC Pain subscale score to Week 16 and 24 (endpoint for summary only).
•Treatment Response: Reduction in the WOMAC Pain subscale of =30%, =50%, =70% and =90%, at Weeks 2, 4, 8, 12, 16, 24, and 32.
•Treatment Response: Reduction in the WOMAC Physical Function subscale of =30%, =50%, =70% and =90% at Weeks 2, 4, 8, 12, 16, 24, and 32.
•Cumulative distribution of percent change from Baseline in the WOMAC Physical Function subscale score to Week 16 and 24 (endpoint for summary only).
•Treatment Response: Improvement of =2 points in Patient’s Global Assessment of Osteoarthritis at Weeks 2, 4, 8, 12, 16, 24, and 32.
•Average pain score in the index knee or hip change from Baseline to Weeks 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24, 28 and 32.
•WOMAC Stiffness subscale change from Baseline to Weeks 2, 4, 8, 12, 16, 24 and 32.
•WOMAC Average score change from Baseline to Weeks 2, 4, 8, 12, 16, 24, and 32.
•WOMAC Pain Subscale Item: Pain When Walking on a Flat Surface, change from Baseline to Weeks 2, 4, 8, 12, 16, 24, and 32.
•WOMAC Pain Subscale Item: Pain When Going Up or Downstairs, change from Baseline to Weeks 2, 4, 8, 12, 16, 24, and 32.
•Work Productivity and Activity Impairment Questionnaire for Osteoarthritis (WPAI:OA) impairment scores change from Baseline to Weeks, 8, 16 and 24.
•EQ 5D-5L Health State Utility and Five Items (Mobility; Self-Care; Usual Activities; Pain/Discomfort; Anxiety/Depression) change from Baseline to Weeks 8, 16 and 24.
•Patient Reported Treatment Impact Assessment-Modified (mPRTI) at Weeks 16 and 24.
•Health Care Resource Utilization at Baseline, and Weeks 32 and 48.
•Incidence and time to discontinuation due to Lack of Efficacy.
•Usage of rescue medication (incidence and number of days of use) during Weeks 2, 4, 8, 12, 16, 24, and 32.
•Usage of rescue medication (amount taken) during Weeks 2, 4, 8, 12, 16 and 24.

Safety Measures
•Adverse Events.
•Standard safety assessments (safety laboratory testing [chemistry, hematology], sitting vital signs, electrocardiogram (ECG; 12-lead).
•Joint Safety Adjudication outcomes.
•Total joint replacements.
•Orthostatic (supine / standing) blood pressure assessments.
•Survey of Autonomic Symptom scores.
•Neurologic exam (Neuropathy Impairment Score [NIS]).
•Anti tanezumab antibody assessments.
•Physical examinations.

Secondary ID(s)

BB-IND 11,680

A4091057

Source(s) of Monetary Support

Pfizer Inc, 235 East 42nd Street, New York, NY 10017

Ethics review

Status: Approved
Approval date: 19/04/2016
Contact:

Results

• Results available: Yes
• Date Posted: 08/11/2019
• Date Completed: 14/11/2018
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2013-004508-21/results