Clinical Trials Register

Summary
EudraCT Number:	2013-004508-21
Sponsor's Protocol Code Number:	A4091057
National Competent Authority:	Hungary - National Institute of Pharmacy
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2015-12-21
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Hungary - National Institute of Pharmacy

A.2

EudraCT number

2013-004508-21

A.3

Full title of the trial

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

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A.4.1

Sponsor's protocol code number

A4091057

A.5.4

Other Identifiers

Name:

US IND

Number:

BB-IND 11,680

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Pfizer Inc, 235 East 42nd Street, New York, NY 10017
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Pfizer Inc, 235 East 42nd Street, New York, NY 10017
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Pfizer Inc
B.5.2	Functional name of contact point	ClinicalTrials.gov call Center
B.5.3	Address:
B.5.3.1	Street Address	235 East 42nd Street
B.5.3.2	Town/ city	New York
B.5.3.3	Post code	NY 10017
B.5.3.4	Country	United States
B.5.4	Telephone number	+1800718 1021
B.5.5	Fax number	+1303739 1119
B.5.6	E-mail	clinicaltrials.govcallcenter@pfizer.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Tanezumab
D.3.2	Product code	PF-04383119
D.3.4	Pharmaceutical form	Solution for injection/infusion in pre-filled syringe
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Tanezumab
D.3.9.1	CAS number	880266-57-9
D.3.9.2	Current sponsor code	PF-04383119
D.3.9.3	Other descriptive name	RI624, RN624
D.3.9.4	EV Substance Code	SUB33975
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	2.5
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	Yes
D.3.11.13.1	Other medicinal product type	recombinant humanised monoclonal antibody
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Tanezumab
D.3.2	Product code	PF-04383119
D.3.4	Pharmaceutical form	Solution for injection/infusion in pre-filled syringe
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Tanezumab
D.3.9.1	CAS number	880266-57-9
D.3.9.2	Current sponsor code	PF-04383119
D.3.9.3	Other descriptive name	RI624, RN624
D.3.9.4	EV Substance Code	SUB33975
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	5
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	Yes
D.3.11.13.1	Other medicinal product type	recombinant humanised monoclonal antibody

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for injection in pre-filled syringe
D.8.4	Route of administration of the placebo	Subcutaneous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Osteoarthritis of the hip or knee

E.1.1.1

Medical condition in easily understood language

Osteoarthritis of the hip or knee

E.1.1.2

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	18.1
E.1.2	Level	LLT
E.1.2	Classification code	10023476
E.1.2	Term	Knee osteoarthritis
E.1.2	System Organ Class	100000004859

E.1.2 Medical condition or disease under investigation

E.1.2	Version	18.1
E.1.2	Level	LLT
E.1.2	Classification code	10020108
E.1.2	Term	Hips osteoarthritis
E.1.2	System Organ Class	100000004859

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

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

E.2.2

Secondary objectives of the trial

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

E.2.3

Trial contains a sub-study

E.3

Principal 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.

E.4

Principal 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.

E.5 End points

E.5.1

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.

E.5.1.1

Timepoint(s) of evaluation of this end point

Timepoints are listed with the Endpoints.

E.5.2

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.

E.5.2.1

Timepoint(s) of evaluation of this end point

Timepoints are listed with the Endpoints.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

Yes

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Biomarker data analysis will be conducted according to the tanezumab
biomarker analysis plan.

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Austria

Bulgaria

Finland

France

Germany

Hungary

Italy

Japan

Poland

Portugal

Romania

Slovakia

Spain

Sweden

United Kingdom

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

last scheduled procedure shown in the Schedule of Activities for the last participant

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

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

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

690

F.4.2.2

In the whole clinical trial

810

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

After completion of the clinical trial participants will receive standard ofcare treatment in accordance with their standard medical care. Subjects who undergo total knee, hip or shoulder joint replacement surgery during the study (Double-blind Treatment Period or Follow-up Period) will be followed for 24 weeks after the procedure as part of a separate protocol (Study A4091064), provided the subject consents.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2016-02-29

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-02-19

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2018-11-14

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