A PHASE 3 RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTICENTER STUDY OF THE ANALGESIC EFFICACY AND SAFETY OF THE SUBCUTANEOUS ADMINISTRATION OF TANEZUMAB (PF-04383119) IN SUBJECTS WITH CANCER PAIN PREDOMINANTLY DUE TO BONE METASTASIS RECEIVING BACKGROUND OPIOID THERAPY

• Register: EUCTR
• Last refreshed on: 4 December 2023
• Main ID: EUCTR2013-002223-42-ES
• Date of registration: 05/10/2015
• 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 (PF-04383119) IN SUBJECTS WITH CANCER PAIN PREDOMINANTLY DUE TO BONE METASTASIS RECEIVING BACKGROUND OPIOID THERAPY
• Scientific title: A PHASE 3 RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTICENTER STUDY OF THE ANALGESIC EFFICACY AND SAFETY OF THE SUBCUTANEOUS ADMINISTRATION OF TANEZUMAB (PF-04383119) IN SUBJECTS WITH CANCER PAIN PREDOMINANTLY DUE TO BONE METASTASIS RECEIVING BACKGROUND OPIOID THERAPY
• Date of first enrolment: 15/10/2015
• Target sample size: 255
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-002223-42
• 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

Australia, Austria, Belgium, Brazil, China, Czech Republic, France, Germany, Hungary, Japan, Korea, Republic of, Poland, Romania, Serbia, 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:
1. Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study.
2. Subject is willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
3. Male or female, 18 years of age or older.
4. Weight is at least 45 kg at Screening.
5. Subject has prostate cancer, breast cancer, renal cell cancer, lung cancer, colon cancer or multiple myeloma diagnosed as having metastasized to bone.
6. Imaging confirmation of bone metastasis at Screening or within 120 days prior to the Screening visit as specified in the protocol. Bone scan confirmation of bone metastasis is required at Screening Visit if radiographic confirmation of bone metastasis within 120 days prior to Screening is lacking.
7. Subject is expected to require daily opioid medication throughout the course of the study.
8. Subject willing to not use prohibited medications (including NSAIDs) throughout the duration of the study.
9. Average Pain Score 5 or higher at Screening for the index bone metastasis cancer pain site.
10. Patient's Global Assessment of Cancer Pain must be «fair», «poor» or «very poor» at Screening.
11. Eastern Cooperative Oncology Group (ECOG) Performance Status Score of 0, 1, or 2 at Screening.
12. Adequate bone marrow function at Screening as defined in the protocol.
13. Adequate renal function at Screening as defined in the protocol.
14. Adequate liver function at Screening as defined in the protocol.
15. International Normalized Ratio (INR) or prothrombin time (PT) <1.5 x ULN at Screening (confirmed by a repeat test if needed), provided the subject is not being treated with anticoagulant medication. For subjects being treated with anticoagulants, the INR should be within the range recommended for the specific clinical indication.
16. Female subjects of childbearing potential and at risk for pregnancy must agree to use at least one highly effective method of contraception throughout the study and for 112 days (16 weeks) after the last dose of assigned subcutaneous study medication.
17. Female subjects who are not of childbearing potential (ie, must meet at least one of the following criteria):
- Have undergone documented hysterectomy and/or bilateral oophorectomy;
- Have medically confirmed ovarian failure; or
- Achieved postmenopausal 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.
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 161
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 94

Exclusion criteria:
1. The subject's pain is related to an oncologic emergency.
2. The subject has brain metastasis or leptomeningeal metastasis.
3. The subject's pain is primarily classified as neuropathic, visceral or unknown in nature, has resulted from prior cancer therapy, is due to infection or is otherwise not predominantly related to a bone metastasis.
4. Systemic treatment for the primary malignancy or bone metastasis, including chemotherapy, hormonal treatment, bisphosphonates and denosumab started within 3 months of Screening or new systemic treatment is known to be needed at Screening.
5. Receipt of radiopharmaceutical treatment or radiotherapy for treatment of bone metastasis within 4 weeks of Screening.
6. Diagnosis of osteoarthritis of the knee or hip as defined by the American College of Rheumatology (ACR) combined clinical and radiographic criteria.
7. Subjects with symptoms and radiographic findings consistent with osteoarthritis in the shoulder.
8. History or radiographic evidence of orthopedic conditions that may increase the risk of joint safety conditions during the study as defined in the protocol.
9. Signs and symptoms of clinically significant cardiac disease within 6 months of the study as defined in the protocol or subjects with any other cardiovascular illness that in the opinion of the investigator would render a subject unsuitable to participate in the study.
10. Subjects with orthostatic hypotension or evidence for an autonomic neuropathy at Screening as defined in the protocol.
11. History, diagnosis, or signs and symptoms of clinically significant neurological disease as described in the protocol.
12. Planned surgical procedure during the duration of the study
13. Subjects considered unfit for surgery as defined in the protocol.

For the rest of the exclusion criteria, please refer to the protocol


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

Health Condition(s) or Problem(s) studied

Metastatic Bone Pain
MedDRA version: 18.0 Level: LLT Classification code 10049038 Term: Metastatic bone pain System Organ Class: 100000004864

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

Intervention(s)

Product Name: Tanezumab
Product Code: PF-04383119
Pharmaceutical Form: Solution for injection 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: 10-
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 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: 20-
Pharmaceutical form of the placebo: Solution for injection in pre-filled syringe
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Primary end point(s): Change from Baseline to Week 8 in the daily average pain intensity in the index bone metastasis cancer pain site.

Secondary Objective: Evaluate the safety of tanezumab 20 mg SC versus matching placebo SC and tanezumab 10 mg SC versus matching placebo SC in subjects, with cancer pain predominantly due to bone metastasis, receiving background opioid therapy.

Main Objective: -Demonstrate superior analgesic efficacy of tanezumab 20 mg SC versus matching placebo SC and/or tanezumab 10 mg SC versus matching placebo SC at Week 8 in subjects, with cancer pain predominantly due to bone metastasis, receiving background opioid therapy.

Timepoint(s) of evaluation of this end point: Please refer to the protocol

Secondary Outcome(s)

Secondary end point(s): Efficacy Measures:
-Change from Baseline to Weeks 1, 2, 4, 6, 12, 16 and 24 in the daily average pain intensity NRS score in the index bone metastasis cancer pain site.
-Change from Baseline to Weeks 1, 2, 4, 6, 8, 12, 16 and 24 in the daily worst pain intensity NRS score in the index bone metastasis cancer pain site.
-Change from Baseline to Weeks 1, 2, 4, 6, 8, 12, 16 and 24 in the weekly average pain intensity NRS score in non-index cancer pain sites.
-Change from Baseline to Weeks 1, 2, 4, 6, 8, 12, 16 and 24 in the weekly worst pain intensity NRS score in non-index cancer pain sites.
-Change from Baseline to Weeks 1, 2, 4, 6, 8, 12, 16 and 24 in the daily average pain intensity NRS score in the non-index visceral cancer pain sites.
-Change from Baseline to Weeks 1, 2, 4, 6, 8, 12, 16 and 24 in the daily worst pain intensity NRS score in the non-index visceral cancer pain site.
-Change from Baseline to Weeks 2, 4, 8, 16 and 24 in the Brief Pain Inventory (BPI) average pain scores obtained at study visits.
-Change from Baseline to Weeks 2, 4, 8, 16 and 24 in the BPI worst pain scores obtained at study visits.
-Response as defined by a 30%, 50%, 70%, and 90% or higher reduction from Baseline in the daily average and daily worst pain intensity NRS score in the index bone metastasis cancer pain site at Weeks 1, 2, 4, 6, 8, 12, 16 and 24.
-Change from Baseline in Patient's Global Assessment of Cancer Pain at Weeks 2, 4, 8, 16 and 24.
-Response defined as an improvement of 2 or higher points in Patient's Global Assessment of Cancer Pain at Weeks 2, 4, 8, 16 and 24.
-Change from Baseline to Weeks 2, 4, 8, 16 and 24 in the BPI Pain Interference with Function Composite Score and individual pain interference item scores obtained at study visits.
-EuroQol 5 Dimension (EQ-5D-5L) dimensions and overall health utility score at Baseline and Weeks 8, 16 and 24.

Opioid Use and Opioid Adverse Effects Measures

-Average daily total opioid consumption (in mg of morphine equivalent doses) at Weeks 1, 2, 4, 6, 8, 12, 16 and 24.
-Average number of doses of rescue medication required per week at Weeks 1, 2, 4, 6, 8, 12, 16 and 24.
-Change from Baseline in the weekly Opioid-Related Symptom Distress Scale at Weeks 2, 4, 8, 16, and 24.

Safety Measures

-Adverse events.
-Standard safety assessments (safety laboratory testing [chemistry, hematology], sitting vital signs, ECG [12-lead]).
-Orthostatic (supine/standing) blood pressure assessment.
-Weight measurements.
-Physical examinations.
-Joint safety adjudication outcomes.
-Total joint replacements.
-Neurologic examination (Neuropathy Impairment Score [NIS]).
-Survey of Autonomic Symptom scores.
-Anti-drug antibody (ADA) assessments.

Refer to protocol for other endpoints

Timepoint(s) of evaluation of this end point: Please refer to the protocol

Secondary ID(s)

2013-002223-42-AT

A4091061

Source(s) of Monetary Support

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

Ethics review

Status: Approved
Approval date: 08/10/2015
Contact:

Results

• Results available: Yes
• Date Posted: 09/07/2022
• Date Completed: 25/06/2021
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2013-002223-42/results