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NCT02697773

Efficacy and Safety of a Subcutaneous Tanezumab Titration Dosing Regimen in Subjects With Moderate to Severe Osteoarthritis of the Hip or Knee

Completed Phase 3 Results posted Last updated 3 May 2021
What this trial tests

Phase 3 trial testing Placebo in Osteoarthritis, Knee in 698 participants. Completed in 14 May 2018.

Timeline
21 January 2016
Primary endpoint
5 December 2017
14 May 2018

Quick facts

Lead sponsorPfizer
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment698
Start date21 January 2016
Primary completion5 December 2017
Estimated completion14 May 2018
Sites87 locations across Canada, United States, Puerto Rico

Drugs / interventions tested

Conditions studied

Sponsor

Pfizer — full company profile →

Who can join

18 and older, any sex, with Osteoarthritis, Knee or Osteoarthritis, Hip. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Week 16 Primary · Baseline, Week 16

WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with osteoarthritis. The WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis of index joint (knee or hip) during past 48 hours. It was calculated as the mean of scores from 5 individual questions scored on a numerical rating scale (NRS) of 0 (no pain) to 10 (extreme pain), where higher scores indicated higher pain.

GroupValue95% CI
Placebo-2.64± 0.23
Tanezumab 2.5 mg-3.23± 0.23
Tanezumab 2.5/5 mg-3.37± 0.22
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Week 16 Primary · Baseline, Week 16

WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with osteoarthritis. Physical function refers to participant's ability to move around and perform usual activities of daily living. The WOMAC physical function subscale is a 17-item questionnaire used to assess the degree of difficulty experienced due to osteoarthritis in index joint (knee or hip) during past 48 hours. It was calculated as mean of the scores from 17 individual questions scored on a NRS of 0 (minimu

GroupValue95% CI
Placebo-2.56± 0.22
Tanezumab 2.5 mg-3.22± 0.22
Tanezumab 2.5/5 mg-3.45± 0.22
Change From Baseline in Patient's Global Assessment (PGA) of Osteoarthritis at Week 16 Primary · Baseline, Week 16

PGA of osteoarthritis was assessed by asking a question from participants: "Considering all the ways your osteoarthritis in your knee or hip (index joint) affects you, how are you doing today?" Participants responded on a scale ranging from 1-5, where 1=very good (no symptom and no limitation of normal activities), 2= good (mild symptoms and no limitation of normal activities), 3= fair (moderate symptoms and limitation of some normal activities), 4= poor (severe symptoms and inability to carry out most normal activities), and 5 = very poor (very severe symptoms and inability to carry out all n

GroupValue95% CI
Placebo-0.65± 0.08
Tanezumab 2.5 mg-0.87± 0.08
Tanezumab 2.5/5 mg-0.90± 0.08
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Weeks 2, 4, 8 and 12 Secondary · Baseline, Weeks 2, 4, 8 and 12

WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with osteoarthritis. The WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis of index joint (knee or hip) during past 48 hours. It was calculated as the mean of scores from 5 individual questions scored on NRS of 0 (no pain) to 10 (extreme pain), where higher scores indicated higher pain.

Change at Week 2
GroupValue95% CI
Placebo-2.20± 0.21
Tanezumab 2.5 mg-2.87± 0.21
Tanezumab 2.5/5 mg-2.89± 0.21
Change at Week 4
GroupValue95% CI
Placebo-2.40± 0.21
Tanezumab 2.5 mg-3.28± 0.21
Tanezumab 2.5/5 mg-3.27± 0.21
Change at Week 8
GroupValue95% CI
Placebo-2.61± 0.21
Tanezumab 2.5 mg-3.20± 0.21
Tanezumab 2.5/5 mg-3.02± 0.21
Change at Week 12
GroupValue95% CI
Placebo-2.83± 0.23
Tanezumab 2.5 mg-3.61± 0.22
Tanezumab 2.5/5 mg-3.69± 0.22
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Week 24 Secondary · Baseline, Week 24

WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with osteoarthritis. The WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis of index joint (knee or hip) during past 48 hours. It was calculated as the mean of scores from 5 individual questions scored on NRS of 0 (no pain) to 10 (extreme pain), where higher scores indicated higher pain.

Baseline
GroupValue95% CI
Placebo7.30± 1.15
Tanezumab 2.5 mg7.08± 1.16
Tanezumab 2.5/5 mg7.33± 1.26
Change at Week 24
GroupValue95% CI
Placebo-3.07± 2.43
Tanezumab 2.5 mg-2.80± 2.50
Tanezumab 2.5/5 mg-2.95± 2.49
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Weeks 2, 4, 8 and 12 Secondary · Baseline, Weeks 2, 4, 8 and 12

WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with osteoarthritis. Physical function refers to participant's ability to move around and perform usual activities of daily living. The WOMAC physical function subscale is a 17-item questionnaire used to assess the degree of difficulty experienced due to osteoarthritis in index joint (knee or hip) during past 48 hours. It was calculated as mean of the scores from 17 individual questions scored on a NRS of 0 (minimu

Change at Week 2
GroupValue95% CI
Placebo-2.14± 0.21
Tanezumab 2.5 mg-2.89± 0.21
Tanezumab 2.5/5 mg-3.05± 0.21
Change at Week 4
GroupValue95% CI
Placebo-2.28± 0.21
Tanezumab 2.5 mg-3.30± 0.21
Tanezumab 2.5/5 mg-3.38± 0.21
Change at Week 8
GroupValue95% CI
Placebo-2.55± 0.21
Tanezumab 2.5 mg-3.17± 0.21
Tanezumab 2.5/5 mg-3.12± 0.21
Change at Week 12
GroupValue95% CI
Placebo-2.75± 0.22
Tanezumab 2.5 mg-3.61± 0.22
Tanezumab 2.5/5 mg-3.80± 0.22
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Week 24 Secondary · Baseline, Week 24

WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with osteoarthritis. Physical function refers to participant's ability to move around and perform usual activities of daily living. The WOMAC physical function subscale is a 17-item questionnaire used to assess the degree of difficulty experienced due to osteoarthritis in index joint (knee or hip) during past 48 hours. It was calculated as mean of the scores from 17 individual questions scored on a NRS of 0 (minimu

Baseline
GroupValue95% CI
Placebo7.38± 1.12
Tanezumab 2.5 mg7.18± 1.11
Tanezumab 2.5/5 mg7.39± 1.18
Change at Week 24
GroupValue95% CI
Placebo-3.03± 2.37
Tanezumab 2.5 mg-2.85± 2.51
Tanezumab 2.5/5 mg-3.01± 2.46
Change From Baseline in Patient's Global Assessment (PGA) of Osteoarthritis at Weeks 2, 4, 8 and 12 Secondary · Baseline, Weeks 2, 4, 8 and 12

PGA of osteoarthritis was assessed by asking a question from participants: "Considering all the ways your osteoarthritis in your knee or hip (index joint) affects you, how are you doing today?" Participants responded on a scale ranging from 1-5, where 1=very good (no symptom and no limitation of normal activities), 2= good (mild symptoms and no limitation of normal activities), 3= fair (moderate symptoms and limitation of some normal activities), 4= poor (severe symptoms and inability to carry out most normal activities), and 5 = very poor (very severe symptoms and inability to carry out all n

Change at Week 2
GroupValue95% CI
Placebo-0.74± 0.07
Tanezumab 2.5 mg-0.91± 0.07
Tanezumab 2.5/5 mg-0.87± 0.07
Change at Week 4
GroupValue95% CI
Placebo-0.75± 0.07
Tanezumab 2.5 mg-1.01± 0.07
Tanezumab 2.5/5 mg-0.97± 0.07
Change at Week 8
GroupValue95% CI
Placebo-0.82± 0.07
Tanezumab 2.5 mg-0.97± 0.07
Tanezumab 2.5/5 mg-0.91± 0.07
Change at Week 12
GroupValue95% CI
Placebo-0.83± 0.08
Tanezumab 2.5 mg-1.01± 0.08
Tanezumab 2.5/5 mg-1.11± 0.08
Change From Baseline in Patient's Global Assessment (PGA) of Osteoarthritis at Week 24 Secondary · Baseline, Week 24

PGA of osteoarthritis was assessed by asking a question from participants: "Considering all the ways your osteoarthritis in your knee or hip (index joint) affects you, how are you doing today?" Participants responded on a scale ranging from 1-5, where 1=very good (no symptom and no limitation of normal activities), 2= good (mild symptoms and no limitation of normal activities), 3= fair (moderate symptoms and limitation of some normal activities), 4= poor (severe symptoms and inability to carry out most normal activities), and 5 = very poor (very severe symptoms and inability to carry out all n

Baseline
GroupValue95% CI
Placebo3.46± 0.57
Tanezumab 2.5 mg3.42± 0.60
Tanezumab 2.5/5 mg3.53± 0.62
Change at Week 24
GroupValue95% CI
Placebo-0.87± 0.85
Tanezumab 2.5 mg-0.72± 0.93
Tanezumab 2.5/5 mg-0.91± 1.03
Percentage of Participants Meeting Outcomes Measures in Arthritis Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) Responder Index Secondary · Weeks 2, 4, 8, 12, 16 and 24

Participants were considered as OMERACT-OARSI responders: if the change (improvement) from baseline to week of interest was greater than or equal to (\>=) 50 percent and greater or equal to (\>=) 2 units in either WOMAC pain subscale or physical function subscale score; if change (improvement) from baseline to week of interest was \>=20 percent and \>=1 unit in at least 2 of the following: 1) WOMAC pain subscale score, 2) WOMAC physical function subscale score, 3) PGA of osteoarthritis. WOMAC pain subscale assess amount of pain experienced (score: 0 \[no pain\] to 10 \[extreme pain\], higher s

Week 2
GroupValue95% CI
Placebo50.4
Tanezumab 2.5 mg65.4
Tanezumab 2.5/5 mg67.4
Week 4
GroupValue95% CI
Placebo58.6
Tanezumab 2.5 mg74.0
Tanezumab 2.5/5 mg74.7
Week 8
GroupValue95% CI
Placebo61.6
Tanezumab 2.5 mg67.5
Tanezumab 2.5/5 mg69.5
Week 12
GroupValue95% CI
Placebo66.4
Tanezumab 2.5 mg77.5
Tanezumab 2.5/5 mg81.1
Week 16
GroupValue95% CI
Placebo65.1
Tanezumab 2.5 mg72.7
Tanezumab 2.5/5 mg79.0
Week 24
GroupValue95% CI
Placebo68.1
Tanezumab 2.5 mg66.5
Tanezumab 2.5/5 mg68.8
Percentage of Participants Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Reduction >= 30 Percent (%), >=50%, >=70% and >=90% Response Secondary · Week 2, 4, 8, 12, 16 and 24

Percentage of participants with reduction in WOMAC pain intensity of at least (\>=) 30%, 50%, 70% and 90% at Weeks 2, 4, 8, 12, 16 and 24 compared to baseline were classified as responders to WOMAC pain subscale and are reported here. WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with osteoarthritis. The WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis of index joint (knee or hip) during past 48

Week 2: At least 30% reduction
GroupValue95% CI
Placebo38.8
Tanezumab 2.5 mg56.3
Tanezumab 2.5/5 mg56.2
Week 2: At least 50% reduction
GroupValue95% CI
Placebo22.8
Tanezumab 2.5 mg38.5
Tanezumab 2.5/5 mg38.2
Week 2: At least 70% reduction
GroupValue95% CI
Placebo15.5
Tanezumab 2.5 mg25.5
Tanezumab 2.5/5 mg24.5
Week 2: At least 90% reduction
GroupValue95% CI
Placebo6.9
Tanezumab 2.5 mg13.4
Tanezumab 2.5/5 mg9.4
Week 4: At least 30% reduction
GroupValue95% CI
Placebo47.0
Tanezumab 2.5 mg65.4
Tanezumab 2.5/5 mg63.5
Week 4: At least 50% reduction
GroupValue95% CI
Placebo30.2
Tanezumab 2.5 mg48.5
Tanezumab 2.5/5 mg48.5
Week 4: At least 70% reduction
GroupValue95% CI
Placebo16.4
Tanezumab 2.5 mg29.4
Tanezumab 2.5/5 mg29.6
Week 4: At least 90% reduction
GroupValue95% CI
Placebo8.2
Tanezumab 2.5 mg16.0
Tanezumab 2.5/5 mg15.5
Percentage of Participants With Cumulative Percent Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Week 16 Secondary · Baseline to Week 16

WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with OA. The WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to osteoarthritis of index joint during past 48 hours. It was calculated as the mean of scores from 5 individual questions scored on a NRS of 0 (no pain) to 10 (extreme pain), where higher scores indicated higher pain. Total score range for WOMAC pain subscale score was 0 (no pain) to 10 (extreme pain), wher

>=0%
GroupValue95% CI
Placebo82.3
Tanezumab 2.5 mg87.4
Tanezumab 2.5/5 mg88.4
>=10%
GroupValue95% CI
Placebo79.3
Tanezumab 2.5 mg81.8
Tanezumab 2.5/5 mg85.4
>=20%
GroupValue95% CI
Placebo65.5
Tanezumab 2.5 mg74.0
Tanezumab 2.5/5 mg79.0
>=30%
GroupValue95% CI
Placebo54.7
Tanezumab 2.5 mg68.0
Tanezumab 2.5/5 mg70.4
>=40%
GroupValue95% CI
Placebo45.7
Tanezumab 2.5 mg63.2
Tanezumab 2.5/5 mg66.1
>=50%
GroupValue95% CI
Placebo37.9
Tanezumab 2.5 mg54.5
Tanezumab 2.5/5 mg57.1
>=60%
GroupValue95% CI
Placebo31.5
Tanezumab 2.5 mg44.2
Tanezumab 2.5/5 mg44.6
>=70%
GroupValue95% CI
Placebo25.0
Tanezumab 2.5 mg34.6
Tanezumab 2.5/5 mg36.5

Adverse events — posted to ClinicalTrials.gov

Time frame: Baseline up to Week 40 (end of study). Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo
Serious: 9/232 (4%)
Deaths: 0/232
Tanezumab 2.5 mg
Serious: 7/231 (3%)
Deaths: 0/231
Tanezumab 2.5/5 mg
Serious: 11/233 (5%)
Deaths: 2/233

Serious adverse events (28 terms)

ReactionSystemPlaceboTanezumab 2.5 mgTanezumab 2.5/5 mg
Chest painGeneral disorders
OsteoarthritisMusculoskeletal and connective tissue disorders
Iron deficiency anaemiaBlood and lymphatic system disorders
Myocardial infarctionCardiac disorders
DiarrhoeaGastrointestinal disorders
VomitingGastrointestinal disorders
Arthritis bacterialInfections and infestations
PneumoniaInfections and infestations
ArthralgiaMusculoskeletal and connective tissue disorders
Endometrial adenocarcinomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Invasive ductal breast carcinomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Non-small cell lung cancer stage IVNeoplasms benign, malignant and unspecified (incl cysts and polyps)
NephrolithiasisRenal and urinary disorders
Pulmonary embolismRespiratory, thoracic and mediastinal disorders
Gastric ulcerGastrointestinal disorders
Non-cardiac chest painGeneral disorders
Abdominal hernia infectionInfections and infestations
AppendicitisInfections and infestations
Bacterial infectionInfections and infestations
CellulitisInfections and infestations
SpondylolisthesisMusculoskeletal and connective tissue disorders
Breast cancerNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Haemorrhagic strokeNervous system disorders
Completed suicidePsychiatric disorders
Other adverse events (315 terms — click to expand)

ReactionSystemPlaceboTanezumab 2.5 mgTanezumab 2.5/5 mg
ArthralgiaMusculoskeletal and connective tissue disorders
NasopharyngitisInfections and infestations
Musculoskeletal painMusculoskeletal and connective tissue disorders
FallInjury, poisoning and procedural complications
Back painMusculoskeletal and connective tissue disorders
Upper respiratory tract infectionInfections and infestations
HeadacheNervous system disorders
Joint swellingMusculoskeletal and connective tissue disorders
Pain in extremityMusculoskeletal and connective tissue disorders
BronchitisInfections and infestations
ParaesthesiaNervous system disorders
DiarrhoeaGastrointestinal disorders
Oedema peripheralGeneral disorders
HypoaesthesiaNervous system disorders
SinusitisInfections and infestations
HypertensionVascular disorders
InfluenzaInfections and infestations
Ligament sprainInjury, poisoning and procedural complications
Limb injuryInjury, poisoning and procedural complications
Muscle strainInjury, poisoning and procedural complications
Joint stiffnessMusculoskeletal and connective tissue disorders
Muscle spasmsMusculoskeletal and connective tissue disorders
OsteoarthritisMusculoskeletal and connective tissue disorders
Sinus bradycardiaCardiac disorders
NauseaGastrointestinal disorders
RashSkin and subcutaneous tissue disorders
Urinary incontinenceRenal and urinary disorders
DizzinessNervous system disorders
Herpes zosterInfections and infestations
Urinary tract infectionInfections and infestations
Procedural painInjury, poisoning and procedural complications
BursitisMusculoskeletal and connective tissue disorders
MyalgiaMusculoskeletal and connective tissue disorders
Neck painMusculoskeletal and connective tissue disorders
TendonitisMusculoskeletal and connective tissue disorders
Rapidly progressive osteoarthritisMusculoskeletal and connective tissue disorders
BradycardiaCardiac disorders
CataractEye disorders
Dry eyeEye disorders
ConstipationGastrointestinal disorders

Most-reported serious reactions: Chest pain, Osteoarthritis, Iron deficiency anaemia, Myocardial infarction, Diarrhoea, Vomiting, Arthritis bacterial, Pneumonia.

Data from ClinicalTrials.gov NCT02697773 adverse events section.

Sponsor's own description

The primary purpose of this study is to evaluate the efficacy of a titration arm of tanezumab in which treatment is started at a lower dose (2.5 mg) and increased to a higher dose (5 mg) at Week 8, compared to giving 2 doses of tanezumab 2.5 mg or 2 doses of placebo. The study also evaluates the safety of the treatment regimens.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Antibodies to watch in 2020.
    Kaplon H, Muralidharan M, Schneider Z, Reichert JM. · · 2020 · cited 332× · PMID 31847708 · DOI 10.1080/19420862.2019.1703531
  2. Antibodies to watch in 2019.
    Kaplon H, Reichert JM. · · 2019 · cited 324× · PMID 30516432 · DOI 10.1080/19420862.2018.1556465
  3. Antibodies to watch in 2017.
    Reichert JM. · · 2017 · cited 194× · PMID 27960628 · DOI 10.1080/19420862.2016.1269580
  4. Antibodies to watch in 2018.
    Kaplon H, Reichert JM. · · 2018 · cited 179× · PMID 29300693 · DOI 10.1080/19420862.2018.1415671
  5. Recent advances in the treatment of osteoarthritis.
    Grässel S, Muschter D. · · 2020 · cited 172× · PMID 32419923 · DOI 10.12688/f1000research.22115.1
  6. Effect of Tanezumab on Joint Pain, Physical Function, and Patient Global Assessment of Osteoarthritis Among Patients With Osteoarthritis of the Hip or Knee: A Randomized Clinical Trial.
    Schnitzer TJ, Easton R, Pang S, Levinson DJ, et al · · 2019 · cited 139× · PMID 31265100 · DOI 10.1001/jama.2019.8044
  7. The emerging role of fibroblast-like synoviocytes-mediated synovitis in osteoarthritis: An update.
    Han D, Fang Y, Tan X, Jiang H, et al · · 2020 · cited 106× · PMID 32686306 · DOI 10.1111/jcmm.15669
  8. Osteoarthritis Pain.
    Yu H, Huang T, Lu WW, Tong L, et al · · 2022 · cited 93× · PMID 35563035 · DOI 10.3390/ijms23094642

Verify or expand the search:

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Trials testing the same drug.

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Trials by the same sponsor.

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