Long-Term Safety and Efficacy Study of Fasinumab in Patients With Pain Due to Osteoarthritis (OA) of the Knee or Hip

NCT02683239 | Completed Phase 3 Results DMC

• 2 other identifiers: R475-PN-15232015-003783-36
• Study Type: interventional
• Target: 5,331
• Locations: 20 countries
• Sites: 147

Brief Summary

The primary objective of the study is to describe the safety and tolerability of fasinumab, including adverse events of special interest (AESIs), in patients with pain due to radiographically-confirmed OA of the knee or hip.

Conditions

Osteoarthritis of the Knee or Hip

Outcome Measures

Primary Outcomes (14)

• Number of Participants With Any Treatment-Emergent Adverse Event (TEAE)

  Baseline up to week 52

• Number of Participants With Any Serious TEAE

  Baseline up to week 52

• Number of Participants With Any Adverse Event (AE) up to Week 72

  Baseline up to week 72

• Number of Participants With Any Serious AE up to Week 72

  Baseline up to week 72

• Number of Participants With Adjudicated Arthropathy (AA)

  Adjudicated arthropathy (AA) is a composite term that encompasses the following conditions: Rapidly progressive OA type 1 and 2, Subchondral insufficiency fractures, and Primary Osteonecrosis. AAs were also evaluated to determine if they met Destructive Arthropathy criteria.

  Baseline up to week 52 and week 72

• Number of Participants With Adjudicated Arthropathy (AA) Meeting Destructive Arthropathy (DA) Criteria

  DA is a unique clinical form of rapidly destructive arthropathy over and above that seen in the normal progression of OA. DA criteria can be associated with Rapidly Progressive OA type 2, Subchondral Insufficiency fracture, and Primary Osteonecrosis confirmed by an arthropathy adjudication committee.

  Baseline up to week 52 and week 72

• Number of Participants With at Least One Peripheral Sensory Event That Required a Neurology Consultation

  Any participant with a peripheral sensory event that persisted for 2 months was referred for a neurology or other specialty consultation and reported as an adverse event of special interest (AESI).

  Baseline up to week 72

• Number of Participants With Sympathetic Nervous System (SNS) Dysfunction

  Potential events of sympathetic nervous system (SNS) dysfunction were monitored throughout the study through physical examination, AE reporting, assessment of orthostatic hypotension, and the Survey of Autonomic Symptoms. Sympathetic nervous system dysfunction was diagnosed after consultation with an appropriate specialist, such as a neurologist and/or cardiologist.

  Baseline up to week 72

• Number of Participants With at Least One All-Cause Joint Replacement (JR) Surgery

  All joint replacement surgery events regardless of cause at weeks 52 and 72. An end of study phone contact was also conducted approximately 52 weeks following the last dose of study drug.

  Baseline up to weeks 52, 72, and end of study (52 weeks post last dose)

• Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values up to Week 52

  Number of participants with potentially clinically significant abnormal values in hematology, chemistry, and urinalysis during the treatment period were reported. Clinical significance was determined by the investigator.

  Baseline to week 52

• Number of Participants With Potentially Clinically Significant Abnormal Laboratory Values Post-Treatment up to Week 72

  Number of participants with potentially clinically significant abnormal values in hematology, chemistry, and urinalysis during the post-treatment period were reported. Clinical significance was determined by the investigator.

  End of treatment up to week 72

• Number of Participants With Anti-drug Antibody (ADA) up to Week 72

  Immunogenicity was characterized by ADA responses \& titers. Responses categories: Negative - ADA negative response at all time points, regardless of missing samples; Pre-existing immunoreactivity - ADA positive response at baseline with all post first dose negative results or positive response at baseline with all post first dose ADA responses less than (\<) 9-fold over baseline titer levels; Treatment-boosted response - positive response in the assay post first dose, greater than or equal to (≥) 9-fold over baseline titer levels, when baseline results are positive; Treatment-emergent response - ADA positive response in the fasinumab ADA assay post first dose when baseline results = negative or missing.

  Baseline up to week 72

• Change From Baseline to Week 16 in the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Pain Subscale Score

  The WOMAC index is comprised of 24 parameters grouped in 3 subscales (pain-5 questions, physical function -17 questions and stiffness - 2 questions), with 0-10 grading of each question. The scores for each subscale are summed up, divided by number of questions, and each subscale is reported using Numerical Rating Scale score of 0-10. In addition to subscales, a total score is provided as the sum of normalized subscale scores divided by three, and reported using a Numerical Rating Scale score of 0-10. Higher scores indicate worse pain, stiffness and functional limitations.

  Baseline to Week 16

• Change From Baseline to Week 16 in WOMAC Physical Function Subscale Score

  The WOMAC index is comprised of 24 parameters grouped in 3 subscales (pain-5 questions, physical function -17 questions and stiffness - 2 questions), with 0-10 grading of each question. The scores for each subscale are summed up, divided by number of questions, and each subscale is reported using Numerical Rating Scale score of 0-10. In addition to subscales, a total score is provided as the sum of normalized subscale scores divided by three, and reported using a Numerical Rating Scale score of 0-10. Higher scores indicate worse pain, stiffness and functional limitations.

  Baseline to Week 16

Secondary Outcomes (2)

• Change From Baseline to Week 16 in Patient Global Assessment (PGA) Score of Osteoarthritis

  Baseline to Week 16

• Number of Participants With ≥30% Reduction From Baseline to Week 16 in the WOMAC Pain Subscale Score

  Baseline to Week 16

Study Arms (3)

Fasinumab dosing regimen 1

EXPERIMENTAL

Drug: Fasinumab

Fasinumab dosing regimen 2

EXPERIMENTAL

Drug: Fasinumab

Placebo

EXPERIMENTAL

Drug: Placebo

Interventions

Fasinumab DRUG

Participants will receive sub-cutaneous (SC) injections of fasinumab

Also known as: REGN475

Fasinumab dosing regimen 1; Fasinumab dosing regimen 2

Placebo DRUG

Participants will receive sub-cutaneous (SC) injections of matching placebo

Placebo

Eligibility Criteria

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

You may qualify if:

• Male or female ≥18 years of age at the screening visit
• Clinical diagnosis of OA of the knee or hip based on the American College of Rheumatology criteria with radiologic evidence of OA (K-L score ≥2) for the index joint at the screening visit
• Moderate to severe pain in the index joint defined as a Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) average pain subscale score of ≥4
• A history of 12 weeks of analgesic use for OA of the knee or hip
• History of regular use of analgesic medications for OA pain

You may not qualify if:

• History or presence at the screening visit of non OA inflammatory joint disease
• History or presence on imaging of arthropathy, stress fracture, recent stress fracture, neuropathic joint arthropathy, hip dislocation, knee dislocation, congenital hip dysplasia with degenerative joint disease, extensive subchondral cysts, evidence of bone fragmentation or collapse, or primary metastatic tumor with the exception of chondromas or pathologic fracture during the screening period
• Signs or symptoms of carpal tunnel syndrome within 6 months of screening
• Patient is not a candidate for MRI
• Is scheduled for a joint replacement surgery to be performed during the study period
• Systemic (i.e., oral or intramuscular) corticosteroids within 30 days prior to the screening visit.
• History or presence at the screening visit of multiple sclerosis, autonomic neuropathy, diabetic neuropathy, or other peripheral neuropathy, including reflex sympathetic dystrophy
• History or diagnosis of chronic autonomic failure syndrome including pure autonomic failure, multiple system atrophy
• Pregnant or breast-feeding women
• Women of childbearing potential who have a positive pregnancy test result or do not have their pregnancy test result at baseline

Sponsors & Collaborators

• Regeneron Pharmaceuticals: lead
• Teva Pharmaceutical Industries, Ltd.: collaborator

Study Sites (149)

Regeneron Investigational Site

Birmingham, Alabama, 35211, United States

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Regeneron Investigational Site #1

Chandler, Arizona, 85224, United States

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Regeneron Investigational Site #2

Chandler, Arizona, 85224, United States

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Regeneron Investigational Site

Glendale, Arizona, 85308, United States

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Regeneron Investigational Site

Mesa, Arizona, 85213, United States

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Regeneron Investigational Site (4 locations)

Phoenix, Arizona, 85018, United States

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Regeneron Investigational Site

Tempe, Arizona, 85224, United States

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Regeneron Investigational Site (2 locations)

Tucson, Arizona, 85712, United States

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Little Rock, Arkansas, 72205, United States

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Beverly Hills, California, 90211, United States

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Carlsbad, California, 92008, United States

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San Diego, California, 92103, United States

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San Marcos, California, 92078, United States

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Vista, California, 92083, United States

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Aurora, Colorado, 80014, United States

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Colorado Springs, Colorado, 80909, United States

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Golden, Colorado, 80401, United States

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Littleton, Colorado, 80127, United States

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Clearwater, Florida, 33765, United States

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Orlando, Florida, 32801, United States

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Pinellas Park, Florida, 33781, United States

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Atlanta, Georgia, 30328, United States

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Regeneron Investigational Site (3 locations)

Chicago, Illinois, 60602, United States

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Evansville, Illinois, 47714, United States

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Kansas City, Kansas, 64114, United States

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Frederick, Maryland, 21702, United States

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Worcester, Massachusetts, 01605, United States

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Richfield, Minnesota, 55423, United States

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Regeneron Investigational Site #1

St Louis, Missouri, 63141, United States

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Regeneron Investigational Site #2

St Louis, Missouri, 63141, United States

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Elkhorn, Nebraska, 68022, United States

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Fremont, Nebraska, 68025, United States

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Omaha, Nebraska, 68144, United States

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Las Vegas, Nevada, 89128, United States

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Jamaica, New York, 11432, United States

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New York, New York, 10036, United States

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High Point, North Carolina, 27262, United States

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Akron, Ohio, 44311, United States

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Cincinnati, Ohio, 45219, United States

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Columbus, Ohio, 43212, United States

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Oklahoma City, Oklahoma, 73119, United States

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Duncansville, Pennsylvania, 16635, United States

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Anderson, South Carolina, 29621, United States

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Greer, South Carolina, 29651, United States

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Regeneron Investigational Site #1

Dallas, Texas, 75234, United States

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Regeneron Investigational Site #2

Dallas, Texas, 75234, United States

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Houston, Texas, 77008, United States

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Lubbock, Texas, 79424, United States

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Plano, Texas, 75093, United States

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San Antonio, Texas, 78229, United States

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Regeneron Investigational Site

Burgas, 8000, Bulgaria

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Regeneron Investigational Site #1

Plovdiv, 4000, Bulgaria

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Regeneron Investigational Site #2

Plovdiv, 4002, Bulgaria

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Regeneron Investigational Site #3

Plovdiv, 4004, Bulgaria

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Regeneron Investigational Site #1

Sofia, 1000, Bulgaria

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Regeneron Investigational Site #2

Sofia, 1612, Bulgaria

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Stara Zagora, 6000, Bulgaria

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Santiago, 8331143, Chile

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Bogotá, 110221, Colombia

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Medellín, 50003, Colombia

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Aalborg, 9000, Denmark

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Ballerup Municipality, 2750, Denmark

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Vejle, DK 7100, Denmark

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Paide, 72713, Estonia

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Tallinn, 10128, Estonia

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Leipzig, Saxony, 04103, Germany

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Berlin, 1267, Germany

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Regeneron Investigational Sites

Bochum, 44787, Germany

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Frankfurt, 60313, Germany

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Magdeburg, 39120, Germany

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Central, Hong Kong

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Budapest, 1036, Hungary

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Debrecen, 4025, Hungary

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Gyula, 5700, Hungary

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Hatvan, 3000, Hungary

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Zalaegerszeg, 8900, Hungary

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Florence, 50139, Italy

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Naples, 80138, Italy

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Alytus, LT-62114, Lithuania

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Kaunas, 48259, Lithuania

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Šiauliai, LT-76231, Lithuania

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Vilnius, 10323, Lithuania

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Mexicali, Baja Californina, 21100, Mexico

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Guadalajara, Jalisco, 44160, Mexico

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Guadalajara, Jalisco, 44660, Mexico

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Cuauhtémoc, Mexico City, 06100, Mexico

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Cuauhtémoc, Mexico City, 06700, Mexico

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Distrito Federal, Mexico City, 03100, Mexico

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Mexico City, Mexico City, 11850, Mexico

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Cuernavaca, Morelos, 62290, Mexico

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Culiacán, Sinaloa, 80000, Mexico

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Mérida, Yucatán, 97000, Mexico

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Mérida, Yucatán, C.P. 97070, Mexico

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Lima, 27, Peru

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Gdansk, 80-382, Poland

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Gdynia, 81-537, Poland

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Katowice, 40-040, Poland

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Krakow, 31-501, Poland

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Lodz, 90-368, Poland

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Poznan, 60-702, Poland

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Regeneron Investigational Site #1

Warsaw, 01-192, Poland

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Regeneron Investigational Site #2

Warsaw, 01-192, Poland

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Wroclaw, 50-381, Poland

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Regeneron Investigational Site #2

Bucharest, 021611, Romania

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Regeneron Investigational Site #1

Bucharest, 30463, Romania

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Kazan', 420012, Russia

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Novosibirsk, 630091, Russia

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Samara, 443095, Russia

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Tomsk, 634050, Russia

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Regeneron Investigational Site #2

Yaroslavl, 150003, Russia

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Regeneron Investigational Site #1

Yaroslavl, 150007, Russia

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Regeneron Investigational Site #1

Pretoria, Gauteng, 0184, South Africa

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Regeneron Investigational Site #2

Pretoria, Gauteng, 0184, South Africa

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Bloemfontein, 9301, South Africa

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Cape Town, 7530, South Africa

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Kempton Park, 1619, South Africa

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Parow, 7500, South Africa

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Port Elizabeth, 6001, South Africa

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Pretoria, 0122, South Africa

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Roodepoort, 1724, South Africa

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Somerset West, 7130, South Africa

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Soweto, 1818, South Africa

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A Coruña, 15006, Spain

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Barcelona, 08025, Spain

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Madrid, 28100, Spain

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Seville, 41010, Spain

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Malmo, Skåne County, 211 52, Sweden

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Borås, 50630, Sweden

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Gothenburg, 413 45, Sweden

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Helsingborg, 25220, Sweden

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Linköping, 587 58, Sweden

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Lund, 222 22, Sweden

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Uppsala, 75237, Sweden

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Vällingby, 16268, Sweden

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Cherkasy, 18009, Ukraine

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Regeneron Investigational Site #3

Kyiv, 02002, Ukraine

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Regeneron Investigational Site #1

Kyiv, 03037, Ukraine

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Regeneron Investigational Site #2

Kyiv, 03049, Ukraine

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Lviv, 79495, Ukraine

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Birmingham, B15 2SQ, United Kingdom

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Chorley, PR7 7NA, United Kingdom

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Glasgow, G20 0SP, United Kingdom

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Hexham, NE46 1QJ, United Kingdom

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Liverpool, L22 0LG, United Kingdom

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Manchester, M15 6SE, United Kingdom

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Middlesex, HA6 2RN, United Kingdom

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Reading, RG2 0TG, United Kingdom

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Romford, RM1 3PJ, United Kingdom

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Sidcup, DA14 6LT, United Kingdom

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MeSH Terms

Conditions

Osteoarthritis, Knee

Interventions

fasinumab

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Clinical Trials Administrator
• Organization: Regeneron Pharmaceuticals, Inc

clinicaltrials@regeneron.com

844-734-6643

Study Officials

• Clinical Trial Management

  Regeneron Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• 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: January 28, 2016
• First Posted: February 17, 2016
• Study Start: February 17, 2016
• Primary Completion: December 1, 2020
• Study Completion: June 15, 2021
• Last Updated: October 13, 2023
• Results First Posted: October 13, 2023

Record last verified: 2023-10

Locations

IT (2); ZA (11); ES (4); LI (4); SE (8); RU (6); RO (2); HK (1); PE (1); CL (1); DE (5); US (50); DK (3); CO (2); ME (11); PL (9); BU (7); UA (5); GB (10); HU (5)