Study to Assess if ABP710 is Safe & Effective in Treating Moderate to Severe Rheumatoid Arthritis Compared to Infliximab

Arthritis, Rheumatoid Clinical Trial

Official title:

A Randomized, Double-Blind Phase 3 Study to Assess the Efficacy and Safety of ABP 710 Compared to Infliximab in Subjects With Moderate to Severe Rheumatoid Arthritis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02937701
• Other study ID #: 20140111
• Secondary ID: 2014-004704-29
• Status: Completed
• Phase: Phase 3
• Start date: October 10, 2016
• Est. completion date: August 13, 2018

Study information

• Verified date: August 2019
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The main purpose of the study was to compare rheumatoid arthritis symptom improvement in participants who were given ABP 710 to those who were given infliximab, 22 weeks after starting treatment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 558
• Est. completion date: August 13, 2018
• Est. primary completion date: April 16, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Subject (man or woman) is = 18 and = 80 years old.

• Subject is diagnosed with rheumatoid arthritis (RA) as determined by meeting the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism classification criteria for RA.

• Subject has RA duration of at least 3 months.

• Subject has active RA defined as = 6 swollen joints and = 6 tender joints (based on 66/68 joint count excluding distal interphalangeal joints) at screening and baseline and at least 1 of the following at screening:

• erythrocyte sedimentation rate = 28 mm/hr

• serum C-reactive protein > 1.0 mg/dL

• Subject has a positive rheumatoid factor or anti-cyclic citrullinated peptide at screening.

• Subject has taken methotrexate (MTX) for = 12 consecutive weeks and is on a stable dose of oral or subcutaneous MTX 7.5 to 25 mg/week for = 8 weeks before receiving the investigational product and is willing to remain on a stable dose throughout the study.

• For a subject on nonsteroidal anti-inflammatory drugs (NSAIDs) or low potency analgesics such as tramadol, Soma Compounds, Fioricet, or Fiorinal, the dose should be stable for = 2 weeks before screening.

• For a subject on oral corticosteroids (= 10 mg prednisone or equivalent), the dose should be stable for = 4 weeks before screening.

• Subject has no known history of active tuberculosis.

• Subject has a negative test for tuberculosis during screening defined as either:

• negative purified protein derivative (PPD) defined as < 5 mm of induration at 48 to 72 hours after test is placed OR

• negative Quantiferon test

• Subject with a positive PPD and a history of Bacillus Calmette-Guérin vaccination is allowed with a negative Quantiferon test.

• Subject with a positive PPD test (without a history of Bacillus Calmette-Guérin vaccination) or a subject with a positive or indeterminate Quantiferon test is allowed if they have all of the following:

• no symptoms of tuberculosis according to the worksheet provided by the sponsor, Amgen Inc.

• documented history of adequate prophylaxis initiation before receiving investigational product in accordance with local recommendations

• no known exposure to a case of active tuberculosis after most recent prophylaxis

Exclusion Criteria:

• Subject has a history of prosthetic or native joint infection.

• Subject has an active infection or history of infections as follows:

• any active infection for which systemic anti-infectives were used within 28 days before first dose of investigational product

• a serious infection, defined as requiring hospitalization or intravenous (IV) anti-infective(s) within 8 weeks before the first dose of investigational product

• recurrent or chronic infections or other active infection that, in the opinion of the investigator, might cause this study to be detrimental to the subject

• Subject has a positive blood test for human immunodeficiency virus (HIV).

• Subject has a positive hepatitis B surface antigen, hepatitis B core antibody, or hepatitis C virus antibody result at screening.

• Subject has uncontrolled, clinically significant systemic disease such as diabetes mellitus, cardiovascular disease including moderate or severe heart failure (New York Heart Association Class III/IV), renal disease, liver disease, or hypertension.

• Subject had a malignancy within 5 years EXCEPT for treated and considered cured cutaneous squamous or basal cell carcinoma, in situ cervical cancer, OR in situ breast ductal carcinoma.

• Subject has a history of neurologic symptoms suggestive of central or peripheral nervous system demyelinating disease.

• Subject has a major chronic inflammatory disease or connective tissue disease other than RA, with the exception of secondary Sjögren's syndrome.

• Subject has a concurrent medical condition that, in the opinion of the investigator, could cause this study to be detrimental to the subject.

• Subject has laboratory abnormalities at screening, including any of the following:

• hemoglobin < 9 g/dL

• platelet count < 100 000/mm³

• white blood cell count < 3 000/mm³

• aspartate aminotransferase and/or alanine aminotransferase = 2.0 x the upper limit of normal

• creatinine clearance < 50 mL/min (Cockroft-Gault formula)

• any other laboratory abnormality, that, in the opinion of the investigator, will prevent the subject from completing the study or will interfere with the interpretation of the study results.

• Subject has used commercially available or investigational biologic therapies for RA as follows:

• anakinra, etanercept within 1 month before the first dose of investigational product

• abatacept, tocilizumab, adalimumab, golimumab, certolizumab within 3 months before the first dose of investigational product

• other experimental or commercially available biologic therapies for RA within 3 months or 5 half-lives (whichever is longer) before the first dose of investigational product

• rituximab within 9 months before the investigational product along with evidence of incomplete B cell recovery

• Subject has received live vaccines within 28 days before the first dose of investigational product or plans to receive live vaccines during the course of the study.

• Subject has previously received Remicade® (infliximab) or a biosimilar of infliximab.

• Woman who is pregnant or breast feeding, or plans to become pregnant while enrolled in the study and for 6 months after the last dose of investigational product.

• Women of childbearing potential (ie, neither surgically sterile nor postmenopausal) and do not agree to use adequate contraception (eg, true abstinence, sterilization, birth control pills, Depo-Provera® [medroxyprogesterone] injections, or contraceptive implants) while on study and for 6 months after the last dose of investigational product.

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid

Intervention

Biological:
• ABP 710
Administered by intravenous infusion
• Infliximab
Administered by intravenous infusion

Locations

Country	Name	City	State
Australia	Research Site	Fitzroy	Victoria
Australia	Research Site	Woodville	South Australia
Bulgaria	Research Site	Pleven
Bulgaria	Research Site	Plovdiv
Bulgaria	Research Site	Plovdiv
Bulgaria	Research Site	Sliven
Bulgaria	Research Site	Sofia	Sofiya
Bulgaria	Research Site	Varna
Canada	Research Site	Saint Johns	Newfoundland and Labrador
Canada	Research Site	Victoria	British Columbia
Czechia	Research Site	Brno	Jihormoravsky KRAJ
Czechia	Research Site	Hlucín	Moravskoslezsky
Czechia	Research Site	Liberec	Severocesky KRAJ
Czechia	Research Site	Ostrava	Severomoravsky KRAJ
Czechia	Research Site	Pardubice	Vychodocesky KRAJ
Czechia	Research Site	Praha 2	Praha
Czechia	Research Site	Praha 3	Praha
Czechia	Research Site	Zlín	Severomoravsky KRAJ
Germany	Research Site	Bad Doberan	Mecklenburg-vorpommern
Germany	Research Site	Hamburg
Germany	Research Site	Hildesheim	Niedersachsen
Germany	Research Site	Magdeburg	Sachsen-anhalt
Hungary	Research Site	Gyor	Gyor-moson-sopron
Hungary	Research Site	Gyula	Bekes
Hungary	Research Site	Szentes	Csongrad
Hungary	Research Site	Veszprém	Veszprem
Poland	Research Site	Bialystok	Podlaskie
Poland	Research Site	Bydgoszcz	Kujawsko-pomorskie
Poland	Research Site	Elblag	Warminsko-mazurskie
Poland	Research Site	Gdansk	Pomorskie
Poland	Research Site	Katowice	Slaskie
Poland	Research Site	Kraków	Malopolskie
Poland	Research Site	Lódz	Lodzkie
Poland	Research Site	Lublin	Lubelskie
Poland	Research Site	Poznan	Wielkopolskie
Poland	Research Site	Poznan	Wielkopolskie
Poland	Research Site	Poznan	Wielkopolskie
Poland	Research Site	Poznan	Wielkopolskie
Poland	Research Site	Poznan	Wielkopolskie
Poland	Research Site	Stalowa Wola	Podkarpackie
Poland	Research Site	Torun	Kujawsko-pomorskie
Poland	Research Site	Warszawa	Mazowieckie
Poland	Research Site	Warszawa	Mazowieckie
Poland	Research Site	Wroclaw	Dolnoslaskie
Spain	Research Site	Barcelona
Spain	Research Site	Madrid
Spain	Research Site	Sevilla
United States	Research Site	Aventura	Florida
United States	Research Site	Carrollton	Texas
United States	Research Site	Charleston	South Carolina
United States	Research Site	Charlotte	North Carolina
United States	Research Site	Covina	California
United States	Research Site	Dallas	Texas
United States	Research Site	Flowood	Mississippi
United States	Research Site	Grand Blanc	Michigan
United States	Research Site	Hemet	California
United States	Research Site	Houston	Texas
United States	Research Site	Huntsville	Alabama
United States	Research Site	League City	Texas
United States	Research Site	Lexington	Kentucky
United States	Research Site	Memphis	Tennessee
United States	Research Site	Miami Lakes	Florida
United States	Research Site	Omaha	Nebraska
United States	Research Site	Orlando	Florida
United States	Research Site	Peoria	Arizona
United States	Research Site	Plano	Texas
United States	Research Site	Saint Louis	Missouri
United States	Research Site	Sarasota	Florida
United States	Research Site	Tuscaloosa	Alabama
United States	Research Site	Upland	California
United States	Research Site	Van Nuys	California
United States	Research Site	Vero Beach	Florida
United States	Research Site	Voorhees	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Countries where clinical trial is conducted

United States,  Australia,  Bulgaria,  Canada,  Czechia,  Germany,  Hungary,  Poland,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 22	The primary efficacy endpoint was the response difference (RD) of 20% improvement in ACR core set measurements (ACR20) at week 22.; A positive ACR20 response is defined if the following 3 criteria for improvement from baseline were met: = 20% improvement in 68 tender joint count; = 20% improvement in 66 swollen joint count; and; = 20% improvement in at least 3 of the 5 following parameters: Patient's assessment of disease-related pain (measured on a 100 mm visual analog scale [VAS]); Patient's global health assessment (measured on a 100 mm VAS); Investigator's global health assessment (measured on a 100 mm VAS); Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]); C-reactive protein concentration.	Baseline and week 22
Secondary	Percentage of Participants With an ACR20 Response Through Week 14	A positive ACR20 response is defined if the following 3 criteria for improvement from baseline were met: = 20% improvement in 68 tender joint count; = 20% improvement in 66 swollen joint count; and; = 20% improvement in at least 3 of the 5 following parameters: Patient's assessment of disease-related pain (measured on a 100 mm visual analog scale [VAS]); Patient's global health assessment (measured on a 100 mm VAS); Investigator's global health assessment (measured on a 100 mm VAS); Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]); C-reactive protein concentration.	Baseline and weeks 2, 6, and 14
Secondary	Percentage of Participants With an ACR20 Response After Week 22	A positive ACR20 response is defined if the following 3 criteria for improvement from baseline were met: = 20% improvement in 68 tender joint count; = 20% improvement in 66 swollen joint count; and; = 20% improvement in at least 3 of the 5 following parameters: Patient's assessment of disease-related pain (measured on a 100 mm visual analog scale [VAS]); Patient's global health assessment (measured on a 100 mm VAS); Investigator's global health assessment (measured on a 100 mm VAS); Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]); C-reactive protein concentration.	Baseline and weeks 30, 34, 38, 46, and 50
Secondary	Percentage of Participants With an ACR50 Response Through Week 22	A positive ACR50 response is defined if the following 3 criteria for improvement from baseline were met: = 50% improvement in 68 tender joint count; = 50% improvement in 66 swollen joint count; and; = 50% improvement in at least 3 of the 5 following parameters: Patient's assessment of disease-related pain (measured on a 100 mm visual analog scale [VAS]); Patient's global health assessment (measured on a 100 mm VAS); Investigator's global health assessment (measured on a 100 mm VAS); Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]); C-reactive protein concentration.	Baseline and weeks 2, 6, 14, and 22
Secondary	Percentage of Participants With an ACR50 Response After Week 22	A positive ACR50 response is defined if the following 3 criteria for improvement from baseline were met: = 50% improvement in 68 tender joint count; = 50% improvement in 66 swollen joint count; and; = 50% improvement in at least 3 of the 5 following parameters: Patient's assessment of disease-related pain (measured on a 100 mm visual analog scale [VAS]); Patient's global health assessment (measured on a 100 mm VAS); Investigator's global health assessment (measured on a 100 mm VAS); Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]); C-reactive protein concentration.	Baseline and weeks 30, 34, 38, 46, and 50
Secondary	Percentage of Participants With an ACR70 Response Through Week 22	A positive ACR70 response is defined if the following 3 criteria for improvement from baseline were met: = 70% improvement in 68 tender joint count; = 70% improvement in 66 swollen joint count; and; = 70% improvement in at least 3 of the 5 following parameters: Patient's assessment of disease-related pain (measured on a 100 mm visual analog scale [VAS]); Patient's global health assessment (measured on a 100 mm VAS); Investigator's global health assessment (measured on a 100 mm VAS); Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]); C-reactive protein concentration.	Baseline and weeks 2, 6, 14, and 22
Secondary	Percentage of Participants With an ACR70 Response After Week 22	A positive ACR70 response is defined if the following 3 criteria for improvement from baseline were met: = 70% improvement in 68 tender joint count; = 70% improvement in 66 swollen joint count; and; = 70% improvement in at least 3 of the 5 following parameters: Patient's assessment of disease-related pain (measured on a 100 mm visual analog scale [VAS]); Patient's global health assessment (measured on a 100 mm VAS); Investigator's global health assessment (measured on a 100 mm VAS); Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]); C-reactive protein concentration.	Baseline and weeks 30, 34, 38, 46, and 50
Secondary	Change From Baseline in Disease Activity Score 28 (DAS28) Through Week 22	The DAS28 measures the severity of disease at a specific time and is derived from the following variables: 28 tender joint count; 28 swollen joint count; C-reactive protein (CRP); Patient's global health assessment measured on a 100 mm VAS, where 0 mm = no RA activity and 100 mm = worst RA activity imaginable.; DAS28(CRP) scores range from 0 to approximately 10, with the upper bound dependent on the highest possible level of CRP. A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission.	Baseline and weeks 2, 6, 14, and 22
Secondary	Change From Baseline in Disease Activity Score 28 (DAS28) After Week 22	The DAS28 measures the severity of disease at a specific time and is derived from the following variables: 28 tender joint count; 28 swollen joint count; C-reactive protein (CRP); Patient's global health assessment measured on a 100 mm VAS, where 0 mm = no RA activity and 100 mm = worst RA activity imaginable.; DAS28(CRP) scores range from 0 to approximately 10, with the upper bound dependent on the highest possible level of CRP. A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission.	Baseline and weeks 30, 34, 38, 46, and 50

External Links

•   AmgenTrials clinical trials website