Study to Assess if ABP 798 is Safe & Effective in Treating Moderate to Severe Rheumatoid Arthritis (RA) Compared to Rituximab

Arthritis, Rheumatoid Clinical Trial

Official title:

A Randomized, Double-blind Study to Compare Pharmacokinetics and Pharmacodynamics, Efficacy and Safety of ABP 798 With Rituximab in Subjects With Moderate to Severe Rheumatoid Arthritis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02792699
• Other study ID #: 20130108
• Secondary ID: 2013-005543-90
• Status: Completed
• Phase: Phase 3
• Start date: May 17, 2016
• Est. completion date: October 8, 2018

Study information

• Verified date: October 2020
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This trial is designed to determine what effects the human body has on the investigational medicine, ABP 798, and what effects the body has on the investigational medicine after you have been given it, and if this is comparable to what is seen for the licensed medicine, rituximab, in patients with moderate or severe RA.

This study will also assess if the investigational medicine is safe and effective in treating moderate or severe RA compared to the licensed medicine.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 311
• Est. completion date: October 8, 2018
• Est. primary completion date: October 8, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Men or women = 18 and = 80 years old

• Subjects must be diagnosed with rheumatoid arthritis for at least 6 months before baseline

• Active RA defined as = 6 swollen joints and = 6 tender joints at screening and baseline and at least one of the following at screening:

• erythrocyte sedimentation rate (ESR) = 28 mm/hr

• serum C-reactive protein (CRP) > 1.0 mg/dL

• Subjects must be taking methotrexate (MTX) for = 12 consecutive weeks and on a stable dose of MTX 7.5 to 25 mg/week for = 8 weeks prior to receiving the investigational product (IP), and be willing to remain on a stable dose throughout the study

• Subject has no known history of active tuberculosis

Exclusion Criteria:

• Class IV RA, Felty's syndrome or history of prosthetic or native joint infection

• Major chronic inflammatory disease or connective tissue disease other than RA, with the exception of secondary Sjögren's syndrome

• Use of commercially available or investigational biologic therapies for RA as follows:

• anakinra, etanercept within 1 month prior to first dose of IP

• infliximab, abatacept, tocilizumab, golimumab, certolizumab within 3 months prior to first dose of IP

• other experimental or commercially available biologic therapies for RA within 3 months or 5 half-lives (whichever is longer) prior to first dose of IP

• Previous receipt of rituximab or a biosimilar of rituximab

Other Inclusion/Exclusion criteria may apply

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid

Intervention

Drug:
• ABP 798
Supplied as a 10 mg/mL liquid concentrate for intravenous (IV) administration.
• Rituximab (US)
Supplied as a 10 mg/mL liquid concentrate for IV administration.
• Rituximab (EU)
Supplied as a 10 mg/mL liquid concentrate for IV administration.

Locations

Country	Name	City	State
Bulgaria	Research Site	Plovdiv
Bulgaria	Research Site	Sofia	Sofiya
Bulgaria	Research Site	Sofia	Sofiya
Estonia	Research Site	Tallinn	Harjuma
Estonia	Research Site	Tartu
Germany	Research Site	Bad Nauheim	Hessen
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Magdeburg	Sachsen-anhalt
Hungary	Research Site	Budapest	Pest
Hungary	Research Site	Gyula	Bekes
Hungary	Research Site	Szentes	Csongrad
Hungary	Research Site	Szombathely	VAS
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	Stalowa Wola	Podkarpackie
Poland	Research Site	Warszawa	Mazowieckie
Poland	Research Site	Wroclaw	Dolnoslaskie
United States	Research Site	Aventura	Florida
United States	Research Site	Carrollton	Texas
United States	Research Site	Charlotte	North Carolina
United States	Research Site	Dallas	Texas
United States	Research Site	Duncansville	Pennsylvania
United States	Research Site	Edgewater	Florida
United States	Research Site	Flowood	Mississippi
United States	Research Site	Hialeah	Florida
United States	Research Site	Idaho Falls	Idaho
United States	Research Site	Lansing	Michigan
United States	Research Site	Las Vegas	Nevada
United States	Research Site	League City	Texas
United States	Research Site	Lexington	Kentucky
United States	Research Site	Los Angeles	California
United States	Research Site	Memphis	Tennessee
United States	Research Site	Mesquite	Texas
United States	Research Site	Oklahoma City	Oklahoma
United States	Research Site	Olympia	Washington
United States	Research Site	Orangeburg	South Carolina
United States	Research Site	Orlando	Florida
United States	Research Site	Plano	Texas
United States	Research Site	Spokane	Washington
United States	Research Site	Summerville	South Carolina
United States	Research Site	Thousand Oaks	California
United States	Research Site	Tuscaloosa	Alabama
United States	Research Site	Upland	California
United States	Research Site	Vero Beach	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Countries where clinical trial is conducted

United States,  Bulgaria,  Estonia,  Germany,  Hungary,  Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) After the Second Infusion of the First Dose	Area under the serum concentration-time curve from time 0 extrapolated to infinity (AUCinf) following the second infusion of the first dose (day 15). Concentrations of ABP-798 and rituximab were quantified using a validated electrochemiluminescent method. AUCinf was estimated using the linear trapezoidal rule.	Day 15, pre-dose, end of infusion, and 3, 6, 24, and 48 hours, and 2, 6, and 10 weeks postdose.
Primary	Maximum Observed Drug Concentration (Cmax) After the Second Infusion of the First Dose	Maximum observed concentration following the second infusion of the first dose (day 15). Concentrations of ABP-798 and rituximab were quantified using a validated electrochemiluminescent method.	Day 15, pre-dose, end of infusion, and 3, 6, 24, and 48 hours, and 2, 6, and 10 weeks postdose.
Secondary	Area Under the Serum Concentration-time Curve From Predose on Day 1 to 14 Days Postdose (AUC0-14day)	Area under the serum concentration-time curve from time 0 on day 1 prior to the first infusion of the first dose to 14 days postdose. Concentrations of ABP-798 and rituximab were quantified using a validated electrochemiluminescent method. AUC0-14day was estimated using the linear trapezoidal rule.	Day 1, predose, at end of infusion, 3, 6, 24, and 48 hours postdose and day 15, predose.
Secondary	Area Under the Serum Concentration-time Curve From Predose on Day 1 to Week 12 (AUC0-12wk)	Area under the serum concentration-time curve from time 0 on day 1 prior to the first infusion of the first dose to week 12. Concentrations of ABP-798 and rituximab were quantified using a validated electrochemiluminescent method. AUC0-12wk was estimated using the linear trapezoidal rule.	Day 1, predose, at end of infusion, 3, 6, 24, and 48 hours postdose; day 15, predose, end of infusion, 3, 6, 24, and 48 hour postdose, and at days 29, 57, and 85 (week 12).
Secondary	Maximum Observed Drug Concentration (Cmax) After the First Infusion of the First Dose	Concentrations of ABP-798 and rituximab were quantified using a validated electrochemiluminescent method.	Day 1, predose, at end of infusion, 3, 6, 24, and 48 hours postdose and day 15, predose.
Secondary	Time of Maximum Observed Drug Concentration (Tmax) After the First and Second Infusions of the First Dose	Concentrations of ABP-798 and rituximab were quantified using a validated electrochemiluminescent method.	Day 1, predose, at end of infusion, 3, 6, 24, and 48 hours postdose; day 15, predose, end of infusion, 3, 6, 24, and 48 hours postdose, and at days 29, 57, and 85 (week 12).
Secondary	Last Measurable Serum Concentration After the Second Infusion up to Week 12 (Clast)	Concentrations of ABP-798 and rituximab were quantified using a validated electrochemiluminescent method.	Day 15, predose, end of infusion, 3, 6, 24, and 48 hours postdose, and at days 29, 57, and 85 (week 12).
Secondary	Terminal Elimination Half-life (t1/2)	Concentrations of ABP-798 and rituximab were quantified using a validated electrochemiluminescent method.	Day 1, predose, at end of infusion, 3, 6, 24, and 48 hours postdose; day 15, predose, end of infusion, 3, 6, 24, and 48 hours postdose, and at days 29, 57, and 85 (week 12).
Secondary	Terminal Elimination Rate Constant (?z)	Concentrations of ABP-798 and rituximab were quantified using a validated electrochemiluminescent method.	Day 1, predose, at end of infusion, 3, 6, 24, and 48 hours postdose; day 15, predose, end of infusion, 3, 6, 24, and 48 hours postdose, and at days 29, 57 and 85 (week 12).
Secondary	Clearance (CL)	Concentrations of ABP-798 and rituximab were quantified using a validated electrochemiluminescent method.	Day 1, predose, at end of infusion, 3, 6, 24, and 48 hours postdose; day 15, predose, end of infusion, 3, 6, 24, and 48 hours postdose, and at days 29, 57, and 85 (week 12).
Secondary	Mean Residence Time (MRT)	Concentrations of ABP-798 and rituximab were quantified using a validated electrochemiluminescent method.	Day 1, predose, at end of infusion, 3, 6, 24, and 48 hours postdose; day 15, predose, end of infusion, 3, 6, 24, and 48 hours postdose, and at days 29, 57, and 85 (week 12).
Secondary	Percent of AUC Extrapolation (AUC%Extrap)	Percent of AUC extrapolated to infinity in AUCinf. Concentrations of ABP-798 and rituximab were quantified using a validated electrochemiluminescent method.	Day 15, predose, end of infusion, 3, 6, 24, and 48 hours postdose, and at days 29, 57, and 85 (week 12).
Secondary	AUC0-12 wk/AUCinf	Concentrations of ABP-798 and rituximab were quantified using a validated electrochemiluminescent method.	Day 1, predose, at end of infusion, 3, 6, 24, and 48 hours postdose; day 15, predose, end of infusion, 3, 6, 24, and 48 hours postdose, and at days 29, 57, and 85 (week 12).
Secondary	Change From Baseline in Disease Activity Score 28-CRP at Week 24	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 Week 24
Secondary	Change From Baseline in Disease Activity Score 28-CRP at Weeks 8, 12, 40, and 48	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 8, 12, 40, and 48
Secondary	Percentage of Participants With an ACR20 Response	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 8, 12, 24, 40, and 48
Secondary	Percentage of Participants With an ACR50 Response	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 8, 12, 24, 40, and 48
Secondary	Percentage of Participants With an ACR70 Response	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 8, 12, 24, 40, and 48
Secondary	Hybrid ACR	The hybrid ACR combines the ACR 20/50/70 response with the mean percent change in all 7 ACR core components, thus providing a percent improvement from baseline on a continuous scale. For each participant, the mean percent improvement from baseline across the 7 ACR core set measures (tender joint count, swollen joint count, Patient's Global Assessment of Disease Activity, Investigator's Global Assessment of Disease Activity, disability index of the HAQ, and CRP) was calculated (a positive change indicates improvement, and the maximum worst change is limited to -100%) and the ACR20, ACR50, and ACR70 response is determined. The hybrid ACR is determined from a reference table taking into account both ACR response and mean percent improvement in the core set measures. Scores can range from -100% (maximal worsening) to 100% (maximal improvement).	Baseline and weeks 8, 12, 24, 40, and 48
Secondary	Percentage of Participants With Complete Depletion in CD19+ Cell Count on Day 3	Complete depletion of cluster of differentiation (CD) 19 positive cells was defined as a CD19+ cell count < 20 cell/µL (0.02 x 10? cell/L).	Day 3
Secondary	Duration of Complete Depletion in CD19+ Cell Count	Duration of CD19+ B-cell complete depletion was defined as the time from the first incidence of complete depletion of CD19+ cell count (CD19+ cell count < 20 cells/µL) to when the CD19+ cell count first increased to = 20 cells/µL. Participants whose CD19+ cell count did not increase to = 20 cells/µL were censored at the last CD19+ assessment date.	CD19+ cell count was assessed at baseline, days 2, 3, weeks 4, 24, and 48
Secondary	Number of Participants With Adverse Events After the First Dose	Adverse events (AEs) were graded by the investigator according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 4.03, where Grade 1 = mild AE, Grade 2 = moderate AE, Grade 3 = severe AE, Grade 4 = life-threatening AE, and Grade 5 = death due to AE.; A serious AE (SAE) was defined as an AE that met at least 1 of the following serious criteria: fatal; life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; congenital anomaly/birth defect; other medically important serious event. The adverse events of interest prespecified for this study included infusion reactions including hypersensitivity, cardiac disorders, serious infections, progressive multifocal leukoencephalopathy, hematological reactions, hepatitis B reactivation, opportunistic infections, hypogammaglobulinemia, severe mucocutaneous reactions, and gastrointestinal perforation.	From day 1 until the first infusion of the second dose (week 24)
Secondary	Number of Participants Who Developed Anti-drug Antibodies	Samples were first tested in an electrochemiluminescence (ECL)-based bridging immunoassay to detect antibodies capable of binding to ABP 798/rituximab (Binding Antibody Assay). Samples confirmed to be positive for binding antibodies were subsequently tested in a cell-based assay to determine neutralizing activity against ABP 798/rituximab (Neutralizing Antibody Assay).; Developing antibody incidence was defined as participants with a negative or no binding antibody result at baseline and a positive antibody result at any post-baseline time point.	Day 1 through the end of study (48 weeks).
Secondary	Number of Participants With Clinically Significant Laboratory Findings	Clinically significant clinical laboratory findings were defined as laboratory results that were = Grade 3, based on the CTCAE version 4.03.	Day 1 through the end of study (48 weeks).

External Links

•   AmgenTrials clinical trials website