Clinical trial NCT02792699: Study to Assess if ABP 798 is Safe & Effective in Treating Moderate to Severe Rheumatoid Arthritis (RA) Compared to Rituximab
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Arthritis, Rheumatoid
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2016-06-07
Enrollment: 311
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) After the Second Infusion of the First Dose
timeFrame: Day 15, pre-dose, end of infusion, and 3, 6, 24, and 48 hours, and 2, 6, and 10 weeks postdose.
measure: Maximum Observed Drug Concentration (Cmax) After the Second Infusion of the First Dose
timeFrame: Day 15, pre-dose, end of infusion, and 3, 6, 24, and 48 hours, and 2, 6, and 10 weeks postdose.
Secondary outcomes:
measure: Area Under the Serum Concentration-time Curve From Predose on Day 1 to 14 Days Postdose (AUC0-14day)
timeFrame: Day 1, predose, at end of infusion, 3, 6, 24, and 48 hours postdose and day 15, predose.
measure: Area Under the Serum Concentration-time Curve From Predose on Day 1 to Week 12 (AUC0-12wk)
timeFrame: 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).
measure: Maximum Observed Drug Concentration (Cmax) After the First Infusion of the First Dose
timeFrame: Day 1, predose, at end of infusion, 3, 6, 24, and 48 hours postdose and day 15, predose.
measure: Time of Maximum Observed Drug Concentration (Tmax) After the First and Second Infusions of the First Dose
timeFrame: 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).
measure: Last Measurable Serum Concentration After the Second Infusion up to Week 12 (Clast)
timeFrame: Day 15, predose, end of infusion, 3, 6, 24, and 48 hours postdose, and at days 29, 57, and 85 (week 12).
measure: Terminal Elimination Half-life (t1/2)
timeFrame: 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).
measure: Terminal Elimination Rate Constant (λz)
timeFrame: 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).
measure: Clearance (CL)
timeFrame: 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).
measure: Mean Residence Time (MRT)
timeFrame: 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).
measure: Percent of AUC Extrapolation (AUC%Extrap)
timeFrame: Day 15, predose, end of infusion, 3, 6, 24, and 48 hours postdose, and at days 29, 57, and 85 (week 12).
measure: AUC0-12 wk/AUCinf
timeFrame: 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).
measure: Change From Baseline in Disease Activity Score 28-CRP at Week 24
timeFrame: Baseline and Week 24
measure: Change From Baseline in Disease Activity Score 28-CRP at Weeks 8, 12, 40, and 48
timeFrame: Baseline and weeks 8, 12, 40, and 48
measure: Percentage of Participants With an ACR20 Response
timeFrame: Baseline and Weeks 8, 12, 24, 40, and 48
measure: Percentage of Participants With an ACR50 Response
timeFrame: Baseline and Weeks 8, 12, 24, 40, and 48
measure: Percentage of Participants With an ACR70 Response
timeFrame: Baseline and Weeks 8, 12, 24, 40, and 48
measure: Hybrid ACR
timeFrame: Baseline and weeks 8, 12, 24, 40, and 48
measure: Percentage of Participants With Complete Depletion in CD19+ Cell Count on Day 3
timeFrame: Day 3
measure: Duration of Complete Depletion in CD19+ Cell Count
timeFrame: CD19+ cell count was assessed at baseline, days 2, 3, weeks 4, 24, and 48
measure: Number of Participants With Adverse Events After the First Dose
timeFrame: From day 1 until the first infusion of the second dose (week 24)
measure: Number of Participants Who Developed Anti-drug Antibodies
timeFrame: Day 1 through the end of study (48 weeks).
measure: Number of Participants With Clinically Significant Laboratory Findings
timeFrame: Day 1 through the end of study (48 weeks).
Other outcomes:
Locations:
city: Tuscaloosa
country: United States
facility: Research Site
state: Alabama
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Thousand Oaks
country: United States
facility: Research Site
state: California
city: Upland
country: United States
facility: Research Site
state: California
city: Aventura
country: United States
facility: Research Site
state: Florida
city: Edgewater
country: United States
facility: Research Site
state: Florida
city: Hialeah
country: United States
facility: Research Site
state: Florida
city: Orlando
country: United States
facility: Research Site
state: Florida
city: Vero Beach
country: United States
facility: Research Site
state: Florida
city: Idaho Falls
country: United States
facility: Research Site
state: Idaho
city: Lexington
country: United States
facility: Research Site
state: Kentucky
city: Lansing
country: United States
facility: Research Site
state: Michigan
city: Flowood
country: United States
facility: Research Site
state: Mississippi
city: Las Vegas
country: United States
facility: Research Site
state: Nevada
city: Charlotte
country: United States
facility: Research Site
state: North Carolina
city: Oklahoma City
country: United States
facility: Research Site
state: Oklahoma
city: Duncansville
country: United States
facility: Research Site
state: Pennsylvania
city: Orangeburg
country: United States
facility: Research Site
state: South Carolina
city: Summerville
country: United States
facility: Research Site
state: South Carolina
city: Memphis
country: United States
facility: Research Site
state: Tennessee
city: Carrollton
country: United States
facility: Research Site
state: Texas
city: Dallas
country: United States
facility: Research Site
state: Texas
city: League City
country: United States
facility: Research Site
state: Texas
city: Mesquite
country: United States
facility: Research Site
state: Texas
city: Plano
country: United States
facility: Research Site
state: Texas
city: Olympia
country: United States
facility: Research Site
state: Washington
city: Spokane
country: United States
facility: Research Site
state: Washington
city: Sofia
country: Bulgaria
facility: Research Site
state: Sofiya
city: Sofia
country: Bulgaria
facility: Research Site
state: Sofiya
city: Plovdiv
country: Bulgaria
facility: Research Site
city: Tallinn
country: Estonia
facility: Research Site
state: Harjuma
city: Tartu
country: Estonia
facility: Research Site
city: Bad Nauheim
country: Germany
facility: Research Site
state: Hessen
city: Magdeburg
country: Germany
facility: Research Site
state: Sachsen-anhalt
city: Berlin
country: Germany
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Gyula
country: Hungary
facility: Research Site
state: Bekes
city: Szentes
country: Hungary
facility: Research Site
state: Csongrad
city: Budapest
country: Hungary
facility: Research Site
state: Pest
city: Szombathely
country: Hungary
facility: Research Site
state: VAS
city: Veszprém
country: Hungary
facility: Research Site
state: Veszprem
city: Wrocław
country: Poland
facility: Research Site
state: Dolnoslaskie
city: Bydgoszcz
country: Poland
facility: Research Site
state: Kujawsko-pomorskie
city: Łódź
country: Poland
facility: Research Site
state: Lodzkie
city: Lublin
country: Poland
facility: Research Site
state: Lubelskie
city: Kraków
country: Poland
facility: Research Site
state: Malopolskie
city: Warszawa
country: Poland
facility: Research Site
state: Mazowieckie
city: Stalowa Wola
country: Poland
facility: Research Site
state: Podkarpackie
city: Białystok
country: Poland
facility: Research Site
state: Podlaskie
city: Gdańsk
country: Poland
facility: Research Site
state: Pomorskie
city: Katowice
country: Poland
facility: Research Site
state: Slaskie
city: Elbląg
country: Poland
facility: Research Site
state: Warminsko-mazurskie
city: Poznań
country: Poland
facility: Research Site
state: Wielkopolskie
city: Poznań
country: Poland
facility: Research Site
state: Wielkopolskie
city: Poznań
country: Poland
facility: Research Site
state: Wielkopolskie
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: Burmester G, Chien D, Chow V, Gessner M, Pan J, Cohen S. A Randomized, Double-Blind Study Comparing Pharmacokinetics and Pharmacodynamics of Proposed Biosimilar ABP 798 With Rituximab Reference Product in Subjects With Moderate to Severe Rheumatoid Arthritis. Clin Pharmacol Drug Dev. 2020 Nov;9(8):1003-1014. doi: 10.1002/cpdd.845. Epub 2020 Jul 5.