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

NCT02792699 | Completed Phase 3 Results DMC

• 2 other identifiers: 201301082013-005543-90
• Study Type: interventional
• Target: 311
• Locations: 6 countries
• Sites: 55

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.

Conditions

Arthritis, Rheumatoid

Outcome Measures

Primary Outcomes (2)

• 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.

• 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 Outcomes (22)

• Area Under the Serum Concentration-time Curve From Predose on Day 1 to 14 Days Postdose (AUC0-14day)

  Day 1, predose, at end of infusion, 3, 6, 24, and 48 hours postdose and day 15, predose.

• Area Under the Serum Concentration-time Curve From Predose on Day 1 to Week 12 (AUC0-12wk)

  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).

• Maximum Observed Drug Concentration (Cmax) After the First Infusion of the First Dose

  Day 1, predose, at end of infusion, 3, 6, 24, and 48 hours postdose and day 15, predose.

• Time of Maximum Observed Drug Concentration (Tmax) After the First and Second Infusions of the First Dose

  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).

• Last Measurable Serum Concentration After the Second Infusion up to Week 12 (Clast)

  Day 15, predose, end of infusion, 3, 6, 24, and 48 hours postdose, and at days 29, 57, and 85 (week 12).

Study Arms (3)

ABP 798 / ABP 798

EXPERIMENTAL

Participants received ABP 798 on days 1 and 15 (dose 1) and a second dose of ABP 798 at weeks 24 and 26 (dose 2). Each dose consisted of two 1000 mg intravenous infusions 2 weeks apart.

Drug: ABP 798

Rituximab (US) / ABP 798

ACTIVE COMPARATOR

Participants received rituximab (United States \[US\] formulation) on days 1 and 15 (dose 1) and transitioned to receive ABP 798 at weeks 24 and 26 (dose 2). Each dose consisted of two 1000 mg intravenous infusions 2 weeks apart.

Drug: ABP 798; Drug: Rituximab (US)

Rituximab (EU) / Rituximab (EU)

ACTIVE COMPARATOR

Participants received rituximab (European Union \[EU\] formulation) on days 1 and 15 (dose 1) and a second dose of rituximab (EU formulation) at weeks 24 and 26 (dose 2). Each dose consisted of two 1000 mg intravenous infusions 2 weeks apart.

Drug: Rituximab (EU)

Interventions

ABP 798 DRUG

Supplied as a 10 mg/mL liquid concentrate for intravenous (IV) administration.

ABP 798 / ABP 798; Rituximab (US) / ABP 798

Rituximab (US) DRUG

Supplied as a 10 mg/mL liquid concentrate for IV administration.

Also known as: Rituxan®

Rituximab (US) / ABP 798

Rituximab (EU) DRUG

Supplied as a 10 mg/mL liquid concentrate for IV administration.

Also known as: MabThera®

Rituximab (EU) / Rituximab (EU)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Amgen: lead

Study Sites (55)

Research Site

Tuscaloosa, Alabama, 35406, United States

Location

Research Site

Los Angeles, California, 90095-1670, United States

Location

Research Site

Thousand Oaks, California, 91360, United States

Location

Research Site

Upland, California, 91786, United States

Location

Research Site

Aventura, Florida, 33180, United States

Location

Research Site

Edgewater, Florida, 32132, United States

Location

Research Site

Hialeah, Florida, 33012, United States

Location

Research Site

Orlando, Florida, 32810, United States

Location

Research Site

Vero Beach, Florida, 32960, United States

Location

Research Site

Idaho Falls, Idaho, 83404, United States

Location

Research Site

Lexington, Kentucky, 40504, United States

Location

Research Site

Lansing, Michigan, 48910, United States

Location

Research Site

Flowood, Mississippi, 39232, United States

Location

Research Site

Las Vegas, Nevada, 89128, United States

Location

Research Site

Charlotte, North Carolina, 28210, United States

Location

Research Site

Oklahoma City, Oklahoma, 73112, United States

Location

Research Site

Duncansville, Pennsylvania, 16635, United States

Location

Research Site

Orangeburg, South Carolina, 29118, United States

Location

Research Site

Summerville, South Carolina, 29486, United States

Location

Research Site

Memphis, Tennessee, 38119, United States

Location

Research Site

Carrollton, Texas, 75007-1601, United States

Location

Research Site

Dallas, Texas, 75231, United States

Location

Research Site

League City, Texas, 77573, United States

Location

Research Site

Mesquite, Texas, 75150, United States

Location

Research Site

Plano, Texas, 75024, United States

Location

Research Site

Olympia, Washington, 98502, United States

Location

Research Site

Spokane, Washington, 99204, United States

Location

Research Site

Sofia, Sofia, 1233, Bulgaria

Location

Research Site

Sofia, Sofia, 1612, Bulgaria

Location

Research Site

Plovdiv, 4003, Bulgaria

Location

Research Site

Tallinn, Harjuma, 10117, Estonia

Location

Research Site

Tartu, 50106, Estonia

Location

Research Site

Bad Nauheim, Hesse, 61231, Germany

Location

Research Site

Magdeburg, Saxony-Anhalt, 39120, Germany

Location

Research Site

Berlin, 10117, Germany

Location

Research Site

Berlin, 13125, Germany

Location

Research Site

Gyula, Bekes County, 5700, Hungary

Location

Research Site

Szentes, Csongrád megye, 6600, Hungary

Location

Research Site

Budapest, Pest County, 1083, Hungary

Location

Research Site

Szombathely, Vas County, 9700, Hungary

Location

Research Site

Veszprém, Veszprém megye, 8200, Hungary

Location

Research Site

Poznan, Greater Poland Voivodeship, 60-218, Poland

Location

Research Site

Poznan, Greater Poland Voivodeship, 60-529, Poland

Location

Research Site

Poznan, Greater Poland Voivodeship, 61-397, Poland

Location

Research Site

Bydgoszcz, Kuyavian-Pomeranian Voivodeship, 85-168, Poland

Location

Research Site

Krakow, Lesser Poland Voivodeship, 30-033, Poland

Location

Research Site

Wroclaw, Lower Silesian Voivodeship, 50-556, Poland

Location

Research Site

Lublin, Lublin Voivodeship, 20-582, Poland

Location

Research Site

Warsaw, Masovian Voivodeship, 02-637, Poland

Location

Research Site

Stalowa Wola, Podkarpackie Voivodeship, 37-450, Poland

Location

Research Site

Bialystok, Podlaskie Voivodeship, 15-297, Poland

Location

Research Site

Gdansk, Pomeranian Voivodeship, 80-382, Poland

Location

Research Site

Katowice, Silesian Voivodeship, 40-282, Poland

Location

Research Site

Elblag, Warmian-Masurian Voivodeship, 82-300, Poland

Location

Research Site

Lodz, Łódź Voivodeship, 91-363, Poland

Location

Related Publications (1)

• 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.

  PMID: 32627420 DERIVED

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Rituximab

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

medinfo@amgen.com

866-572-6436

Study Officials

• MD

  Amgen

  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: April 25, 2016
• First Posted: June 7, 2016
• Study Start: May 17, 2016
• Primary Completion: October 8, 2018
• Study Completion: October 8, 2018
• Last Updated: October 6, 2020
• Results First Posted: October 23, 2019

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the link below.

Locations

BU (3); DE (4); HU (5); US (27); PL (14); ES (2)