A Study of the Pharmacokinetics and Safety of MK-8808 (MK-8808-002 EXT 1)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01390441
First received: July 7, 2011
Last updated: May 9, 2014
Last verified: May 2014
  Purpose

This is a study of the overall safety, tolerability, and pharmacokinetics (PK) of MK-8808 versus rituximab (MabThera™ and Rituxan™) and in participants with moderate to severe rheumatoid arthritis (RA) concomitantly treated with methotrexate. Participants will be enrolled in two parts and analysis of data from Part A will be performed while Part B is enrolling. Participants will receive one or two courses of therapy, with each course including two infusions of study drugs.


Condition Intervention Phase
Rheumatoid Arthritis
Biological: MK-8808 500 mg/m^2
Biological: Rituximab 500 mg/m^2
Drug: Methotrexate
Biological: MabThera (rituximab) 500 mg/m^2
Biological: Rituxan (rituximab) 500 mg/m^2
Biological: MK-8808 1000 mg
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Two-Part, Phase I Randomized, Double-Blind, Active-Comparator Controlled, Parallel Group Study to Assess the Pharmacokinetics, Safety, and Tolerability of MK-8808 and to Compare the Pharmacokinetics of MK-8808 With Rituximab (MabThera™ and Rituxan™) in Patients With Rheumatoid Arthritis (RA)

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Area Under the Curve from Day 0 to Day 84 (AUC[0-84day]) after a single course of treatment-Part A [ Time Frame: Day 0 to Day 84 (Part A) ] [ Designated as safety issue: No ]
  • Area Under the Curve from Day 0 to Day 84 (AUC[0-84day]) after a single course of treatment-Part B [ Time Frame: Day 0 to Day 84 (Part B) ] [ Designated as safety issue: No ]
  • Number of Participants with Adverse Events (AEs)-Part C [ Time Frame: Week 52 to Week 106 ] [ Designated as safety issue: Yes ]
  • Number of Participants Discontinuing Treatment Due to AEs-Part C [ Time Frame: Week 52 to Week 106 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Maximum concentration (Cmax) after the second infusion of a single course of treatment-Part A [ Time Frame: Day 15 ] [ Designated as safety issue: No ]
  • Cmax after the second infusion of a single course of treatment-Part B [ Time Frame: Day 197 ] [ Designated as safety issue: No ]

Enrollment: 100
Study Start Date: July 2011
Study Completion Date: April 2014
Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MK-8808: Part A Biological: MK-8808 500 mg/m^2
Intravenously on Day 1 (500mg/m^2) and Day 15 (500mg/m^2) consistent with product labeling information.
Drug: Methotrexate
Stable oral dose (10-25 mg/week orally)
Other Names:
  • Trexall™
  • Rheumatrex™
Active Comparator: Rituximab: Part A Biological: Rituximab 500 mg/m^2
Intravenously on Day 1 (500mg/m^2) and Day 15 (500mg/m^2).
Other Names:
  • MabThera™
  • Rituxan™
Drug: Methotrexate
Stable oral dose (10-25 mg/week orally)
Other Names:
  • Trexall™
  • Rheumatrex™
Experimental: MK-8808: Part B Biological: MK-8808 500 mg/m^2
Intravenously on Day 1 (500mg/m^2) and Day 15 (500mg/m^2) consistent with product labeling information.
Drug: Methotrexate
Stable oral dose (10-25 mg/week orally)
Other Names:
  • Trexall™
  • Rheumatrex™
Active Comparator: MabThera (rituximab): Part B Drug: Methotrexate
Stable oral dose (10-25 mg/week orally)
Other Names:
  • Trexall™
  • Rheumatrex™
Biological: MabThera (rituximab) 500 mg/m^2
Intravenously on Day 1 (500mg/m^2) and Day 15 (500mg/m^2).
Experimental: Rituxan (rituximab): Part B Drug: Methotrexate
Stable oral dose (10-25 mg/week orally)
Other Names:
  • Trexall™
  • Rheumatrex™
Biological: Rituxan (rituximab) 500 mg/m^2
Intravenously on Day 1 (500mg/m^2) and Day 15 (500mg/m^2).
Other Name: Rituximab
Experimental: MK-8808: Part C Drug: Methotrexate
Stable oral dose (10-25 mg/week orally)
Other Names:
  • Trexall™
  • Rheumatrex™
Biological: MK-8808 1000 mg
Two infusions consisting of 1000 mg of MK-8808 will be administered intravenously to participants in the extension study with the first occurring at study Week 54 and the second at study Week 56. An additional two infusions consisting of 1000 mg of MK-8808 will be administered intravenously, at the discretion of the treating physician, to participants in the extension study with the first occurring at study Week 80 and the second at study Week 82.

Detailed Description:

The extension portion of the study (Part C) will sequentially follow the base study beginning at Week 52 and continue for an additional 54 weeks. All participants who meet eligibility criteria and continue into the study extension will be treated with open-label MK-8808. Participants randomized to MK-8808 in the base study will remain on the same therapy. Participants randomized to rituximab (MabThera™ or Rituxan™) in the base study will be switched to MK-8808 for the extension study.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Female participants of reproductive potential must demonstrate a serum β-hCG level consistent with the nongravid state at the prestudy (screening) visit, and a negative urine pregnancy test within 24 hours prior to all doses and and agree to use (and/or have their partner use) two acceptable methods of birth control beginning at least 2 weeks prior to administration of the first dose of study drug, throughout the study (including washout intervals between treatment periods/panels) and until at least 12 months after administration of the last dose of study drug in the last treatment period
  • The participant has a Body Mass Index (BMI) ≤35 kg/m2 at the prestudy (screening) visit
  • For Part A Only: The participant has a BSA ≤2.0 m2 at the prestudy (screening) visit.
  • Has satisfied at least 4 of 7 American Rheumatology Association (ARA) 1987 revised criteria for the diagnosis of rheumatoid arthritis
  • Is American College of Rheumatology (ACR) Functional Class I, II, or III
  • Had a diagnosis of RA made at least 6 months prior to the prestudy (screening) visit, was ≥ 16 years of age when diagnosed, and has active disease
  • Is on a stable oral, intramuscular, or subcutaneous dose of methotrexate and is continuing to take methotrexate
  • Has an inadequate response or intolerance to at least one disease-modifying antirheumatic drug (DMARD)
  • For Part A: Participant is either naïve to biological therapy for RA or has had an inadequate response to previous or current treatment with an anti-TNF treatment (patient could have failed up to three anti-TNF agents treatments) or participant has had intolerance up to three anti-TNF treatments.
  • For Part B: Participant has had an inadequate response to previous or current treatment with an anti-TNF treatment (patient could have failed up to three anti-TNF agents treatments) or participant has had intolerance up to three anti-TNF treatments
  • Participant has no clinically significant abnormality on electrocardiogram (ECG) performed at the prestudy (screening) visit and/or prior to administration of the initial dose of study drug
  • For Part B Only: Participant is positive for rheumatoid factor (RF) or, if negative for RF, is positive for anti-CCP at screening visit
  • For Part C Only: Participant must have completed the first 52 weeks of treatment in the base study
  • For Part C Only: Participant achieved a minimum 20% response from baseline on the American College of Rheumatology (ACR) Responder Index (ACR20) at Visit 19 (last visit for the base study)

Exclusion Criteria:

  • Mentally or legally incapacitated, has significant emotional problems at the time of the prestudy (screening) visit or during the conduct of the study or has a history of a clinically significant psychiatric disorder over the last 5 years
  • Creatinine clearance of ≤ 80 mL/min
  • History of stroke, chronic seizures or major neurological disorder
  • History of neoplastic disease, except treated basal cell carcinoma or carcinoma in situ or other malignancies which have been successfully treated ≥ 5 years
  • History of leukemia, lymphoma, malignant melanoma, or myeloproliferative disease regardless of the time since treatment
  • History of coronary artery disease, congestive heart failure (New York Heart Association Class I-IV), or a history of clinically significant arrhythmia (including any history of atrial fibrillation, atrial flutter, or any sustained ventricular arrhythmia)
  • Hypersensitivity or allergy to rituximab or any of the excipients of MK-8808 or rituximab (MabThera™ or Rituxan™)
  • History of a rheumatic autoimmune disease other than RA (e.g. systemic lupus erythematosus (SLE), polymyositis, etc.)
  • Severe active infection of any type or history of a medically serious infection as defined by a history of treatment requiring hospitalization, long term intravenous (IV) outpatient treatment for systemic bacterial, viral or fungal infection, use of I.V. antibiotics within 30-days of screening, or use of antibiotic therapy three or more times in the last six months prior to screening
  • History of opportunistic infection
  • Active-virus vaccination within 4 weeks
  • Active tuberculosis with or without adequate treatment, history of latent tuberculosis without written confirmation from health care provider of adequate prophylaxis or any evidence of tuberculosis on a chest X-ray (CRX) performed within 3 months of dosing
  • Chronic hepatitis B or hepatitis C infection or has human immunodeficiency virus (HIV) infection
  • Previously treated with rituximab (MabThera™ or Rituxan™) or any investigational anti-CD20 antibody
  • Active use or planned use of a prohibited DMARD during the course of study participation, and/or insufficient washout from a prohibited DMARD at the time of the planned first dose of MK-8808/rituximab (MabThera™ or Rituxan™)
  • Had major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks
  • Participated in another investigational study with length of time within at least 5 half-lives of the previous investigational study drug
  • Pregnant or breastfeeding or expecting to conceive
  • Allergy to murine proteins
  • Allergy or sensitivity to components of the drug vial or any of the materials used for infusion
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01390441     History of Changes
Other Study ID Numbers: 8808-002
Study First Received: July 7, 2011
Last Updated: May 9, 2014
Health Authority: Ukraine: Ministry of Health

Keywords provided by Merck Sharp & Dohme Corp.:
Rheumatoid arthritis
RA
Rituximab
Rituxan
MabThera
Methotrexate
Rheumatrex
Trexall
MK-8808

Additional relevant MeSH terms:
Rituximab
Arthritis
Arthritis, Rheumatoid
Autoimmune Diseases
Connective Tissue Diseases
Immune System Diseases
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Methotrexate
Abortifacient Agents
Abortifacient Agents, Nonsteroidal
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antirheumatic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Physiological Effects of Drugs
Reproductive Control Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014