Back to resultsA Study of the Pharmacokinetics and Safety of MK-8808 (MK-8808-002)
Primary Purpose
Rheumatoid Arthritis
Status
Terminated
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
MK-8808
MabThera® (rituximab)
Methotrexate
Rituxan® (rituximab)
Methylprednisolone
Acetaminophen
Loratadine
Sponsored by
About this trial
This is an interventional treatment trial for Rheumatoid Arthritis focused on measuring Rheumatoid arthritis, RA, Rituximab, Rituxan, MabThera, Methotrexate, Rheumatrex, Trexall, MK-8808
Eligibility Criteria
Inclusion Criteria:
- Female participants of reproductive potential must demonstrate a serum β-human chorionic gonadotropin (hCG) level consistent with the nongravid state at the pre-study (screening) visit, and a negative urine pregnancy test within 24 hours prior to all doses 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/m^2 at the prestudy (screening) visit
- For Part A Only: The participant has a body surface are (BSA) ≤2.0 m^2 at the prestudy (screening) visit.
- Has satisfied at least 4 of 7 American Rheumatology Association (ARA) 1987 revised criteria for the diagnosis of RA
- 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, IM, or SC 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-tumor necrosis factor (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 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 of the cervix 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 IV outpatient treatment for systemic bacterial, viral or fungal infection, use of IV 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 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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Experimental
Active Comparator
Experimental
Active Comparator
Experimental
Arm Label
Part A: MK-8808 500 mg/m^2 / Extension A: MK-8808 1000 mg
Part A: MabThera® 500 mg/m^2 / Extension A: MK-8808 1000 mg
Part B: MK-8808 1000 mg / Extension B: MK-8808 1000 mg
Part B: MabThera® 1000 mg / Extension B: MK-8808 1000 mg
Part B: Rituxan® 1000 mg / Extension B: MK-8808 1000 mg
Arm Description
During the Treatment Period, participants receive one course of MK-8808 (500 mg/m^2) administered intravenously (IV) on Day 1 and Day 15 (with a second optional course of treatment at Weeks 26 and 28). Participants are followed up to Week 52 in the Treatment Period. During the Extension Period, participants receive open-label MK-8808 (1000 mg) administered IV at Week 54 and Week 56 (with a second optional course at Weeks 80 and 82). Participants are followed up to Week 106 in the Extension Period. Methotrexate 12.5 to 25 mg/week is administered either orally, subcutaneously (SC), or intramuscularly (IM) for the duration of the trial. A 10 mg dose may be administered if a greater dose is not tolerated.
During the Treatment Period, participants receive one course of MabThera® (500 mg/m^2) administered IV on Day 1 and Day 15 (with a second optional course of treatment at Weeks 26 and 28). Participants are followed up to Week 52 in the Treatment Period. During the Extension Period, participants receive open label MK-8808 (1000 mg) administered IV at Week 54 and Week 56 (with a second optional course at Weeks 80 and 82). Participants are followed up to Week 106 in the Extension Period. Methotrexate 12.5 to 25 mg/week is administered either orally, SC, or IM for the duration of the trial. A 10 mg dose may be administered if a greater dose is not tolerated.
In the Treatment Period, participants receive one course of MK-8808 (1000 mg) administered IV on Day 1 and Day 15 (with a second optional course of treatment at Weeks 26 and 28). Participants are followed up to Week 52 in the Treatment Period. In the Extension Period, participants receive open label MK-8808 (1000 mg) adminstered IV at Week 54 and Week 56 (with a second optional course at Weeks 80 and 82). Participants are followed up to Week 106 in the Extension Period. Methotrexate 12.5 to 25 mg/week is administered either orally, SC, or IM for the duration of the trial. A 10 mg dose may be administered if a greater dose is not tolerated.
In the Treatment Period, participants receive one course of MabThera® (1000 mg) administered IV on Day 1 and Day 15 (with a second optional course of treatment at Weeks 26 and 28). Participants are followed up to Week 52 in the Treatment Period. In the Extension Period, participants receive open label MK-8808 (1000 mg) administered IV at Week 54 and Week 56 (with a second optional course at Weeks 80 and 82). Participants are followed up to Week 106 in the Extension Period. Methotrexate 12.5 to 25 mg/week is administered either orally, SC, or IM for the duration of the trial. A 10 mg dose may be administered if a greater dose is not tolerated.
In the Treatment Period, participants receive one course of Rituxan® (1000 mg) administered IV on Day 1 and Day 15 (with a second optional course of treatment at Weeks 26 and 28). Participants are followed up to Week 52 in the Treatment Period. In the Extension Period, participants receive open label MK-8808 (1000 mg) administered IV at Week 54 and Week 56 (with a second optional course at Weeks 80 and 82). Participants are followed up to Week 106 in the Extension Period. Methotrexate 12.5 to 25 mg/week is administered either orally, SC, or IM for the duration of the trial. A 10 mg dose may be administered if a greater dose is not tolerated.
Outcomes
Primary Outcome Measures
Part A: Area Under the Concentration-time Curve From Day 0 to Day 84 (AUC0-84day) After a Single Course of Treatment
AUC is a measure of the amount of drug in the plasma over time; samples are collected at intervals from pre-dose up to 84 days after the dose. Descriptive data values and associated dispersion measures (confidence intervals) are expressed in terms of the factor 10E6.
Part B: Area Under the Concentration-time Curve From Day 0 to Day 84 (AUC0-84day) After a Single Course of Treatment
AUC is a measure of the amount of drug in the plasma over time; samples are collected at intervals from pre-dose up to 84 days after the dose.
Number of Participants Who Experienced at Least One Adverse Event
An adverse event is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure.
Number of Participants Who Discontinued Study Drug Due to Adverse Events
Discontinuation/withdrawal of study treatment due to an adverse event was performed at the discretion of the investigator or the Sponsor for safety concerns. An adverse event is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure.
Number of Participants With Immunoglobulin G (IgG) Response in the Extension Study
Serum IgG levels are determined over course of therapy with MK-8808 in the Extension Study.
Number of Participants Positive for Anti-Drug Antibody (ADA) Formation in the Extension Study
Serum ADA positivity is determined over course of therapy with MK-8808 in the Extension Study.
Secondary Outcome Measures
Part A: Maximum Concentration (Cmax) After the Second Infusion of a Single Course of Treatment
Cmax is a measure of the maximum plasma concentration of drug; samples are collected on Day 15 after the second infusion of the first course of treatment. Descriptive data values and associated dispersion measures (confidence intervals) are expressed in terms of the factor 10E3.
Part B: Cmax After the Second Infusion of a Single Course of Treatment
Cmax is a measure of the maximum plasma concentration of drug; samples are collected on Day 15 after the second infusion of the first course of treatment.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01390441
Brief Title
A Study of the Pharmacokinetics and Safety of MK-8808 (MK-8808-002)
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 EU-approved MabThera® and US-licensed Rituxan® in Patients With Rheumatoid Arthritis (RA)
Study Type
Interventional
2. Study Status
Record Verification Date
May 2016
Overall Recruitment Status
Terminated
Why Stopped
The study was terminated early by the Sponsor for business reasons.
Study Start Date
July 2011 (undefined)
Primary Completion Date
April 2014 (Actual)
Study Completion Date
April 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is a study of the overall safety, tolerability, and pharmacokinetics (PK) of MK-8808 versus rituximab (MabThera® and Rituxan®) in participants with moderate to severe RA with an inadequate response or intolerance to methotrexate.
Detailed Description
In Part A of the base study, participants are randomized to either MK-8808 or MabThera®. In Part B of the base study, participants are randomized to either MK-8808, MabThera®, or Rituxan®. Participants enrolled in Part A are not eligible to participate in Part B. In both Parts A and B, participants will receive one or two courses of therapy, with each course including two infusions of the study drugs.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis
Keywords
Rheumatoid arthritis, RA, Rituximab, Rituxan, MabThera, Methotrexate, Rheumatrex, Trexall, MK-8808
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
100 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Part A: MK-8808 500 mg/m^2 / Extension A: MK-8808 1000 mg
Arm Type
Experimental
Arm Description
During the Treatment Period, participants receive one course of MK-8808 (500 mg/m^2) administered intravenously (IV) on Day 1 and Day 15 (with a second optional course of treatment at Weeks 26 and 28). Participants are followed up to Week 52 in the Treatment Period.
During the Extension Period, participants receive open-label MK-8808 (1000 mg) administered IV at Week 54 and Week 56 (with a second optional course at Weeks 80 and 82). Participants are followed up to Week 106 in the Extension Period.
Methotrexate 12.5 to 25 mg/week is administered either orally, subcutaneously (SC), or intramuscularly (IM) for the duration of the trial. A 10 mg dose may be administered if a greater dose is not tolerated.
Arm Title
Part A: MabThera® 500 mg/m^2 / Extension A: MK-8808 1000 mg
Arm Type
Active Comparator
Arm Description
During the Treatment Period, participants receive one course of MabThera® (500 mg/m^2) administered IV on Day 1 and Day 15 (with a second optional course of treatment at Weeks 26 and 28). Participants are followed up to Week 52 in the Treatment Period.
During the Extension Period, participants receive open label MK-8808 (1000 mg) administered IV at Week 54 and Week 56 (with a second optional course at Weeks 80 and 82). Participants are followed up to Week 106 in the Extension Period.
Methotrexate 12.5 to 25 mg/week is administered either orally, SC, or IM for the duration of the trial. A 10 mg dose may be administered if a greater dose is not tolerated.
Arm Title
Part B: MK-8808 1000 mg / Extension B: MK-8808 1000 mg
Arm Type
Experimental
Arm Description
In the Treatment Period, participants receive one course of MK-8808 (1000 mg) administered IV on Day 1 and Day 15 (with a second optional course of treatment at Weeks 26 and 28). Participants are followed up to Week 52 in the Treatment Period.
In the Extension Period, participants receive open label MK-8808 (1000 mg) adminstered IV at Week 54 and Week 56 (with a second optional course at Weeks 80 and 82). Participants are followed up to Week 106 in the Extension Period.
Methotrexate 12.5 to 25 mg/week is administered either orally, SC, or IM for the duration of the trial. A 10 mg dose may be administered if a greater dose is not tolerated.
Arm Title
Part B: MabThera® 1000 mg / Extension B: MK-8808 1000 mg
Arm Type
Active Comparator
Arm Description
In the Treatment Period, participants receive one course of MabThera® (1000 mg) administered IV on Day 1 and Day 15 (with a second optional course of treatment at Weeks 26 and 28). Participants are followed up to Week 52 in the Treatment Period.
In the Extension Period, participants receive open label MK-8808 (1000 mg) administered IV at Week 54 and Week 56 (with a second optional course at Weeks 80 and 82). Participants are followed up to Week 106 in the Extension Period.
Methotrexate 12.5 to 25 mg/week is administered either orally, SC, or IM for the duration of the trial. A 10 mg dose may be administered if a greater dose is not tolerated.
Arm Title
Part B: Rituxan® 1000 mg / Extension B: MK-8808 1000 mg
Arm Type
Experimental
Arm Description
In the Treatment Period, participants receive one course of Rituxan® (1000 mg) administered IV on Day 1 and Day 15 (with a second optional course of treatment at Weeks 26 and 28). Participants are followed up to Week 52 in the Treatment Period.
In the Extension Period, participants receive open label MK-8808 (1000 mg) administered IV at Week 54 and Week 56 (with a second optional course at Weeks 80 and 82). Participants are followed up to Week 106 in the Extension Period.
Methotrexate 12.5 to 25 mg/week is administered either orally, SC, or IM for the duration of the trial. A 10 mg dose may be administered if a greater dose is not tolerated.
Intervention Type
Biological
Intervention Name(s)
MK-8808
Intervention Description
MK-8808 500 mg/m^2 administered by IV on Day 1 and Day 15 or MK-8808 1000 mg administered by IV at Week 54 and Week 56
Intervention Type
Biological
Intervention Name(s)
MabThera® (rituximab)
Other Intervention Name(s)
Rituxan®, Rituximab
Intervention Description
MabThera® 500 mg/m^2 or 1000 mg administered by IV on Day 1 and Day 15
Intervention Type
Drug
Intervention Name(s)
Methotrexate
Other Intervention Name(s)
Trexall®, Rheumatrex®
Intervention Description
Methotrexate 10-25 mg administered orally, SC, or IM as a weekly stable dose
Intervention Type
Biological
Intervention Name(s)
Rituxan® (rituximab)
Other Intervention Name(s)
Rituximab
Intervention Description
Rituxan® 1000 mg administered by IV on Day 1 and Day 15
Intervention Type
Drug
Intervention Name(s)
Methylprednisolone
Intervention Description
Methylprednisolone 100 mg administered IV before initiation of each infusion as pre-medication to reduce the incidence and severity of infusion reactions
Intervention Type
Drug
Intervention Name(s)
Acetaminophen
Other Intervention Name(s)
Paracetamol
Intervention Description
Acetaminophen 1000 to 1350 mg administered orally before initiation of each infusion as pre-medication to reduce the incidence and severity of infusion reactions
Intervention Type
Drug
Intervention Name(s)
Loratadine
Other Intervention Name(s)
Claritin®
Intervention Description
Loratidine 10 mg administered orally before initiation of each infusion as pre-medication to reduce the incidence and severity of infusion reactions
Primary Outcome Measure Information:
Title
Part A: Area Under the Concentration-time Curve From Day 0 to Day 84 (AUC0-84day) After a Single Course of Treatment
Description
AUC is a measure of the amount of drug in the plasma over time; samples are collected at intervals from pre-dose up to 84 days after the dose. Descriptive data values and associated dispersion measures (confidence intervals) are expressed in terms of the factor 10E6.
Time Frame
Day 1 (pre- and post-dose), Day 3, Day 5, Day 8, Day 15, Day 17, Day 19, Day 22, Day 29, Day 43, Day 57, Day 85
Title
Part B: Area Under the Concentration-time Curve From Day 0 to Day 84 (AUC0-84day) After a Single Course of Treatment
Description
AUC is a measure of the amount of drug in the plasma over time; samples are collected at intervals from pre-dose up to 84 days after the dose.
Time Frame
Day 1 (pre- and post-dose), Day 3, Day 5, Day 8, Day 15, Day 17, Day 19, Day 22, Day 29, Day 43, Day 57, Day 85
Title
Number of Participants Who Experienced at Least One Adverse Event
Description
An adverse event is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure.
Time Frame
Parts A and B: Up to 52 weeks; Extension A and B: Up to 106 weeks
Title
Number of Participants Who Discontinued Study Drug Due to Adverse Events
Description
Discontinuation/withdrawal of study treatment due to an adverse event was performed at the discretion of the investigator or the Sponsor for safety concerns. An adverse event is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure.
Time Frame
Parts A and B: Up to Week 28; Extension A and B: Up to 82 weeks
Title
Number of Participants With Immunoglobulin G (IgG) Response in the Extension Study
Description
Serum IgG levels are determined over course of therapy with MK-8808 in the Extension Study.
Time Frame
Week 54, Week 68, Week 80, Week 94, Week 106
Title
Number of Participants Positive for Anti-Drug Antibody (ADA) Formation in the Extension Study
Description
Serum ADA positivity is determined over course of therapy with MK-8808 in the Extension Study.
Time Frame
Week 54, Week 56, Week 68, Week 80, Week 82, Week 94, Week 106
Secondary Outcome Measure Information:
Title
Part A: Maximum Concentration (Cmax) After the Second Infusion of a Single Course of Treatment
Description
Cmax is a measure of the maximum plasma concentration of drug; samples are collected on Day 15 after the second infusion of the first course of treatment. Descriptive data values and associated dispersion measures (confidence intervals) are expressed in terms of the factor 10E3.
Time Frame
Day 15
Title
Part B: Cmax After the Second Infusion of a Single Course of Treatment
Description
Cmax is a measure of the maximum plasma concentration of drug; samples are collected on Day 15 after the second infusion of the first course of treatment.
Time Frame
Day 15
Other Pre-specified Outcome Measures:
Title
Part A: Number of ACR20, ACR50, and ACR70 Responders at Week 24
Description
American College of Rheumatology (ACR) Responder Index is based on a set of evaluations: the Investigator Tender Joint Count/Number of Tender Joints (out of 68 Joints); Investigator Swollen Joint Count/Number of Swollen Joints (out of 66 Joints); Patient Global Assessment of Disease Activity (PGAD); Investigator Global Assessment of Disease Activity (IGAD); Patient Global Assessment of Pain (PGAP); Health Assessment Questionnaire Disability Index (HAQ-DI); and ESR. ACR response indicates percent change (ie, improvement) from baseline (20%, 50%, 70%) PGAD & IGAD: assessment of function on a 4-point Likert scale: 0=very well to 3=unable to do PGAP: pain due to arthritis measured on a 0-100 mm visual analog scale: Left hand marker-"no pain"; right hand marker-"extreme pain" HAQ-DI: assessment of 8 daily living activities (dress/groom; arise; eat; walk; reach; grip; hygiene; common daily activities) on 4-point Likert scale: 0=no difficulty to 3=unable to do
Time Frame
Week 24
Title
Part B: Number of ACR20, ACR50, and ACR70 Responders at Week 24
Description
American College of Rheumatology (ACR) Responder Index is based on a set of evaluations: the Investigator Tender Joint Count/Number of Tender Joints (out of 68 Joints); Investigator Swollen Joint Count/Number of Swollen Joints (out of 66 Joints); Patient Global Assessment of Disease Activity (PGAD); Investigator Global Assessment of Disease Activity (IGAD); Patient Global Assessment of Pain (PGAP); Health Assessment Questionnaire Disability Index (HAQ-DI); and ESR. ACR response indicates percent change (ie, improvement) from baseline (20%, 50%, 70%) PGAD & IGAD: assessment of function on a 4-point Likert scale: 0=very well to 3=unable to do PGAP: pain due to arthritis measured on a 0-100 mm visual analog scale: Left hand marker-"no pain"; right hand marker-"extreme pain" HAQ-DI: assessment of 8 daily living activities (dress/groom; arise; eat; walk; reach; grip; hygiene; common daily activities) on 4-point Likert scale: 0=no difficulty to 3=unable to do
Time Frame
Week 24
Title
Change From Baseline in Disease Activity in 28 Joints C-Reactive Protein Score (DAS28-CRP) by Time-point
Description
The DAS28-CRP is a combination scoring method for function using the European League against Rheumatism (EULAR) 28 joint count and the CRP value. The DAS28-CRP scores range from 2.0 to 10.0 with higher values indicating a higher disease activity. A DAS28-CRP below the score of 2.6 is interpreted as Remission. CRP values below lower limit of quantification (LLQ) (<0.4 mg/dL) were set to 0.2 mg/dL in the calculation of DAS28-CRP.
Time Frame
Baseline, Week 6, Week 12
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Female participants of reproductive potential must demonstrate a serum β-human chorionic gonadotropin (hCG) level consistent with the nongravid state at the pre-study (screening) visit, and a negative urine pregnancy test within 24 hours prior to all doses 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/m^2 at the prestudy (screening) visit
For Part A Only: The participant has a body surface are (BSA) ≤2.0 m^2 at the prestudy (screening) visit.
Has satisfied at least 4 of 7 American Rheumatology Association (ARA) 1987 revised criteria for the diagnosis of RA
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, IM, or SC 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-tumor necrosis factor (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 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 of the cervix 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 IV outpatient treatment for systemic bacterial, viral or fungal infection, use of IV 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 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Merck Sharp & Dohme LLC
Official's Role
Study Director
12. IPD Sharing Statement
Learn more about this trial
A Study of the Pharmacokinetics and Safety of MK-8808 (MK-8808-002)
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