Rheumatoid ArthritisPhase 1NCT01390441
A Study of the Pharmacokinetics and Safety of MK-8808 (MK-8808-002)
A Phase 1 study testing MK-8808, MabThera® (rituximab) and Methotrexate in people with Rheumatoid Arthritis, run by Merck Sharp & Dohme LLC.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- MK-8808, MabThera® (rituximab) and Methotrexate
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- No sites listed yet
- Study dates
- Jul 2011to Apr 2014
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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)
Who cannot join
- 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)
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- 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
About this study
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)
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.
Read the 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.
- Conditions
- Rheumatoid Arthritis
- Being tested
- MK-8808, MabThera® (rituximab), Methotrexate, Rituxan® (rituximab), Methylprednisolone
- Keywords
- Rheumatoid arthritis, RA, Rituximab, Rituxan, MabThera, Methotrexate, Rheumatrex, Trexall, MK-8808
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MK-8808Biological
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
MabThera® (rituximab)Biological
Also called Rituxan®, Rituximab
MabThera® 500 mg/m^2 or 1000 mg administered by IV on Day 1 and Day 15
MethotrexateDrug
Also called Trexall®, Rheumatrex®
Methotrexate 10-25 mg administered orally, SC, or IM as a weekly stable dose
Rituxan® (rituximab)Biological
Also called Rituximab
Rituxan® 1000 mg administered by IV on Day 1 and Day 15
Methylprednisolone 100 mg administered IV before initiation of each infusion as pre-medication to reduce the incidence and severity of infusion reactions
AcetaminophenDrug
Also called Paracetamol
Acetaminophen 1000 to 1350 mg administered orally before initiation of each infusion as pre-medication to reduce the incidence and severity of infusion reactions
LoratadineDrug
Also called Claritin®
Loratidine 10 mg administered orally before initiation of each infusion as pre-medication to reduce the incidence and severity of infusion reactions
| Study group | Role | What they receive |
|---|---|---|
| Part A: MK-8808 500 mg/m^2 / Extension A: MK-8808 1000 mg | Experimental | 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. Receives: Biological: MK-8808; Drug: Methotrexate; Drug: Methylprednisolone; Drug: Acetaminophen; Drug: Loratadine |
| Part A: MabThera® 500 mg/m^2 / Extension A: MK-8808 1000 mg | Active comparator | 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. Receives: Biological: MK-8808; Biological: MabThera® (rituximab); Drug: Methotrexate; Drug: Methylprednisolone; Drug: Acetaminophen; Drug: Loratadine |
| Part B: MK-8808 1000 mg / Extension B: MK-8808 1000 mg | Experimental | 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. Receives: Biological: MK-8808; Drug: Methotrexate; Drug: Methylprednisolone; Drug: Acetaminophen; Drug: Loratadine |
| Part B: MabThera® 1000 mg / Extension B: MK-8808 1000 mg | Active comparator | 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. Receives: Biological: MK-8808; Biological: MabThera® (rituximab); Drug: Methotrexate; Drug: Methylprednisolone; Drug: Acetaminophen; Drug: Loratadine |
| Part B: Rituxan® 1000 mg / Extension B: MK-8808 1000 mg | Experimental | 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. Receives: Biological: MK-8808; Drug: Methotrexate; Biological: Rituxan® (rituximab); Drug: Methylprednisolone; Drug: Acetaminophen; Drug: Loratadine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
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.
Measured: 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
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.
Measured: Parts A and B: Up to 52 weeks; Extension A and B: Up to 106 weeks
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.
Measured: Parts A and B: Up to Week 28; Extension A and B: Up to 82 weeks
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.
Measured: Week 54, Week 68, Week 80, Week 94, Week 106
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.
Measured: Week 54, Week 56, Week 68, Week 80, Week 82, Week 94, Week 106
Secondary outcomes (2)
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.
Measured: Day 15
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.
Measured: Day 15
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jul 2011 (estimated)
- Study startJul 2011
- Primary completionApr 2014
- Study completionApr 2014
Why it stopped: The study was terminated early by the Sponsor for business reasons.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01390441
- Sponsor's protocol ID
- 8808-002
- Status last verified
- May 2016
- First submitted
- 7 Jul 2011
- Last updated
- 20 Jul 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Jul 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT01390441
- Acronym / sponsor ID
- 8808-002
- Conditions
- Rheumatoid Arthritis
- Keywords
- Rheumatoid arthritis, RA, Rituximab, Rituxan, MabThera, Methotrexate, Rheumatrex, Trexall
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was terminated early by the Sponsor for business reasons.
- Enrolment
- 100 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- Jul 2011
- Primary completion
- Apr 2014 (actual)
- Study completion
- Apr 2014 (actual)
- First posted
- 11 Jul 2011 (estimated)
- Results
- Posted 20 Jul 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Part A: MK-8808 500 mg/m^2 / Extension A: MK-8808 1000 mg | Experimental | Biological: MK-8808, Drug: Methotrexate, Drug: Methylprednisolone, Drug: Acetaminophen, Drug: LoratadineDuring 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. |
| Part A: MabThera® 500 mg/m^2 / Extension A: MK-8808 1000 mg | Active comparator | Biological: MK-8808, Biological: MabThera® (rituximab), Drug: Methotrexate, Drug: Methylprednisolone, Drug: Acetaminophen, Drug: LoratadineDuring 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. |
| Part B: MK-8808 1000 mg / Extension B: MK-8808 1000 mg | Experimental | Biological: MK-8808, Drug: Methotrexate, Drug: Methylprednisolone, Drug: Acetaminophen, Drug: LoratadineIn 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. |
| Part B: MabThera® 1000 mg / Extension B: MK-8808 1000 mg | Active comparator | Biological: MK-8808, Biological: MabThera® (rituximab), Drug: Methotrexate, Drug: Methylprednisolone, Drug: Acetaminophen, Drug: LoratadineIn 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. |
| Part B: Rituxan® 1000 mg / Extension B: MK-8808 1000 mg | Experimental | Biological: MK-8808, Drug: Methotrexate, Biological: Rituxan® (rituximab), Drug: Methylprednisolone, Drug: Acetaminophen, Drug: LoratadineIn 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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
Key exclusion criteria (20 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MK-8808MK-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 | Biological | 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 |
| MabThera® (rituximab)Also: Rituxan®, RituximabMabThera® 500 mg/m^2 or 1000 mg administered by IV on Day 1 and Day 15 | Biological | Part A: MabThera® 500 mg/m^2 / Extension A: MK-8808 1000 mg, Part B: MabThera® 1000 mg / Extension B: MK-8808 1000 mg |
| MethotrexateAlso: Trexall®, Rheumatrex®Methotrexate 10-25 mg administered orally, SC, or IM as a weekly stable dose | Drug | 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 |
| Rituxan® (rituximab)Also: RituximabRituxan® 1000 mg administered by IV on Day 1 and Day 15 | Biological | Part B: Rituxan® 1000 mg / Extension B: MK-8808 1000 mg |
| MethylprednisoloneMethylprednisolone 100 mg administered IV before initiation of each infusion as pre-medication to reduce the incidence and severity of infusion reactions | Drug | 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 |
| AcetaminophenAlso: ParacetamolAcetaminophen 1000 to 1350 mg administered orally before initiation of each infusion as pre-medication to reduce the incidence and severity of infusion reactions | Drug | 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 |
| LoratadineAlso: Claritin®Loratidine 10 mg administered orally before initiation of each infusion as pre-medication to reduce the incidence and severity of infusion reactions | Drug | 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 |
Primary outcome
Part A: Area Under the Concentration-time Curve From Day 0 to Day 84 (AUC0-84day) After a Single Course of Treatment
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
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
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
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
Time frame: Parts A and B: Up to 52 weeks; Extension A and B: Up to 106 weeks
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
Time frame: Parts A and B: Up to Week 28; Extension A and B: Up to 82 weeks
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
Time frame: Week 54, Week 68, Week 80, Week 94, Week 106
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
Time frame: Week 54, Week 56, Week 68, Week 80, Week 82, Week 94, Week 106
Serum ADA positivity is determined over course of therapy with MK-8808 in the Extension Study.
2 secondary outcomes
Part A: Maximum Concentration (Cmax) After the Second Infusion of a Single Course of Treatment
Time frame: Day 15
Part B: Cmax After the Second Infusion of a Single Course of Treatment
Time frame: Day 15
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jul 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Merck Sharp & Dohme LLC
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing MK-8808, MabThera® (rituximab) and Methotrexate in people with Rheumatoid Arthritis, run by Merck Sharp & Dohme LLC.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 20 Jul 2016. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Jul 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Part A: Area Under the Concentration-time Curve From Day 0 to Day 84 (AUC0-84day) After a Single Course of Treatment (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). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jul 2016.