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TerminatedNCT01390441Updated Jul 20, 2016Results posted

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

A Phase 1 interventional study of MK-8808 and MabThera® (rituximab) in Rheumatoid Arthritis, sponsored by Merck Sharp & Dohme LLC. Terminated. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2016-07-20.

Sponsored by Merck Sharp & Dohme LLC · Phase 1, Interventional, and Treatment

Why this study was terminated
The study was terminated early by the Sponsor for business reasons.
Phase
Phase 1
Study type
Interventional
Enrollment
100
Allocation
Randomized
Ages
18 Years to 65 Years
Sex
All
01

Study 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 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.

02

Conditions studied

  • Rheumatoid Arthritis

Keywords

  • Rheumatoid arthritis
  • RA
  • Rituximab
  • Rituxan
  • MabThera
  • Methotrexate
  • Rheumatrex
  • Trexall
  • MK-8808
03

In context

Arthritis

3,554 studies on the registry are indexed under Arthritis; 317 are open to participants now.

This study's enrollment of 100 is above the median of 90 across 2,377 interventional studies indexed under Arthritis.

Browse Arthritis studies →

Lead sponsor

Merck Sharp & Dohme LLC is the lead sponsor of 2,114 studies on the registry; 133 are open to participants now.

Of its 489 completed or terminated interventional studies of FDA-regulated products, 362 (74%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 65 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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
05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
100 participants (actual)

Study arms

  • Experimental
    Part A: MK-8808 500 mg/m^2 / Extension A: MK-8808 1000 mg

    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.

    Biological: MK-8808 · Drug: Methotrexate · Drug: Methylprednisolone · Drug: Acetaminophen · Drug: Loratadine

  • Active comparator
    Part A: MabThera® 500 mg/m^2 / Extension A: MK-8808 1000 mg

    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.

    Biological: MK-8808 · Biological: MabThera® (rituximab) · Drug: Methotrexate · Drug: Methylprednisolone · Drug: Acetaminophen · Drug: Loratadine

  • Experimental
    Part B: MK-8808 1000 mg / Extension B: MK-8808 1000 mg

    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.

    Biological: MK-8808 · Drug: Methotrexate · Drug: Methylprednisolone · Drug: Acetaminophen · Drug: Loratadine

  • Active comparator
    Part B: MabThera® 1000 mg / Extension B: MK-8808 1000 mg

    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.

    Biological: MK-8808 · Biological: MabThera® (rituximab) · Drug: Methotrexate · Drug: Methylprednisolone · Drug: Acetaminophen · Drug: Loratadine

  • Experimental
    Part B: Rituxan® 1000 mg / Extension B: MK-8808 1000 mg

    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.

    Biological: MK-8808 · Drug: Methotrexate · Biological: Rituxan® (rituximab) · Drug: Methylprednisolone · Drug: Acetaminophen · Drug: Loratadine

Interventions

  • BiologicalMK-8808

    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

  • BiologicalMabThera® (rituximab)

    MabThera® 500 mg/m\^2 or 1000 mg administered by IV on Day 1 and Day 15

    Also known as: Rituxan®, Rituximab

  • DrugMethotrexate

    Methotrexate 10-25 mg administered orally, SC, or IM as a weekly stable dose

    Also known as: Trexall®, Rheumatrex®

  • BiologicalRituxan® (rituximab)

    Rituxan® 1000 mg administered by IV on Day 1 and Day 15

    Also known as: Rituximab

  • DrugMethylprednisolone

    Methylprednisolone 100 mg administered IV before initiation of each infusion as pre-medication to reduce the incidence and severity of infusion reactions

  • DrugAcetaminophen

    Acetaminophen 1000 to 1350 mg administered orally before initiation of each infusion as pre-medication to reduce the incidence and severity of infusion reactions

    Also known as: Paracetamol

  • DrugLoratadine

    Loratidine 10 mg administered orally before initiation of each infusion as pre-medication to reduce the incidence and severity of infusion reactions

    Also known as: Claritin®

06

What researchers measure

Primary outcomes

  1. 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.

    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

  2. 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.

    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

  3. 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.

    Time frame: Parts A and B: Up to 52 weeks; Extension A and B: Up to 106 weeks

  4. 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.

    Time frame: Parts A and B: Up to Week 28; Extension A and B: Up to 82 weeks

  5. 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.

    Time frame: Week 54, Week 68, Week 80, Week 94, Week 106

  6. 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.

    Time frame: Week 54, Week 56, Week 68, Week 80, Week 82, Week 94, Week 106

Secondary outcomes

  1. 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.

    Time frame: Day 15

  2. 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.

    Time frame: Day 15

Other outcomes

  1. Part A: Number of ACR20, ACR50, and ACR70 Responders at Week 24

    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

  2. Part B: Number of ACR20, ACR50, and ACR70 Responders at Week 24

    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

  3. Change From Baseline in Disease Activity in 28 Joints C-Reactive Protein Score (DAS28-CRP) by Time-point

    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

07

Results

Posted Jul 20, 2016

Participant flow

The study enrolled participants 18 to 65 years of age with a diagnosis of moderate/severe rheumatoid arthritis (RA), naive to treatment or having failed \>=1 anti-TNF agent, and on a stable dose of methotrexate. Not all participants completing the Treatment Period entered the Extension Period due to study early termination.

Treatment Period
Participant flow — Treatment Period
MilestonePart A: MK-8808 500 mg/m^2 / Extension A: MK-8808 1000 mgPart A: MabThera® 500 mg/m^2 / Extension A: MK-8808 1000 mgPart B: MK-8808 1000 mg / Extension B: MK-8808 1000 mgPart B: MabThera® 1000 mg / Extension B: MK-8808 1000 mgPart B: Rituxan® 1000 mg / Extension B: MK-8808 1000 mg
Started2322181918
Completed2221867
Not completed11101311
Withdrew: Protocol violation01000
Withdrew: Physician decision00010
Withdrew: Lack of efficacy00001
Withdrew: Unknown due to early stopping of study008117
Withdrew: Adverse event00112
Withdrew: Withdrawal by subject00101
Withdrew: Lost to follow-up10000
Extension Period
Participant flow — Extension Period
MilestonePart A: MK-8808 500 mg/m^2 / Extension A: MK-8808 1000 mgPart A: MabThera® 500 mg/m^2 / Extension A: MK-8808 1000 mgPart B: MK-8808 1000 mg / Extension B: MK-8808 1000 mgPart B: MabThera® 1000 mg / Extension B: MK-8808 1000 mgPart B: Rituxan® 1000 mg / Extension B: MK-8808 1000 mg
Started1513113
Completed1212103
Not completed31010
Withdrew: Protocol violation31010

Outcome measures

PrimaryPart 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.

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
Reported as:
Geometric mean · hr*mg/mL
Part A: Area Under the Concentration-time Curve From Day 0 to Day 84 (AUC0-84day) After a Single Course of Treatment
hr*mg/mLPart A: MK-8808 500 mg/m^2Part A: MabThera® 500 mg/m^2
Part A: Area Under the Concentration-time Curve From Day 0 to Day 84 (AUC0-84day) After a Single Course of Treatment110.56 (94.51 to 129.32)110.12 (91.97 to 131.84)
Statistical analysis
  • Part A: MK-8808 500 mg/m^2 vs Part A: MabThera® 500 mg/m^2 · ANOVA · Geometric mean ratio: 1.00 · 90% CI 0.87 to 1.16
PrimaryPart 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.

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

No measurements were reported for this outcome.

PrimaryNumber 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.

Time frame:
Parts A and B: Up to 52 weeks; Extension A and B: Up to 106 weeks
Reported as:
Number · Participants
Number of Participants Who Experienced at Least One Adverse Event
ParticipantsPart A: MK-8808 500 mg/m^2Part A: MabThera 500 mg/m^2Part B: MK-8808 1000 mgPart B: MabThera 1000 mgPart B: Rituxan 1000 mgExtension A: MK-8808 500 mg/m^2 /MK-8808 1000 mgExtension A: MabThera 500 mg/m^2 /MK-8808 1000 mgExtension B: MK-8808 1000 mg /MK-8808 1000 mgExtension B: MabThera 1000 mg /MK-8808 1000 mgExtension B: Rituxan1000 mg/MK-8808 1000 mg
Number of Participants Who Experienced at Least One Adverse Event182112161322000
Statistical analysis
  • Part A: MK-8808 500 mg/m^2 vs Part A: MabThera 500 mg/m^2 · Miettinen-Nurminen · Percent difference: -17.2 · 95% CI -38.6 to 3.6
  • Part B: MK-8808 1000 mg vs Part B: MabThera 1000 mg · Miettinen-Nurminen · Percent difference: -17.5 · 95% CI -44.4 to 10.9
  • Part B: MK-8808 1000 mg vs Part B: Rituxan 1000 mg · Miettinen-Nurminen · Percent difference: -5.6 · 95% CI -34.9 to 24.6
  • Part B: MabThera 1000 mg vs Part B: Rituxan 1000 mg · Miettinen-Nurminen · Percent differnce: 12.0 · 95% CI -15.6 to 38.9
PrimaryNumber 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.

Time frame:
Parts A and B: Up to Week 28; Extension A and B: Up to 82 weeks
Reported as:
Number · Participants
Number of Participants Who Discontinued Study Drug Due to Adverse Events
ParticipantsPart A: MK-8808 500 mg/m^2Part A: MabThera® 500 mg/m^2Part B: MK-8808 1000 mgPart B: MabThera® 1000 mgPart B: Rituxan® 1000 mgExtension A: MK-8808 500 mg/m^2 /MK-8808 1000 mgExtension A: MabThera® 500 mg/m^2 /MK-8808 1000 mgExtension B: MK-8808 1000 mg /MK-8808 1000 mgExtension B: MabThera® 1000 mg /MK-8808 1000 mgExtension B: Rituxan® 1000 mg/MK-8808 1000 mg
Number of Participants Who Discontinued Study Drug Due to Adverse Events2211200000
SecondaryPart 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.

Time frame:
Day 15
Reported as:
Geometric mean · ng/mL
Part A: Maximum Concentration (Cmax) After the Second Infusion of a Single Course of Treatment
ng/mLPart A: MK-8808 500 mg/m^2Part A: MabThera® 500 mg/m^2
Part A: Maximum Concentration (Cmax) After the Second Infusion of a Single Course of Treatment326.49 (287.72 to 370.49)332.39 (287.48 to 384.31)
Statistical analysis
  • Part A: MK-8808 500 mg/m^2 vs Part A: MabThera® 500 mg/m^2 · ANOVA · Geometric mean ratio: 0.98 · 90% CI 0.87 to 1.1
SecondaryPart 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.

Time frame:
Day 15

No measurements were reported for this outcome.

Other pre-specifiedPart A: Number of ACR20, ACR50, and ACR70 Responders at Week 24

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
Reported as:
Number · Participants
Part A: Number of ACR20, ACR50, and ACR70 Responders at Week 24
ParticipantsPart A: MK-8808 500 mg/m^2Part A: MabThera® 500 mg/m^2
ACR202320
ACR501615
ACR7044
Other pre-specifiedPart B: Number of ACR20, ACR50, and ACR70 Responders at Week 24

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
Reported as:
Number · Participants
Part B: Number of ACR20, ACR50, and ACR70 Responders at Week 24
ParticipantsPart B: MK-8808 1000 mgPart B: MabThera® 1000 mgPart B: Rituxan® 1000 mg
ACR20161715
ACR50121213
ACR70211
Other pre-specifiedChange From Baseline in Disease Activity in 28 Joints C-Reactive Protein Score (DAS28-CRP) by Time-point

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
Reported as:
Mean · Score
Change From Baseline in Disease Activity in 28 Joints C-Reactive Protein Score (DAS28-CRP) by Time-point
ScorePart A: MK-8808 500 mg/m^2Part A: MabThera® 500 mg/m^2
Week 6 (n=22, n=20)-1.39 ± 1.02-1.16 ± 1.26
Week 12 (n=21, n=21)-1.68 ± 1.12-2.04 ± 1.39
Statistical analysis
  • Part A: MK-8808 500 mg/m^2 vs Part A: MabThera® 500 mg/m^2 · ANCOVA · Mean difference (final values): -0.2 · 95% CI -0.9 to 0.5The model included a term for treatment.
  • Part A: MK-8808 500 mg/m^2 vs Part A: MabThera® 500 mg/m^2 · ANCOVA · Mean difference (final values): 0.4 · 95% CI -0.4 to 1.2The model included a term for treatment.
PrimaryNumber 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.

Time frame:
Week 54, Week 68, Week 80, Week 94, Week 106

No measurements were reported for this outcome.

PrimaryNumber 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.

Time frame:
Week 54, Week 56, Week 68, Week 80, Week 82, Week 94, Week 106

No measurements were reported for this outcome.

Adverse events

Collected over Parts A and B: Up to 52 weeks; Extension A and B: Up to 106 weeks. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Part A: MK-8808 500 mg/m^2—1/23 (4.3%)15/23 (65.2%)
Part A: MabThera 500 mg/m^2—1/22 (4.5%)17/22 (77.3%)
Part B: MK-8808 1000 mg—2/18 (11.1%)11/18 (61.1%)
Part B: MabThera 1000 mg—0/19 (0%)16/19 (84.2%)
Part B: Rituxan 1000 mg—0/18 (0%)13/18 (72.2%)
Extension A: MK-8808 500 mg/m^2 /MK-8808 1000 mg—0/15 (0%)2/15 (13.3%)
Extension A: MabThera® 500 mg/m^2 /MK-8808 1000 mg—0/13 (0%)2/13 (15.4%)
Extension B: MK-8808 1000 mg /MK-8808 1000 mg—0/1 (0%)0/1 (0%)
Extension B: MabThera® 1000 mg /MK-8808 1000 mg—0/1 (0%)0/1 (0%)
Extension B: Rituxan® 1000 mg/MK-8808 1000 mg—0/3 (0%)0/3 (0%)
Most frequent serious events
Most frequent serious events
EventPart A: MK-8808 500 mg/m^2Part A: MabThera 500 mg/m^2Part B: MK-8808 1000 mgPart B: MabThera 1000 mgPart B: Rituxan 1000 mgExtension A: MK-8808 500 mg/m^2 /MK-8808 1000 mgExtension A: MabThera® 500 mg/m^2 /MK-8808 1000 mgExtension B: MK-8808 1000 mg /MK-8808 1000 mgExtension B: MabThera® 1000 mg /MK-8808 1000 mgExtension B: Rituxan® 1000 mg/MK-8808 1000 mg
LeukopeniaBlood and lymphatic system disorders0/230/221/180/190/180/150/130/10/10/3
Lower limb fractureInjury, poisoning and procedural complications0/230/221/180/190/180/150/130/10/10/3
Spinal column stenosisMusculoskeletal and connective tissue disorders0/231/220/180/190/180/150/130/10/10/3
PneumoniaInfections and infestations1/230/220/180/190/180/150/130/10/10/3
Most frequent other events
Showing 10 of 72
Most frequent other events
EventPart A: MK-8808 500 mg/m^2Part A: MabThera 500 mg/m^2Part B: MK-8808 1000 mgPart B: MabThera 1000 mgPart B: Rituxan 1000 mgExtension A: MK-8808 500 mg/m^2 /MK-8808 1000 mgExtension A: MabThera® 500 mg/m^2 /MK-8808 1000 mgExtension B: MK-8808 1000 mg /MK-8808 1000 mgExtension B: MabThera® 1000 mg /MK-8808 1000 mgExtension B: Rituxan® 1000 mg/MK-8808 1000 mg
Throat irritationRespiratory, thoracic and mediastinal disorders3/231/220/184/190/180/150/130/10/10/3
InfluenzaInfections and infestations0/233/222/181/190/181/150/130/10/10/3
CoughRespiratory, thoracic and mediastinal disorders0/233/220/180/190/180/150/130/10/10/3
Hepatitis CInfections and infestations3/231/220/180/190/180/150/130/10/10/3
Infusion related reactionInjury, poisoning and procedural complications3/232/220/180/191/180/150/130/10/10/3
HeadacheNervous system disorders3/232/221/180/191/180/150/130/10/10/3
BronchitisInfections and infestations0/231/222/181/190/180/150/130/10/10/3
NasopharyngitisInfections and infestations1/230/220/181/192/180/150/130/10/10/3
Respiratory tract infectionInfections and infestations1/231/220/180/192/180/150/130/10/10/3
HypersensitivityImmune system disorders0/231/220/182/190/180/150/130/10/10/3

Baseline characteristics

Age, Continuous
Age, Continuous(years)Part A: MK-8808 500 mg/m^2Part A: MabThera® 500 mg/m^2Part B: MK-8808 1000 mgPart B: MabThera® 1000 mgPart B: Rituxan® 1000 mgTotal
Mean51.7 ± 6.751.5 ± 8.446.4 ± 10.948.7 ± 12.446.2 ± 10.549.1 ± 9.9
Sex: Female, Male
Sex: Female, Male(Participants)Part A: MK-8808 500 mg/m^2Part A: MabThera® 500 mg/m^2Part B: MK-8808 1000 mgPart B: MabThera® 1000 mgPart B: Rituxan® 1000 mgTotal
Female201914161584
Male3343316
08

Study locations

No study locations are listed for this record.

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jul 20, 2016, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT01390441
Lead sponsor
Merck Sharp & Dohme LLC
Responsible party
Sponsor
First posted
Jul 11, 2011
Start date
Jul 2011
Primary completion
Apr 2014
Completion
Apr 2014
Results posted
Jul 20, 2016
Last update
Jul 20, 2016

Study contacts

Medical Director
study director · Merck Sharp & Dohme LLC

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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