Ulcerative Colitis
Conditions
Brief summary
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and immunogenicity of MK-6194 in participants with active UC.
Interventions
DRUGMK-6194
Subcutaneous injection
DRUGMK-6194-matching placebo
Subcutaneous injection
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of UC at least 3 months prior to screening. * Mildly to severely active UC. * Inadequate response, loss of response, or intolerance to at least 1 prior conventional therapy, and no more than 2 prior advanced therapies. * Participants at risk for colorectal cancer must have a colonoscopy prior to or at screening as follows: * Participants \> 50 years of age must have documentation of a colonoscopy within 3 years of the screening visit to exclude adenomatous polyps. Participants whose adenomas have been completely excised at screening are eligible. * Participants with extensive colitis for ≥ 8 years, or disease limited to the left side of the colon for ≥ 10 years, must either have had a full colonoscopy to assess for the presence of dysplasia within 1 year before first administration of study drug or a full colonoscopy to assess for the presence of malignancy at the screening visit. * No evidence of active tuberculosis (TB), latent TB, or inadequately treated TB. * Women of childbearing potential (WOCBP) and males with female partners of childbearing potential must utilize highly effective contraceptive methods beginning 4 weeks prior to first dose of study drug and continue for 30 days after the last dose of study drug. * Body mass index (BMI) 18 to 35 kg/m\^2 inclusive and weight ≥ 50 kg.
Exclusion criteria
* Prior treatment with recombinant IL-2 or modified IL-2 therapy, including MK-6194 (PT101). * Known sensitivity to MK-6194 (PT101) or its excipients. * Known history of hypersensitivity to interleukin-2 (IL-2). * Disease limited to the rectum (i.e., within 15 cm of the anal verge). * Diagnosis of toxic megacolon. * Suspected or known colon stricture or stenosis. * Diagnosis of Crohn's disease, or indeterminant colitis. * Has severe colitis as evidenced by: * Current hospitalization for the treatment of UC * Likely to require a colectomy within 12 weeks of baseline in the opinion of the Investigator * At least 4 symptoms of severe colitis as identified at screening or baseline visits. * Previously had surgery for UC, or likely to require surgery for UC during the study period in the opinion of the Investigator. * History of abnormal thallium stress test or functional cardiac function test. * History of significant cardiac, pulmonary, renal, hepatic, or central nervous system (CNS) impairment. * Active clinically significant infection, or any infection requiring hospitalization or treatment with intravenous anti-infectives within 8 weeks of randomization, or any infection requiring oral anti-infective therapy within 6 weeks of randomization. * History of opportunistic infection. * History of symptomatic herpes zoster within 16 weeks of randomization, or any history of disseminated herpes simplex, disseminated herpes zoster, ophthalmic zoster, or central nervous system (CNS) zoster. * Currently on any chronic systemic (oral or IV) anti-infective therapy for chronic infection (such as pneumocystis, cytomegalovirus, herpes zoster, or atypical mycobacteria). * Currently receiving lymphocyte depleting therapy. * History of abnormal pulmonary function tests. * Participants with organ or tissue allograft. * Malignancy within 5 years of screening, with the exception of adequately treated or excised non-metastatic basal cell or squamous cell cancer of the skin. * Exposure to advanced therapy within 5 half-lives of the Day 1 visit, or documentation of detectable drug during screening. * Received a live attenuated vaccine \< 1 month prior to screening or is planning to receive a live attenuated vaccine during the study period or within 12 weeks of the end of participation in the study. * Is pregnant or nursing or is planning to become pregnant during the study. * Any uncontrolled or clinically significant concurrent systemic disease other than UC.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced an Adverse Event (AE) | Up to approximately 85 days | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. |
| Number of Participants Who Interrupted or Discontinued Study Treatment Due to an AE | Up to approximately 72 days | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to thestudy intervention |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Minimum Concentration (Cmin) of MK-6194 | Predose on all days of dosing; 12, 24-48, and 120 hours (as available) post dose on the first and last day of dosing; and once each week up to approximately day 85 | Blood samples were collected at pre-specified time points to determine the minimum concentration (Cmin) of MK-6194 present in each participant's serum. A participant's Cmin was defined as the minimum concentration of MK-6194 observed in serum over the entire course of the study for that individual and was calculated by taking the minimum over all observed MK-6194 serum concentrations. Geometric mean and geometric coefficient of variation of Cmin were calculated for each dosing group. |
| Apparent Half-life (t1/2) of MK-6194 | Final day of dosing at 12, 24-48 hours, and 120 hours (as available) post-dose; from the last day of dosing once each week up to approximately day 85 | Blood samples were collected at pre-specified time points to determine the apparent half-life (t1/2) of MK-6194. Noncompartmental analysis was used to calculate t1/2 for each participant using the terminal elimination phase after the final dose. Geometric mean and geometric coefficient of variation of t1/2 were calculated for each dosing group. |
| Apparent Clearance (CL/F) of MK-6194 | Final day of dosing at 12, 24-48 hours, and 120 hours (as available) post-dose; from the last day of dosing once each week up to approximately day 85 | Blood samples were collected at pre-specified time points to determine the apparent clearance (CL/F) of MK-6194 observed in serum. Noncompartmental analysis was used to calculate CL/F for each participant using the terminal elimination phase after the final dose. Geometric mean and geometric coefficient of variation of CL/F were calculated for each dosing group. |
| Apparent Volume of Distribution (Vd/F) of MK-6194 | Final day of dosing at 12, 24-48 hours, and 120 hours (as available) post-dose; from the last day of dosing once each week up to approximately day 85 | Blood samples were collected at pre-specified time points to determine the apparent volume of distribution (Vd/F) of MK-6194 observed in serum. Noncompartmental analysis was used to calculate Vd/F for each participant using the terminal elimination phase after the final dose. Geometric mean and geometric coefficient of variation of Vd/F were calculated for each dosing group. |
| Area Under the Concentration Time-curve From Time 0 to the Last Quantifiable Concentration (AUC0-t) | Predose on all days of dosing; 12, 24-48, and 120 hours (as available) post dose on the first and last day of dosing; and once each week up to approximately day 85 | Blood samples were collected at pre-specified timepoints to determine the AUC0-t of MK-6194. AUC0-t is defined as the area under the concentration-time curve from time=0 (Day 1 predose) to the last quantifiable concentration. Noncompartmental analysis was used to calculate AUC0-t for each participant. Geometric mean and geometric coefficient of variation of AUC0-t were calculated for each dosing group. |
| Maximum Concentration (Cmax) of MK-6194 | Predose on all days of dosing; 12, 24-48, and 120 hours (as available) post dose on the first and last day of dosing; and once each week up to approximately day 85. | Blood samples were collected at pre-specified time points to determine each participant's maximum concentration (Cmax). A participant's Cmax was defined as the maximum concentration of MK-6194 observed in serum over the entire course of the study for that individual and was calculated by taking the maximum over all observed MK-6194 serum concentrations. Geometric mean and geometric coefficient of variation of Cmax were calculated for each dosing group. |
| Change in Number of Peripheral Regulatory T-cells (Tregs) in Whole Blood | Pre-dose (baseline) and weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 | Blood samples were collected at pre-specified time points and analyzed by flow cytometry. The absolute change in the number of peripheral Tregs in whole blood was assessed. |
| Change in Number of Natural Killer (NK) Cells in Whole Blood | Pre-dose (baseline) and weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 | Blood samples were collected at pre-specified time points and analyzed by flow cytometry. The change in the number of NK cells in whole blood is presented. |
| Change in Number of Conventional T Cells (Tcons) in Whole Blood | Pre-dose (baseline) and weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 | Blood samples were collected at pre-specified time points and analyzed by flow cytometry. The change in the number of Tcons in whole blood is presented. |
| Titer of Anti-drug Antibody (ADA) to MK-6194 | Pre dose (week 0) and Weeks 4, 8, 12 | Blood samples were collected for the determination of ADA to MK-6194 using a screening assay, ADA titer using a confirmatory assay, and neutralizing antibody to MK-6194 in participants with confirmed positive titers |
| Area Under the Curve From Time 0 to Infinity (AUC0-inf) of MK-6194 | Predose on all days of dosing; 12, 24-48, and 120 hours (as available) post dose on the first and last day of dosing; and once each week up to approximately day 85 | Blood samples were collected at pre-specified timepoints to determine the AUC0-inf of MK-6194. AUC0-inf is defined as the area under the concentration-time curve from time=0 (Day 1 predose) to time=infinity. Noncompartmental analysis was used to calculate AUC0-inf for each participant; the portion of the AUC following the last observed concentration was assumed to follow an exponential elimination. Geometric mean and geometric coefficient of variation of AUC0-inf were calculated for each dosing group. |
| Time to Cmax (Tmax) of MK-6194 | Predose on all days of dosing; 12, 24-48, and 120 hours (as available) post dose on the first and last day of dosing; and once each week up to approximately day 85 | Blood samples were collected at pre-specified time points to determine maximum concentration (Cmax) of MK-6194 in each participant's serum and corresponding time of maximum concentration (Tmax). A participant's Tmax was defined as the time post-dose that the maximum concentration of MK-6194 was observed in serum. The median and range of Tmax were calculated for each dosing group. |
Countries
Georgia, Germany, Hungary, Moldova, Poland, Ukraine, United Kingdom, United States
Participant flow
Recruitment details
Upon concluding the Initial Blinded Treatment (IBT) phase, participants could either complete the study or enter one of the next 2 phases. Participants who achieved clinical response could enter the continued blinded treatment (CBT) phase and continue receiving the same treatment as the IBT phase. Participants who did not achieve clinical response could enter an open label (OL) phase and receive MK-6194 at the same dose/regimen of their IBT cohort for active MK-6194 treatment.
Participants by arm
| Arm | Count |
|---|---|
| MK-6194 Low Dose - Interval 1 (Less Frequent) Participants received low dose of MK-6194 at specified less frequent intervals | 7 |
| MK-6194 Medium Dose- Interval 2 (More Frequent) Participants received medium dose of MK-6194 at specified more frequent intervals | 11 |
| MK-6194 High Dose - Interval 2 (More Frequent) Participants received high dose of MK-6194 at specified more frequent intervals | 18 |
| MK-6194 High Dose - Interval 1 (Less Frequent) Participants received high dose MK-6194 at specified less frequent intervals | 10 |
| Placebo Participants received MK-6194-matching placebo via subcutaneous injection, administered either at interval 1 or interval 2 | 11 |
| Total | 57 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 2 | 2 | 0 | 2 |
Baseline characteristics
| Characteristic | Placebo | Total | MK-6194 Low Dose - Interval 1 (Less Frequent) | MK-6194 Medium Dose- Interval 2 (More Frequent) | MK-6194 High Dose - Interval 2 (More Frequent) | MK-6194 High Dose - Interval 1 (Less Frequent) |
|---|---|---|---|---|---|---|
| Age, Continuous | 35.6 Years STANDARD_DEVIATION 11.85 | 43.2 Years STANDARD_DEVIATION 12.31 | 43.4 Years STANDARD_DEVIATION 11.59 | 43.4 Years STANDARD_DEVIATION 14.64 | 47.7 Years STANDARD_DEVIATION 11.43 | 43.3 Years STANDARD_DEVIATION 10.11 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 5 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants | 51 Participants | 5 Participants | 11 Participants | 18 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 10 Participants | 55 Participants | 7 Participants | 10 Participants | 18 Participants | 10 Participants |
| Sex: Female, Male Female | 5 Participants | 24 Participants | 4 Participants | 5 Participants | 7 Participants | 3 Participants |
| Sex: Female, Male Male | 6 Participants | 33 Participants | 3 Participants | 6 Participants | 11 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 11 | 0 / 18 | 0 / 10 | 0 / 11 | 0 / 2 | 0 / 1 | 0 / 2 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 4 | 0 / 4 |
| other Total, other adverse events | 7 / 7 | 10 / 11 | 18 / 18 | 10 / 10 | 7 / 11 | 2 / 2 | 1 / 1 | 2 / 2 | 2 / 3 | 1 / 3 | 1 / 3 | 3 / 4 | 3 / 4 |
| serious Total, serious adverse events | 1 / 7 | 0 / 11 | 1 / 18 | 0 / 10 | 0 / 11 | 0 / 2 | 0 / 1 | 0 / 2 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 4 | 0 / 4 |
Outcome results
Primary
Number of Participants Who Experienced an Adverse Event (AE)
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
Time frame: Up to approximately 85 days
Population: All participants who received at least one dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MK-6194 Low Dose - Interval 1 (Less Frequent) | Number of Participants Who Experienced an Adverse Event (AE) | 7 Participants |
| MK-6194 Medium Dose- Interval 2 (More Frequent) | Number of Participants Who Experienced an Adverse Event (AE) | 10 Participants |
| MK-6194 High Dose - Interval 2 (More Frequent) | Number of Participants Who Experienced an Adverse Event (AE) | 18 Participants |
| MK-6194 High Dose - Interval 1 (Less Frequent) | Number of Participants Who Experienced an Adverse Event (AE) | 10 Participants |
| Placebo | Number of Participants Who Experienced an Adverse Event (AE) | 7 Participants |
Primary
Number of Participants Who Interrupted or Discontinued Study Treatment Due to an AE
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to thestudy intervention
Time frame: Up to approximately 72 days
Population: All participants who received at least one dose of study drug
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MK-6194 Low Dose - Interval 1 (Less Frequent) | Number of Participants Who Interrupted or Discontinued Study Treatment Due to an AE | 1 Participants |
| MK-6194 Medium Dose- Interval 2 (More Frequent) | Number of Participants Who Interrupted or Discontinued Study Treatment Due to an AE | 0 Participants |
| MK-6194 High Dose - Interval 2 (More Frequent) | Number of Participants Who Interrupted or Discontinued Study Treatment Due to an AE | 2 Participants |
| MK-6194 High Dose - Interval 1 (Less Frequent) | Number of Participants Who Interrupted or Discontinued Study Treatment Due to an AE | 0 Participants |
| Placebo | Number of Participants Who Interrupted or Discontinued Study Treatment Due to an AE | 1 Participants |
Secondary
Apparent Clearance (CL/F) of MK-6194
Blood samples were collected at pre-specified time points to determine the apparent clearance (CL/F) of MK-6194 observed in serum. Noncompartmental analysis was used to calculate CL/F for each participant using the terminal elimination phase after the final dose. Geometric mean and geometric coefficient of variation of CL/F were calculated for each dosing group.
Time frame: Final day of dosing at 12, 24-48 hours, and 120 hours (as available) post-dose; from the last day of dosing once each week up to approximately day 85
Population: All randomized participants who received at least 1 dose of study intervention and who had least 1 valid analytical result at baseline, at least 1 post-dose analytical result and had no major relevant protocol or dosing deviations that could potentially affect the PK profile. Per protocol, samples from participants receiving placebo were not analyzed for PK values.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| MK-6194 Low Dose - Interval 1 (Less Frequent) | Apparent Clearance (CL/F) of MK-6194 | 0.00 L/hours | Geometric Coefficient of Variation 66.28 |
| MK-6194 Medium Dose- Interval 2 (More Frequent) | Apparent Clearance (CL/F) of MK-6194 | 0.01 L/hours | Geometric Coefficient of Variation 82.72 |
| MK-6194 High Dose - Interval 2 (More Frequent) | Apparent Clearance (CL/F) of MK-6194 | 0.01 L/hours | Geometric Coefficient of Variation 95.07 |
| MK-6194 High Dose - Interval 1 (Less Frequent) | Apparent Clearance (CL/F) of MK-6194 | 0.01 L/hours | Geometric Coefficient of Variation 78.7 |
Secondary
Apparent Half-life (t1/2) of MK-6194
Blood samples were collected at pre-specified time points to determine the apparent half-life (t1/2) of MK-6194. Noncompartmental analysis was used to calculate t1/2 for each participant using the terminal elimination phase after the final dose. Geometric mean and geometric coefficient of variation of t1/2 were calculated for each dosing group.
Time frame: Final day of dosing at 12, 24-48 hours, and 120 hours (as available) post-dose; from the last day of dosing once each week up to approximately day 85
Population: All randomized participants who received at least 1 dose of study intervention and who had least 1 valid analytical result at baseline, at least 1 post-dose analytical result and had no major relevant protocol or dosing deviations that could potentially affect the PK profile. Per protocol, samples from participants receiving placebo were not analyzed for PK values.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| MK-6194 Low Dose - Interval 1 (Less Frequent) | Apparent Half-life (t1/2) of MK-6194 | 193.28 hours | Geometric Coefficient of Variation 66.51 |
| MK-6194 Medium Dose- Interval 2 (More Frequent) | Apparent Half-life (t1/2) of MK-6194 | 52.84 hours | Geometric Coefficient of Variation 23.89 |
| MK-6194 High Dose - Interval 2 (More Frequent) | Apparent Half-life (t1/2) of MK-6194 | 42.06 hours | Geometric Coefficient of Variation 80.41 |
| MK-6194 High Dose - Interval 1 (Less Frequent) | Apparent Half-life (t1/2) of MK-6194 | 96.09 hours | Geometric Coefficient of Variation 16.51 |
Secondary
Apparent Volume of Distribution (Vd/F) of MK-6194
Blood samples were collected at pre-specified time points to determine the apparent volume of distribution (Vd/F) of MK-6194 observed in serum. Noncompartmental analysis was used to calculate Vd/F for each participant using the terminal elimination phase after the final dose. Geometric mean and geometric coefficient of variation of Vd/F were calculated for each dosing group.
Time frame: Final day of dosing at 12, 24-48 hours, and 120 hours (as available) post-dose; from the last day of dosing once each week up to approximately day 85
Population: All randomized participants who received at least 1 dose of study intervention and who had least 1 valid analytical result at baseline, at least 1 post-dose analytical result and had no major relevant protocol or dosing deviations that could potentially affect the PK profile. Per protocol, samples from participants who received placebo were not analyzed for PK values.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| MK-6194 Low Dose - Interval 1 (Less Frequent) | Apparent Volume of Distribution (Vd/F) of MK-6194 | 1.61 Liters | Geometric Coefficient of Variation 121.12 |
| MK-6194 Medium Dose- Interval 2 (More Frequent) | Apparent Volume of Distribution (Vd/F) of MK-6194 | 0.82 Liters | Geometric Coefficient of Variation 96.99 |
| MK-6194 High Dose - Interval 2 (More Frequent) | Apparent Volume of Distribution (Vd/F) of MK-6194 | 0.55 Liters | Geometric Coefficient of Variation 226.96 |
| MK-6194 High Dose - Interval 1 (Less Frequent) | Apparent Volume of Distribution (Vd/F) of MK-6194 | 0.81 Liters | Geometric Coefficient of Variation 93.17 |
Secondary
Area Under the Concentration Time-curve From Time 0 to the Last Quantifiable Concentration (AUC0-t)
Blood samples were collected at pre-specified timepoints to determine the AUC0-t of MK-6194. AUC0-t is defined as the area under the concentration-time curve from time=0 (Day 1 predose) to the last quantifiable concentration. Noncompartmental analysis was used to calculate AUC0-t for each participant. Geometric mean and geometric coefficient of variation of AUC0-t were calculated for each dosing group.
Time frame: Predose on all days of dosing; 12, 24-48, and 120 hours (as available) post dose on the first and last day of dosing; and once each week up to approximately day 85
Population: All randomized participants who received at least 1 dose of study intervention and who had least 1 valid analytical result at baseline, at least 1 post-dose analytical result and had no major relevant protocol or dosing deviations that could potentially affect the PK profile. Per protocol, samples from participants who received placebo were not analyzed for PK values.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| MK-6194 Low Dose - Interval 1 (Less Frequent) | Area Under the Concentration Time-curve From Time 0 to the Last Quantifiable Concentration (AUC0-t) | 955.51 ng*hour/mL | Geometric Coefficient of Variation 39.92 |
| MK-6194 Medium Dose- Interval 2 (More Frequent) | Area Under the Concentration Time-curve From Time 0 to the Last Quantifiable Concentration (AUC0-t) | 2080.46 ng*hour/mL | Geometric Coefficient of Variation 55.64 |
| MK-6194 High Dose - Interval 2 (More Frequent) | Area Under the Concentration Time-curve From Time 0 to the Last Quantifiable Concentration (AUC0-t) | 3546.54 ng*hour/mL | Geometric Coefficient of Variation 67.17 |
| MK-6194 High Dose - Interval 1 (Less Frequent) | Area Under the Concentration Time-curve From Time 0 to the Last Quantifiable Concentration (AUC0-t) | 3203.50 ng*hour/mL | Geometric Coefficient of Variation 117.92 |
Secondary
Area Under the Curve From Time 0 to Infinity (AUC0-inf) of MK-6194
Blood samples were collected at pre-specified timepoints to determine the AUC0-inf of MK-6194. AUC0-inf is defined as the area under the concentration-time curve from time=0 (Day 1 predose) to time=infinity. Noncompartmental analysis was used to calculate AUC0-inf for each participant; the portion of the AUC following the last observed concentration was assumed to follow an exponential elimination. Geometric mean and geometric coefficient of variation of AUC0-inf were calculated for each dosing group.
Time frame: Predose on all days of dosing; 12, 24-48, and 120 hours (as available) post dose on the first and last day of dosing; and once each week up to approximately day 85
Population: All randomized participants who received at least 1 dose of study intervention and who had least 1 valid analytical result at baseline, at least 1 post-dose analytical result and had no major relevant protocol or dosing deviations that could potentially affect the PK profile. Per protocol, samples from participants who received placebo were not analyzed for PK values.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| MK-6194 Low Dose - Interval 1 (Less Frequent) | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of MK-6194 | 899.08 ng*hour/mL | Geometric Coefficient of Variation 36.53 |
| MK-6194 Medium Dose- Interval 2 (More Frequent) | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of MK-6194 | 2036.51 ng*hour/mL | Geometric Coefficient of Variation 71.46 |
| MK-6194 High Dose - Interval 2 (More Frequent) | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of MK-6194 | 3437.33 ng*hour/mL | Geometric Coefficient of Variation 65.59 |
| MK-6194 High Dose - Interval 1 (Less Frequent) | Area Under the Curve From Time 0 to Infinity (AUC0-inf) of MK-6194 | 3169.11 ng*hour/mL | Geometric Coefficient of Variation 120.37 |
Secondary
Change in Number of Conventional T Cells (Tcons) in Whole Blood
Blood samples were collected at pre-specified time points and analyzed by flow cytometry. The change in the number of Tcons in whole blood is presented.
Time frame: Pre-dose (baseline) and weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12
Population: All randomized participants who received at least 1 dose of study intervention and who had least 1 valid analytical result at baseline, at least 1 post-dose analytical result and had no major relevant protocol or dosing deviations that could potentially affect the pharmacodynamic profile
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| MK-6194 Low Dose - Interval 1 (Less Frequent) | Change in Number of Conventional T Cells (Tcons) in Whole Blood | Week 2 | 106.1 Cells/uL | Geometric Coefficient of Variation 124.15 |
| MK-6194 Low Dose - Interval 1 (Less Frequent) | Change in Number of Conventional T Cells (Tcons) in Whole Blood | Week 10 | 271.1 Cells/uL | Geometric Coefficient of Variation 81.5 |
| MK-6194 Low Dose - Interval 1 (Less Frequent) | Change in Number of Conventional T Cells (Tcons) in Whole Blood | Week 6 | 114.3 Cells/uL | Geometric Coefficient of Variation 119.18 |
| MK-6194 Low Dose - Interval 1 (Less Frequent) | Change in Number of Conventional T Cells (Tcons) in Whole Blood | Week 9 | 250.3 Cells/uL | Geometric Coefficient of Variation 39.38 |
| MK-6194 Low Dose - Interval 1 (Less Frequent) | Change in Number of Conventional T Cells (Tcons) in Whole Blood | Week 5 | 456.3 Cells/uL | Geometric Coefficient of Variation 28.23 |
| MK-6194 Low Dose - Interval 1 (Less Frequent) | Change in Number of Conventional T Cells (Tcons) in Whole Blood | Week 4 | 280.2 Cells/uL | Geometric Coefficient of Variation 116.12 |
| MK-6194 Low Dose - Interval 1 (Less Frequent) | Change in Number of Conventional T Cells (Tcons) in Whole Blood | Week 8 | 381.1 Cells/uL | Geometric Coefficient of Variation 34.64 |
| MK-6194 Low Dose - Interval 1 (Less Frequent) | Change in Number of Conventional T Cells (Tcons) in Whole Blood | Week 1 | 216.9 Cells/uL | Geometric Coefficient of Variation 94.52 |
| MK-6194 Low Dose - Interval 1 (Less Frequent) | Change in Number of Conventional T Cells (Tcons) in Whole Blood | Week 7 | 137.7 Cells/uL | Geometric Coefficient of Variation 84.27 |
| MK-6194 Low Dose - Interval 1 (Less Frequent) | Change in Number of Conventional T Cells (Tcons) in Whole Blood | Week 3 | 347.3 Cells/uL | Geometric Coefficient of Variation 129.76 |
| MK-6194 Low Dose - Interval 1 (Less Frequent) | Change in Number of Conventional T Cells (Tcons) in Whole Blood | Week 12 | 122.6 Cells/uL | Geometric Coefficient of Variation 134.2 |
| MK-6194 Medium Dose- Interval 2 (More Frequent) | Change in Number of Conventional T Cells (Tcons) in Whole Blood | Week 10 | 33.4 Cells/uL | Geometric Coefficient of Variation 115.44 |
| MK-6194 Medium Dose- Interval 2 (More Frequent) | Change in Number of Conventional T Cells (Tcons) in Whole Blood | Week 8 | 109.0 Cells/uL | Geometric Coefficient of Variation 84.28 |
| MK-6194 Medium Dose- Interval 2 (More Frequent) | Change in Number of Conventional T Cells (Tcons) in Whole Blood | Week 1 | 220.8 Cells/uL | Geometric Coefficient of Variation 94.37 |
| MK-6194 Medium Dose- Interval 2 (More Frequent) | Change in Number of Conventional T Cells (Tcons) in Whole Blood | Week 9 | 164.1 Cells/uL | Geometric Coefficient of Variation 51.01 |
| MK-6194 Medium Dose- Interval 2 (More Frequent) | Change in Number of Conventional T Cells (Tcons) in Whole Blood | Week 2 | 100.8 Cells/uL | Geometric Coefficient of Variation 67.5 |
| MK-6194 Medium Dose- Interval 2 (More Frequent) | Change in Number of Conventional T Cells (Tcons) in Whole Blood | Week 3 | 81.1 Cells/uL | Geometric Coefficient of Variation 98.95 |
| MK-6194 Medium Dose- Interval 2 (More Frequent) | Change in Number of Conventional T Cells (Tcons) in Whole Blood | Week 4 | 122.4 Cells/uL | Geometric Coefficient of Variation 61.71 |
| MK-6194 Medium Dose- Interval 2 (More Frequent) | Change in Number of Conventional T Cells (Tcons) in Whole Blood | Week 11 | 76.1 Cells/uL | Geometric Coefficient of Variation 59.2 |
| MK-6194 Medium Dose- Interval 2 (More Frequent) | Change in Number of Conventional T Cells (Tcons) in Whole Blood | Week 5 | 100.6 Cells/uL | Geometric Coefficient of Variation 74.36 |
| MK-6194 Medium Dose- Interval 2 (More Frequent) | Change in Number of Conventional T Cells (Tcons) in Whole Blood | Week 6 | 57.9 Cells/uL | Geometric Coefficient of Variation 101.25 |
| MK-6194 Medium Dose- Interval 2 (More Frequent) | Change in Number of Conventional T Cells (Tcons) in Whole Blood | Week 12 | 73.2 Cells/uL | Geometric Coefficient of Variation 96.94 |
| MK-6194 Medium Dose- Interval 2 (More Frequent) | Change in Number of Conventional T Cells (Tcons) in Whole Blood | Week 7 | 103.6 Cells/uL | Geometric Coefficient of Variation 68.22 |
| MK-6194 High Dose - Interval 2 (More Frequent) | Change in Number of Conventional T Cells (Tcons) in Whole Blood | Week 3 | 123.7 Cells/uL | Geometric Coefficient of Variation 111.06 |
| MK-6194 High Dose - Interval 2 (More Frequent) | Change in Number of Conventional T Cells (Tcons) in Whole Blood | Week 8 | 63.5 Cells/uL | Geometric Coefficient of Variation 82.18 |
| MK-6194 High Dose - Interval 2 (More Frequent) | Change in Number of Conventional T Cells (Tcons) in Whole Blood | Week 2 | 105.4 Cells/uL | Geometric Coefficient of Variation 121.23 |
| MK-6194 High Dose - Interval 2 (More Frequent) | Change in Number of Conventional T Cells (Tcons) in Whole Blood | Week 7 | 68.6 Cells/uL | Geometric Coefficient of Variation 87.88 |
| MK-6194 High Dose - Interval 2 (More Frequent) | Change in Number of Conventional T Cells (Tcons) in Whole Blood | Week 6 | 0.0 Cells/uL | Geometric Coefficient of Variation 101.48 |
| MK-6194 High Dose - Interval 2 (More Frequent) | Change in Number of Conventional T Cells (Tcons) in Whole Blood | Week 9 | 128.8 Cells/uL | Geometric Coefficient of Variation 89.61 |
| MK-6194 High Dose - Interval 2 (More Frequent) | Change in Number of Conventional T Cells (Tcons) in Whole Blood | Week 11 | 90.5 Cells/uL | Geometric Coefficient of Variation 80.69 |
| MK-6194 High Dose - Interval 2 (More Frequent) | Change in Number of Conventional T Cells (Tcons) in Whole Blood | Week 5 | 126.2 Cells/uL | Geometric Coefficient of Variation 75.69 |
| MK-6194 High Dose - Interval 2 (More Frequent) | Change in Number of Conventional T Cells (Tcons) in Whole Blood | Week 10 | 50.7 Cells/uL | Geometric Coefficient of Variation 98.06 |
| MK-6194 High Dose - Interval 2 (More Frequent) | Change in Number of Conventional T Cells (Tcons) in Whole Blood | Week 4 | 73.3 Cells/uL | Geometric Coefficient of Variation 108.47 |
| MK-6194 High Dose - Interval 2 (More Frequent) | Change in Number of Conventional T Cells (Tcons) in Whole Blood | Week 12 | 99.9 Cells/uL | Geometric Coefficient of Variation 77.32 |
| MK-6194 High Dose - Interval 2 (More Frequent) | Change in Number of Conventional T Cells (Tcons) in Whole Blood | Week 1 | 91.2 Cells/uL | Geometric Coefficient of Variation 105.12 |
| MK-6194 High Dose - Interval 1 (Less Frequent) | Change in Number of Conventional T Cells (Tcons) in Whole Blood | Week 9 | 192.2 Cells/uL | Geometric Coefficient of Variation 71.43 |
| MK-6194 High Dose - Interval 1 (Less Frequent) | Change in Number of Conventional T Cells (Tcons) in Whole Blood | Week 5 | 166.8 Cells/uL | Geometric Coefficient of Variation 76.19 |
| MK-6194 High Dose - Interval 1 (Less Frequent) | Change in Number of Conventional T Cells (Tcons) in Whole Blood | Week 1 | 189.6 Cells/uL | Geometric Coefficient of Variation 66.58 |
| MK-6194 High Dose - Interval 1 (Less Frequent) | Change in Number of Conventional T Cells (Tcons) in Whole Blood | Week 3 | 192.8 Cells/uL | Geometric Coefficient of Variation 60.55 |
| MK-6194 High Dose - Interval 1 (Less Frequent) | Change in Number of Conventional T Cells (Tcons) in Whole Blood | Week 4 | 163.4 Cells/uL | Geometric Coefficient of Variation 72.06 |
| MK-6194 High Dose - Interval 1 (Less Frequent) | Change in Number of Conventional T Cells (Tcons) in Whole Blood | Week 6 | 193.9 Cells/uL | Geometric Coefficient of Variation 68.59 |
| MK-6194 High Dose - Interval 1 (Less Frequent) | Change in Number of Conventional T Cells (Tcons) in Whole Blood | Week 7 | 154.5 Cells/uL | Geometric Coefficient of Variation 70.64 |
| MK-6194 High Dose - Interval 1 (Less Frequent) | Change in Number of Conventional T Cells (Tcons) in Whole Blood | Week 8 | 159.1 Cells/uL | Geometric Coefficient of Variation 66.12 |
| MK-6194 High Dose - Interval 1 (Less Frequent) | Change in Number of Conventional T Cells (Tcons) in Whole Blood | Week 2 | 184.1 Cells/uL | Geometric Coefficient of Variation 67.77 |
| MK-6194 High Dose - Interval 1 (Less Frequent) | Change in Number of Conventional T Cells (Tcons) in Whole Blood | Week 10 | 147.3 Cells/uL | Geometric Coefficient of Variation 72.31 |
| MK-6194 High Dose - Interval 1 (Less Frequent) | Change in Number of Conventional T Cells (Tcons) in Whole Blood | Week 12 | 153.3 Cells/uL | Geometric Coefficient of Variation 70.03 |
| Placebo | Change in Number of Conventional T Cells (Tcons) in Whole Blood | Week 7 | 66.1 Cells/uL | Geometric Coefficient of Variation 87.17 |
| Placebo | Change in Number of Conventional T Cells (Tcons) in Whole Blood | Week 6 | 53.8 Cells/uL | Geometric Coefficient of Variation 90.84 |
| Placebo | Change in Number of Conventional T Cells (Tcons) in Whole Blood | Week 12 | 73.4 Cells/uL | Geometric Coefficient of Variation 82.45 |
| Placebo | Change in Number of Conventional T Cells (Tcons) in Whole Blood | Week 10 | 83.2 Cells/uL | Geometric Coefficient of Variation 92.61 |
| Placebo | Change in Number of Conventional T Cells (Tcons) in Whole Blood | Week 4 | 63.3 Cells/uL | Geometric Coefficient of Variation 105.58 |
| Placebo | Change in Number of Conventional T Cells (Tcons) in Whole Blood | Week 3 | 127.7 Cells/uL | Geometric Coefficient of Variation 52.96 |
| Placebo | Change in Number of Conventional T Cells (Tcons) in Whole Blood | Week 11 | 102.0 Cells/uL | Geometric Coefficient of Variation 45.66 |
| Placebo | Change in Number of Conventional T Cells (Tcons) in Whole Blood | Week 1 | 57.6 Cells/uL | Geometric Coefficient of Variation 79 |
| Placebo | Change in Number of Conventional T Cells (Tcons) in Whole Blood | Week 5 | 79.3 Cells/uL | Geometric Coefficient of Variation 66.49 |
| Placebo | Change in Number of Conventional T Cells (Tcons) in Whole Blood | Week 2 | 0.0 Cells/uL | Geometric Coefficient of Variation 71.58 |
| Placebo | Change in Number of Conventional T Cells (Tcons) in Whole Blood | Week 9 | 141.5 Cells/uL | Geometric Coefficient of Variation 63.25 |
| Placebo | Change in Number of Conventional T Cells (Tcons) in Whole Blood | Week 8 | 50.6 Cells/uL | Geometric Coefficient of Variation 93.8 |
Secondary
Change in Number of Natural Killer (NK) Cells in Whole Blood
Blood samples were collected at pre-specified time points and analyzed by flow cytometry. The change in the number of NK cells in whole blood is presented.
Time frame: Pre-dose (baseline) and weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12
Population: All randomized participants who received at least 1 dose of study intervention and who had least 1 valid analytical result at baseline, at least 1 post-dose analytical result and had no major relevant protocol or dosing deviations that could potentially affect the pharmacodynamic profile
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| MK-6194 Low Dose - Interval 1 (Less Frequent) | Change in Number of Natural Killer (NK) Cells in Whole Blood | Week 3 | 479.5 Cells/uL | Geometric Coefficient of Variation 85.51 |
| MK-6194 Low Dose - Interval 1 (Less Frequent) | Change in Number of Natural Killer (NK) Cells in Whole Blood | Week 10 | 159.6 Cells/uL | Geometric Coefficient of Variation 59.86 |
| MK-6194 Low Dose - Interval 1 (Less Frequent) | Change in Number of Natural Killer (NK) Cells in Whole Blood | Week 6 | 169.0 Cells/uL | Geometric Coefficient of Variation 88.11 |
| MK-6194 Low Dose - Interval 1 (Less Frequent) | Change in Number of Natural Killer (NK) Cells in Whole Blood | Week 1 | 109.3 Cells/uL | Geometric Coefficient of Variation 117.56 |
| MK-6194 Low Dose - Interval 1 (Less Frequent) | Change in Number of Natural Killer (NK) Cells in Whole Blood | Week 7 | 224.8 Cells/uL | Geometric Coefficient of Variation 83.09 |
| MK-6194 Low Dose - Interval 1 (Less Frequent) | Change in Number of Natural Killer (NK) Cells in Whole Blood | Week 2 | 124.7 Cells/uL | Geometric Coefficient of Variation 83.32 |
| MK-6194 Low Dose - Interval 1 (Less Frequent) | Change in Number of Natural Killer (NK) Cells in Whole Blood | Week 8 | 272.9 Cells/uL | Geometric Coefficient of Variation 54.62 |
| MK-6194 Low Dose - Interval 1 (Less Frequent) | Change in Number of Natural Killer (NK) Cells in Whole Blood | Week 4 | 292.2 Cells/uL | Geometric Coefficient of Variation 48.38 |
| MK-6194 Low Dose - Interval 1 (Less Frequent) | Change in Number of Natural Killer (NK) Cells in Whole Blood | Week 9 | 195.5 Cells/uL | Geometric Coefficient of Variation 4.35 |
| MK-6194 Low Dose - Interval 1 (Less Frequent) | Change in Number of Natural Killer (NK) Cells in Whole Blood | Week 12 | 70.6 Cells/uL | Geometric Coefficient of Variation 125.61 |
| MK-6194 Low Dose - Interval 1 (Less Frequent) | Change in Number of Natural Killer (NK) Cells in Whole Blood | Week 5 | 281.5 Cells/uL | Geometric Coefficient of Variation 27.43 |
| MK-6194 Medium Dose- Interval 2 (More Frequent) | Change in Number of Natural Killer (NK) Cells in Whole Blood | Week 9 | 92.8 Cells/uL | Geometric Coefficient of Variation 94.04 |
| MK-6194 Medium Dose- Interval 2 (More Frequent) | Change in Number of Natural Killer (NK) Cells in Whole Blood | Week 10 | 26.4 Cells/uL | Geometric Coefficient of Variation 83.25 |
| MK-6194 Medium Dose- Interval 2 (More Frequent) | Change in Number of Natural Killer (NK) Cells in Whole Blood | Week 1 | 0.0 Cells/uL | Geometric Coefficient of Variation 149.43 |
| MK-6194 Medium Dose- Interval 2 (More Frequent) | Change in Number of Natural Killer (NK) Cells in Whole Blood | Week 12 | 67.6 Cells/uL | Geometric Coefficient of Variation 60.56 |
| MK-6194 Medium Dose- Interval 2 (More Frequent) | Change in Number of Natural Killer (NK) Cells in Whole Blood | Week 6 | 59.3 Cells/uL | Geometric Coefficient of Variation 72.56 |
| MK-6194 Medium Dose- Interval 2 (More Frequent) | Change in Number of Natural Killer (NK) Cells in Whole Blood | Week 2 | 76.1 Cells/uL | Geometric Coefficient of Variation 62.77 |
| MK-6194 Medium Dose- Interval 2 (More Frequent) | Change in Number of Natural Killer (NK) Cells in Whole Blood | Week 5 | 42.1 Cells/uL | Geometric Coefficient of Variation 76.34 |
| MK-6194 Medium Dose- Interval 2 (More Frequent) | Change in Number of Natural Killer (NK) Cells in Whole Blood | Week 11 | 42.3 Cells/uL | Geometric Coefficient of Variation 94.19 |
| MK-6194 Medium Dose- Interval 2 (More Frequent) | Change in Number of Natural Killer (NK) Cells in Whole Blood | Week 4 | 52.8 Cells/uL | Geometric Coefficient of Variation 67.48 |
| MK-6194 Medium Dose- Interval 2 (More Frequent) | Change in Number of Natural Killer (NK) Cells in Whole Blood | Week 7 | 0.0 Cells/uL | Geometric Coefficient of Variation 112.85 |
| MK-6194 Medium Dose- Interval 2 (More Frequent) | Change in Number of Natural Killer (NK) Cells in Whole Blood | Week 3 | 50.3 Cells/uL | Geometric Coefficient of Variation 73.79 |
| MK-6194 Medium Dose- Interval 2 (More Frequent) | Change in Number of Natural Killer (NK) Cells in Whole Blood | Week 8 | 38.4 Cells/uL | Geometric Coefficient of Variation 113.46 |
| MK-6194 High Dose - Interval 2 (More Frequent) | Change in Number of Natural Killer (NK) Cells in Whole Blood | Week 10 | 46.0 Cells/uL | Geometric Coefficient of Variation 111.12 |
| MK-6194 High Dose - Interval 2 (More Frequent) | Change in Number of Natural Killer (NK) Cells in Whole Blood | Week 8 | 43.7 Cells/uL | Geometric Coefficient of Variation 148.37 |
| MK-6194 High Dose - Interval 2 (More Frequent) | Change in Number of Natural Killer (NK) Cells in Whole Blood | Week 9 | 72.8 Cells/uL | Geometric Coefficient of Variation 74.2 |
| MK-6194 High Dose - Interval 2 (More Frequent) | Change in Number of Natural Killer (NK) Cells in Whole Blood | Week 2 | 48.6 Cells/uL | Geometric Coefficient of Variation 81.2 |
| MK-6194 High Dose - Interval 2 (More Frequent) | Change in Number of Natural Killer (NK) Cells in Whole Blood | Week 3 | 44.2 Cells/uL | Geometric Coefficient of Variation 110.61 |
| MK-6194 High Dose - Interval 2 (More Frequent) | Change in Number of Natural Killer (NK) Cells in Whole Blood | Week 4 | 0.0 Cells/uL | Geometric Coefficient of Variation 102.83 |
| MK-6194 High Dose - Interval 2 (More Frequent) | Change in Number of Natural Killer (NK) Cells in Whole Blood | Week 1 | 43.2 Cells/uL | Geometric Coefficient of Variation 86.39 |
| MK-6194 High Dose - Interval 2 (More Frequent) | Change in Number of Natural Killer (NK) Cells in Whole Blood | Week 5 | 53.8 Cells/uL | Geometric Coefficient of Variation 61.16 |
| MK-6194 High Dose - Interval 2 (More Frequent) | Change in Number of Natural Killer (NK) Cells in Whole Blood | Week 11 | 47.0 Cells/uL | Geometric Coefficient of Variation 91.92 |
| MK-6194 High Dose - Interval 2 (More Frequent) | Change in Number of Natural Killer (NK) Cells in Whole Blood | Week 6 | 54.7 Cells/uL | Geometric Coefficient of Variation 80.71 |
| MK-6194 High Dose - Interval 2 (More Frequent) | Change in Number of Natural Killer (NK) Cells in Whole Blood | Week 12 | 58.4 Cells/uL | Geometric Coefficient of Variation 84.39 |
| MK-6194 High Dose - Interval 2 (More Frequent) | Change in Number of Natural Killer (NK) Cells in Whole Blood | Week 7 | 73.2 Cells/uL | Geometric Coefficient of Variation 66.16 |
| MK-6194 High Dose - Interval 1 (Less Frequent) | Change in Number of Natural Killer (NK) Cells in Whole Blood | Week 9 | 94.0 Cells/uL | Geometric Coefficient of Variation 75.86 |
| MK-6194 High Dose - Interval 1 (Less Frequent) | Change in Number of Natural Killer (NK) Cells in Whole Blood | Week 1 | 110.0 Cells/uL | Geometric Coefficient of Variation 61.9 |
| MK-6194 High Dose - Interval 1 (Less Frequent) | Change in Number of Natural Killer (NK) Cells in Whole Blood | Week 2 | 108.5 Cells/uL | Geometric Coefficient of Variation 55.48 |
| MK-6194 High Dose - Interval 1 (Less Frequent) | Change in Number of Natural Killer (NK) Cells in Whole Blood | Week 3 | 68.4 Cells/uL | Geometric Coefficient of Variation 62.2 |
| MK-6194 High Dose - Interval 1 (Less Frequent) | Change in Number of Natural Killer (NK) Cells in Whole Blood | Week 4 | 78.9 Cells/uL | Geometric Coefficient of Variation 73.4 |
| MK-6194 High Dose - Interval 1 (Less Frequent) | Change in Number of Natural Killer (NK) Cells in Whole Blood | Week 5 | 133.2 Cells/uL | Geometric Coefficient of Variation 87.96 |
| MK-6194 High Dose - Interval 1 (Less Frequent) | Change in Number of Natural Killer (NK) Cells in Whole Blood | Week 6 | 140.3 Cells/uL | Geometric Coefficient of Variation 78.1 |
| MK-6194 High Dose - Interval 1 (Less Frequent) | Change in Number of Natural Killer (NK) Cells in Whole Blood | Week 7 | 82.0 Cells/uL | Geometric Coefficient of Variation 93.62 |
| MK-6194 High Dose - Interval 1 (Less Frequent) | Change in Number of Natural Killer (NK) Cells in Whole Blood | Week 8 | 86.9 Cells/uL | Geometric Coefficient of Variation 49.1 |
| MK-6194 High Dose - Interval 1 (Less Frequent) | Change in Number of Natural Killer (NK) Cells in Whole Blood | Week 10 | 87.1 Cells/uL | Geometric Coefficient of Variation 99.38 |
| MK-6194 High Dose - Interval 1 (Less Frequent) | Change in Number of Natural Killer (NK) Cells in Whole Blood | Week 12 | 45.6 Cells/uL | Geometric Coefficient of Variation 119.58 |
| Placebo | Change in Number of Natural Killer (NK) Cells in Whole Blood | Week 8 | 30.4 Cells/uL | Geometric Coefficient of Variation 125.05 |
| Placebo | Change in Number of Natural Killer (NK) Cells in Whole Blood | Week 7 | 44.9 Cells/uL | Geometric Coefficient of Variation 119.1 |
| Placebo | Change in Number of Natural Killer (NK) Cells in Whole Blood | Week 12 | 40.9 Cells/uL | Geometric Coefficient of Variation 121.6 |
| Placebo | Change in Number of Natural Killer (NK) Cells in Whole Blood | Week 10 | 84.5 Cells/uL | Geometric Coefficient of Variation 91.34 |
| Placebo | Change in Number of Natural Killer (NK) Cells in Whole Blood | Week 6 | 55.3 Cells/uL | Geometric Coefficient of Variation 124.75 |
| Placebo | Change in Number of Natural Killer (NK) Cells in Whole Blood | Week 5 | 65.0 Cells/uL | Geometric Coefficient of Variation 129.61 |
| Placebo | Change in Number of Natural Killer (NK) Cells in Whole Blood | Week 11 | 41.1 Cells/uL | Geometric Coefficient of Variation 163.74 |
| Placebo | Change in Number of Natural Killer (NK) Cells in Whole Blood | Week 4 | 42.1 Cells/uL | Geometric Coefficient of Variation 131.09 |
| Placebo | Change in Number of Natural Killer (NK) Cells in Whole Blood | Week 3 | 64.1 Cells/uL | Geometric Coefficient of Variation 87.37 |
| Placebo | Change in Number of Natural Killer (NK) Cells in Whole Blood | Week 1 | 34.40 Cells/uL | Geometric Coefficient of Variation 60.38 |
| Placebo | Change in Number of Natural Killer (NK) Cells in Whole Blood | Week 9 | 53.2 Cells/uL | Geometric Coefficient of Variation 81.75 |
| Placebo | Change in Number of Natural Killer (NK) Cells in Whole Blood | Week 2 | 19.2 Cells/uL | Geometric Coefficient of Variation 160.68 |
Secondary
Change in Number of Peripheral Regulatory T-cells (Tregs) in Whole Blood
Blood samples were collected at pre-specified time points and analyzed by flow cytometry. The absolute change in the number of peripheral Tregs in whole blood was assessed.
Time frame: Pre-dose (baseline) and weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12
Population: All randomized participants who received at least 1 dose of study intervention and who had least 1 valid analytical result at baseline, at least 1 post-dose analytical result and had no major relevant protocol or dosing deviations that could potentially affect the pharmacodynamic profile.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| MK-6194 Low Dose - Interval 1 (Less Frequent) | Change in Number of Peripheral Regulatory T-cells (Tregs) in Whole Blood | Week 8 | 3.9 Cells/uL | Geometric Coefficient of Variation 25 |
| MK-6194 Low Dose - Interval 1 (Less Frequent) | Change in Number of Peripheral Regulatory T-cells (Tregs) in Whole Blood | Week 6 | 9.0 Cells/uL | Geometric Coefficient of Variation 32.73 |
| MK-6194 Low Dose - Interval 1 (Less Frequent) | Change in Number of Peripheral Regulatory T-cells (Tregs) in Whole Blood | Week 2 | 15.2 Cells/uL | Geometric Coefficient of Variation 45.43 |
| MK-6194 Low Dose - Interval 1 (Less Frequent) | Change in Number of Peripheral Regulatory T-cells (Tregs) in Whole Blood | Week 7 | 4.0 Cells/uL | Geometric Coefficient of Variation 53.29 |
| MK-6194 Low Dose - Interval 1 (Less Frequent) | Change in Number of Peripheral Regulatory T-cells (Tregs) in Whole Blood | Week 1 | 16.6 Cells/uL | Geometric Coefficient of Variation 46.1 |
| MK-6194 Low Dose - Interval 1 (Less Frequent) | Change in Number of Peripheral Regulatory T-cells (Tregs) in Whole Blood | Week 3 | 12.2 Cells/uL | Geometric Coefficient of Variation 113.83 |
| MK-6194 Low Dose - Interval 1 (Less Frequent) | Change in Number of Peripheral Regulatory T-cells (Tregs) in Whole Blood | Week 10 | 2.3 Cells/uL | Geometric Coefficient of Variation 24.74 |
| MK-6194 Low Dose - Interval 1 (Less Frequent) | Change in Number of Peripheral Regulatory T-cells (Tregs) in Whole Blood | Week 4 | 5.1 Cells/uL | Geometric Coefficient of Variation 71.2 |
| MK-6194 Low Dose - Interval 1 (Less Frequent) | Change in Number of Peripheral Regulatory T-cells (Tregs) in Whole Blood | Week 9 | 6.0 Cells/uL | Geometric Coefficient of Variation 121.24 |
| MK-6194 Low Dose - Interval 1 (Less Frequent) | Change in Number of Peripheral Regulatory T-cells (Tregs) in Whole Blood | Week 5 | 33.9 Cells/uL | Geometric Coefficient of Variation 61.55 |
| MK-6194 Low Dose - Interval 1 (Less Frequent) | Change in Number of Peripheral Regulatory T-cells (Tregs) in Whole Blood | Week 12 | 5.9 Cells/uL | Geometric Coefficient of Variation 16.67 |
| MK-6194 Medium Dose- Interval 2 (More Frequent) | Change in Number of Peripheral Regulatory T-cells (Tregs) in Whole Blood | Week 3 | 24.5 Cells/uL | Geometric Coefficient of Variation 95.4 |
| MK-6194 Medium Dose- Interval 2 (More Frequent) | Change in Number of Peripheral Regulatory T-cells (Tregs) in Whole Blood | Week 1 | 24.0 Cells/uL | Geometric Coefficient of Variation 130.34 |
| MK-6194 Medium Dose- Interval 2 (More Frequent) | Change in Number of Peripheral Regulatory T-cells (Tregs) in Whole Blood | Week 7 | 32.3 Cells/uL | Geometric Coefficient of Variation 44.51 |
| MK-6194 Medium Dose- Interval 2 (More Frequent) | Change in Number of Peripheral Regulatory T-cells (Tregs) in Whole Blood | Week 5 | 0.0 Cells/uL | Geometric Coefficient of Variation 66.63 |
| MK-6194 Medium Dose- Interval 2 (More Frequent) | Change in Number of Peripheral Regulatory T-cells (Tregs) in Whole Blood | Week 6 | 12.9 Cells/uL | Geometric Coefficient of Variation 73.27 |
| MK-6194 Medium Dose- Interval 2 (More Frequent) | Change in Number of Peripheral Regulatory T-cells (Tregs) in Whole Blood | Week 9 | 21.1 Cells/uL | Geometric Coefficient of Variation 76.45 |
| MK-6194 Medium Dose- Interval 2 (More Frequent) | Change in Number of Peripheral Regulatory T-cells (Tregs) in Whole Blood | Week 8 | 9.4 Cells/uL | Geometric Coefficient of Variation 101.4 |
| MK-6194 Medium Dose- Interval 2 (More Frequent) | Change in Number of Peripheral Regulatory T-cells (Tregs) in Whole Blood | Week 2 | 8.4 Cells/uL | Geometric Coefficient of Variation 78.56 |
| MK-6194 Medium Dose- Interval 2 (More Frequent) | Change in Number of Peripheral Regulatory T-cells (Tregs) in Whole Blood | Week 4 | 9.5 Cells/uL | Geometric Coefficient of Variation 78.31 |
| MK-6194 Medium Dose- Interval 2 (More Frequent) | Change in Number of Peripheral Regulatory T-cells (Tregs) in Whole Blood | Week 11 | 17.8 Cells/uL | Geometric Coefficient of Variation 79.9 |
| MK-6194 Medium Dose- Interval 2 (More Frequent) | Change in Number of Peripheral Regulatory T-cells (Tregs) in Whole Blood | Week 10 | 15.4 Cells/uL | Geometric Coefficient of Variation 55.42 |
| MK-6194 Medium Dose- Interval 2 (More Frequent) | Change in Number of Peripheral Regulatory T-cells (Tregs) in Whole Blood | Week 12 | 12.1 Cells/uL | Geometric Coefficient of Variation 56.51 |
| MK-6194 High Dose - Interval 2 (More Frequent) | Change in Number of Peripheral Regulatory T-cells (Tregs) in Whole Blood | Week 2 | 0.0 Cells/uL | Geometric Coefficient of Variation 84.52 |
| MK-6194 High Dose - Interval 2 (More Frequent) | Change in Number of Peripheral Regulatory T-cells (Tregs) in Whole Blood | Week 1 | 36.5 Cells/uL | Geometric Coefficient of Variation 76.68 |
| MK-6194 High Dose - Interval 2 (More Frequent) | Change in Number of Peripheral Regulatory T-cells (Tregs) in Whole Blood | Week 3 | 31.7 Cells/uL | Geometric Coefficient of Variation 92.24 |
| MK-6194 High Dose - Interval 2 (More Frequent) | Change in Number of Peripheral Regulatory T-cells (Tregs) in Whole Blood | Week 4 | 12.8 Cells/uL | Geometric Coefficient of Variation 82.29 |
| MK-6194 High Dose - Interval 2 (More Frequent) | Change in Number of Peripheral Regulatory T-cells (Tregs) in Whole Blood | Week 5 | 20.9 Cells/uL | Geometric Coefficient of Variation 78.63 |
| MK-6194 High Dose - Interval 2 (More Frequent) | Change in Number of Peripheral Regulatory T-cells (Tregs) in Whole Blood | Week 6 | 9.8 Cells/uL | Geometric Coefficient of Variation 100.16 |
| MK-6194 High Dose - Interval 2 (More Frequent) | Change in Number of Peripheral Regulatory T-cells (Tregs) in Whole Blood | Week 7 | 27.1 Cells/uL | Geometric Coefficient of Variation 69.98 |
| MK-6194 High Dose - Interval 2 (More Frequent) | Change in Number of Peripheral Regulatory T-cells (Tregs) in Whole Blood | Week 8 | 8.8 Cells/uL | Geometric Coefficient of Variation 62.2 |
| MK-6194 High Dose - Interval 2 (More Frequent) | Change in Number of Peripheral Regulatory T-cells (Tregs) in Whole Blood | Week 9 | 22.3 Cells/uL | Geometric Coefficient of Variation 83.28 |
| MK-6194 High Dose - Interval 2 (More Frequent) | Change in Number of Peripheral Regulatory T-cells (Tregs) in Whole Blood | Week 10 | 11.3 Cells/uL | Geometric Coefficient of Variation 76.11 |
| MK-6194 High Dose - Interval 2 (More Frequent) | Change in Number of Peripheral Regulatory T-cells (Tregs) in Whole Blood | Week 11 | 24.6 Cells/uL | Geometric Coefficient of Variation 82.3 |
| MK-6194 High Dose - Interval 2 (More Frequent) | Change in Number of Peripheral Regulatory T-cells (Tregs) in Whole Blood | Week 12 | 6.4 Cells/uL | Geometric Coefficient of Variation 89.54 |
| MK-6194 High Dose - Interval 1 (Less Frequent) | Change in Number of Peripheral Regulatory T-cells (Tregs) in Whole Blood | Week 1 | 31.0 Cells/uL | Geometric Coefficient of Variation 48.95 |
| MK-6194 High Dose - Interval 1 (Less Frequent) | Change in Number of Peripheral Regulatory T-cells (Tregs) in Whole Blood | Week 10 | 16.3 Cells/uL | Geometric Coefficient of Variation 91.23 |
| MK-6194 High Dose - Interval 1 (Less Frequent) | Change in Number of Peripheral Regulatory T-cells (Tregs) in Whole Blood | Week 9 | 42.1 Cells/uL | Geometric Coefficient of Variation 63.99 |
| MK-6194 High Dose - Interval 1 (Less Frequent) | Change in Number of Peripheral Regulatory T-cells (Tregs) in Whole Blood | Week 2 | 29.8 Cells/uL | Geometric Coefficient of Variation 100.53 |
| MK-6194 High Dose - Interval 1 (Less Frequent) | Change in Number of Peripheral Regulatory T-cells (Tregs) in Whole Blood | Week 12 | 0.0 Cells/uL | Geometric Coefficient of Variation 77.22 |
| MK-6194 High Dose - Interval 1 (Less Frequent) | Change in Number of Peripheral Regulatory T-cells (Tregs) in Whole Blood | Week 4 | 4.8 Cells/uL | Geometric Coefficient of Variation 115.02 |
| MK-6194 High Dose - Interval 1 (Less Frequent) | Change in Number of Peripheral Regulatory T-cells (Tregs) in Whole Blood | Week 6 | 18.9 Cells/uL | Geometric Coefficient of Variation 58.45 |
| MK-6194 High Dose - Interval 1 (Less Frequent) | Change in Number of Peripheral Regulatory T-cells (Tregs) in Whole Blood | Week 3 | 15.2 Cells/uL | Geometric Coefficient of Variation 77.36 |
| MK-6194 High Dose - Interval 1 (Less Frequent) | Change in Number of Peripheral Regulatory T-cells (Tregs) in Whole Blood | Week 8 | 7.7 Cells/uL | Geometric Coefficient of Variation 101.49 |
| MK-6194 High Dose - Interval 1 (Less Frequent) | Change in Number of Peripheral Regulatory T-cells (Tregs) in Whole Blood | Week 7 | 7.4 Cells/uL | Geometric Coefficient of Variation 130.11 |
| MK-6194 High Dose - Interval 1 (Less Frequent) | Change in Number of Peripheral Regulatory T-cells (Tregs) in Whole Blood | Week 5 | 35.5 Cells/uL | Geometric Coefficient of Variation 65.56 |
| Placebo | Change in Number of Peripheral Regulatory T-cells (Tregs) in Whole Blood | Week 11 | 3.5 Cells/uL | Geometric Coefficient of Variation 117.48 |
| Placebo | Change in Number of Peripheral Regulatory T-cells (Tregs) in Whole Blood | Week 7 | 0.0 Cells/uL | Geometric Coefficient of Variation 66.82 |
| Placebo | Change in Number of Peripheral Regulatory T-cells (Tregs) in Whole Blood | Week 4 | 0.0 Cells/uL | Geometric Coefficient of Variation 120.87 |
| Placebo | Change in Number of Peripheral Regulatory T-cells (Tregs) in Whole Blood | Week 1 | 0.0 Cells/uL | Geometric Coefficient of Variation 107.2 |
| Placebo | Change in Number of Peripheral Regulatory T-cells (Tregs) in Whole Blood | Week 8 | 0.0 Cells/uL | Geometric Coefficient of Variation 102.85 |
| Placebo | Change in Number of Peripheral Regulatory T-cells (Tregs) in Whole Blood | Week 3 | 4.4 Cells/uL | Geometric Coefficient of Variation 96.26 |
| Placebo | Change in Number of Peripheral Regulatory T-cells (Tregs) in Whole Blood | Week 9 | 4.3 Cells/uL | Geometric Coefficient of Variation 101.64 |
| Placebo | Change in Number of Peripheral Regulatory T-cells (Tregs) in Whole Blood | Week 2 | 6.0 Cells/uL | Geometric Coefficient of Variation 109.31 |
| Placebo | Change in Number of Peripheral Regulatory T-cells (Tregs) in Whole Blood | Week 12 | 4.7 Cells/uL | Geometric Coefficient of Variation 91.2 |
| Placebo | Change in Number of Peripheral Regulatory T-cells (Tregs) in Whole Blood | Week 10 | 3.5 Cells/uL | Geometric Coefficient of Variation 146.88 |
| Placebo | Change in Number of Peripheral Regulatory T-cells (Tregs) in Whole Blood | Week 6 | 0.0 Cells/uL | Geometric Coefficient of Variation 61.81 |
| Placebo | Change in Number of Peripheral Regulatory T-cells (Tregs) in Whole Blood | Week 5 | 0.0 Cells/uL | Geometric Coefficient of Variation 92.71 |
Secondary
Maximum Concentration (Cmax) of MK-6194
Blood samples were collected at pre-specified time points to determine each participant's maximum concentration (Cmax). A participant's Cmax was defined as the maximum concentration of MK-6194 observed in serum over the entire course of the study for that individual and was calculated by taking the maximum over all observed MK-6194 serum concentrations. Geometric mean and geometric coefficient of variation of Cmax were calculated for each dosing group.
Time frame: Predose on all days of dosing; 12, 24-48, and 120 hours (as available) post dose on the first and last day of dosing; and once each week up to approximately day 85.
Population: All randomized participants who received at least 1 dose of study intervention and who had least 1 valid analytical result at baseline, at least 1 post-dose analytical result and had no major relevant protocol or dosing deviations that could potentially affect the pharmacokinetic (PK) profile. Per protocol, samples from participants who received placebo were not analyzed for PK values.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| MK-6194 Low Dose - Interval 1 (Less Frequent) | Maximum Concentration (Cmax) of MK-6194 | 9.55 ng/mL | Geometric Coefficient of Variation 67.8 |
| MK-6194 Medium Dose- Interval 2 (More Frequent) | Maximum Concentration (Cmax) of MK-6194 | 30.02 ng/mL | Geometric Coefficient of Variation 95.85 |
| MK-6194 High Dose - Interval 2 (More Frequent) | Maximum Concentration (Cmax) of MK-6194 | 51.80 ng/mL | Geometric Coefficient of Variation 71.97 |
| MK-6194 High Dose - Interval 1 (Less Frequent) | Maximum Concentration (Cmax) of MK-6194 | 52.78 ng/mL | Geometric Coefficient of Variation 178.96 |
Secondary
Minimum Concentration (Cmin) of MK-6194
Blood samples were collected at pre-specified time points to determine the minimum concentration (Cmin) of MK-6194 present in each participant's serum. A participant's Cmin was defined as the minimum concentration of MK-6194 observed in serum over the entire course of the study for that individual and was calculated by taking the minimum over all observed MK-6194 serum concentrations. Geometric mean and geometric coefficient of variation of Cmin were calculated for each dosing group.
Time frame: Predose on all days of dosing; 12, 24-48, and 120 hours (as available) post dose on the first and last day of dosing; and once each week up to approximately day 85
Population: All randomized participants who received at least 1 dose of study intervention and who had least 1 valid analytical result at baseline, at least 1 post-dose analytical result and had no major relevant protocol or dosing deviations that could potentially affect the PK profile. Per protocol, samples participants receiving placebo were not analyzed for PK values.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| MK-6194 Low Dose - Interval 1 (Less Frequent) | Minimum Concentration (Cmin) of MK-6194 | 0.08 ng/mL | Geometric Coefficient of Variation 0 |
| MK-6194 Medium Dose- Interval 2 (More Frequent) | Minimum Concentration (Cmin) of MK-6194 | 0.08 ng/mL | Geometric Coefficient of Variation 0 |
| MK-6194 High Dose - Interval 2 (More Frequent) | Minimum Concentration (Cmin) of MK-6194 | 0.09 ng/mL | Geometric Coefficient of Variation 97.7 |
| MK-6194 High Dose - Interval 1 (Less Frequent) | Minimum Concentration (Cmin) of MK-6194 | 0.08 ng/mL | Geometric Coefficient of Variation 0 |
Secondary
Time to Cmax (Tmax) of MK-6194
Blood samples were collected at pre-specified time points to determine maximum concentration (Cmax) of MK-6194 in each participant's serum and corresponding time of maximum concentration (Tmax). A participant's Tmax was defined as the time post-dose that the maximum concentration of MK-6194 was observed in serum. The median and range of Tmax were calculated for each dosing group.
Time frame: Predose on all days of dosing; 12, 24-48, and 120 hours (as available) post dose on the first and last day of dosing; and once each week up to approximately day 85
Population: All randomized participants who received at least 1 dose of study intervention and who had least 1 valid analytical result at baseline, at least 1 post-dose analytical result and had no major relevant protocol or dosing deviations that could potentially affect he pharmacokinetic (PK) profile. Per protocol, samples from participants receiving placebo were not analyzed for PK values.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MK-6194 Low Dose - Interval 1 (Less Frequent) | Time to Cmax (Tmax) of MK-6194 | 12.00 hours |
| MK-6194 Medium Dose- Interval 2 (More Frequent) | Time to Cmax (Tmax) of MK-6194 | 12.00 hours |
| MK-6194 High Dose - Interval 2 (More Frequent) | Time to Cmax (Tmax) of MK-6194 | 12.05 hours |
| MK-6194 High Dose - Interval 1 (Less Frequent) | Time to Cmax (Tmax) of MK-6194 | 12.10 hours |
Secondary
Titer of Anti-drug Antibody (ADA) to MK-6194
Blood samples were collected for the determination of ADA to MK-6194 using a screening assay, ADA titer using a confirmatory assay, and neutralizing antibody to MK-6194 in participants with confirmed positive titers
Time frame: Pre dose (week 0) and Weeks 4, 8, 12
Population: All randomized participants who received at least 1 dose of study intervention and who had least 1 valid analytical result at baseline, at least 1 post-dose analytical result and had no major relevant protocol or dosing deviations that could potentially affect the pharmacodynamic profile. ADA titer was assessed only in participants who were ADA positive.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| MK-6194 Low Dose - Interval 1 (Less Frequent) | Titer of Anti-drug Antibody (ADA) to MK-6194 | Week 12 | 640.0 Titer |
| MK-6194 Low Dose - Interval 1 (Less Frequent) | Titer of Anti-drug Antibody (ADA) to MK-6194 | Week 8 | 160.0 Titer |
| MK-6194 Medium Dose- Interval 2 (More Frequent) | Titer of Anti-drug Antibody (ADA) to MK-6194 | Week 0 | 20.0 Titer |
| MK-6194 Medium Dose- Interval 2 (More Frequent) | Titer of Anti-drug Antibody (ADA) to MK-6194 | Week 4 | 20.0 Titer |
| MK-6194 Medium Dose- Interval 2 (More Frequent) | Titer of Anti-drug Antibody (ADA) to MK-6194 | Week 8 | 20.0 Titer |
| MK-6194 Medium Dose- Interval 2 (More Frequent) | Titer of Anti-drug Antibody (ADA) to MK-6194 | Week 12 | 40.0 Titer |
| MK-6194 High Dose - Interval 2 (More Frequent) | Titer of Anti-drug Antibody (ADA) to MK-6194 | Week 8 | 20.0 Titer |
| MK-6194 High Dose - Interval 2 (More Frequent) | Titer of Anti-drug Antibody (ADA) to MK-6194 | Week 12 | 20.0 Titer |
| MK-6194 High Dose - Interval 2 (More Frequent) | Titer of Anti-drug Antibody (ADA) to MK-6194 | Week 4 | 20.0 Titer |
| MK-6194 High Dose - Interval 1 (Less Frequent) | Titer of Anti-drug Antibody (ADA) to MK-6194 | Week 4 | 20.0 Titer |
| MK-6194 High Dose - Interval 1 (Less Frequent) | Titer of Anti-drug Antibody (ADA) to MK-6194 | Week 0 | 20.0 Titer |
| MK-6194 High Dose - Interval 1 (Less Frequent) | Titer of Anti-drug Antibody (ADA) to MK-6194 | Week 8 | 20.0 Titer |
| MK-6194 High Dose - Interval 1 (Less Frequent) | Titer of Anti-drug Antibody (ADA) to MK-6194 | Week 12 | 40.0 Titer |