Back to resultsMultiple Ascending Dose Trial of MSB0010841 (Anti-IL17A/F Nanobody) in Psoriasis Subjects
Primary Purpose
Psoriasis
Status
Completed
Phase
Phase 1
Locations
Germany
Study Type
Interventional
Intervention
MSB0010841
MSB0010841
MSB0010841
MSB0010841
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Psoriasis focused on measuring Psoriasis, MSB0010841, Anti-IL17A/F Nanobody, M1095
Eligibility Criteria
Inclusion Criteria:
- Chronic plaque psoriasis for at least 6 months before screening
- Greater than or equal to (>=) 10% of BSA with plaques
- Psoriasis Area and Severity Index (PASI) >=12
- Static Physician's Global Assessment (sPGA) >=3 (where scores range from 0 [clear of disease] to 5 [severe disease]) at the screening and baseline visits
- Other protocol defined inclusion criteria could apply
Exclusion Criteria:
- Any condition, including protocol-specified laboratory findings and findings in the medical history or in the pre-trial assessments which in the Investigator's opinion constitutes a risk or a contraindication for the subject's participation in the trial or that could interfere with the trial objectives, conduct or evaluation
- Currently having a form of non-plaque psoriasis as specified in the protocol
- Drug induced psoriasis
- Biological treatments as specified in the protocol, within 3 months prior to Day 1
- Systemic immunosuppressants or phototherapy as specified in the protocol, within 1 month prior to Day 1
- Use of anti-coagulant medications and/or antiplatelet medications as defined in the protocol
- Use of aspirin as defined in the protocol
- Topical corticosteroid treatments other than low-strength or lower-mid strength corticosteroids on the face, scalp, axillae, and/or groin within 1 month prior to Day 1
- Any previous treatment with an agent targeting interleukin (IL)-17, IL-12 and/or IL-23 as specified in the protocol
- Other protocol defined exclusion criteria could apply
Sites / Locations
- Please contact the Merck KGaA Communication Center
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Experimental
Experimental
Experimental
Experimental
Placebo Comparator
Arm Label
MSB0010841 30 mg
MSB0010841 60 mg
MSB0010841 120 mg
MSB0010841 240 mg
Placebo
Arm Description
Outcomes
Primary Outcome Measures
Number of Subjects With Treatment Emergent Adverse Events (TEAEs)
An adverse event (AE) was defined as any untoward medical occurrence which does not necessarily have a causal relationship with this the study drug. An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug or worsening of pre-existing medical condition, whether or not related to study drug. TEAEs were the AEs occurring or worsening after treatment administration.
Number of Subjects With Local Injection Site Reactions (ISRs)
The injection site was assessed by the Principal Investigator (PI) or his/her designee for local reactions such as redness, swelling, indurations or bruising, and by the subject for itching. Redness and bruising were scaled as None (no visible redness or bruising present); Mild (less than or equal to [<=] 2.0 centimeters [cm] redness or bruising area); Moderate (greater than [>] 2 to <=5.0 cm redness or bruising area); Severe (>5.0 cm redness or bruising area). Swelling was scaled as None (no swelling detected); Mild (palpable 'firmness' only); Moderate (<= 4 cm swelling); Severe (>4 cm swelling). Induration was scaled as None (no induration); Mild (able to move skin parallel to plane (sliding) and perpendicular to skin (pinching up); Moderate (able to slide skin, unable to pinch skin); Severe (unable to slide or pinch skin). Itching was scaled as No itching; Mild itching; Moderate itching and Severe itching. Subjects who reported any of the local ISRs were reported.
Amount of Pain at Injection Site Assessed By Visual Analog Scale (VAS)
Subjects were asked to assess their severity of injection site pain on a 100 millimeter (mm) VAS, where 0 = no pain and 100 = worst possible pain. Mean of amount of pain was calculated for the subjects having a value > 0. Maximum values per subjects (over injection site areas) are used for counting the amount of pain at injection site. Maximum pain scores recorded among all participants analysed in each arm are reported for each time point.
Percentage of Subjects With Anti-MSB0010841 Binding Antibodies (Anti-Drug Antibodies [ADA])
Data were presented for MSB0010841 combined group and placebo.
Levels of Anti-MSB0010841 Antibody Titers
Levels of Pre-existing Anti-MSB0010841 Antibody Titers
MSB0010841 Serum Concentration Over Time After First Dose
MSB0010841 Serum Concentration Over Time After Second Dose
MSB0010841 Serum Concentration Over Time After Third Dose
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUC0-t) Post First Dose of MSB0010841
Area under the serum concentration-time curve (AUC) from time zero to the last sampling time point at which the concentration is at or above lower limit of quantification (LLOQ).
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUC0-t) Post Third Dose of MSB0010841
Area under the serum concentration-time curve (AUC) from time zero to the last sampling time point at which the concentration is at or above LLOQ.
Area Under the Concentration-Time Curve From Time Zero up to Time Tau (AUCtau) Post First Dose of MSB0010841
Area under the concentration-time curve from time zero up to time Tau, where Tau is the dosing interval (336 hours).
Area Under the Concentration-Time Curve From Time Zero up to Time Tau (AUCtau) Post Third Dose of MSB0010841
Area under the concentration-time curve from time zero up to time Tau, where Tau is the dosing interval (336 hours).
Area Under the Concentration-time Curve From Time Zero to Infinity (AUC 0-inf) Post Third Dose of MSB0010841
Area under the serum concentration-time curve from time zero to infinity (AUC0-inf). AUC0-infcalculated as AUC0-t + AUCextra. AUCextra represents the extrapolated part of AUC0-inf calculated by Clast calc/λz, where Clast calc is the calculated concentration at the last sampling time point at which the measured concentration is at or above LLOQ and λz is the terminal rate constant determined from the terminal slope of the log transformed concentration curve using linear regression on terminal data points of the curve.
Observed Serum Concentration Immediately Before First Dose (Cpre) of MSB0010841
The observed serum concentration immediately before the first dose.
Observed Serum Concentration Immediately Before Third Dose (Cpre) of MSB0010841
The observed serum concentration immediately before the third dose.
Minimum Concentration Observed (Cmin) During First Dosing Interval of MSB0010841
The observed minimum serum concentration determined directly from the serum concentration-time profile of each subject.
Minimum Concentration Observed (Cmin) During Third Dosing Interval of MSB0010841
The observed minimum serum concentration determined directly from the serum concentration-time profile of each subject.
Maximum Concentration Observed (Cmax) Post First Dose of MSB0010841
Maximum Concentration Observed (Cmax) Post Third Dose of MSB0010841
Average Concentration (Cav) Post First Dose of MSB0010841
Cav was calculated by AUCtau/tau. Where tau is the dosing interval (336 hours).
Average Concentration (Cav) Post Third Dose of MSB0010841
Cav was calculated by AUCtau/tau. Where tau is the dosing interval (336 hours).
Mean Residence Time (MRT0-t) Post First Dose of MSB0010841
MRT is the average time at which the number of absorbed molecules reside in the body, after single-dose administration, and calculated as AUMC(0-t)/AUC(0-t) where AUMC(0-t) is area under the plasma concentration-time first moment curve from time zero to time t (336 hours) and AUC(0-t) is the area under the plasma concentration-time curve from time zero to tome t (336 hours).
Mean Residence Time (MRT0-t) Post Third Dose of MSB0010841
MRT is the average time at which the number of absorbed molecules reside in the body, after single-dose administration, and calculated as AUMC(0-t)/AUC(0-t) where AUMC(0-t) is area under the plasma concentration-time first moment curve from time zero to time t (336 hours) and AUC(0-t) is the area under the plasma concentration-time curve from time zero to tome t (336 hours).
Mean Residence Time of Drug in the Body From Time Zero Extrapolated to Infinity (MRT(0-inf) Post Third Dose of MSB0010841
Mean residence time of drug in the body from time zero extrapolated to infinity, based on the last predicted concentration at tlast.
Time to Reach Maximum Observed Concentration (Tmax) Post First Dose of MSB0010841
Time to Maximum Observed Concentration (Tmax) Post Second Dose of MSB0010841
Time to Reach Maximum Observed Concentration (Tmax) Post Third Dose of MSB0010841
Apparent Terminal Half-life (t1/2) Post Third Dose of MSB0010841
Terminal half-life is the time measured for the concentration to decrease by one half. Terminal half-life is calculated by dividing the natural logarithm to the base e (Log e) multiplied by (*) 2/ λz, where 'λz' is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
Terminal Rate Constant (λz) Post Third Dose of MSB0010841
Terminal rate constant was determined from the terminal slope of the logtransformed concentration curve using linear regression on terminal data points of the curve
Apparent Clearance (CL/f) Post Third Dose of MSB0010841
Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Apparent clearance after oral dose (CL/f) is influenced by the fraction absorbed.
Apparent Volume of Distribution During Terminal Phase (Vz/f) Post Third Dose of MSB0010841
Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug. Apparent volume of distribution during the terminal phase, calculated as Vz = Dose/AUC0-inf multiplied by elimination rate constant [λz]) following first dose and Dose/(AUCtau multiplied by λz) after third dose.
Percentage Peak-Trough Fluctuation (PTF) Post First Dose of MSB0010841
The peak trough fluctuation within one dosing interval, calculated as PTF (%) = ([Cmax - Cmin]/Cav ) multiplied by 100
Percentage Peak-Trough Fluctuation (PTF) Post Third Dose of MSB0010841
The peak trough fluctuation within one dosing interval, calculated as PTF (%) = ([Cmax - Cmin]/Cav ) multiplied by 100
Accumulation Ratio of Cmax (Racc (Cmax))
Accumulation ratio for Cmax was calculated as Cmax, after third dose / Cmax, after first dose.
Accumulation Ratio of AUC (Racc(AUC))
Accumulation ratio for AUC, calculated as area under the serum concentration-time curve within one complete dosing interval at third dose divided by area under the serum concentration-time curve within one complete dosing interval at first dose.
Maximum Observed Concentration (Cmax) Post Second Dose of MSB0010841
Observed Serum Concentration Immediately Before Second Dose (Cpre) of MSB0010841
The observed serum concentration immediately before second dose.
Secondary Outcome Measures
Percentage of Subjects With 50% or 75% Improvement From Baseline in Psoriasis Area and Severity Index (PASI) Score
PASI: a physician assessed index that measured psoriasis severity and evaluated erythema, infiltration, and desquamation (scaling) on different body areas including the head, upper extremities, the trunk, and lower extremities. T Erythema, infiltration, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). The total qualitative score (sum of erythema, thickness, and scaling scores) was multiplied by the degree of involvement for each anatomic region and then multiplied by a constant. These values for each anatomic region are summed to yield the PASI score. PASI score ranged from 0 to 72, with higher scores reflecting greater disease severity. PASI 50% or 75% was defined as the percentage of participants who achieved >=50 or 75% improvement in PASI score from Baseline.
Mean Change From Baseline in Psoriasis Area and Severity Index (PASI) Score at Day 43
PASI: a physician assessed index that measured psoriasis severity and evaluated erythema, infiltration, and desquamation (scaling) on different body areas including the head, upper extremities, the trunk, and lower extremities. T Erythema, infiltration, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). The total qualitative score (sum of erythema, thickness, and scaling scores) was multiplied by the degree of involvement for each anatomic region and then multiplied by a constant. These values for each anatomic region are summed to yield the PASI score. PASI score ranged from 0 to 72, with higher scores reflecting greater disease severity. PASI 50% or 75% was defined as the percentage of subjects who achieved >=50 or 75% improvement in PASI score from Baseline.
Percentage of Subjects With Static Physician's Global Assessment (sPGA) Score of Minimal or Clear and With at Least 2 Level Reduction From Baseline
The static Physician's Global Assessment (sPGA) scale rated the investigator's overall clinical assessment of a subjects plaque thickness, erythema, and scaling on a 6-point scale ranging from 0 (clear, except for residual discoloration) to 5 (majority of plaques have severe thickness, erythema, and scale). To assign a sPGA score, the investigator examined all psoriatic lesions and assigned a severity score ranging from 0 to 5 for thickness, erythema, and scaling. Scores for thickness, erythema, and scaling are summed and the mean of these 3 scores equals the overall sPGA score. Overall sPGA score ranged from 0 to 5, where lower scores indicate clinical improvement. Percentage of subjects who achieved a sPGA rating of 0 (clear) or 1 (minimal) and had at Least 2 level reduction from Baseline score were reported.
Mean Percent Change From Baseline in the Body Surface Area (BSA) Affected by Psoriasis at Day 8, 15, 22, 29, 36, 43, 50 and 85
The BSA is the physician's evaluation for the extent of disease. The entire body area is divided into 4 districts: head, upper limbs, trunk and lower limbs to which corresponds the 10%, 20%, 30% and 40% of the entire body surface respectively. The investigator assesses the percentage of the subjects' body surface area affected by psoriasis in each district. The final affected BSA value is the sum of the percentage of each district.
Percentage of Subjects With Exacerbation of Psoriasis
Psoriasis exacerbation was defined as either a worsening of 25% over the baseline value of the PASI score (PASI score at any visit >=125% of baseline PASI).
Full Information
NCT ID
NCT02156466
First Posted
May 23, 2014
Last Updated
November 28, 2016
Sponsor
Merck KGaA, Darmstadt, Germany
1. Study Identification
Unique Protocol Identification Number
NCT02156466
Brief Title
Multiple Ascending Dose Trial of MSB0010841 (Anti-IL17A/F Nanobody) in Psoriasis Subjects
Official Title
Multicenter, Phase I, Randomized, Double-Blind, Placebo-Controlled Trial to Assess the Safety, Tolerability, Immunogenicity, Pharmacokinetics, Pharmacodynamics and Efficacy of Multiple Ascending Doses of Subcutaneous MSB0010841 (Anti-IL17A/F Nanobody) in Male and Female Subjects With Moderate to Severe Psoriasis
Study Type
Interventional
2. Study Status
Record Verification Date
November 2016
Overall Recruitment Status
Completed
Study Start Date
August 2014 (undefined)
Primary Completion Date
August 2015 (Actual)
Study Completion Date
August 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck KGaA, Darmstadt, Germany
4. Oversight
5. Study Description
Brief Summary
This is a multicenter, Phase 1, randomized, double-blind, placebo-controlled trial in subjects with moderate to severe psoriasis to assess the safety, tolerability, immunogenicity, pharmacokinetics (PK), pharmacodynamics (PD) and efficacy of multiple subcutaneous ascending doses of MSB0010841 (Anti-interleukin-17A/F [Anti-IL-17A/F] Nanobody).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Psoriasis
Keywords
Psoriasis, MSB0010841, Anti-IL17A/F Nanobody, M1095
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
41 (Actual)
8. Arms, Groups, and Interventions
Arm Title
MSB0010841 30 mg
Arm Type
Experimental
Arm Title
MSB0010841 60 mg
Arm Type
Experimental
Arm Title
MSB0010841 120 mg
Arm Type
Experimental
Arm Title
MSB0010841 240 mg
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
MSB0010841
Other Intervention Name(s)
Anti-IL-17A/F Nanobody, M1095
Intervention Description
MSB0010841(Anti- IL-17A/F Nanobody) will be administered at a dose of 30 mg as SC injection every other week (Day 1, Day 15 and Day 29) for a total duration of 6 weeks.
Intervention Type
Drug
Intervention Name(s)
MSB0010841
Other Intervention Name(s)
Anti-IL-17A/F Nanobody, M1095
Intervention Description
MSB0010841 will be administered at a dose of 60 mg as SC injection every other week (Day 1, Day 15 and Day 29) for a total duration of 6 weeks.
Intervention Type
Drug
Intervention Name(s)
MSB0010841
Other Intervention Name(s)
Anti-IL-17A/F Nanobody, M1095
Intervention Description
MSB0010841 will be administered at a dose of 120 mg as SC injection every other week (Day 1, Day 15 and Day 29) for a total duration of 6 weeks.
Intervention Type
Drug
Intervention Name(s)
MSB0010841
Other Intervention Name(s)
Anti-IL-17A/F Nanobody, M1095
Intervention Description
MSB0010841 will be administered at a dose of 240 mg as SC injection every other week (Day 1, Day 15 and Day 29) for a total duration of 6 weeks.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo matched to MSB0010841 will be administered as SC injection every other week (Day 1, Day 15 and Day 29) for a total duration of 6 weeks.
Primary Outcome Measure Information:
Title
Number of Subjects With Treatment Emergent Adverse Events (TEAEs)
Description
An adverse event (AE) was defined as any untoward medical occurrence which does not necessarily have a causal relationship with this the study drug. An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug or worsening of pre-existing medical condition, whether or not related to study drug. TEAEs were the AEs occurring or worsening after treatment administration.
Time Frame
Baseline up to Day 85
Title
Number of Subjects With Local Injection Site Reactions (ISRs)
Description
The injection site was assessed by the Principal Investigator (PI) or his/her designee for local reactions such as redness, swelling, indurations or bruising, and by the subject for itching. Redness and bruising were scaled as None (no visible redness or bruising present); Mild (less than or equal to [<=] 2.0 centimeters [cm] redness or bruising area); Moderate (greater than [>] 2 to <=5.0 cm redness or bruising area); Severe (>5.0 cm redness or bruising area). Swelling was scaled as None (no swelling detected); Mild (palpable 'firmness' only); Moderate (<= 4 cm swelling); Severe (>4 cm swelling). Induration was scaled as None (no induration); Mild (able to move skin parallel to plane (sliding) and perpendicular to skin (pinching up); Moderate (able to slide skin, unable to pinch skin); Severe (unable to slide or pinch skin). Itching was scaled as No itching; Mild itching; Moderate itching and Severe itching. Subjects who reported any of the local ISRs were reported.
Time Frame
Day 1, 2,8, 15, 16, 22, 29, 30, 36, 43
Title
Amount of Pain at Injection Site Assessed By Visual Analog Scale (VAS)
Description
Subjects were asked to assess their severity of injection site pain on a 100 millimeter (mm) VAS, where 0 = no pain and 100 = worst possible pain. Mean of amount of pain was calculated for the subjects having a value > 0. Maximum values per subjects (over injection site areas) are used for counting the amount of pain at injection site. Maximum pain scores recorded among all participants analysed in each arm are reported for each time point.
Time Frame
Day 1, 2, 8, 15, 16, 22, 29, 30, 36, 43
Title
Percentage of Subjects With Anti-MSB0010841 Binding Antibodies (Anti-Drug Antibodies [ADA])
Description
Data were presented for MSB0010841 combined group and placebo.
Time Frame
Baseline up to Day 85
Title
Levels of Anti-MSB0010841 Antibody Titers
Time Frame
Day 8, 15 (pre-dose), 22, 29 (pre-dose), 36, 43, 63 and 85
Title
Levels of Pre-existing Anti-MSB0010841 Antibody Titers
Time Frame
Pre-dose on Day 1
Title
MSB0010841 Serum Concentration Over Time After First Dose
Time Frame
0 hours (pre-dose), 6, 12, 24, 32, 72, 96, 168, 336 hours post-first dose (Day 1)
Title
MSB0010841 Serum Concentration Over Time After Second Dose
Time Frame
0 hours (pre-dose), 24, 72, 96, 168, 336 hours post-second dose (Day 15)
Title
MSB0010841 Serum Concentration Over Time After Third Dose
Time Frame
0 hours (pre-dose), 6, 12, 24, 32, 72, 96, 168, 336, 504, 816, 1056, 1344 hours post-third dose (Day 29)
Title
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUC0-t) Post First Dose of MSB0010841
Description
Area under the serum concentration-time curve (AUC) from time zero to the last sampling time point at which the concentration is at or above lower limit of quantification (LLOQ).
Time Frame
0 hours (pre-dose), 6, 12, 24, 32, 72, 96, 168, 336 hours post-first dose (Day 1)
Title
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUC0-t) Post Third Dose of MSB0010841
Description
Area under the serum concentration-time curve (AUC) from time zero to the last sampling time point at which the concentration is at or above LLOQ.
Time Frame
0 hours (pre-dose), 6, 12, 24, 32, 72, 96, 168, 336, 504, 816, 1056, 1344 hours post-third dose (Day 29)
Title
Area Under the Concentration-Time Curve From Time Zero up to Time Tau (AUCtau) Post First Dose of MSB0010841
Description
Area under the concentration-time curve from time zero up to time Tau, where Tau is the dosing interval (336 hours).
Time Frame
0 hours (pre-dose), 6, 12, 24, 32, 72, 96, 168, 336 hours post-first dose (Day 1)
Title
Area Under the Concentration-Time Curve From Time Zero up to Time Tau (AUCtau) Post Third Dose of MSB0010841
Description
Area under the concentration-time curve from time zero up to time Tau, where Tau is the dosing interval (336 hours).
Time Frame
0 hours (pre-dose), 6, 12, 24, 32, 72, 96, 168, 336 hours post-third dose (Day 29)
Title
Area Under the Concentration-time Curve From Time Zero to Infinity (AUC 0-inf) Post Third Dose of MSB0010841
Description
Area under the serum concentration-time curve from time zero to infinity (AUC0-inf). AUC0-infcalculated as AUC0-t + AUCextra. AUCextra represents the extrapolated part of AUC0-inf calculated by Clast calc/λz, where Clast calc is the calculated concentration at the last sampling time point at which the measured concentration is at or above LLOQ and λz is the terminal rate constant determined from the terminal slope of the log transformed concentration curve using linear regression on terminal data points of the curve.
Time Frame
0 hours (pre-dose), 6, 12, 24, 32, 72, 96, 168, 336, 504, 816, 1056, 1344 hours post-third dose (Day 29)
Title
Observed Serum Concentration Immediately Before First Dose (Cpre) of MSB0010841
Description
The observed serum concentration immediately before the first dose.
Time Frame
Pre-dose (0 hours) on Day 1
Title
Observed Serum Concentration Immediately Before Third Dose (Cpre) of MSB0010841
Description
The observed serum concentration immediately before the third dose.
Time Frame
Pre-dose (0 hours) on Day 29
Title
Minimum Concentration Observed (Cmin) During First Dosing Interval of MSB0010841
Description
The observed minimum serum concentration determined directly from the serum concentration-time profile of each subject.
Time Frame
0 hours (pre-dose), 6, 12, 24, 32, 72, 96, 168, 336 hours post-first dose (Day 1)
Title
Minimum Concentration Observed (Cmin) During Third Dosing Interval of MSB0010841
Description
The observed minimum serum concentration determined directly from the serum concentration-time profile of each subject.
Time Frame
0 hours (pre-dose), 6, 12, 24, 32, 72, 96, 168, 336, 504, 816, 1056, 1344 hours post-third dose (Day 29)
Title
Maximum Concentration Observed (Cmax) Post First Dose of MSB0010841
Time Frame
0 hours (pre-dose), 6, 12, 24, 32, 72, 96, 168, 336 hours post-first dose (Day 1)
Title
Maximum Concentration Observed (Cmax) Post Third Dose of MSB0010841
Time Frame
0 hours (pre-dose), 6, 12, 24, 32, 72, 96, 168, 336, 504, 816, 1056, 1344 hours post-third dose (Day 29)
Title
Average Concentration (Cav) Post First Dose of MSB0010841
Description
Cav was calculated by AUCtau/tau. Where tau is the dosing interval (336 hours).
Time Frame
0 hours (pre-dose), 6, 12, 24, 32, 72, 96, 168, 336 hours post-first dose (Day 1)
Title
Average Concentration (Cav) Post Third Dose of MSB0010841
Description
Cav was calculated by AUCtau/tau. Where tau is the dosing interval (336 hours).
Time Frame
0 hours (pre-dose), 6, 12, 24, 32, 72, 96, 168, 336, 504, 816, 1056, 1344 hours post-third dose (Day 29)
Title
Mean Residence Time (MRT0-t) Post First Dose of MSB0010841
Description
MRT is the average time at which the number of absorbed molecules reside in the body, after single-dose administration, and calculated as AUMC(0-t)/AUC(0-t) where AUMC(0-t) is area under the plasma concentration-time first moment curve from time zero to time t (336 hours) and AUC(0-t) is the area under the plasma concentration-time curve from time zero to tome t (336 hours).
Time Frame
0 hours (pre-dose), 6, 12, 24, 32, 72, 96, 168, 336 hours post-first dose (Day 1)
Title
Mean Residence Time (MRT0-t) Post Third Dose of MSB0010841
Description
MRT is the average time at which the number of absorbed molecules reside in the body, after single-dose administration, and calculated as AUMC(0-t)/AUC(0-t) where AUMC(0-t) is area under the plasma concentration-time first moment curve from time zero to time t (336 hours) and AUC(0-t) is the area under the plasma concentration-time curve from time zero to tome t (336 hours).
Time Frame
0 hours (pre-dose), 6, 12, 24, 32, 72, 96, 168, 336 hours post-third dose (Day 29)
Title
Mean Residence Time of Drug in the Body From Time Zero Extrapolated to Infinity (MRT(0-inf) Post Third Dose of MSB0010841
Description
Mean residence time of drug in the body from time zero extrapolated to infinity, based on the last predicted concentration at tlast.
Time Frame
0 hours (pre-dose), 6, 12, 24, 32, 72, 96, 168, 336, 504, 816, 1056, 1344 hours post-third dose (Day 29)
Title
Time to Reach Maximum Observed Concentration (Tmax) Post First Dose of MSB0010841
Time Frame
0 hours (pre-dose), 6, 12, 24, 32, 72, 96, 168, 336 hours post-first dose (Day 1)
Title
Time to Maximum Observed Concentration (Tmax) Post Second Dose of MSB0010841
Time Frame
0 hours (pre-dose), 24, 72, 96, 168, 336 hours post-second dose (Day 15)
Title
Time to Reach Maximum Observed Concentration (Tmax) Post Third Dose of MSB0010841
Time Frame
0 hours (pre-dose), 6, 12, 24, 32, 72, 96, 168, 336, 504, 816, 1056, 1344 hours post-third dose (Day 29)
Title
Apparent Terminal Half-life (t1/2) Post Third Dose of MSB0010841
Description
Terminal half-life is the time measured for the concentration to decrease by one half. Terminal half-life is calculated by dividing the natural logarithm to the base e (Log e) multiplied by (*) 2/ λz, where 'λz' is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
Time Frame
0 hours (pre-dose), 6, 12, 24, 32, 72, 96, 168, 336, 504, 816, 1056, 1344 hours post-third dose (Day 29)
Title
Terminal Rate Constant (λz) Post Third Dose of MSB0010841
Description
Terminal rate constant was determined from the terminal slope of the logtransformed concentration curve using linear regression on terminal data points of the curve
Time Frame
0 hours (pre-dose), 6, 12, 24, 32, 72, 96, 168, 336, 504, 816, 1056, 1344 hours post-third dose (Day 29)
Title
Apparent Clearance (CL/f) Post Third Dose of MSB0010841
Description
Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Apparent clearance after oral dose (CL/f) is influenced by the fraction absorbed.
Time Frame
0 hours (pre-dose), 6, 12, 24, 32, 72, 96, 168, 336, 504, 816, 1056, 1344 hours post-third dose (Day 29)
Title
Apparent Volume of Distribution During Terminal Phase (Vz/f) Post Third Dose of MSB0010841
Description
Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug. Apparent volume of distribution during the terminal phase, calculated as Vz = Dose/AUC0-inf multiplied by elimination rate constant [λz]) following first dose and Dose/(AUCtau multiplied by λz) after third dose.
Time Frame
0 hours (pre-dose), 6, 12, 24, 32, 72, 96, 168, 336, 504, 816, 1056, 1344 hours post-third dose (Day 29)
Title
Percentage Peak-Trough Fluctuation (PTF) Post First Dose of MSB0010841
Description
The peak trough fluctuation within one dosing interval, calculated as PTF (%) = ([Cmax - Cmin]/Cav ) multiplied by 100
Time Frame
0 hours (pre-dose), 6, 12, 24, 32, 72, 96, 168, 336 hours post-first dose (Day 1)
Title
Percentage Peak-Trough Fluctuation (PTF) Post Third Dose of MSB0010841
Description
The peak trough fluctuation within one dosing interval, calculated as PTF (%) = ([Cmax - Cmin]/Cav ) multiplied by 100
Time Frame
0 hours (pre-dose), 6, 12, 24, 32, 72, 96, 168, 336, 504, 816, 1056, 1344 hours post-third dose (Day 29)
Title
Accumulation Ratio of Cmax (Racc (Cmax))
Description
Accumulation ratio for Cmax was calculated as Cmax, after third dose / Cmax, after first dose.
Time Frame
0 hours (pre-dose), 6, 12, 24, 32, 72, 96, 168, 336 hours post-first dose (Day 1) and 0 hours (pre-dose), 6, 12, 24, 32, 72, 96, 168, 336, 504, 816, 1056, 1344 hours post-third dose (Day 29)
Title
Accumulation Ratio of AUC (Racc(AUC))
Description
Accumulation ratio for AUC, calculated as area under the serum concentration-time curve within one complete dosing interval at third dose divided by area under the serum concentration-time curve within one complete dosing interval at first dose.
Time Frame
0 hours (pre-dose), 6, 12, 24, 32, 72, 96, 168, 336 hours post-first dose (Day 1) and 0 hours (pre-dose), 6, 12, 24, 32, 72, 96, 168, 336, 504, 816, 1056, 1344 hours post-third dose (Day 29)
Title
Maximum Observed Concentration (Cmax) Post Second Dose of MSB0010841
Time Frame
0 hours (pre-dose), 24, 72, 96, 168, 336 hours post-second dose (Day 15)
Title
Observed Serum Concentration Immediately Before Second Dose (Cpre) of MSB0010841
Description
The observed serum concentration immediately before second dose.
Time Frame
Pre-dose (0 hours) on Day 15
Secondary Outcome Measure Information:
Title
Percentage of Subjects With 50% or 75% Improvement From Baseline in Psoriasis Area and Severity Index (PASI) Score
Description
PASI: a physician assessed index that measured psoriasis severity and evaluated erythema, infiltration, and desquamation (scaling) on different body areas including the head, upper extremities, the trunk, and lower extremities. T Erythema, infiltration, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). The total qualitative score (sum of erythema, thickness, and scaling scores) was multiplied by the degree of involvement for each anatomic region and then multiplied by a constant. These values for each anatomic region are summed to yield the PASI score. PASI score ranged from 0 to 72, with higher scores reflecting greater disease severity. PASI 50% or 75% was defined as the percentage of participants who achieved >=50 or 75% improvement in PASI score from Baseline.
Time Frame
Baseline up to Day 85
Title
Mean Change From Baseline in Psoriasis Area and Severity Index (PASI) Score at Day 43
Description
PASI: a physician assessed index that measured psoriasis severity and evaluated erythema, infiltration, and desquamation (scaling) on different body areas including the head, upper extremities, the trunk, and lower extremities. T Erythema, infiltration, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). The total qualitative score (sum of erythema, thickness, and scaling scores) was multiplied by the degree of involvement for each anatomic region and then multiplied by a constant. These values for each anatomic region are summed to yield the PASI score. PASI score ranged from 0 to 72, with higher scores reflecting greater disease severity. PASI 50% or 75% was defined as the percentage of subjects who achieved >=50 or 75% improvement in PASI score from Baseline.
Time Frame
Baseline, Day 43
Title
Percentage of Subjects With Static Physician's Global Assessment (sPGA) Score of Minimal or Clear and With at Least 2 Level Reduction From Baseline
Description
The static Physician's Global Assessment (sPGA) scale rated the investigator's overall clinical assessment of a subjects plaque thickness, erythema, and scaling on a 6-point scale ranging from 0 (clear, except for residual discoloration) to 5 (majority of plaques have severe thickness, erythema, and scale). To assign a sPGA score, the investigator examined all psoriatic lesions and assigned a severity score ranging from 0 to 5 for thickness, erythema, and scaling. Scores for thickness, erythema, and scaling are summed and the mean of these 3 scores equals the overall sPGA score. Overall sPGA score ranged from 0 to 5, where lower scores indicate clinical improvement. Percentage of subjects who achieved a sPGA rating of 0 (clear) or 1 (minimal) and had at Least 2 level reduction from Baseline score were reported.
Time Frame
Day 8, 15, 22, 29, 36, 43, 50, 85
Title
Mean Percent Change From Baseline in the Body Surface Area (BSA) Affected by Psoriasis at Day 8, 15, 22, 29, 36, 43, 50 and 85
Description
The BSA is the physician's evaluation for the extent of disease. The entire body area is divided into 4 districts: head, upper limbs, trunk and lower limbs to which corresponds the 10%, 20%, 30% and 40% of the entire body surface respectively. The investigator assesses the percentage of the subjects' body surface area affected by psoriasis in each district. The final affected BSA value is the sum of the percentage of each district.
Time Frame
Baseline, Day 8, 15, 22, 29, 36, 43, 50 and 85
Title
Percentage of Subjects With Exacerbation of Psoriasis
Description
Psoriasis exacerbation was defined as either a worsening of 25% over the baseline value of the PASI score (PASI score at any visit >=125% of baseline PASI).
Time Frame
Baseline up to Day 85
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Chronic plaque psoriasis for at least 6 months before screening
Greater than or equal to (>=) 10% of BSA with plaques
Psoriasis Area and Severity Index (PASI) >=12
Static Physician's Global Assessment (sPGA) >=3 (where scores range from 0 [clear of disease] to 5 [severe disease]) at the screening and baseline visits
Other protocol defined inclusion criteria could apply
Exclusion Criteria:
Any condition, including protocol-specified laboratory findings and findings in the medical history or in the pre-trial assessments which in the Investigator's opinion constitutes a risk or a contraindication for the subject's participation in the trial or that could interfere with the trial objectives, conduct or evaluation
Currently having a form of non-plaque psoriasis as specified in the protocol
Drug induced psoriasis
Biological treatments as specified in the protocol, within 3 months prior to Day 1
Systemic immunosuppressants or phototherapy as specified in the protocol, within 1 month prior to Day 1
Use of anti-coagulant medications and/or antiplatelet medications as defined in the protocol
Use of aspirin as defined in the protocol
Topical corticosteroid treatments other than low-strength or lower-mid strength corticosteroids on the face, scalp, axillae, and/or groin within 1 month prior to Day 1
Any previous treatment with an agent targeting interleukin (IL)-17, IL-12 and/or IL-23 as specified in the protocol
Other protocol defined exclusion criteria could apply
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Responsible
Organizational Affiliation
Merck KGaA, Darmstadt, Germany
Official's Role
Study Director
Facility Information:
Facility Name
Please contact the Merck KGaA Communication Center
City
Darmstadt
Country
Germany
12. IPD Sharing Statement
Learn more about this trial
Multiple Ascending Dose Trial of MSB0010841 (Anti-IL17A/F Nanobody) in Psoriasis Subjects
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