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MSB0010841

Phase 1

Psoriasis | Small molecule | Dermatology |Merck & Company, Inc.|Last Updated: Jan 19, 2017

Success Probability

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Trial Design

RandomizedDouble-BlindPLACEBO_CONTROLLED
Total Trials1
Total Enrollment41

FDA Designations

No designations recorded

Clinical trial landscape

MSB0010841 · 1 trial · 1 indication

Phase 1 1
NCT02156466Multiple Ascending Dose Trial of MSB0010841 (Anti-IL17A/F Nanobody) in Psoriasis SubjectsPsoriasis
COMPLETED41 Analytics
PHASE1COMPLETED
Multiple Ascending Dose Trial of MSB0010841 (Anti-IL17A/F Nanobody) in Psoriasis Subjects
PsoriasisUnlock trial analytics

Study Endpoints

Primary Endpoints

Number of Subjects With Treatment Emergent Adverse Events (TEAEs)
Baseline up to Day 85

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)
Day 1, 2,8, 15, 16, 22, 29, 30, 36, 43

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)
Day 1, 2, 8, 15, 16, 22, 29, 30, 36, 43

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])
Baseline up to Day 85

Data were presented for MSB0010841 combined group and placebo.

Levels of Anti-MSB0010841 Antibody Titers
Day 8, 15 (pre-dose), 22, 29 (pre-dose), 36, 43, 63 and 85
Levels of Pre-existing Anti-MSB0010841 Antibody Titers
Pre-dose on Day 1
MSB0010841 Serum Concentration Over Time After First Dose
0 hours (pre-dose), 6, 12, 24, 32, 72, 96, 168, 336 hours post-first dose (Day 1)
MSB0010841 Serum Concentration Over Time After Second Dose
0 hours (pre-dose), 24, 72, 96, 168, 336 hours post-second dose (Day 15)
MSB0010841 Serum Concentration Over Time After Third Dose
0 hours (pre-dose), 6, 12, 24, 32, 72, 96, 168, 336, 504, 816, 1056, 1344 hours post-third dose (Day 29)
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUC0-t) Post First Dose of MSB0010841
0 hours (pre-dose), 6, 12, 24, 32, 72, 96, 168, 336 hours post-first dose (Day 1)

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
0 hours (pre-dose), 6, 12, 24, 32, 72, 96, 168, 336, 504, 816, 1056, 1344 hours post-third dose (Day 29)

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
0 hours (pre-dose), 6, 12, 24, 32, 72, 96, 168, 336 hours post-first dose (Day 1)

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
0 hours (pre-dose), 6, 12, 24, 32, 72, 96, 168, 336 hours post-third dose (Day 29)

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
0 hours (pre-dose), 6, 12, 24, 32, 72, 96, 168, 336, 504, 816, 1056, 1344 hours post-third dose (Day 29)

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
Pre-dose (0 hours) on Day 1

The observed serum concentration immediately before the first dose.

Observed Serum Concentration Immediately Before Third Dose (Cpre) of MSB0010841
Pre-dose (0 hours) on Day 29

The observed serum concentration immediately before the third dose.

Minimum Concentration Observed (Cmin) During First Dosing Interval of MSB0010841
0 hours (pre-dose), 6, 12, 24, 32, 72, 96, 168, 336 hours post-first dose (Day 1)

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
0 hours (pre-dose), 6, 12, 24, 32, 72, 96, 168, 336, 504, 816, 1056, 1344 hours post-third dose (Day 29)

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
0 hours (pre-dose), 6, 12, 24, 32, 72, 96, 168, 336 hours post-first dose (Day 1)
Maximum Concentration Observed (Cmax) Post Third Dose of MSB0010841
0 hours (pre-dose), 6, 12, 24, 32, 72, 96, 168, 336, 504, 816, 1056, 1344 hours post-third dose (Day 29)
Average Concentration (Cav) Post First Dose of MSB0010841
0 hours (pre-dose), 6, 12, 24, 32, 72, 96, 168, 336 hours post-first dose (Day 1)

Cav was calculated by AUCtau/tau. Where tau is the dosing interval (336 hours).

Average Concentration (Cav) Post Third Dose of MSB0010841
0 hours (pre-dose), 6, 12, 24, 32, 72, 96, 168, 336, 504, 816, 1056, 1344 hours post-third dose (Day 29)

Cav was calculated by AUCtau/tau. Where tau is the dosing interval (336 hours).

Mean Residence Time (MRT0-t) Post First Dose of MSB0010841
0 hours (pre-dose), 6, 12, 24, 32, 72, 96, 168, 336 hours post-first dose (Day 1)

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
0 hours (pre-dose), 6, 12, 24, 32, 72, 96, 168, 336 hours post-third dose (Day 29)

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
0 hours (pre-dose), 6, 12, 24, 32, 72, 96, 168, 336, 504, 816, 1056, 1344 hours post-third dose (Day 29)

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
0 hours (pre-dose), 6, 12, 24, 32, 72, 96, 168, 336 hours post-first dose (Day 1)
Time to Maximum Observed Concentration (Tmax) Post Second Dose of MSB0010841
0 hours (pre-dose), 24, 72, 96, 168, 336 hours post-second dose (Day 15)
Time to Reach Maximum Observed Concentration (Tmax) Post Third Dose of MSB0010841
0 hours (pre-dose), 6, 12, 24, 32, 72, 96, 168, 336, 504, 816, 1056, 1344 hours post-third dose (Day 29)
Apparent Terminal Half-life (t1/2) Post Third Dose of MSB0010841
0 hours (pre-dose), 6, 12, 24, 32, 72, 96, 168, 336, 504, 816, 1056, 1344 hours post-third dose (Day 29)

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
0 hours (pre-dose), 6, 12, 24, 32, 72, 96, 168, 336, 504, 816, 1056, 1344 hours post-third dose (Day 29)

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
0 hours (pre-dose), 6, 12, 24, 32, 72, 96, 168, 336, 504, 816, 1056, 1344 hours post-third dose (Day 29)

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
0 hours (pre-dose), 6, 12, 24, 32, 72, 96, 168, 336, 504, 816, 1056, 1344 hours post-third dose (Day 29)

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
0 hours (pre-dose), 6, 12, 24, 32, 72, 96, 168, 336 hours post-first dose (Day 1)

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
0 hours (pre-dose), 6, 12, 24, 32, 72, 96, 168, 336, 504, 816, 1056, 1344 hours post-third dose (Day 29)

The peak trough fluctuation within one dosing interval, calculated as PTF (%) = (\[Cmax - Cmin\]/Cav ) multiplied by 100

Accumulation Ratio of Cmax (Racc (Cmax))
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)

Accumulation ratio for Cmax was calculated as Cmax, after third dose / Cmax, after first dose.

Accumulation Ratio of AUC (Racc(AUC))
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)

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
0 hours (pre-dose), 24, 72, 96, 168, 336 hours post-second dose (Day 15)
Observed Serum Concentration Immediately Before Second Dose (Cpre) of MSB0010841
Pre-dose (0 hours) on Day 15

The observed serum concentration immediately before second dose.

Secondary Endpoints

Percentage of Subjects With 50% or 75% Improvement From Baseline in Psoriasis Area and Severity Index (PASI) Score
Baseline up to Day 85
Mean Change From Baseline in Psoriasis Area and Severity Index (PASI) Score at Day 43
Baseline, Day 43
Percentage of Subjects With Static Physician's Global Assessment (sPGA) Score of Minimal or Clear and With at Least 2 Level Reduction From Baseline
Day 8, 15, 22, 29, 36, 43, 50, 85
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Study Design & Arms

AllocationRANDOMIZED
MaskingTRIPLE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
MSB0010841 30 mgEXPERIMENTAL -
MSB0010841 60 mgEXPERIMENTAL -
MSB0010841 120 mgEXPERIMENTAL -
MSB0010841 240 mgEXPERIMENTAL -
PlaceboPLACEBO_COMPARATOR -

Interventions

NameTypeDescription
MSB0010841DRUGMSB0010841(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.
PlaceboDRUGPlacebo 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.
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Eligibility Criteria

Age Range18 Years to 70 Years
SexALL
Healthy VolunteersNo
Study Sites1

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 \[s...

Countries:Germany
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Frequently asked questions about MSB0010841

What is MSB0010841 used for?

MSB0010841 is an investigational small molecule being developed for the treatment of psoriasis, a dermatological condition. It is currently in Phase 1 clinical development and is not yet approved by regulatory authorities.

Who makes MSB0010841?

MSB0010841 is being developed by Merck & Company, Inc., which trades under the ticker symbol MRK on the stock market. The company is conducting clinical trials to evaluate the drug's safety and efficacy in patients with psoriasis.

What phase is MSB0010841 in?

MSB0010841 is in Phase 1 clinical development. It is an investigational drug, meaning it has not been approved by regulatory agencies and is still undergoing clinical trials to assess its safety and effectiveness in treating psoriasis.

What clinical trials is MSB0010841 in?

MSB0010841 has one completed Phase 1 clinical trial registered under NCT02156466, titled 'Multiple Ascending Dose Trial of MSB0010841 (Anti-IL17A/F Nanobody) in Psoriasis Subjects.' This randomized, double-blind, placebo-controlled trial enrolled 41 participants in Germany.

How does MSB0010841 work?

MSB0010841 is an anti-IL17A/F nanobody, meaning it targets and neutralizes the inflammatory cytokines IL-17A and IL-17F. By blocking these signaling molecules, the drug aims to reduce the immune-driven inflammation that contributes to psoriasis symptoms.

Is MSB0010841 FDA approved?

MSB0010841 is not FDA approved. It is an investigational drug currently in Phase 1 clinical development for psoriasis. The drug has completed one clinical trial, but it has not yet received regulatory approval for any indication.