Clinical trial NCT02156466: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Psoriasis
Keywords: Psoriasis
MSB0010841
Anti-IL17A/F Nanobody
M1095
Lead sponsor: Merck KGaA, Darmstadt, Germany
Sponsor class: INDUSTRY
First posted: 2014-06-05
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


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

Primary outcomes:
measure: Number of Subjects With Treatment Emergent Adverse Events (TEAEs)
timeFrame: Baseline up to Day 85
measure: Number of Subjects With Local Injection Site Reactions (ISRs)
timeFrame: Day 1, 2,8, 15, 16, 22, 29, 30, 36, 43
measure: Amount of Pain at Injection Site Assessed By Visual Analog Scale (VAS)
timeFrame: Day 1, 2, 8, 15, 16, 22, 29, 30, 36, 43
measure: Percentage of Subjects With Anti-MSB0010841 Binding Antibodies (Anti-Drug Antibodies [ADA])
timeFrame: Baseline up to Day 85
measure: Levels of Anti-MSB0010841 Antibody Titers
timeFrame: Day 8, 15 (pre-dose), 22, 29 (pre-dose), 36, 43, 63 and 85
measure: Levels of Pre-existing Anti-MSB0010841 Antibody Titers
timeFrame: Pre-dose on Day 1
measure: MSB0010841 Serum Concentration Over Time After First Dose
timeFrame: 0 hours (pre-dose), 6, 12, 24, 32, 72, 96, 168, 336 hours post-first dose (Day 1)
measure: MSB0010841 Serum Concentration Over Time After Second Dose
timeFrame: 0 hours (pre-dose), 24, 72, 96, 168, 336 hours post-second dose (Day 15)
measure: MSB0010841 Serum Concentration Over Time After Third Dose
timeFrame: 0 hours (pre-dose), 6, 12, 24, 32, 72, 96, 168, 336, 504, 816, 1056, 1344 hours post-third dose (Day 29)
measure: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUC0-t) Post First Dose of MSB0010841
timeFrame: 0 hours (pre-dose), 6, 12, 24, 32, 72, 96, 168, 336 hours post-first dose (Day 1)
measure: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUC0-t) Post Third Dose of MSB0010841
timeFrame: 0 hours (pre-dose), 6, 12, 24, 32, 72, 96, 168, 336, 504, 816, 1056, 1344 hours post-third dose (Day 29)
measure: Area Under the Concentration-Time Curve From Time Zero up to Time Tau (AUCtau) Post First Dose of MSB0010841
timeFrame: 0 hours (pre-dose), 6, 12, 24, 32, 72, 96, 168, 336 hours post-first dose (Day 1)
measure: Area Under the Concentration-Time Curve From Time Zero up to Time Tau (AUCtau) Post Third Dose of MSB0010841
timeFrame: 0 hours (pre-dose), 6, 12, 24, 32, 72, 96, 168, 336 hours post-third dose (Day 29)
measure: Area Under the Concentration-time Curve From Time Zero to Infinity (AUC 0-inf) Post Third Dose of MSB0010841
timeFrame: 0 hours (pre-dose), 6, 12, 24, 32, 72, 96, 168, 336, 504, 816, 1056, 1344 hours post-third dose (Day 29)
measure: Observed Serum Concentration Immediately Before First Dose (Cpre) of MSB0010841
timeFrame: Pre-dose (0 hours) on Day 1
measure: Observed Serum Concentration Immediately Before Third Dose (Cpre) of MSB0010841
timeFrame: Pre-dose (0 hours) on Day 29
measure: Minimum Concentration Observed (Cmin) During First Dosing Interval of MSB0010841
timeFrame: 0 hours (pre-dose), 6, 12, 24, 32, 72, 96, 168, 336 hours post-first dose (Day 1)
measure: Minimum Concentration Observed (Cmin) During Third Dosing Interval of MSB0010841
timeFrame: 0 hours (pre-dose), 6, 12, 24, 32, 72, 96, 168, 336, 504, 816, 1056, 1344 hours post-third dose (Day 29)
measure: Maximum Concentration Observed (Cmax) Post First Dose of MSB0010841
timeFrame: 0 hours (pre-dose), 6, 12, 24, 32, 72, 96, 168, 336 hours post-first dose (Day 1)
measure: Maximum Concentration Observed (Cmax) Post Third Dose of MSB0010841
timeFrame: 0 hours (pre-dose), 6, 12, 24, 32, 72, 96, 168, 336, 504, 816, 1056, 1344 hours post-third dose (Day 29)
measure: Average Concentration (Cav) Post First Dose of MSB0010841
timeFrame: 0 hours (pre-dose), 6, 12, 24, 32, 72, 96, 168, 336 hours post-first dose (Day 1)
measure: Average Concentration (Cav) Post Third Dose of MSB0010841
timeFrame: 0 hours (pre-dose), 6, 12, 24, 32, 72, 96, 168, 336, 504, 816, 1056, 1344 hours post-third dose (Day 29)
measure: Mean Residence Time (MRT0-t) Post First Dose of MSB0010841
timeFrame: 0 hours (pre-dose), 6, 12, 24, 32, 72, 96, 168, 336 hours post-first dose (Day 1)
measure: Mean Residence Time (MRT0-t) Post Third Dose of MSB0010841
timeFrame: 0 hours (pre-dose), 6, 12, 24, 32, 72, 96, 168, 336 hours post-third dose (Day 29)
measure: Mean Residence Time of Drug in the Body From Time Zero Extrapolated to Infinity (MRT(0-inf) Post Third Dose of MSB0010841
timeFrame: 0 hours (pre-dose), 6, 12, 24, 32, 72, 96, 168, 336, 504, 816, 1056, 1344 hours post-third dose (Day 29)
measure: Time to Reach Maximum Observed Concentration (Tmax) Post First Dose of MSB0010841
timeFrame: 0 hours (pre-dose), 6, 12, 24, 32, 72, 96, 168, 336 hours post-first dose (Day 1)
measure: Time to Maximum Observed Concentration (Tmax) Post Second Dose of MSB0010841
timeFrame: 0 hours (pre-dose), 24, 72, 96, 168, 336 hours post-second dose (Day 15)
measure: Time to Reach Maximum Observed Concentration (Tmax) Post Third Dose of MSB0010841
timeFrame: 0 hours (pre-dose), 6, 12, 24, 32, 72, 96, 168, 336, 504, 816, 1056, 1344 hours post-third dose (Day 29)
measure: Apparent Terminal Half-life (t1/2) Post Third Dose of MSB0010841
timeFrame: 0 hours (pre-dose), 6, 12, 24, 32, 72, 96, 168, 336, 504, 816, 1056, 1344 hours post-third dose (Day 29)
measure: Terminal Rate Constant (λz) Post Third Dose of MSB0010841
timeFrame: 0 hours (pre-dose), 6, 12, 24, 32, 72, 96, 168, 336, 504, 816, 1056, 1344 hours post-third dose (Day 29)
measure: Apparent Clearance (CL/f) Post Third Dose of MSB0010841
timeFrame: 0 hours (pre-dose), 6, 12, 24, 32, 72, 96, 168, 336, 504, 816, 1056, 1344 hours post-third dose (Day 29)
measure: Apparent Volume of Distribution During Terminal Phase (Vz/f) Post Third Dose of MSB0010841
timeFrame: 0 hours (pre-dose), 6, 12, 24, 32, 72, 96, 168, 336, 504, 816, 1056, 1344 hours post-third dose (Day 29)
measure: Percentage Peak-Trough Fluctuation (PTF) Post First Dose of MSB0010841
timeFrame: 0 hours (pre-dose), 6, 12, 24, 32, 72, 96, 168, 336 hours post-first dose (Day 1)
measure: Percentage Peak-Trough Fluctuation (PTF) Post Third Dose of MSB0010841
timeFrame: 0 hours (pre-dose), 6, 12, 24, 32, 72, 96, 168, 336, 504, 816, 1056, 1344 hours post-third dose (Day 29)
measure: Accumulation Ratio of Cmax (Racc (Cmax))
timeFrame: 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)
measure: Accumulation Ratio of AUC (Racc(AUC))
timeFrame: 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)
measure: Maximum Observed Concentration (Cmax) Post Second Dose of MSB0010841
timeFrame: 0 hours (pre-dose), 24, 72, 96, 168, 336 hours post-second dose (Day 15)
measure: Observed Serum Concentration Immediately Before Second Dose (Cpre) of MSB0010841
timeFrame: Pre-dose (0 hours) on Day 15
Secondary outcomes:
measure: Percentage of Subjects With 50% or 75% Improvement From Baseline in Psoriasis Area and Severity Index (PASI) Score
timeFrame: Baseline up to Day 85
measure: Mean Change From Baseline in Psoriasis Area and Severity Index (PASI) Score at Day 43
timeFrame: Baseline, Day 43
measure: Percentage of Subjects With Static Physician's Global Assessment (sPGA) Score of Minimal or Clear and With at Least 2 Level Reduction From Baseline
timeFrame: Day 8, 15, 22, 29, 36, 43, 50, 85
measure: 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
timeFrame: Baseline, Day 8, 15, 22, 29, 36, 43, 50 and 85
measure: Percentage of Subjects With Exacerbation of Psoriasis
timeFrame: Baseline up to Day 85
Other outcomes:
Locations:
city: Darmstadt
country: Germany
facility: Please contact the Merck KGaA Communication Center
Study officials:
affiliation: Merck KGaA, Darmstadt, Germany
name: Medical Responsible
role: STUDY_DIRECTOR
References: