Phase 1
Completed N=41
Multiple Ascending Dose Trial of MSB0010841 (Anti-IL17A/F Nanobody) in Psoriasis Subjects
Source: ClinicalTrials.gov NCT02156466 ↗Enrolled (actual)
41
Serious AEs
2.4%
Results posted
Jan 2017
Primary outcomePrimary: Number of Subjects With Treatment Emergent Adverse Events (TEAEs) — 6; 5; 5; 6 subjects
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).
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Subjects With Treatment Emergent Adverse Events (TEAEs) |
6; 5; 5; 6; 6 | — |
| PRIMARY Number of Subjects With Local Injection Site Reactions (ISRs) |
8; 8; 8; 9; 8; 8 | — |
| PRIMARY Amount of Pain at Injection Site Assessed By Visual Analog Scale (VAS) |
7; 4; 7; 4; NA; 1 | — |
| PRIMARY Percentage of Subjects With Anti-MSB0010841 Binding Antibodies (Anti-Drug Antibodies [ADA]) |
30.3; 37.5 | — |
| PRIMARY Levels of Anti-MSB0010841 Antibody Titers |
3.68; 3.68; 3.68; 3.68; 0; 2.28 | — |
| PRIMARY Levels of Pre-existing Anti-MSB0010841 Antibody Titers |
2.98; 3.68; 3.68; 2.98; 0; 0 | — |
| PRIMARY MSB0010841 Serum Concentration Over Time After First Dose |
12.6; 0.0; 0.0; 0.0; 907.5; 2097.1 | — |
| PRIMARY MSB0010841 Serum Concentration Over Time After Second Dose |
1704.3; 3951.0; 6768.4; 11605.8; 3808.0; 7268.9 | — |
| PRIMARY MSB0010841 Serum Concentration Over Time After Third Dose |
2306.5; 4492.9; 10417.7; 16173.6; 3483.9; 6200.1 | — |
| PRIMARY Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUC0-t) Post First Dose of MSB0010841 |
33.6; 69.3; 126.3; 216.5 | — |
| PRIMARY Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUC0-t) Post Third Dose of MSB0010841 |
93.7; 170.3; 371.7; 663.4 | — |
| PRIMARY Area Under the Concentration-Time Curve From Time Zero up to Time Tau (AUCtau) Post First Dose of MSB0010841 |
32.4; 68.3; 114.6; 222.2 | — |
| PRIMARY Area Under the Concentration-Time Curve From Time Zero up to Time Tau (AUCtau) Post Third Dose of MSB0010841 |
54.2; 104.1; 203.2; 397.6 | — |
| PRIMARY Area Under the Concentration-time Curve From Time Zero to Infinity (AUC 0-inf) Post Third Dose of MSB0010841 |
97.6; 174.9; 392.6; 680.9 | — |
| PRIMARY Observed Serum Concentration Immediately Before First Dose (Cpre) of MSB0010841 |
0.01; 0.00; 0.00; 0.00 | — |
| PRIMARY Observed Serum Concentration Immediately Before Third Dose (Cpre) of MSB0010841 |
2.31; 4.49; 10.42; 16.17 | — |
| PRIMARY Minimum Concentration Observed (Cmin) During First Dosing Interval of MSB0010841 |
0.01; 0.00; 0.00; 0.00 | — |
| PRIMARY Minimum Concentration Observed (Cmin) During Third Dosing Interval of MSB0010841 |
2.30; 4.34; 10.03; 16.17 | — |
| PRIMARY Maximum Concentration Observed (Cmax) Post First Dose of MSB0010841 |
3.3; 7.4; 12.5; 20.8 | — |
| PRIMARY Maximum Concentration Observed (Cmax) Post Third Dose of MSB0010841 |
5.14; 11.32; 19.74; 37.93 | — |
| PRIMARY Average Concentration (Cav) Post First Dose of MSB0010841 |
2.315; 4.881; 8.187; 15.868 | — |
| PRIMARY Average Concentration (Cav) Post Third Dose of MSB0010841 |
3.87; 7.44; 14.51; 28.40 | — |
| PRIMARY Mean Residence Time (MRT0-t) Post First Dose of MSB0010841 |
6.528; 6.691; 6.638; 6.771 | — |
| PRIMARY Mean Residence Time (MRT0-t) Post Third Dose of MSB0010841 |
17.57; 15.68; 19.26; 16.38 | — |
| PRIMARY Mean Residence Time of Drug in the Body From Time Zero Extrapolated to Infinity (MRT(0-inf) Post Third Dose of MSB0010841 |
17.57; 15.68; 19.26; 16.38 | — |
| PRIMARY Time to Reach Maximum Observed Concentration (Tmax) Post First Dose of MSB0010841 |
72.39; 71.68; 52.00; 72.23 | — |
| PRIMARY Time to Maximum Observed Concentration (Tmax) Post Second Dose of MSB0010841 |
84.2; 72.0; 83.4; 72.0 | — |
| PRIMARY Time to Reach Maximum Observed Concentration (Tmax) Post Third Dose of MSB0010841 |
31.5; 31.0; 72.0; 72.0 | — |
| PRIMARY Apparent Terminal Half-life (t1/2) Post Third Dose of MSB0010841 |
10.63; 10.50; 12.19; 10.25 | — |
| PRIMARY Terminal Rate Constant (λz) Post Third Dose of MSB0010841 |
0.00; 0.00; 0.00; 0.00 | — |
| PRIMARY Apparent Clearance (CL/f) Post Third Dose of MSB0010841 |
0.55; 0.58; 0.59; 0.60 | — |
| PRIMARY Apparent Volume of Distribution During Terminal Phase (Vz/f) Post Third Dose of MSB0010841 |
8.49; 8.73; 10.39; 8.92 | — |
| PRIMARY Percentage Peak-Trough Fluctuation (PTF) Post First Dose of MSB0010841 |
140.28; 152.47; 144.37; 135.89 | — |
| PRIMARY Percentage Peak-Trough Fluctuation (PTF) Post Third Dose of MSB0010841 |
75.26; 95.65; 71.17; 76.03 | — |
| PRIMARY Accumulation Ratio of Cmax (Racc (Cmax)) |
1.56; 1.52; 1.56; 1.81 | — |
| PRIMARY Accumulation Ratio of AUC (Racc(AUC)) |
1.61; 1.50; 1.61; 1.83 | — |
| PRIMARY Maximum Observed Concentration (Cmax) Post Second Dose of MSB0010841 |
4.26; 9.06; 18.59; 30.98 | — |
| PRIMARY Observed Serum Concentration Immediately Before Second Dose (Cpre) of MSB0010841 |
1.65; 3.74; 6.34; 11.44 | — |
| SECONDARY Percentage of Subjects With 50% or 75% Improvement From Baseline in Psoriasis Area and Severity Index (PASI) Score |
100; 100; 100; 100; 50; 88 | — |
| SECONDARY Mean Change From Baseline in Psoriasis Area and Severity Index (PASI) Score at Day 43 |
16.91; 19.76; 23.35; 18.38; 25.49; -13.93 | — |
| SECONDARY Percentage of Subjects With Static Physician's Global Assessment (sPGA) Score of Minimal or Clear and With at Least 2 Level Reduction From Baseline |
0; 38; 13; 11; 0; 25 | — |
| SECONDARY 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 |
0.4; -30.0; -13.7; -12.5; 2.9; 0.4 | — |
| SECONDARY Percentage of Subjects With Exacerbation of Psoriasis |
0; 0; 0; 0; 12.5 | — |
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
Data sourced from ClinicalTrials.gov (NCT02156466). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.