Psoriasis
Conditions
Brief summary
This is a multi-center phase 2b study in subjects with moderate to severe chronic plaque-type psoriasis. Approximately 300 subjects will be enrolled at approximately 60 investigator sites in North America and Europe.
Interventions
DRUGM1095 (Sonelokimab)
M1095 (Sonelokimab) is a trivalent monomeric nanobody® that neutralizes interleukins IL-17A, IL-17F, and IL-17A/F.
DRUGPlacebo
Placebo contains no active drug.
DRUGSecukinumab
Secukinumab is a human immunoglobulin G1 (IgG1) monoclonal antibody that selectively binds IL-17A.
Sponsors
Avillion LLP
Bond Avillion 2 Development LP
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Male and female subjects between 18 and 75 years of age. 2. Moderate to severe plaque-type psoriasis for at least 6 months. 3. Subject is a candidate for systemic biologic therapy. 4. Subject has IGA ≥3, involved body surface area (BSA) ≥10%, and PASI ≥12 at screening and at baseline. 5. Subject is able to comply with the study procedures. 6. Subject must provide informed consent.
Exclusion criteria
(Main): 1. Non-plaque type psoriasis, drug-induced psoriasis, or other skin conditions (e.g., eczema). (Psoriatic arthritis is allowed). 2. Other medical conditions, including planned surgery or active infection / history of infection, as defined in the study protocol. Subjects will be screened for tuberculosis and hepatitis B / hepatitis C. 3. Laboratory abnormalities at screening, as defined in the study protocol. 4. Prior use of systemic or topical treatments for psoriasis, as defined in the study protocol. 5. Prior use of any compound targeting IL-17, more than two biologic therapies, ustekinumab within 6 months, or TNF targeting therapies within 12 weeks. 6. History of suicidal thoughts within 12 months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With an Investigator's Global Assessment (IGA) Score of 0 or 1 | Week 12, as compared to Week 0 (baseline) | The primary endpoint is achievement of an IGA score of 0 or 1 at Week 12, with an IGA reduction of at least 2 points from baseline. The percentage of subjects in the Intent to Treat (ITT) Analysis Set with an IGA score of 0 or 1 at Week 12 will be used to compare treatment arms. IGA is the Investigator's Global Assessment of the extent of psoriasis, with 0 = clear of psoriasis, 1 = almost clear, 2 = mild psoriasis, 3 = moderate psoriasis, and 4 = severe psoriasis (the worst assessment on this scale). Higher scores in the IGA indicate a worse outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a Psoriasis Area and Severity Index (PASI) Reduction of 100% (i.e. Clear of Psoriasis) | Week 12, as compared to Week 0 (baseline) | PASI 100, i.e. a subject's psoriasis has completely cleared at Week 12, compared to baseline. |
| Number of Participants With a Psoriasis Area and Severity Index (PASI) Reduction of 90% (i.e. a 90% Improvement in Psoriasis) | Week 12, as compared to baseline | PASI 90, i.e. a subject's psoriasis has cleared by 90% at Week 12, compared to baseline |
| Number of Participants With a Psoriasis Area and Severity Index (PASI) Reduction of 75% (i.e. a 75% Improvement in Psoriasis) | Week 12, as compared to Week 0 (baseline) | PASI 75, i.e. a subject's psoriasis has cleared by 75% at Week 12, compared to baseline |
Countries
Bulgaria, Canada, Czechia, Germany, Hungary, Poland, United States
Participant flow
Recruitment details
Subjects were adults aged 18-75 years with stable, moderate to severe plaque type psoriasis for \>6 months prior to randomisation, and who were candidates for systemic biologic therapy.
Participants by arm
| Arm | Count |
|---|---|
| M1095 30mg M1095, 30 mg, given at Week 0, 2, 4, 8, 12 and every four weeks.
M1095: M1095 is a trivalent monomeric nanobody® that neutralizes interleukins IL-17A, IL-17F, and IL-17A/F. | 52 |
| M1095 60mg M1095, 60 mg, given at Week 0, 2, 4, 8, 12 and every four weeks.
M1095: M1095 is a trivalent monomeric nanobody® that neutralizes interleukins IL-17A, IL-17F, and IL-17A/F. | 52 |
| M1095 120mg - Regimen 1 M1095, 120 mg, given at Week 0, 2, 4, 8, 12 and every eight weeks.
M1095: M1095 is a trivalent monomeric nanobody® that neutralizes interleukins IL-17A, IL-17F, and IL-17A/F. | 53 |
| M1095 120mg - Regimen 2 M1095, 120 mg, given at Week 0, 2, 4, 6, 8, 10, 12 and every four weeks.
M1095: M1095 is a trivalent monomeric nanobody® that neutralizes interleukins IL-17A, IL-17F, and IL-17A/F. | 51 |
| Placebo / M1095 120mg Placebo, given at Week 0, 1, 2, 3, 4, 6, 8 and 10, then M1095, 120mg, given at Week 12, 14, 16, and every four weeks.
M1095: M1095 is a trivalent monomeric nanobody® that neutralizes interleukins IL-17A, IL-17F, and IL-17A/F.
Placebo: Placebo contains no active drug. | 52 |
| Secukinumab Secukinumab, 300mg, given at Week 0, 1, 2, 3, 4, 8, 12 and every four weeks.
Secukinumab: Secukinumab is a human immunoglobulin G1 (IgG1) monoclonal antibody that selectively binds IL-17A. | 53 |
| Total | 313 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Maintenance/Escalation (W12-W24) | Adverse Event | 0 | 0 | 0 | 1 | 1 | 0 |
| Maintenance/Escalation (W12-W24) | Lack of Efficacy | 0 | 0 | 1 | 1 | 0 | 0 |
| Maintenance/Escalation (W12-W24) | Withdrawal by Subject | 0 | 0 | 0 | 0 | 1 | 0 |
| Placebo Controlled Induction (W0 - W12) | Adverse Event | 0 | 0 | 1 | 2 | 0 | 0 |
| Placebo Controlled Induction (W0 - W12) | Lost to Follow-up | 0 | 1 | 1 | 0 | 0 | 1 |
| Placebo Controlled Induction (W0 - W12) | Protocol Violation | 0 | 0 | 1 | 0 | 0 | 0 |
| Placebo Controlled Induction (W0 - W12) | Withdrawal by Subject | 0 | 0 | 0 | 0 | 3 | 1 |
| Response Assess/Dose Hold (W24-W48) | Adverse Event | 1 | 1 | 3 | 0 | 1 | 0 |
| Response Assess/Dose Hold (W24-W48) | Death | 0 | 1 | 0 | 0 | 0 | 0 |
| Response Assess/Dose Hold (W24-W48) | Lost to Follow-up | 0 | 0 | 0 | 2 | 0 | 0 |
| Response Assess/Dose Hold (W24-W48) | Withdrawal by Subject | 0 | 1 | 1 | 2 | 0 | 2 |
Baseline characteristics
| Characteristic | M1095 30mg | M1095 60mg | M1095 120mg - Regimen 1 | M1095 120mg - Regimen 2 | Placebo / M1095 120mg | Secukinumab | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 48.2 years STANDARD_DEVIATION 13.4 | 46.9 years STANDARD_DEVIATION 12.3 | 44.1 years STANDARD_DEVIATION 13.1 | 43.2 years STANDARD_DEVIATION 13.2 | 45.9 years STANDARD_DEVIATION 12.9 | 47.5 years STANDARD_DEVIATION 13.8 | 46.0 years STANDARD_DEVIATION 13.1 |
| Duration of psoriasis (years) | 20.0 years STANDARD_DEVIATION 13.6 | 19.7 years STANDARD_DEVIATION 12.8 | 15.8 years STANDARD_DEVIATION 12.9 | 18.0 years STANDARD_DEVIATION 11.7 | 16.3 years STANDARD_DEVIATION 12.1 | 20.2 years STANDARD_DEVIATION 13.6 | 18.3 years STANDARD_DEVIATION 12.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 3 Participants | 3 Participants | 2 Participants | 1 Participants | 2 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 48 Participants | 49 Participants | 50 Participants | 49 Participants | 51 Participants | 51 Participants | 298 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Height (cm) | 173 centimetres STANDARD_DEVIATION 10.4 | 173 centimetres STANDARD_DEVIATION 9.6 | 174 centimetres STANDARD_DEVIATION 9.89 | 173 centimetres STANDARD_DEVIATION 11.2 | 173 centimetres STANDARD_DEVIATION 10.1 | 172 centimetres STANDARD_DEVIATION 9.98 | 173 centimetres STANDARD_DEVIATION 10.2 |
| Investigator's Global Assessment (IGA) at baseline 3 | 38 Participants | 37 Participants | 39 Participants | 40 Participants | 41 Participants | 38 Participants | 233 Participants |
| Investigator's Global Assessment (IGA) at baseline 4 | 14 Participants | 15 Participants | 14 Participants | 11 Participants | 11 Participants | 15 Participants | 80 Participants |
| Percentage of total Body Surface Area (BSA) affected at baseline | 26.0 % of body surface area affected STANDARD_DEVIATION 15.7 | 24.8 % of body surface area affected STANDARD_DEVIATION 15.6 | 25.3 % of body surface area affected STANDARD_DEVIATION 14.8 | 26.4 % of body surface area affected STANDARD_DEVIATION 12.8 | 26.2 % of body surface area affected STANDARD_DEVIATION 16.7 | 28.1 % of body surface area affected STANDARD_DEVIATION 16.1 | 26.1 % of body surface area affected STANDARD_DEVIATION 15.2 |
| Presence of psoriatic arthritis No | 50 Participants | 47 Participants | 46 Participants | 45 Participants | 49 Participants | 51 Participants | 288 Participants |
| Presence of psoriatic arthritis Yes | 2 Participants | 5 Participants | 7 Participants | 6 Participants | 3 Participants | 2 Participants | 25 Participants |
| Prior biological use (actual) No | 43 Participants | 42 Participants | 44 Participants | 44 Participants | 44 Participants | 46 Participants | 263 Participants |
| Prior biological use (actual) Yes | 9 Participants | 10 Participants | 9 Participants | 7 Participants | 8 Participants | 7 Participants | 50 Participants |
| Psoriasis Area and Severity Index (PASI) at baseline | 20.3 units on a scale STANDARD_DEVIATION 7.91 | 20.7 units on a scale STANDARD_DEVIATION 9.34 | 21.1 units on a scale STANDARD_DEVIATION 8.38 | 20.6 units on a scale STANDARD_DEVIATION 7.15 | 20.5 units on a scale STANDARD_DEVIATION 6.89 | 21.7 units on a scale STANDARD_DEVIATION 8.8 | 20.8 units on a scale STANDARD_DEVIATION 8.08 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 1 Participants | 8 Participants | 2 Participants | 6 Participants | 3 Participants | 22 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 2 Participants | 1 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 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 | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 49 Participants | 48 Participants | 45 Participants | 47 Participants | 44 Participants | 49 Participants | 282 Participants |
| Region of Enrollment Bulgaria | 7 participants | 4 participants | 8 participants | 10 participants | 9 participants | 5 participants | 43 participants |
| Region of Enrollment Canada | 7 participants | 9 participants | 11 participants | 9 participants | 12 participants | 11 participants | 59 participants |
| Region of Enrollment Czechia | 13 participants | 14 participants | 13 participants | 8 participants | 16 participants | 16 participants | 80 participants |
| Region of Enrollment Germany | 1 participants | 2 participants | 2 participants | 2 participants | 2 participants | 2 participants | 11 participants |
| Region of Enrollment Hungary | 6 participants | 8 participants | 6 participants | 4 participants | 5 participants | 4 participants | 33 participants |
| Region of Enrollment Poland | 8 participants | 8 participants | 7 participants | 13 participants | 5 participants | 10 participants | 51 participants |
| Region of Enrollment United States | 10 participants | 7 participants | 6 participants | 5 participants | 3 participants | 5 participants | 36 participants |
| Sex: Female, Male Female | 36 Participants | 38 Participants | 43 Participants | 34 Participants | 39 Participants | 38 Participants | 228 Participants |
| Sex: Female, Male Male | 16 Participants | 14 Participants | 10 Participants | 17 Participants | 13 Participants | 15 Participants | 85 Participants |
| Weight at baseline (kg) | 92.0 kilograms STANDARD_DEVIATION 19 | 91.5 kilograms STANDARD_DEVIATION 20.6 | 89.0 kilograms STANDARD_DEVIATION 18.3 | 93.0 kilograms STANDARD_DEVIATION 22.6 | 91.3 kilograms STANDARD_DEVIATION 24.1 | 90.3 kilograms STANDARD_DEVIATION 22.4 | 91.2 kilograms STANDARD_DEVIATION 21.1 |
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 |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 52 | 0 / 52 | 0 / 52 | 0 / 53 | 0 / 51 | 0 / 53 | 0 / 208 | 1 / 251 | 0 / 51 |
| other Total, other adverse events | 11 / 52 | 13 / 52 | 16 / 52 | 18 / 53 | 15 / 51 | 14 / 53 | 62 / 208 | 57 / 251 | 16 / 51 |
| serious Total, serious adverse events | 1 / 52 | 2 / 52 | 1 / 52 | 1 / 53 | 1 / 51 | 0 / 53 | 5 / 208 | 12 / 251 | 2 / 51 |
Outcome results
Primary
Number of Participants With an Investigator's Global Assessment (IGA) Score of 0 or 1
The primary endpoint is achievement of an IGA score of 0 or 1 at Week 12, with an IGA reduction of at least 2 points from baseline. The percentage of subjects in the Intent to Treat (ITT) Analysis Set with an IGA score of 0 or 1 at Week 12 will be used to compare treatment arms. IGA is the Investigator's Global Assessment of the extent of psoriasis, with 0 = clear of psoriasis, 1 = almost clear, 2 = mild psoriasis, 3 = moderate psoriasis, and 4 = severe psoriasis (the worst assessment on this scale). Higher scores in the IGA indicate a worse outcome.
Time frame: Week 12, as compared to Week 0 (baseline)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| M1095 30mg | Number of Participants With an Investigator's Global Assessment (IGA) Score of 0 or 1 | 25 Participants |
| M1095 60mg | Number of Participants With an Investigator's Global Assessment (IGA) Score of 0 or 1 | 44 Participants |
| M1095 120mg - Normal Load Group | Number of Participants With an Investigator's Global Assessment (IGA) Score of 0 or 1 | 41 Participants |
| M1095 120mg - Augmented Load Group | Number of Participants With an Investigator's Global Assessment (IGA) Score of 0 or 1 | 45 Participants |
| Placebo | Number of Participants With an Investigator's Global Assessment (IGA) Score of 0 or 1 | 0 Participants |
| Secukinumab | Number of Participants With an Investigator's Global Assessment (IGA) Score of 0 or 1 | 41 Participants |
Comparison: Null hypotheses were tested at Week 12 (individual M1095 treatment arms would not be different from placebo with respect to achievement of IGA scores of 0 or 1). The primary analysis was based on the intent-to-treat (ITT) population using a non-responder imputation (NRI) for missing values. Primary treatment comparisons versus placebo were made with the two-sided Cochran-Mantel-Haenszel (CMH) test stratified by actual prior biologic use (yes/no) and body weight (\<=90; \>90kg).p-value: <0.0001Cochran-Mantel-Haenszel
Comparison: Null hypotheses were tested at Week 12 (individual M1095 treatment arms would not be different from placebo with respect to achievement of IGA scores of 0 or 1). The primary analysis was based on the intent-to-treat (ITT) population using a non-responder imputation (NRI) for missing values. Primary treatment comparisons versus placebo were made with the two-sided Cochran-Mantel-Haenszel (CMH) test stratified by actual prior biologic use (yes/no) and body weight (\<=90; \>90kg).p-value: <0.0001Cochran-Mantel-Haenszel
Comparison: Null hypotheses were tested at Week 12 (individual M1095 treatment arms would not be different from placebo with respect to achievement of IGA scores of 0 or 1). The primary analysis was based on the intent-to-treat (ITT) population using a non-responder imputation (NRI) for missing values. Primary treatment comparisons versus placebo were made with the two-sided Cochran-Mantel-Haenszel (CMH) test stratified by actual prior biologic use (yes/no) and body weight (\<=90; \>90kg).p-value: <0.0001Cochran-Mantel-Haenszel
Comparison: Null hypotheses were tested at Week 12 (individual M1095 treatment arms would not be different from placebo with respect to achievement of IGA scores of 0 or 1). The primary analysis was based on the intent-to-treat (ITT) population using a non-responder imputation (NRI) for missing values. Primary treatment comparisons versus placebo were made with the two-sided Cochran-Mantel-Haenszel (CMH) test stratified by actual prior biologic use (yes/no) and body weight (\<=90; \>90kg).p-value: <0.0001Cochran-Mantel-Haenszel
Comparison: Null hypotheses were tested at Week 12 (individual M1095 treatment arms would not be different from placebo with respect to achievement of IGA scores of 0 or 1). The primary analysis was based on the intent-to-treat (ITT) population using a non-responder imputation (NRI) for missing values. Primary treatment comparisons versus placebo were made with the two-sided Cochran-Mantel-Haenszel (CMH) test stratified by actual prior biologic use (yes/no) and body weight (\<=90; \>90kg).p-value: <0.0001Cochran-Mantel-Haenszel
Secondary
Number of Participants With a Psoriasis Area and Severity Index (PASI) Reduction of 100% (i.e. Clear of Psoriasis)
PASI 100, i.e. a subject's psoriasis has completely cleared at Week 12, compared to baseline.
Time frame: Week 12, as compared to Week 0 (baseline)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| M1095 30mg | Number of Participants With a Psoriasis Area and Severity Index (PASI) Reduction of 100% (i.e. Clear of Psoriasis) | 9 Participants |
| M1095 60mg | Number of Participants With a Psoriasis Area and Severity Index (PASI) Reduction of 100% (i.e. Clear of Psoriasis) | 13 Participants |
| M1095 120mg - Normal Load Group | Number of Participants With a Psoriasis Area and Severity Index (PASI) Reduction of 100% (i.e. Clear of Psoriasis) | 20 Participants |
| M1095 120mg - Augmented Load Group | Number of Participants With a Psoriasis Area and Severity Index (PASI) Reduction of 100% (i.e. Clear of Psoriasis) | 17 Participants |
| Placebo | Number of Participants With a Psoriasis Area and Severity Index (PASI) Reduction of 100% (i.e. Clear of Psoriasis) | 0 Participants |
| Secukinumab | Number of Participants With a Psoriasis Area and Severity Index (PASI) Reduction of 100% (i.e. Clear of Psoriasis) | 15 Participants |
Secondary
Number of Participants With a Psoriasis Area and Severity Index (PASI) Reduction of 75% (i.e. a 75% Improvement in Psoriasis)
PASI 75, i.e. a subject's psoriasis has cleared by 75% at Week 12, compared to baseline
Time frame: Week 12, as compared to Week 0 (baseline)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| M1095 30mg | Number of Participants With a Psoriasis Area and Severity Index (PASI) Reduction of 75% (i.e. a 75% Improvement in Psoriasis) | 34 Participants |
| M1095 60mg | Number of Participants With a Psoriasis Area and Severity Index (PASI) Reduction of 75% (i.e. a 75% Improvement in Psoriasis) | 46 Participants |
| M1095 120mg - Normal Load Group | Number of Participants With a Psoriasis Area and Severity Index (PASI) Reduction of 75% (i.e. a 75% Improvement in Psoriasis) | 45 Participants |
| M1095 120mg - Augmented Load Group | Number of Participants With a Psoriasis Area and Severity Index (PASI) Reduction of 75% (i.e. a 75% Improvement in Psoriasis) | 46 Participants |
| Placebo | Number of Participants With a Psoriasis Area and Severity Index (PASI) Reduction of 75% (i.e. a 75% Improvement in Psoriasis) | 0 Participants |
| Secukinumab | Number of Participants With a Psoriasis Area and Severity Index (PASI) Reduction of 75% (i.e. a 75% Improvement in Psoriasis) | 48 Participants |
Secondary
Number of Participants With a Psoriasis Area and Severity Index (PASI) Reduction of 90% (i.e. a 90% Improvement in Psoriasis)
PASI 90, i.e. a subject's psoriasis has cleared by 90% at Week 12, compared to baseline
Time frame: Week 12, as compared to baseline
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| M1095 30mg | Number of Participants With a Psoriasis Area and Severity Index (PASI) Reduction of 90% (i.e. a 90% Improvement in Psoriasis) | 19 Participants |
| M1095 60mg | Number of Participants With a Psoriasis Area and Severity Index (PASI) Reduction of 90% (i.e. a 90% Improvement in Psoriasis) | 34 Participants |
| M1095 120mg - Normal Load Group | Number of Participants With a Psoriasis Area and Severity Index (PASI) Reduction of 90% (i.e. a 90% Improvement in Psoriasis) | 37 Participants |
| M1095 120mg - Augmented Load Group | Number of Participants With a Psoriasis Area and Severity Index (PASI) Reduction of 90% (i.e. a 90% Improvement in Psoriasis) | 39 Participants |
| Placebo | Number of Participants With a Psoriasis Area and Severity Index (PASI) Reduction of 90% (i.e. a 90% Improvement in Psoriasis) | 0 Participants |
| Secukinumab | Number of Participants With a Psoriasis Area and Severity Index (PASI) Reduction of 90% (i.e. a 90% Improvement in Psoriasis) | 34 Participants |