Plaque Psoriasis
Conditions
Brief summary
This was a 12-week treatment, multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-ranging study to evaluate the efficacy and safety of DC-806 in participants with moderate to severe plaque psoriasis. This study evaluated the efficacy, safety, tolerability, and pharmacokinetics (PK) of multiple oral doses of DC-806 in participants with moderate to severe plaque psoriasis.
Interventions
DRUGDC-806
DC-806 was supplied as tablets to be administered orally.
OTHERPlacebo
Matching placebo was supplied as tablets to be administered orally.
Sponsors
DICE Therapeutics, Inc., a wholly owned subsidiary of Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
The Sponsor, participants, Investigators, and study staff responsible for any study procedures was blinded.
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Male or female, 18 to 70 years of age * Body mass index (BMI) of 18 to 40 kg/m2 * All of the following psoriasis criteria: * Clinical diagnosis of plaque psoriasis for ≥6 months before the Baseline visit * Stable moderate to severe chronic plaque psoriasis, defined as ≥10% BSA psoriasis involvement, sPGA score of ≥3, and PASI score ≥12 at the Screening and Baseline visits * Candidate for phototherapy or systemic therapy, as assessed by the Investigator * Women of childbearing potential (WOCBP) and men who are sexually active with WOCBP must be willing to use a highly effective method of contraception during the study and for ≥30 days after the last dose of study drug * Willing to discontinue topical and/or systemic therapies for psoriasis before the first dose of study drug Key
Exclusion criteria
* Have had a clinically significant flare of psoriasis during the 12 weeks before the Baseline visit, as assessed by the Investigator * History of erythrodermic psoriasis, generalized or localized pustular psoriasis, predominantly guttate psoriasis, medication-induced or medication-exacerbated psoriasis * History of chronic infections including human immunodeficiency virus (HIV) or viral hepatitis (hepatitis B virus \[HBV\], hepatitis C virus \[HCV\]) * History of active tuberculosis (TB) * History or evidence of active infection (including but not limited to coronavirus disease 2019 \[COVID-19\] infection) and/or febrile illness within 7 days, serious infections leading to hospitalization and intravenous antibiotic treatment within 90 days, or serious infection requiring antibiotic treatment within 30 days before the first dose of study drug * History of malignancy or lymphoproliferative disease except resected cutaneous squamous cell or basal cell carcinoma that has been treated without recurrence * Presence of active suicidal ideation, or positive suicide behavior using the Baseline/Screening version of the Columbia Suicide Severity Rating Scale (C-SSRS) and with either of the following criteria: * History of suicide attempt (including an actual attempt, interrupted attempt, or aborted attempt) within 5 years before the Screening visit * Suicidal ideation in the past month before the Screening visit as indicated by a positive response (Yes) to either Question 4 or Question 5 of the Baseline/Screening version of the C-SSRS * Participant has experienced primary failure (no response at approved doses after ≥3 months of therapy) to one or more therapeutic agents targeted to IL-17 (including but not limited to secukinumab, ixekizumab, brodalumab, bimekizumab) * Systemic use of known strong and moderate cytochrome P450 (CYP)3A4 inhibitors or strong CYP3A4 inducers from Screening through the end of the study * A 12-lead electrocardiogram (ECG) at Screening that demonstrates clinically significant abnormalities or criteria associated with QT interval abnormalities including prolongation of QT interval corrected for heart rate using Fridericia's formula (QTcF) (\>500 msec) * Laboratory values meeting the following criteria within the screening period before the first dose of study drug: * Serum aspartate transaminase ≥2× upper limit of normal (ULN) * Serum alanine transaminase ≥2×ULN * Serum total, direct, or indirect bilirubin ≥2.0 mg/dL; except for participants with isolated elevation of indirect bilirubin relating to a confirmed diagnosis of Gilbert syndrome * Estimated glomerular filtration rate (GFR) by simplified 4-variable Modification of Diet in Renal Disease (MDRD) formula \<45 mL/min/1.73m2 * Total white blood cell count \<3000/μL * Absolute neutrophil count \<1500/μL * Platelet count \<100,000/μL * Hemoglobin \<9 g/dL * In the opinion of the Investigator or Sponsor, have any uncontrolled clinically significant laboratory abnormality that would affect interpretation of study data or the participant's enrollment in the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving ≥75% Reduction From Baseline in Psoriasis Area and Severity Index (PASI-75) at Week 12 | Week 12 | Participants achieving a PASI-75 without the use of other background antipsoriasis therapy were considered responders. The PASI quantifies the severity of a psoriasis based on lesion severity and the percent of body surface area (BSA) affected. Erythema, thickness, 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 sum of severity scores for erythema, thickness, and scaling is multiplied by the degree of involvement for each anatomic region, and then multiplied by a constant corresponding to the region's percent BSA (0.1, 0.3, 0.2, and 0.4 for the above 4 regions, respectively). The resultant score for each anatomic region is then summed to yield the final PASI score. It ranges from 0 to 72, with higher scores reflecting greater disease severity. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and TEASs Leading to Treatment Discontinuations | Baseline through End of follow-up (Up to 16 weeks) | * A TEAE was defined as any adverse event that began on or after the first dose of study drug or began before the first dose of study drug and worsened on or after the first dose of study drug. * An SAE is any untoward medical occurrence that results in 1 of the following: death, initial or prolonged inpatient hospitalization, a life-threatening experience (that is, immediate risk of dying), persistent or significant disability/incapacity, congenital anomaly/birth defect, or important medical events that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require intervention to prevent 1 of the other outcomes listed in the definition above. |
Countries
Canada, Czechia, Germany, Hungary, Poland, Spain, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received placebo tablets orally twice daily for 12 weeks. | 44 |
| DC-806 200 mg BID Participants received 200 mg of DC-806 tablets orally twice daily for 12 weeks. | 44 |
| DC-806 400 mg BID Participants received 400 mg of DC-806 tablets orally twice daily for 12 weeks. | 46 |
| DC-806 600 mg QD Participants received 600 mg of DC-806 tablets orally once daily for 12 weeks. | 47 |
| DC-806 800 mg BID Participants received 800 mg of DC-806 tablets orally twice daily for 12 weeks. | 47 |
| Total | 228 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Eligibility criteria not met | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Investigator's decision | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 2 | 2 | 2 | 1 |
| Overall Study | Pregnancy of his partner | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Significant protocol noncompliance | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Sponsor's decision | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 11 | 10 | 4 | 3 | 2 |
Baseline characteristics
| Characteristic | Placebo | DC-806 200 mg BID | DC-806 400 mg BID | DC-806 600 mg QD | DC-806 800 mg BID | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 46.7 years STANDARD_DEVIATION 14.24 | 42.3 years STANDARD_DEVIATION 12.68 | 46.0 years STANDARD_DEVIATION 12.35 | 41.6 years STANDARD_DEVIATION 14.25 | 43.4 years STANDARD_DEVIATION 13.76 | 44.0 years STANDARD_DEVIATION 13.51 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 4 Participants | 2 Participants | 6 Participants | 4 Participants | 21 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 39 Participants | 38 Participants | 43 Participants | 40 Participants | 41 Participants | 201 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 1 Participants | 1 Participants | 2 Participants | 6 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 3 Participants | 2 Participants | 3 Participants | 5 Participants | 19 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 0 Participants | 3 Participants | 1 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 1 Participants | 0 Participants | 1 Participants | 5 Participants |
| Race (NIH/OMB) White | 35 Participants | 36 Participants | 43 Participants | 41 Participants | 40 Participants | 195 Participants |
| Sex: Female, Male Female | 11 Participants | 16 Participants | 14 Participants | 14 Participants | 17 Participants | 72 Participants |
| Sex: Female, Male Male | 33 Participants | 28 Participants | 32 Participants | 33 Participants | 30 Participants | 156 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 43 | 0 / 44 | 0 / 46 | 0 / 48 | 0 / 47 |
| other Total, other adverse events | 5 / 43 | 10 / 44 | 6 / 46 | 15 / 48 | 10 / 47 |
| serious Total, serious adverse events | 0 / 43 | 0 / 44 | 0 / 46 | 0 / 48 | 1 / 47 |
Outcome results
Primary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and TEASs Leading to Treatment Discontinuations
* A TEAE was defined as any adverse event that began on or after the first dose of study drug or began before the first dose of study drug and worsened on or after the first dose of study drug. * An SAE is any untoward medical occurrence that results in 1 of the following: death, initial or prolonged inpatient hospitalization, a life-threatening experience (that is, immediate risk of dying), persistent or significant disability/incapacity, congenital anomaly/birth defect, or important medical events that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require intervention to prevent 1 of the other outcomes listed in the definition above.
Time frame: Baseline through End of follow-up (Up to 16 weeks)
Population: All participants from the safety analyses set.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and TEASs Leading to Treatment Discontinuations | TEAEs | 12 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and TEASs Leading to Treatment Discontinuations | TEASs leading to treatment discontinuations | 1 Participants |
| Placebo | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and TEASs Leading to Treatment Discontinuations | SAEs | 0 Participants |
| DC-806 200 mg BID | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and TEASs Leading to Treatment Discontinuations | SAEs | 0 Participants |
| DC-806 200 mg BID | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and TEASs Leading to Treatment Discontinuations | TEAEs | 19 Participants |
| DC-806 200 mg BID | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and TEASs Leading to Treatment Discontinuations | TEASs leading to treatment discontinuations | 0 Participants |
| DC-806 400 mg BID | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and TEASs Leading to Treatment Discontinuations | SAEs | 0 Participants |
| DC-806 400 mg BID | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and TEASs Leading to Treatment Discontinuations | TEAEs | 20 Participants |
| DC-806 400 mg BID | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and TEASs Leading to Treatment Discontinuations | TEASs leading to treatment discontinuations | 0 Participants |
| DC-806 600 mg QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and TEASs Leading to Treatment Discontinuations | TEAEs | 22 Participants |
| DC-806 600 mg QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and TEASs Leading to Treatment Discontinuations | TEASs leading to treatment discontinuations | 0 Participants |
| DC-806 600 mg QD | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and TEASs Leading to Treatment Discontinuations | SAEs | 0 Participants |
| DC-806 800 mg BID | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and TEASs Leading to Treatment Discontinuations | SAEs | 1 Participants |
| DC-806 800 mg BID | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and TEASs Leading to Treatment Discontinuations | TEAEs | 27 Participants |
| DC-806 800 mg BID | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and TEASs Leading to Treatment Discontinuations | TEASs leading to treatment discontinuations | 0 Participants |
Primary
Percentage of Participants Achieving ≥75% Reduction From Baseline in Psoriasis Area and Severity Index (PASI-75) at Week 12
Participants achieving a PASI-75 without the use of other background antipsoriasis therapy were considered responders. The PASI quantifies the severity of a psoriasis based on lesion severity and the percent of body surface area (BSA) affected. Erythema, thickness, 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 sum of severity scores for erythema, thickness, and scaling is multiplied by the degree of involvement for each anatomic region, and then multiplied by a constant corresponding to the region's percent BSA (0.1, 0.3, 0.2, and 0.4 for the above 4 regions, respectively). The resultant score for each anatomic region is then summed to yield the final PASI score. It ranges from 0 to 72, with higher scores reflecting greater disease severity.
Time frame: Week 12
Population: All randomized participants who received at least one dose of the study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Achieving ≥75% Reduction From Baseline in Psoriasis Area and Severity Index (PASI-75) at Week 12 | 13.6 percentage of participants |
| DC-806 200 mg BID | Percentage of Participants Achieving ≥75% Reduction From Baseline in Psoriasis Area and Severity Index (PASI-75) at Week 12 | 6.8 percentage of participants |
| DC-806 400 mg BID | Percentage of Participants Achieving ≥75% Reduction From Baseline in Psoriasis Area and Severity Index (PASI-75) at Week 12 | 21.7 percentage of participants |
| DC-806 600 mg QD | Percentage of Participants Achieving ≥75% Reduction From Baseline in Psoriasis Area and Severity Index (PASI-75) at Week 12 | 17 percentage of participants |
| DC-806 800 mg BID | Percentage of Participants Achieving ≥75% Reduction From Baseline in Psoriasis Area and Severity Index (PASI-75) at Week 12 | 36.2 percentage of participants |
p-value: 0.483995% CI: [0.07, 2.37]Fisher Exact
p-value: 0.411195% CI: [0.51, 6.49]Fisher Exact
p-value: 0.774495% CI: [0.36, 4.99]Fisher Exact
p-value: 0.016495% CI: [1.15, 12.37]Fisher Exact