Moderate to Severe Chronic Plaque Psoriasis
Conditions
Keywords
psoriasis, psoriasis vulgaris, plaque psoriasis, chronic plaque psoriasis
Brief summary
The purpose of this study was to evaluate the safety and effectiveness of an investigational drug called doxercalciferol in participants with moderate to severe chronic plaque psoriasis, in comparison with a placebo (sugar pill). All study related care was provided including doctor visits, physical exams, laboratory tests and study medication. Total length of participation was 28 weeks.
Detailed description
This was a multicenter, randomized, double-blind, placebo-controlled, dose-ranging, parallel group study to evaluate the efficacy and safety of doxercalciferol given orally, once daily for 24 weeks to participants with moderate to severe chronic plaque psoriasis. Participants were randomized and stratified by site and Psoriasis Area Severity Index (PASI) score to one of three active treatment groups or to the placebo group.
Interventions
DRUGDoxercalciferol
DRUGPlacebo
Sponsors
Genzyme, a Sanofi Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participant had moderate to severe chronic plaque psoriasis defined by a body surface area (BSA) involvement greater than or equal to (\>=) 10 percent (%) and plaques with at least a slight elevation above the surrounding normal skin at the Day 1 visit * Participant had a static Physician's Global Assessment (PGA) of moderate or severe at the Day 1 visit * Participant had a minimum PASI score of 10 at the Day 1 visit * Participant was a candidate to receive systemic psoriasis therapy in the opinion of the Investigator * Participant of childbearing potential, was willing to use an effective contraceptive method throughout the study, which included barrier methods, hormones, or intrauterine devices
Exclusion criteria
* Used vitamin D analogues, multivitamin supplements containing greater than (\>) 400 international unit (IU) vitamin D, topical retinoids, topical pimecrolimus, and topical tacrolimus within 14 days prior to the Day 1 visit * Used drugs known to influence serum calcium (such as lithium, digoxin, thiazide diuretics, teriparatide, bisphosphonates, and calcitonin) and multivitamin supplements containing calcium and/or calcium-containing antacids exceeding a total of 1 gram/day within 14 days prior to the Day 1 visit * Used keratolytics or coal tar (except shampoo containing coal tar or salicylic acid) within 14 days prior to the Day 1 visit * Used low potency topical corticosteroids (Classes VI and VII), except on the groin, scalp, palms, soles and face, within 14 days prior to the Day 1 visit * Used medium potency topical corticosteroids (Classes III - V) or high potency topical corticosteroids (Classes I and II) within 14 days prior to the Day 1 visit * Used systemic retinoids, systemic corticosteroids, methotrexate, cyclosporine, azathioprine, thioguanine or other systemic immunosuppressant agents within 28 days prior to the Day 1 visit * Used phototherapy, including Ultraviolet B within 14 days or Psoralen plus Ultraviolet A within 28 days prior to the Day 1 visit * Used a biological agent (including, but not limited to, etanercept, adalimumab, efalizumab, infliximab, or alefacept) within 5 half-lives of the drug prior to the Day 1 visit * Used systemic antibiotics within 14 days prior to the Day 1 visit. Antibiotic treatment of infections during the Treatment Period was not excluded * Used investigational drugs within 28 days prior to the Day 1 visit * Current erythrodermic, guttate, generalized pustular, unstable psoriasis or other chronic active skin conditions that may interfere with the study * Screening visit laboratory result exceeded the following limits: alanine transaminase (ALT) or aspartate transaminase (AST) \>1.5 times the upper limit of normal (ULN); bilirubin \>ULN; serum creatinine, calcium, or phosphorus \>ULN; spot urine calcium/creatinine ratio \>0.4 * History of nephrolithiasis * Chronic kidney disease as evidenced by a calculated glomerular filtration rate (GFR) less than (\<) 60 milliliter/minute/1.73 square meter (mL/min/1.73 m\^2) at the screening visit * Symptomatic coronary or cerebral vascular disease, human immunodeficiency virus, active viral hepatitis, or any other clinically significant, unstable medical condition that would interfere with the completion of the study * Clinically significant electrocardiogram (EKG) abnormality at screening * Any evidence of active malignancy except for basal cell carcinoma of the skin. A history of malignancy was not an exclusion * Active ethanol or drug abuse, excluding tobacco use * Active severe psychiatric illness that could interfere with the conduct of the study * Pregnant or breast-feeding women * Known allergy or hypersensitivity to vitamin D or other ingredients in the study drug formulation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With at Least 50 Percent (%) Reduction in Psoriasis Area Severity Index (PASI) Score at Week 12 or Early Termination | Week 12 or Early Termination | PASI score: range: 0 (no disease) to 72 (maximal disease). Body was divided into head (h), trunk (t), upper (u) and lower (l) extremities. For each section, percent area of skin involved (A) was estimated: 1 (\<10%) to 6 (90% - 100%), and severity was estimated by clinical signs: (erythema \[E\], induration \[I\], and desquamation \[D\]) on a scale: 0=no symptoms, 4=very marked. PASI score= 0.1 (E\[h\] + I\[h\] + D\[h\]) A\[h\] + 0.2 (E\[u\] + I\[u\] + D\[u\]) A\[u\] + 0.3 (E\[t\] + I\[t\] + D\[t\]) A\[t\] + 0.4 (E\[l\] + l\[I\] + D\[l\]) A\[l\]. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With at Least 50 Percent (%) Reduction in Psoriasis Area Severity Index (PASI) Score at Week 24 or Early Termination | Week 24 or Early Termination | PASI score: range: 0 (no disease) to 72 (maximal disease). Body was divided into head (h), trunk (t), upper (u) and lower (l) extremities. For each section, percent area of skin involved (A) was estimated: 1 (\<10%) to 6 (90% - 100%), and severity was estimated by clinical signs: (erythema \[E\], induration \[I\], and desquamation \[D\]) on a scale: 0=no symptoms, 4=very marked. PASI score= 0.1 (E\[h\] + I\[h\] + D\[h\]) A\[h\] + 0.2 (E\[u\] + I\[u\] + D\[u\]) A\[u\] + 0.3 (E\[t\] + I\[t\] + D\[t\]) A\[t\] + 0.4 (E\[l\] + l\[I\] + D\[l\]) A\[l\]. |
| Percentage of Participants With Static Physician's Global Assessment (PGA) Score of Clear or Almost Clear at Week 12, 24 or Early Termination | Week 12 or Early Termination, Week 24 or Early Termination | Static PGA of psoriasis is scored on a 5-point scale (0 = clear to 4 = severe), reflecting a global consideration of the erythema, induration and scaling across all psoriatic lesions. Clear (erythema: no, scale: no, induration: no thickness); Almost Clear (erythema: light pink, scale: fine scale, induration: barely palpable); Mild (erythema: light red, scale: coarse scale on most lesions, induration: slight but visible elevation, indistinct edges); Moderate (erythema: red, scale: coarse adherent scale predominates, induration: moderate elevation with edges); and Severe (erythema: dark red to purple, scale: thickened adherent scale, induration: marked thickness distinct and pronounced edges). Percentage of participants with static PGA score of clear or almost clear are reported. |
Countries
United States
Participant flow
Recruitment details
The study was conducted at 19 centers in the United States of America between April 01, 2008 and June 09, 2009.
Pre-assignment details
A total of 195 participants were screened of which 84 (43.1%) were screen failures; main reason for screen failure was participant did not qualify for randomization. A total of 111 participants were randomized.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo matching to doxercalciferol capsules orally once daily up to Week 24. | 27 |
| Doxercalciferol 2.5 mcg/Day Doxercalciferol 2.5 microgram (mcg) capsule orally once daily up to Week 24. | 31 |
| Doxercalciferol 5 mcg/Day Doxercalciferol 5 mcg capsules orally once daily up to Week 24. | 28 |
| Doxercalciferol 7.5 mcg/Day Doxercalciferol 7.5 mcg capsules orally once daily up to Week 24. | 25 |
| Total | 111 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 3 | 0 |
| Overall Study | Lost to Follow-up | 3 | 3 | 0 | 3 |
| Overall Study | Serum Calcium >11.5 milligram/deciliter | 0 | 0 | 0 | 1 |
| Overall Study | Undefined | 1 | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 5 | 4 | 7 | 4 |
| Overall Study | Worsening of Psoriasis | 4 | 1 | 1 | 4 |
Baseline characteristics
| Characteristic | Total | Doxercalciferol 2.5 mcg/Day | Placebo | Doxercalciferol 5 mcg/Day | Doxercalciferol 7.5 mcg/Day |
|---|---|---|---|---|---|
| Age, Continuous | 44.5 years STANDARD_DEVIATION 13.6 | 40.5 years STANDARD_DEVIATION 12.4 | 44.0 years STANDARD_DEVIATION 11.9 | 49.9 years STANDARD_DEVIATION 12.6 | 44.2 years STANDARD_DEVIATION 16.3 |
| Body Mass Index (BMI) | 32.3 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 8.1 | 33.9 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 8.3 | 32.4 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 7.5 | 30.1 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 6.5 | 32.7 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 9.8 |
| Race/Ethnicity, Customized Asian | 3 participants | 1 participants | 1 participants | 1 participants | 0 participants |
| Race/Ethnicity, Customized Black or African American | 7 participants | 3 participants | 2 participants | 0 participants | 2 participants |
| Race/Ethnicity, Customized Multiple | 2 participants | 0 participants | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 2 participants | 0 participants | 2 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized White | 97 participants | 27 participants | 22 participants | 26 participants | 22 participants |
| Sex: Female, Male Female | 40 Participants | 11 Participants | 9 Participants | 10 Participants | 10 Participants |
| Sex: Female, Male Male | 71 Participants | 20 Participants | 18 Participants | 18 Participants | 15 Participants |
| Week 0/Day 1 Psoriasis Area Severity Index (PASI) Score Greater Than (>) 16 | 50 participants | 15 participants | 12 participants | 12 participants | 11 participants |
| Week 0/Day 1 Psoriasis Area Severity Index (PASI) Score Less Than or Equal to (<=) 16 | 61 participants | 16 participants | 15 participants | 16 participants | 14 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 8 / 27 | 16 / 31 | 14 / 28 | 5 / 25 |
| serious Total, serious adverse events | 0 / 27 | 2 / 31 | 1 / 28 | 1 / 25 |
Outcome results
Primary
Percentage of Participants With at Least 50 Percent (%) Reduction in Psoriasis Area Severity Index (PASI) Score at Week 12 or Early Termination
PASI score: range: 0 (no disease) to 72 (maximal disease). Body was divided into head (h), trunk (t), upper (u) and lower (l) extremities. For each section, percent area of skin involved (A) was estimated: 1 (\<10%) to 6 (90% - 100%), and severity was estimated by clinical signs: (erythema \[E\], induration \[I\], and desquamation \[D\]) on a scale: 0=no symptoms, 4=very marked. PASI score= 0.1 (E\[h\] + I\[h\] + D\[h\]) A\[h\] + 0.2 (E\[u\] + I\[u\] + D\[u\]) A\[u\] + 0.3 (E\[t\] + I\[t\] + D\[t\]) A\[t\] + 0.4 (E\[l\] + l\[I\] + D\[l\]) A\[l\].
Time frame: Week 12 or Early Termination
Population: The Full Analysis Set (FAS) included all safety set-evaluable participants with at least one post-baseline PASI assessment after the date of first dose in the treatment period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With at Least 50 Percent (%) Reduction in Psoriasis Area Severity Index (PASI) Score at Week 12 or Early Termination | 20.0 percentage of participants |
| Doxercalciferol 2.5 mcg/Day | Percentage of Participants With at Least 50 Percent (%) Reduction in Psoriasis Area Severity Index (PASI) Score at Week 12 or Early Termination | 20.0 percentage of participants |
| Doxercalciferol 5 mcg/Day | Percentage of Participants With at Least 50 Percent (%) Reduction in Psoriasis Area Severity Index (PASI) Score at Week 12 or Early Termination | 17.9 percentage of participants |
| Doxercalciferol 7.5 mcg/Day | Percentage of Participants With at Least 50 Percent (%) Reduction in Psoriasis Area Severity Index (PASI) Score at Week 12 or Early Termination | 20.0 percentage of participants |
Comparison: Estimate of the log odds, relative to the Placebo, in participants with at least 50 % reduction in PASI score at Week 12 or early termination was analyzed using exact logistic regression model adjusted for site and baseline PASI strata (\<=16, \>16).p-value: 195% CI: [0.17, 4.22]Regression, Exact Logistic
Comparison: Estimate of the log odds, relative to the Placebo, in participants with at least 50 % reduction in PASI score at Week 12 or early termination was analyzed using exact logistic regression model adjusted for site and baseline PASI strata (\<=16, \>16).p-value: 0.99295% CI: [0.13, 4.14]Regression, Exact Logistic
Comparison: Estimate of the log odds, relative to the Placebo, in participants with at least 50 % reduction in PASI score at Week 12 or early termination was analyzed using exact logistic regression model adjusted for site and baseline PASI strata (\<=16, \>16).p-value: 195% CI: [0.15, 4.59]Regression, Exact Logistic
Secondary
Percentage of Participants With at Least 50 Percent (%) Reduction in Psoriasis Area Severity Index (PASI) Score at Week 24 or Early Termination
PASI score: range: 0 (no disease) to 72 (maximal disease). Body was divided into head (h), trunk (t), upper (u) and lower (l) extremities. For each section, percent area of skin involved (A) was estimated: 1 (\<10%) to 6 (90% - 100%), and severity was estimated by clinical signs: (erythema \[E\], induration \[I\], and desquamation \[D\]) on a scale: 0=no symptoms, 4=very marked. PASI score= 0.1 (E\[h\] + I\[h\] + D\[h\]) A\[h\] + 0.2 (E\[u\] + I\[u\] + D\[u\]) A\[u\] + 0.3 (E\[t\] + I\[t\] + D\[t\]) A\[t\] + 0.4 (E\[l\] + l\[I\] + D\[l\]) A\[l\].
Time frame: Week 24 or Early Termination
Population: FAS included all safety set-evaluable participants with at least one post-baseline PASI assessment after the date of first dose in the treatment period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With at Least 50 Percent (%) Reduction in Psoriasis Area Severity Index (PASI) Score at Week 24 or Early Termination | 36.0 percentage of participants |
| Doxercalciferol 2.5 mcg/Day | Percentage of Participants With at Least 50 Percent (%) Reduction in Psoriasis Area Severity Index (PASI) Score at Week 24 or Early Termination | 20.0 percentage of participants |
| Doxercalciferol 5 mcg/Day | Percentage of Participants With at Least 50 Percent (%) Reduction in Psoriasis Area Severity Index (PASI) Score at Week 24 or Early Termination | 21.4 percentage of participants |
| Doxercalciferol 7.5 mcg/Day | Percentage of Participants With at Least 50 Percent (%) Reduction in Psoriasis Area Severity Index (PASI) Score at Week 24 or Early Termination | 32.0 percentage of participants |
Secondary
Percentage of Participants With Static Physician's Global Assessment (PGA) Score of Clear or Almost Clear at Week 12, 24 or Early Termination
Static PGA of psoriasis is scored on a 5-point scale (0 = clear to 4 = severe), reflecting a global consideration of the erythema, induration and scaling across all psoriatic lesions. Clear (erythema: no, scale: no, induration: no thickness); Almost Clear (erythema: light pink, scale: fine scale, induration: barely palpable); Mild (erythema: light red, scale: coarse scale on most lesions, induration: slight but visible elevation, indistinct edges); Moderate (erythema: red, scale: coarse adherent scale predominates, induration: moderate elevation with edges); and Severe (erythema: dark red to purple, scale: thickened adherent scale, induration: marked thickness distinct and pronounced edges). Percentage of participants with static PGA score of clear or almost clear are reported.
Time frame: Week 12 or Early Termination, Week 24 or Early Termination
Population: FAS included all safety set-evaluable participants with at least one post-baseline PASI assessment after the date of first dose in the treatment period.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With Static Physician's Global Assessment (PGA) Score of Clear or Almost Clear at Week 12, 24 or Early Termination | Week 12 or Early Termination | 0 percentage of participants |
| Placebo | Percentage of Participants With Static Physician's Global Assessment (PGA) Score of Clear or Almost Clear at Week 12, 24 or Early Termination | Week 24 or Early Termination | 8.0 percentage of participants |
| Doxercalciferol 2.5 mcg/Day | Percentage of Participants With Static Physician's Global Assessment (PGA) Score of Clear or Almost Clear at Week 12, 24 or Early Termination | Week 24 or Early Termination | 3.3 percentage of participants |
| Doxercalciferol 2.5 mcg/Day | Percentage of Participants With Static Physician's Global Assessment (PGA) Score of Clear or Almost Clear at Week 12, 24 or Early Termination | Week 12 or Early Termination | 6.7 percentage of participants |
| Doxercalciferol 5 mcg/Day | Percentage of Participants With Static Physician's Global Assessment (PGA) Score of Clear or Almost Clear at Week 12, 24 or Early Termination | Week 12 or Early Termination | 3.6 percentage of participants |
| Doxercalciferol 5 mcg/Day | Percentage of Participants With Static Physician's Global Assessment (PGA) Score of Clear or Almost Clear at Week 12, 24 or Early Termination | Week 24 or Early Termination | 10.7 percentage of participants |
| Doxercalciferol 7.5 mcg/Day | Percentage of Participants With Static Physician's Global Assessment (PGA) Score of Clear or Almost Clear at Week 12, 24 or Early Termination | Week 12 or Early Termination | 0 percentage of participants |
| Doxercalciferol 7.5 mcg/Day | Percentage of Participants With Static Physician's Global Assessment (PGA) Score of Clear or Almost Clear at Week 12, 24 or Early Termination | Week 24 or Early Termination | 16.0 percentage of participants |