An Effectiveness and Safety Study of CNTO 1275 in Patient... | NCT00267956

ID	Type	Description	Link
C0743T10	Other Identifier	Centocor
2005-003525-92	EudraCT Number

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
CNTO1275 (ustekinumab)	Experimental	Group 1: Patients will receive CNTO 1275 63 mg at Weeks 0, 1, 2, and 3. At Weeks 12 and 16, patients will receive placebo to maintain the blind.	Drug: CNTO 1275 63 mg Drug: Placebo
Placebo	Placebo Comparator	Group 2: Patients will receive placebo at Weeks 0, 1, 2, and 3. At Weeks 12 and 16, patients will receive CNTO 1275 63 mg.	Drug: CNTO 1275 63 mg Drug: Placebo

Interventions

Name	Type	Description	Arm Group Labels	Other Names
CNTO 1275 63 mg	Drug	The patients will receive 90 mg (or 63 mg after filtration) subcutaneous injection on Weeks 0, 1, 2, and 3; Placebo subcutaneous injection on Weeks 12 and 16.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Participants With an American College of Rheumatology (ACR) 20 Response at Week 12	ACR 20 response is an improvement of greater than or equal to 20 percentage in both tender and swollen joint count and in 3 to 5 assessments (patient's assessment of pain visual analog scale [VAS] with 0, no pain to 10, worst pain; patient's and physician's global assessment of disease activity VAS scales: overall disease activity [0, very well to 10, very poor and 0, no arthritis activity to 10, extremely active, respectively]; Health Assessment Questionnaire [HAQ]: 20-questions on life activities [0, no difficulty to 3, inability to perform a task]; C-reactive protein[CRP]).	Week 0 to Week 12

Secondary Outcomes

Measure	Description	Time Frame
Number of Participants With an American College of Rheumatology (ACR) 50 Response at Week 12	ACR 50 response is an improvement of greater than or equal to 50 percentage in both tender and swollen joint count and in 3 to 5 assessments (patient's assessment of pain visual analog scale [VAS] with 0, no pain to 10, worst pain; patient's and physician's global assessment of disease activity VAS scales: overall disease activity [0, very well to 10, very poor and 0, no arthritis activity to 10, extremely active, respectively]; Health Assessment Questionnaire [HAQ]: 20-questions on life activities [0, no difficulty to 3, inability to perform a task]; C-reactive protein[CRP]).

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Have had active psoriatic arthritis for at least 6 months prior to administration of first study injection
Have an active plaque psoriasis (defined as a lesion of at least 2 cm in diameter), but not in armpits, on chest between breasts or groin
Women of childbearing potential and all men must be using an effective method of birth control measures (eg, abstinence, oral contraceptives, intrauterine device, barrier method with spermicide, or surgical sterilization) and must agree to continue to use such measures until 12 months after receiving the last injection of study agent
Have an active arthritis despite disease-modifying anti-rheumatic drugs (DMARD) such as leflunomide, gold, sulfasalazine, but not including methotrexate) or non-steroidal anti-inflammatory agents (NSAID) such as aspirin, ibuprofen, naproxen) therapy. DMARD therapy is defined as taking a DMARD for at least 3 months, or evidence of not tolerating DMARD. NSAID therapy is defined as taking an NSAID for at least 4 weeks
If the patients are using methotrexate (MTX), they should have started treatment at least 3 months prior to the first administration of study agent and should have no serious toxic side effects attributable to MTX
Have no signs or symptoms suggestive of active tuberculosis upon medical history, physical examination and chest X-ray

Exclusion Criteria:

Have received DMARDs, other than methotrexate, within 4 weeks prior to the randomization visit
Have used any biologic within the previous 3 months or 5 times the half-life of the biologic, whichever is longer
Have received any oral, intravenous or intramuscular medications/treatments that could affect psoriasis (including, but not limited to, oral or injectable corticosteroids, retinoids, 1,25 dihydroxy vitamin D3 and analogues, psoralens, sulfasalazine, hydroxyurea, fumaric acid derivatives, or phototherapy) within 4 weeks of the randomization visit and/or have used topical medications/treatments that could affect psoriasis (eg, corticosteroids, anthralin, calcipotriene, topical vitamin D derivatives, retinoids, tazarotene, methoxsalen, trimethylpsoralens) within 2 weeks of the randomization visit
Have a history of chronic or recurrent infectious disease, including but not limited to chronic renal infection, chronic chest infection (eg, bronchiectasis), recurrent urinary tract infection (recurrent pyelonephritis or chronic nonremitting cystitis), or open, draining, or infected skin wounds or ulcers
Have a history of latent or active granulomatous infection, including tuberculosis (TB), histoplasmosis, or coccidioidomycosis, prior to screening
Have current signs or symptoms of severe, progressive, or uncontrolled kidney, liver, blood, intestinal, hormonal, lung, heart, nervous, brain, or psychiatric disease
Have any known cancer or have a history of cancer within the previous 5 years (with the following exception: have had basal cell carcinoma or squamous cell carcinoma in situ of the skin that has been treated, with no evidence of recurrence)

Name	Affiliation	Role
Centocor, Inc. Clinical Trial	Centocor, Inc.	Study Director

PubMed Identifier	Type	Citation	Retractions
30739254	Derived	Ghosh S, Gensler LS, Yang Z, Gasink C, Chakravarty SD, Farahi K, Ramachandran P, Ott E, Strober BE. Ustekinumab Safety in Psoriasis, Psoriatic Arthritis, and Crohn's Disease: An Integrated Analysis of Phase II/III Clinical Development Programs. Drug Saf. 2019 Jun;42(6):751-768. doi: 10.1007/s40264-019-00797-3.
19217154	Derived

Results Section

Participant Flow Module

ID	Title	Description
FG000	Placebo (CP)	Controlled period (Week 0-12) - Placebo Group
FG001	Ustekinumab x 4 (CP)	Controlled period (Week 0-12) - Ustekinumab x 4 Group

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Group I: Placebo	Participants received subcutaneous (SC) placebo injection at Weeks 0, 1,2, and 3. At Week (Wk) 12 and Wk 16, placebo participants crossed over to receive ustekinumab (CNTO 1275) SC.
BG001	Group II: Ustekinumab x 4	Participants received SC injection of ustekinumab 90 mg at Wk 0,1,2, and 3. At Wk 12 and Wk 16, participants received placebo SC to maintain the blind. After the first 36 participants were randomized, Centocor became aware that some vials of other study agents not used in this study contained black particulate matter and the filtration procedure was implemented. The resulting dose of ustekinumab after filtration was approximately 0.70 mL, equivalent to 63 mg.
BG002	Total	Total of all reporting groups

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Participants With an American College of Rheumatology (ACR) 20 Response at Week 12

ACR 20 response is an improvement of greater than or equal to 20 percentage in both tender and swollen joint count and in 3 to 5 assessments (patient's assessment of pain visual analog scale [VAS] with 0, no pain to 10, worst pain; patient's and physician's global assessment of disease activity VAS scales: overall disease activity [0, very well to 10, very poor and 0, no arthritis activity to 10, extremely active, respectively]; Health Assessment Questionnaire [HAQ]: 20-questions on life activities [0, no difficulty to 3, inability to perform a task]; C-reactive protein[CRP]).

Intent to treat. All participants randomized were included in the analysis according to the assigned treatment groups. Participant is considered a non- responder if the participant has used any pre-specified prohibited medications or discontinued due to lack of efficacy or participant who have no data for all ACR components at Week 12.

Posted

Number

Participants

Week 0 to Week 12

ID	Title	Description
OG000	Group I: Placebo	Participants received subcutaneous (SC) placebo injection at Weeks 0, 1,2, and 3. At Week (Wk) 12 and Wk 16, placebo participants crossed over to receive ustekinumab (CNTO 1275) SC.
OG001	Group II: Ustekinumab x 4	Participants received SC injection of ustekinumab 90 mg at Wk 0,1,2, and 3. At Wk 12 and Wk 16, participants received placebo SC to maintain the blind. After the first 36 participants were randomized, Centocor became aware that some vials of other study agents not used in this study contained black particulate matter and the filtration procedure was implemented. The resulting dose of ustekinumab after filtration was approximately 0.70 mL, equivalent to 63 mg.

Units	Counts
Participants	OG00070 OG00176

Title

Denominators

Categories

Title	Measurements
	OG00010 OG00132

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Hypothesis: No difference between ustekinumab x 4 and placebo at a significant level of 0.05. Sample Size and power: With 70 partcipants in each treatment group, 5000 repetitions. Assuming a 20% ACR20 response in placebo participants regardless of prior anti-TNF exposure and a 35% ACR 20 and 45% ACR20 response in ustekinumab group for participants who had prior anti-TNF exposure, and who had no prior anti-TNF exposures, the power to detect the treatment difference is 0.85.	Cochran-Mantel-Haenszel (CMH) chi-square	Stratified by subject's prior anti-Tumor Necrosis Factor (TNF) exposure status (Yes/No).	<0.001	The study is designed to maintain a Type I error of 0.05 or less for the primary analysis						95

Secondary

Number of Participants With an American College of Rheumatology (ACR) 50 Response at Week 12

ACR 50 response is an improvement of greater than or equal to 50 percentage in both tender and swollen joint count and in 3 to 5 assessments (patient's assessment of pain visual analog scale [VAS] with 0, no pain to 10, worst pain; patient's and physician's global assessment of disease activity VAS scales: overall disease activity [0, very well to 10, very poor and 0, no arthritis activity to 10, extremely active, respectively]; Health Assessment Questionnaire [HAQ]: 20-questions on life activities [0, no difficulty to 3, inability to perform a task]; C-reactive protein[CRP]).

Posted

Number

Participants

Week 12

ID	Title	Description
OG000	Group I: Placebo	Participants received subcutaneous (SC) placebo injection at Weeks 0, 1,2, and 3. At Week (Wk) 12 and Wk 16, placebo participants crossed over to receive ustekinumab (CNTO 1275) SC.
OG001	Group II: Ustekinumab x 4	Participants received SC injection of ustekinumab 90 mg at Wk 0,1,2, and 3. At Wk 12 and Wk 16, participants received placebo SC to maintain the blind. After the first 36 participants were randomized, Centocor became aware that some vials of other study agents not used in this study contained black particulate matter and the filtration procedure was implemented. The resulting dose of ustekinumab after filtration was approximately 0.70 mL, equivalent to 63 mg.

Secondary

Number of Participants With an American College of Rheumatology (ACR) 70 Response at Week 12

ACR 70 response is an improvement of greater than or equal to 70 percentage in both tender and swollen joint count and in 3 to 5 assessments (patient's assessment of pain visual analog scale [VAS] with 0, no pain to 10, worst pain; patient's and physician's global assessment of disease activity VAS scales: overall disease activity [0, very well to 10, very poor and 0, no arthritis activity to 10, extremely active, respectively]; Health Assessment Questionnaire [HAQ]: 20-questions on life activities [0, no difficulty to 3, inability to perform a task]; C-reactive protein[CRP]).

Intent to treat. All participant randomized were included in the analysis according to the assigned treatment groups. Participant is considered a non- responder if the participant has used any pre-specified prohibited medications or discontinued due to lack of efficacy or participant who have no data for all ACR components at Week 12.

Posted

Number

Participants

Week 12

ID	Title	Description
OG000	Group I: Placebo	Participants received subcutaneous (SC) placebo injection at Weeks 0, 1,2, and 3. At Week (Wk) 12 and Wk 16, placebo participants crossed over to receive ustekinumab (CNTO 1275) SC.
OG001	Group II: Ustekinumab x 4	Participants received SC injection of ustekinumab 90 mg at Wk 0,1,2, and 3. At Wk 12 and Wk 16, participants received placebo SC to maintain the blind. After the first 36 participants were randomized, Centocor became aware that some vials of other study agents not used in this study contained black particulate matter and the filtration procedure was implemented. The resulting dose of ustekinumab after filtration was approximately 0.70 mL, equivalent to 63 mg.

Secondary

Change in Health Assessment Questionnaire (HAQ) at Week 12

The HAQ is a 20-question instrument assesses the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). Responses in each functional area are scored from 0, indicating no difficulty, to 3, indicating inability to perform a task in that area based on the worst score from the questions that pertain to that task. The HAQ score is determined by the average of the 8 scores.

Participants were included in the analysis according to the assigned treatment groups. Zero change is imputed if the participant has used any pre-specified prohibited medications or discontinued due to lack of efficacy. Other missing data were not imputed.

Posted

Median

Inter-Quartile Range

Scores on scale

Week 0 to Week 12

ID	Title	Description
OG000	Group I: Placebo	Participants received subcutaneous (SC) placebo injection at Weeks 0, 1,2, and 3. At Week (Wk) 12 and Wk 16, placebo participants crossed over to receive ustekinumab (CNTO 1275) SC.
OG001	Group II: Ustekinumab x 4	Participants received SC injection of ustekinumab 90 mg at Wk 0,1,2, and 3. At Wk 12 and Wk 16, participants received placebo SC to maintain the blind. After the first 36 participants were randomized, Centocor became aware that some vials of other study agents not used in this study contained black particulate matter and the filtration procedure was implemented. The resulting dose of ustekinumab after filtration was approximately 0.70 mL, equivalent to 63 mg.

Secondary

Number of Participants With Psoriasis Area and Severity Index (PASI) Score of 75 Percent at Week 12

Number of participants achieving greater than or equal to 75 perccentage mprovement PASI at Week 12. PASI is widely used tool for the measurement of severity of psoriasis. This is a test of how bad person's psoriasis is. The combine redness, scaling, and thickness, as well as overall body involvement determine the PASI score. The scale ranges from 0 (best) to 72 (worst).

All participants randomized with baseline ≥ 3% body surface area (BSA) psoriatic involvement and with evaluable measurement are included in the analysis according to the assigned treatment groups. Participant is considered a non- responder if the participant has used any pre-specified prohibited medications or discontinued due to lack of efficacy.

Posted

Number

Participants

Week 12

ID	Title	Description
OG000	Group I: Placebo	Participants received subcutaneous (SC) placebo injection at Weeks 0, 1,2, and 3. At Week (Wk) 12 and Wk 16, placebo participants crossed over to receive ustekinumab (CNTO 1275) SC.
OG001	Group II: Ustekinumab x 4	Participants received SC injection of ustekinumab 90 mg at Wk 0,1,2, and 3. At Wk 12 and Wk 16, participants received placebo SC to maintain the blind. After the first 36 participants were randomized, Centocor became aware that some vials of other study agents not used in this study contained black particulate matter and the filtration procedure was implemented. The resulting dose of ustekinumab after filtration was approximately 0.70 mL, equivalent to 63 mg.

Secondary

Change in Dermatology Life Quality Index (DLQI) at Week 12

Change in Dermatology Life Quality Index (DLQI) from baseline at Week 12. The DLQI is a 10 item questionnaire, is designed to assess the impact of the disease on a participant's quality of life, can be used to assess 6 different aspects that may affect quality of life: symptoms and feelings, daily activities, leisure, work or school performance, personal relationships, and treatment. The score ranges from 0 (better quality of life) to 30 (worse quality of life).

All participants randomized with baseline ≥ 3% body surface area psoriatic involvement were included in the analysis according to the assigned treatment groups. Zero change is imputed if the participant has used any pre-specified prohibited medications or discontinued due to lack of efficacy. Other missing data were not imputed.

Posted

Median

Inter-Quartile Range

Scores on scale

Week 0 to Week 12

ID	Title	Description
OG000	Group I: Placebo	Participants received subcutaneous (SC) placebo injection at Weeks 0, 1,2, and 3. At Week (Wk) 12 and Wk 16, placebo participants crossed over to receive ustekinumab (CNTO 1275) SC.
OG001	Group II: Ustekinumab x 4	Participants received SC injection of ustekinumab 90 mg at Wk 0,1,2, and 3. At Wk 12 and Wk 16, participants received placebo SC to maintain the blind. After the first 36 participants were randomized, Centocor became aware that some vials of other study agents not used in this study contained black particulate matter and the filtration procedure was implemented. The resulting dose of ustekinumab after filtration was approximately 0.70 mL, equivalent to 63 mg.

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo (CP)	Controlled period (Week 0-12) - Placebo Group	3	70	19	70
EG001	Ustekinumab x 4 (CP)	Controlled period (Week 0-12) - Ustekinumab (CNTO 1275) x 4 Group	0	76	29	76
EG002	Placebo -> Ustekinumab (After CP)	After Controlled period (Week 12-36) - receiving Placebo at Weeks 0, 1, 2, and 3 -> receiving ustekinumab at Week 12 and Week 16	4	57	19	57
EG003	Ustekinumab x 4 (After CP)	After Controlled period (Week 12-36) - receiving ustekinumab at Weeks 0, 1, 2, and 3 -> receiving Placebo at Week 12 and Week 16	2	74	24	74

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Cardiac failure congestive	Cardiac disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected70 at risk EG0010 affected76 at risk EG0021 affected57 at risk EG0030 affected74 at risk
Myocardial infarction	Cardiac disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected70 at risk EG0010 affected76 at risk EG0021 affected57 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected70 at risk EG0010 affected76 at risk EG0021 affected57 at risk EG003
Gastric ulcer haemorrhage	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected70 at risk EG0010 affected76 at risk EG0021 affected57 at risk EG003
Chest pain	General disorders	MedDRA 10.0	Systematic Assessment	EG0001 affected70 at risk EG0010 affected76 at risk EG0021 affected57 at risk EG003
Respiratory tract infection	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0000 affected70 at risk EG0010 affected76 at risk EG0020 affected57 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected70 at risk EG0010 affected76 at risk EG0021 affected57 at risk EG003
Haemorrhagic stroke	Nervous system disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected70 at risk EG0010 affected76 at risk EG0021 affected57 at risk EG003
Syncope	Nervous system disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected70 at risk EG0010 affected76 at risk EG0020 affected57 at risk EG003
Hypertension	Vascular disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected70 at risk EG0010 affected76 at risk EG0021 affected57 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Diarrhoea	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0002 affected70 at risk EG0015 affected76 at risk EG0022 affected57 at risk EG0032 affected74 at risk
Nausea	Gastrointestinal disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected70 at risk EG0012 affected76 at risk EG0023 affected57 at risk EG003
Bronchitis	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0000 affected70 at risk EG0010 affected76 at risk EG0023 affected57 at risk EG003
Influenza	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0004 affected70 at risk EG0011 affected76 at risk EG0022 affected57 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0002 affected70 at risk EG0018 affected76 at risk EG0024 affected57 at risk EG003
Sinusitis	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0000 affected70 at risk EG0011 affected76 at risk EG0023 affected57 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 10.0	Systematic Assessment	EG0006 affected70 at risk EG00110 affected76 at risk EG0026 affected57 at risk EG003
C-reactive protein increased	Investigations	MedDRA 10.0	Systematic Assessment	EG0001 affected70 at risk EG0011 affected76 at risk EG0022 affected57 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 10.0	Systematic Assessment	EG0000 affected70 at risk EG0011 affected76 at risk EG0021 affected57 at risk EG003
Headache	Nervous system disorders	MedDRA 10.0	Systematic Assessment	EG0004 affected70 at risk EG0015 affected76 at risk EG0022 affected57 at risk EG003

Facility	Status	City	State	ZIP	Country	Contacts
		Macon	Georgia		United States

ID	Term
D025242	Spondylarthropathies
D025241	Spondylarthritis
D013166	Spondylitis
D013122	Spinal Diseases
D001847	Bone Diseases
D009140	Musculoskeletal Diseases
D001168	Arthritis
D007592	Joint Diseases
D011565	Psoriasis
D017444	Skin Diseases, Papulosquamous
D012871	Skin Diseases
D017437	Skin and Connective Tissue Diseases

ID	Term
D061067	Antibodies, Monoclonal, Humanized
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D012712	Serum Globulins
D005916	Globulins