A Multicentre, Open Label Phase IIIb/IV Study of Subcutaneously Administered Raptiva in the Treatment of Adult Subjects With Moderate to Severe Plaque Psoriasis

• Sponsor: Merck KGaA, Darmstadt, Germany (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00287118
• Collaborator: (none)
• Enrollment: 189
• Location: 1
• Arm: 1
• Actual Duration (Months): 19.1
• Patients Per Site Per Month: 9.9

Study Details

Study Description

Brief Summary

An open-label, multi-center study to establish psoriasis control of moderate to severe plaque psoriasis with Raptiva therapy administered subcutaneously for 24 weeks.

Condition or Disease	Intervention/Treatment	Phase
Candidates for Systemic Therapy for Psoriasis; Psoriasis	Drug: Efalizumab	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 189 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multicentre, Open Label Phase IIIb/IV Study of Subcutaneously Administered Raptiva in the Treatment of Adult Subjects With Moderate to Severe Plaque Psoriasis
• Actual Study Start Date: Oct 27, 2004
• Actual Primary Completion Date: May 30, 2006
• Actual Study Completion Date: May 30, 2006

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Efalizumab	Drug: Efalizumab; Subjects will receive a conditioning dose of 0.7 milligram per kilogram (mg/kg) efalizumab subcutaneously on study Day 0 followed by 1.0 mg/kg efalizumab subcutaneously once a week for 23 weeks.; Other Names: Raptiva

Outcome Measures

Primary Outcome Measures

1. Percentage of Subjects With Physician's Global Assessment (PGA) Ratings of "Excellent" or "Cleared" at Week 24 [Week 24]

   The PGA rating was used to assess the global response of all psoriatic lesions by comparing subject's present condition to baseline photographs or body diagrams. The response was classified as Cleared: 100% improvement of all clinical signs and symptoms compared to baseline; Excellent: 75% to 99% improvement of all signs and symptoms compared to baseline; Good: 50% to 74% improvement of signs and symptoms compared to baseline; Fair: 25% to 49% improvement of signs and symptoms compared to baseline; Slight: 1% to 24% improvement of signs and symptoms compared to baseline; Unchanged: Clinical signs and symptoms unchanged from baseline and Worse: Clinical signs and symptoms deteriorated from baseline.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 17 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• 1. In the opinion of the investigator, candidate for systemic therapy for psoriasis could include:

• Patients with moderate to severe plaque psoriasis defined by Psoriasis Area and Severity Index (PASI) less than (>) 10 and body surface area (BSA) greater than (>) 10

• Patients with the following may also be deemed to require systemic therapy in the judgement of the physician:

• Severe psychosocial disability (in the judgement of the physician), or

• Nail psoriasis, or

• Scalp psoriasis, or

• Palmar plantar psoriasis etc OR

• 1. Subjects who have completed the CLEAR study investigational medicinal product (IMP) 24011 (NCT00256139) and who wish to continue Raptiva (efalizumab) therapy.

• Body weight of 120 kg

• 18 to 75 years old

• For women of childbearing potential and for men whose partner can become pregnant, use of an acceptable method of contraception to prevent pregnancy and agreement to continue to practice an acceptable method of contraception for the duration of their participation in the study up to 3 months after the last dose of Raptiva

• Willingness to hold sun exposure reasonably constant and to avoid use of tanning booths or other ultraviolet (UV) light sources during the study

• Agreement to participate in the study

• Signed informed consent

• Discontinuation of any systemic psoriasis treatment prior to commencement of the study drug. No washout period is required for these agents prior to starting study and receiving first dose of study drug (Raptiva)

• Discontinuation of all biologic agents (other than Raptiva) 3 months prior to receiving first dose of study drug (Raptiva)

• Discontinuation of Psoralen-ultraviolet light A (PUVA), Ultraviolet light B (UVB) treatment 28 days prior to commencement of receiving first dose of study drug.

• Discontinuation of any investigational drug or treatment 3 months prior to study Day 0 or as per washout requirements from previous protocol

• No vaccinations (e.g., tetanus, booster, influenza vaccine) at least 14 days prior to first dose of study drug

• Treatment regimens of b-blockers, Angiotensin-converting enzyme (ACE) inhibitors, antimalarial drugs, quinidine, interferon, or lithium stable for at least 28 days prior to first dose of study drug

Exclusion Criteria:

• Guttate, erythrodermic, or pustular psoriasis as sole or predominant form of psoriasis

• Active rebound of psoriasis during or following discontinuation of the previous Raptiva treatment( PASI >125% from baseline and/or new predominant morphology of psoriasis) when reason was adverse event or lack of efficacy of Raptiva. If it was due to another non drug reason (vaccination, or infection) then the patient can be included in this study.

• History of severe allergic or anaphylactic reactions to humanised monoclonal antibodies

• History of or ongoing uncontrolled bacterial, viral, fungal, or atypical mycobacterial infection

• History of opportunistic infections (e.g., systemic fungal infections, parasites)

• Seropositivity for human immunodeficiency virus (HIV). Patients will undergo mandatory testing at screening. Patients who are positive for HIV will be excluded.

• Pregnancy or lactation

• White blood cell (WBC) count <4000 per Liter (L) or >14,000/L

• Patient with a history of clinically significant thrombocytopenia, bleeding disorders or a platelet count < 00,000 cells/L

• Seropositivity for hepatitis B or C virus Patients will undergo testing at screening. Patients who are positive for hepatitis B antigen or hepatitis C antibody will be excluded.

• Hepatic enzymes >3 times the upper limit of normal

• History of active tuberculosis (TB) or currently undergoing treatment for TB within one year prior to study Day 0. Chest X-ray (within 3 months prior to Study Day 0) is required for high-risk patients. Patients with a positive chest X-ray will be excluded.

• Presence of malignancy within the past 5 years, including lymphoproliferative disorders. Patients with a history of fully resolved basal cell or squamous cell skin cancer may be enrolled.

• Diagnosis of hepatic cirrhosis, regardless of cause or severity

• Serum creatinine >2 times the upper limit of normal

• Hospital admission for cardiac disease, stroke, or pulmonary disease within the last year

• History of substance abuse within the last 5 years

• Any medical condition that, in the judgment of the investigator, would jeopardize the patient's safety following exposure to study drug

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Medical Information Switzerland	Geneva		Switzerland

Sponsors and Collaborators

• Merck KGaA, Darmstadt, Germany

Investigators

• Study Director: Medical Responsible, Merck KGaA, Darmstadt, Germany

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Merck KGaA, Darmstadt, Germany
• ClinicalTrials.gov Identifier: NCT00287118
• Other Study ID Numbers: 25161; CONTROL I Study
• First Posted: Feb 6, 2006
• Last Update Posted: Apr 3, 2018
• Last Verified: Aug 1, 2017

• Additional relevant MeSH terms: Psoriasis

Study Results

Participant Flow

Arm/Group Title	Efalizumab
Arm/Group Description	Subjects received a conditioning dose of 0.7 milligram per kilogram (mg/kg) efalizumab subcutaneously on study Day 0 followed by 1.0 mg/kg efalizumab subcutaneously once a week for 23 weeks.
Period Title: Overall Study
STARTED	189
COMPLETED	137
NOT COMPLETED	52

Baseline Characteristics

Arm/Group Title	Efalizumab
Arm/Group Description	Subjects received a conditioning dose of 0.7 milligram per kilogram (mg/kg) efalizumab subcutaneously on study Day 0 followed by 1.0 mg/kg efalizumab subcutaneously once a week for 23 weeks.
Overall Participants	189
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	46 (12.8)
Sex: Female, Male (Count of Participants)
Female	55 29.1%
Male	134 70.9%

Outcome Measures

1. Primary Outcome

Title	Percentage of Subjects With Physician's Global Assessment (PGA) Ratings of "Excellent" or "Cleared" at Week 24
Description	The PGA rating was used to assess the global response of all psoriatic lesions by comparing subject's present condition to baseline photographs or body diagrams. The response was classified as Cleared: 100% improvement of all clinical signs and symptoms compared to baseline; Excellent: 75% to 99% improvement of all signs and symptoms compared to baseline; Good: 50% to 74% improvement of signs and symptoms compared to baseline; Fair: 25% to 49% improvement of signs and symptoms compared to baseline; Slight: 1% to 24% improvement of signs and symptoms compared to baseline; Unchanged: Clinical signs and symptoms unchanged from baseline and Worse: Clinical signs and symptoms deteriorated from baseline.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

The Intent to Treat (ITT) population consisted of all subjects who received at least 1 dose of trial medication.

Arm/Group Title	Efalizumab
Arm/Group Description	Subjects received a conditioning dose of 0.7 milligram per kilogram (mg/kg) efalizumab subcutaneously on study Day 0 followed by 1.0 mg/kg efalizumab subcutaneously once a week for 23 weeks.
Measure Participants	189
Number (95% Confidence Interval) [percentage of subjects]	46.0

Adverse Events

Arm/Group Title	Efalizumab
Arm/Group Description	Subjects received a conditioning dose of 0.7 milligram per kilogram (mg/kg) efalizumab subcutaneously on study Day 0 followed by 1.0 mg/kg efalizumab subcutaneously once a week for 23 weeks.
All Cause Mortality
	Efalizumab
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Efalizumab
	Affected / at Risk (%)	# Events
Total	21/189 (11.1%)
Cardiac disorders
Tachyarrhythmia	1/189 (0.5%)
Ear and labyrinth disorders
Hypoacusis	1/189 (0.5%)
General disorders
Pyrexia	1/189 (0.5%)
Hepatobiliary disorders
Cholecystitis	1/189 (0.5%)
Infections and infestations
Cytomegalovirus infection	1/189 (0.5%)
Meningitis aseptic	1/189 (0.5%)
Pneumonia	1/189 (0.5%)
Sepsis	1/189 (0.5%)
Tooth abscess	1/189 (0.5%)
Injury, poisoning and procedural complications
Lumbar puncture headache	1/189 (0.5%)
Investigations
Hepatic enzyme increased	1/189 (0.5%)
Prostatic specific antigen increased	1/189 (0.5%)
Musculoskeletal and connective tissue disorders
Arthritis	3/189 (1.6%)
Arthralgia	2/189 (1.1%)
Myalgia	2/189 (1.1%)
Joint swelling	1/189 (0.5%)
Psoriatic arthropathy	1/189 (0.5%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer	1/189 (0.5%)
Nervous system disorders
Intracranial aneurysm	1/189 (0.5%)
Reproductive system and breast disorders
Benign prostatic hyperplasia	1/189 (0.5%)
Skin and subcutaneous tissue disorders
Psoriasis	7/189 (3.7%)
Nail psoriasis	1/189 (0.5%)
Other (Not Including Serious) Adverse Events
	Efalizumab
	Affected / at Risk (%)	# Events
Total	161/189 (85.2%)
Blood and lymphatic system disorders
Leukocytosis	6/189 (3.2%)
Eosinophilia	2/189 (1.1%)
Lymphadenopathy	2/189 (1.1%)
Lymphocytosis	2/189 (1.1%)
Anaemia	1/189 (0.5%)
Lymph node pain	1/189 (0.5%)
Thrombocythaemia	1/189 (0.5%)
Cardiac disorders
Angina pectoris	1/189 (0.5%)
Palpitations	1/189 (0.5%)
Tachycardia	1/189 (0.5%)
Ear and labyrinth disorders
Ear pain	4/189 (2.1%)
Deafness	1/189 (0.5%)
Tinnitus	1/189 (0.5%)
Eye disorders
Conjunctivitis	2/189 (1.1%)
Eye pain	2/189 (1.1%)
Blepharitis	1/189 (0.5%)
Blepharospasm	1/189 (0.5%)
Conjunctival hyperaemia	1/189 (0.5%)
Eye irritation	1/189 (0.5%)
Growth of eyelashes	1/189 (0.5%)
Lacrimation increased	1/189 (0.5%)
Ocular hyperaemia	1/189 (0.5%)
Gastrointestinal disorders
Diarrhoea	14/189 (7.4%)
Nausea	14/189 (7.4%)
Abdominal pain upper	6/189 (3.2%)
Vomiting	6/189 (3.2%)
Dyspepsia	3/189 (1.6%)
Gastritis	3/189 (1.6%)
Toothache	3/189 (1.6%)
Abdominal pain	2/189 (1.1%)
Flatulence	2/189 (1.1%)
Irritable bowel syndrome	2/189 (1.1%)
Abdominal distension	1/189 (0.5%)
Abdominal pain lower	1/189 (0.5%)
Constipation	1/189 (0.5%)
Gingivitis	1/189 (0.5%)
Mouth ulceration	1/189 (0.5%)
Odynophagia	1/189 (0.5%)
Stomatitis	1/189 (0.5%)
Tooth disorder	1/189 (0.5%)
General disorders
Influenza like illness	22/189 (11.6%)
Pyrexia	21/189 (11.1%)
Chills	18/189 (9.5%)
Feeling hot	6/189 (3.2%)
Oedema peripheral	6/189 (3.2%)
Chest pain	4/189 (2.1%)
Asthenia	3/189 (1.6%)
Fatigue	3/189 (1.6%)
Malaise	2/189 (1.1%)
Oedema	2/189 (1.1%)
Pain	2/189 (1.1%)
Feeling cold	1/189 (0.5%)
Hyperthermia	1/189 (0.5%)
Injection site irritation	1/189 (0.5%)
Injection site pain	1/189 (0.5%)
Prostration	1/189 (0.5%)
Thirst	1/189 (0.5%)
Hepatobiliary disorders
Hyperbilirubinaemia	1/189 (0.5%)
Infections and infestations
Influenza	13/189 (6.9%)
Nasopharyngitis	6/189 (3.2%)
Herpes simplex	4/189 (2.1%)
Upper respiratory tract infection	4/189 (2.1%)
Onychomycosis	3/189 (1.6%)
Pneumonia	2/189 (1.1%)
Sinusitis	3/189 (1.6%)
Urinary tract infection	3/189 (1.6%)
Bronchitis	2/189 (1.1%)
Gastroenteritis	2/189 (1.1%)
Tonsillitis	2/189 (1.1%)
Acarodermatitis	1/189 (0.5%)
Body tinea	1/189 (0.5%)
Condyloma acuminatum	1/189 (0.5%)
Cystitis	1/189 (0.5%)
Dental caries	1/189 (0.5%)
Dermatophytosis	1/189 (0.5%)
Enteritis infectious	1/189 (0.5%)
Folliculitis	1/189 (0.5%)
Furuncle	1/189 (0.5%)
Hordeolum	1/189 (0.5%)
Impetigo	1/189 (0.5%)
Nail candida	1/189 (0.5%)
Perineal abscess	1/189 (0.5%)
Pharyngotonsillitis	1/189 (0.5%)
Rash pustular	1/189 (0.5%)
Rhinitis	1/189 (0.5%)
Skin bacterial infection	1/189 (0.5%)
Tinea pedis	1/189 (0.5%)
Tinea versicolour	1/189 (0.5%)
Viral upper respiratory tract infection	1/189 (0.5%)
Injury, poisoning and procedural complications
Eye injury	1/189 (0.5%)
Skin laceration	1/189 (0.5%)
Tooth fracture	1/189 (0.5%)
Investigations
Blood creatine phosphokinase increased	2/189 (1.1%)
Blood creatinine increased	1/189 (0.5%)
Blood glucose increased	1/189 (0.5%)
Blood phosphorus increased	1/189 (0.5%)
Blood pressure increased	1/189 (0.5%)
Blood uric acid increased	1/189 (0.5%)
Culture throat positive	1/189 (0.5%)
Liver function test abnormal	1/189 (0.5%)
Neutrophil count increased	1/189 (0.5%)
Weight decreased	1/189 (0.5%)
Metabolism and nutrition disorders
Diabetes mellitus	3/189 (1.6%)
Hyperglycaemia	3/189 (1.6%)
Anorexia	2/189 (1.1%)
Dyslipidaemia	1/189 (0.5%)
Gout	1/189 (0.5%)
Musculoskeletal and connective tissue disorders
Arthralgia	24/189 (12.7%)
Myalgia	24/189 (12.7%)
Back pain	17/189 (9%)
Arthritis	8/189 (4.2%)
Pain in extremity	8/189 (4.2%)
Monarthritis	3/189 (1.6%)
Psoriatic arthropathy	1/189 (0.5%)
Arthropathy	1/189 (0.5%)
Bone pain	1/189 (0.5%)
Dactylitis	1/189 (0.5%)
Gouty arthritis	1/189 (0.5%)
Intervertebral discitis	1/189 (0.5%)
Muscle contracture	1/189 (0.5%)
Muscle rigidity	1/189 (0.5%)
Muscle spasms	1/189 (0.5%)
Musculoskeletal pain	1/189 (0.5%)
Musculoskeletal stiffness	1/189 (0.5%)
Neck pain	1/189 (0.5%)
Shoulder pain	1/189 (0.5%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Paraproteinaemia	1/189 (0.5%)
Skin papilloma	1/189 (0.5%)
Nervous system disorders
Headache	68/189 (36%)
Dizziness	10/189 (5.3%)
Somnolence	6/189 (3.2%)
Syncope	2/189 (1.1%)
Burning sensation	1/189 (0.5%)
Dysgeusia	1/189 (0.5%)
Syncope vasovagal	1/189 (0.5%)
Tremor	1/189 (0.5%)
Psychiatric disorders
Depression	2/189 (1.1%)
Insomnia	2/189 (1.1%)
Stress	1/189 (0.5%)
Renal and urinary disorders
Dysuria	3/189 (1.6%)
Leukocyturia	1/189 (0.5%)
Nephritis	1/189 (0.5%)
Polyuria	1/189 (0.5%)
Reproductive system and breast disorders
Dysmenorrhoea	1/189 (0.5%)
Erectile dysfunction	1/189 (0.5%)
Genital discharge	1/189 (0.5%)
Ovarian cyst	1/189 (0.5%)
Peyronie's disease	1/189 (0.5%)
Vaginal disorder	1/189 (0.5%)
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal pain	8/189 (4.2%)
Cough	4/189 (2.1%)
Dry throat	2/189 (1.1%)
Dyspnoea	1/189 (0.5%)
Nasal congestion	1/189 (0.5%)
Pharyngeal erythema	1/189 (0.5%)
Skin and subcutaneous tissue disorders
Psoriasis	10/189 (5.3%)
Pruritus	11/189 (5.8%)
Drug eruption	2/189 (1.1%)
Erythema	2/189 (1.1%)
Hyperhidrosis	2/189 (1.1%)
Rash	2/189 (1.1%)
Alopecia	1/189 (0.5%)
Dermatitis atopic	1/189 (0.5%)
Heat rash	1/189 (0.5%)
Prurigo	1/189 (0.5%)
Rash papular	1/189 (0.5%)
Skin exfoliation	1/189 (0.5%)
Skin fissures	1/189 (0.5%)
Vascular disorders
Hypertension	9/189 (4.8%)
Peripheral occlusive disease	1/189 (0.5%)
Phlebitis	1/189 (0.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.