Clinical trial NCT00955279: A Study to Evaluate the Safety and Effectiveness of Ustekinumab or Golimumab Administered Subcutaneously (SC) in Patients With Sarcoidosis
Official title: A Phase 2, Multicenter, Randomized, Double-Blind, Parallel-group, Placebo-controlled Study Evaluating the Safety and Efficacy of Treatment With Ustekinumab or Golimumab in Subjects With Chronic Sarcoidosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Sarcoidosis
Keywords: Ustekinumab
CNTO 1275
Stelara
Golimumab
CNTO 148
Simponi
Sarcoidosis
Sarcoid
Pulmonary Sarcoidosis
Skin Sarcoidosis
Lead sponsor: Centocor, Inc.
Sponsor class: INDUSTRY
First posted: 2009-08-10
Enrollment: 173
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study tests the safety and effectiveness of ustekinumab or golimumab compared to placebo (placebo looks like the drugs being studied, but has no active ingredients). The purpose of this research study is to determine if ustekinumab or golimumab is safe and to determine its effects (good and bad) on patients with chronic sarcoidosis with pulmonary and/or skin involvement. Patients with pulmonary involvement constitute the primary population for analysis, and patients with skin involvement constitute the secondary population; a patient may be in both populations. The study will be conducted at approximately 40 sites globally.

Detailed description: Ustekinumab is approved for dosing in patients with psoriasis and golimumab is approved for dosing in patients with rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis. This study will use either drug in patients with chronic sarcoidosis. Ustekinumab and golimumab are being tested to see if they may be useful in treating chronic sarcoidosis. This study will compare the effects (both good and bad) of ustekinumab and golimumab to those of placebo. The purpose of this study is to evaluate the safety and effectiveness of ustekinumab and golimumab (administered as individual treatments) in patients with chronic sarcoidosis with lung and/or skin involvement who still have symptoms even though receiving current therapy. About 180 patients will take part in the study. While in this study, patients may not take part in any other medical research studies. Ustekinumab and golimumab are not approved by the national health authorities for treatment of chronic sarcoidosis; therefore, they can only be used in a research setting to treat this condition. The screening phase of the study, where the doctor will determine if a patient is eligible for the study, will last 1 to 4 weeks. Patients are put into 1 of 3 groups and each group will get a different treatment. The results of the golimumab group and the ustekinumab group are compared to placebo. Patients will either receive ustekinumab, golimumab or placebo. Placebo looks like ustekinumab and golimumab and is given in the same way, by injection, but contains no active drug. Patients will receive study agent until Week 24 and will continue to be followed through Week 44 for assessment of safety and any other effects after discontinuation of therapy. The patient will continue to take all sarcoidosis medication(s) at current, stable dose for the first part of the study. If the patient remained on a stable steroid dose from Week 0 through Week 16 of the study, the study doctor will begin to taper (lower) the steroid dose. The steroid taper will continue through to the end of the Week 28 visit. The patient will continue to take their other sarcoidosis medication(s) at the same dose for the rest of the study. An independent Data Monitoring Committee will be responsible for reviewing the safety data for the study. Patients will be in the study for about 48 weeks. The end of the study is defined as the last visit of the last patient. A site-specific substudy is being implemented to collect serum and lung samples from patients who are currently enrolled in this study. A separate protocol is being implemented to collect lung fluid and serum samples from normal, healthy subjects to be used as comparators for similar samples obtained in the 1275148SCD2001 substudy. Patients will be randomly assigned to 1 of 3 treatment groups: ustekinumab (180 mg at Week 0, followed by 90 mg at Weeks 8, 16, and 24 with placebo at Weeks 4, 12, and 20), golimumab (200 mg at Week 0, followed by 100 mg at Weeks 4, 8, 12, 16, 20, and 24) or placebo (at Weeks 0, 4, 8, 12, 16, 20, and 24) administered by SC injection.

Eligibility criteria: Inclusion Criteria:

* Patients must have sarcoidosis with onset date of \>=2 years prior to screening with at least 1 of the following: a. pulmonary sarcoidosis defined as 1) a diagnosis of sarcoidosis with evidence of lung parenchymal disease (Stage II, III or IV on chest radiograph), and 2) an FVC of \>=45% and \<=80% of predicted normal value at screening, and 3) an MRC dyspnea score of \>2 at screening, and 4) a 6 minute walk distance between 100 to 550 meters at screening, and 5) \<=15% absolute change in percent-predicted FVC at baseline relative to screening AND/OR b. skin sarcoidosis defined as 1) active chronic skin lesions for \>=3 months either on face or elsewhere on body that have not resolved on current systemic and/or local therapy, and 2) have either: a single lesion of \>=2 cm in longest dimension or multiple (3 or more) lesions with at least 1 lesion having a longest dimension of \>=1 cm, and 3) have an SPGA score \>=2 at screening
* have been receiving treatment with oral corticosteroids and/or 1 or more immunomodulators for \>=3-month period immediately prior to screening
* on a stable dose of these medications for \>=4 weeks before screening

Exclusion Criteria:

* Have a diagnosis of other significant respiratory disorder other than sarcoidosis that would complicate the evaluation of response to treatment
* Have a smoking history of \>=20 pack years
* Have used an investigational drug within 1 month prior to screening or within 5 half-lives of the investigational agent, whichever is longer
* have received previous administration of a treatment with any other therapeutic agent targeted at reducing TNFalpha within 6 months or 5 half-lives of the agent, whichever is longer, prior to screening
* Patients who have previously received biologic anti-TNFalpha agents outside of the above period are allowed to enter the study
* Have previously used cyclophosphamide
* Have previously used or received local therapy (including local injections) within 3 months before the screening visit or used or received treatment with prescription topical creams within 1 month before the screening visit for treatment of sarcoidosis skin lesions
* Have used any therapeutic agent targeted at reducing IL-12 and/or IL-23, including but not limited to, ustekinumab and briakinumab within 6 months or 5 half-lives of the agent, whichever is longer, prior to the screening visit
* have received natalizumab or agents that deplete or modulate the activity of B cells or T cells within 12 months of screening, or, if after receiving these agents, evidence is available at screening of persistent depletion of the targeted lymphocyte population
* have used any antibody (monoclonal or polyclonal) or antibody-based agents \<= 6 months or within 5 half-lives of the biologic prior to the screening visit, whichever is longer

Primary outcomes:
measure: Change From Baseline in Percent-predicted Forced Vital Capacity (FVC) at Week 16
timeFrame: Baseline (Day 1) and Week 16
Secondary outcomes:
measure: Change From Baseline in 6-minute Walk Distance at Week 28
timeFrame: Baseline (Day 1) and Week 28
measure: Change From Baseline in the St. George's Respiratory Questionnaire (SGRQ) Total Score at Week 28
timeFrame: Baseline (Day 1) and Week 28
measure: Percentage of Responders With a Score of Less Than or Equal to 1 on Skin Physician's Global Assessment (SPGA) Scale
timeFrame: Week 28
measure: Change From Baseline in Percent-predicted Forced Vital Capacity (FVC) at Week 28
timeFrame: Baseline (Day 1) and Week 28
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Los Angeles
country: United States
state: California
city: Denver
country: United States
state: Colorado
city: New Haven
country: United States
state: Connecticut
city: Chicago
country: United States
state: Illinois
city: Baltimore
country: United States
state: Maryland
city: Ann Arbor
country: United States
state: Michigan
city: Detroit
country: United States
state: Michigan
city: St Louis
country: United States
state: Missouri
city: Lebanon
country: United States
state: New Hampshire
city: New York
country: United States
state: New York
city: Chapel Hill
country: United States
state: North Carolina
city: Charlotte
country: United States
state: North Carolina
city: Greenville
country: United States
state: North Carolina
city: Cincinnati
country: United States
state: Ohio
city: Cleveland
country: United States
state: Ohio
city: Columbus
country: United States
state: Ohio
city: Philadelphia
country: United States
state: Pennsylvania
city: Pittsburgh
country: United States
state: Pennsylvania
city: Charleston
country: United States
state: South Carolina
city: Spartanburg
country: United States
state: South Carolina
city: Memphis
country: United States
state: Tennessee
city: Dallas
country: United States
state: Texas
city: Colchester
country: United States
state: Vermont
city: Brussel
country: Belgium
city: Leuven
country: Belgium
city: Liege
country: Belgium
city: Arhus C
country: Denmark
city: Arhus
country: Denmark
city: Hellerup
country: Denmark
city: Kobenhavn Nv
country: Denmark
city: Bobigny
country: France
city: Lille
country: France
city: Marseille
country: France
city: Montpellier
country: France
city: Paris
country: France
city: Bad Berka
country: Germany
city: Berlin
country: Germany
city: Essen
country: Germany
city: Freiburg
country: Germany
city: Hannover
country: Germany
city: München
country: Germany
city: Amsterdam Zuidoost
country: Netherlands
city: Rotterdam
country: Netherlands
city: Sittard
country: Netherlands
city: Oslo
country: Norway
city: Trondheim
country: Norway
city: Bucuresti
country: Romania
city: Bristol
country: United Kingdom
city: London
country: United Kingdom
city: Portsmouth
country: United Kingdom
city: Sheffield
country: United Kingdom
city: Southampton
country: United Kingdom
Study officials:
affiliation: Centocor, Inc.
name: Centocor, Inc. Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Judson MA, Mack M, Beaumont JL, Watt R, Barnathan ES, Victorson DE. Validation and important differences for the Sarcoidosis Assessment Tool. A new patient-reported outcome measure. Am J Respir Crit Care Med. 2015 Apr 1;191(7):786-95. doi: 10.1164/rccm.201410-1785OC.
citation: Crommelin HA, Vorselaars AD, van Moorsel CH, Korenromp IH, Deneer VH, Grutters JC. Anti-TNF therapeutics for the treatment of sarcoidosis. Immunotherapy. 2014;6(10):1127-43. doi: 10.2217/imt.14.65.
citation: Judson MA, Baughman RP, Costabel U, Drent M, Gibson KF, Raghu G, Shigemitsu H, Barney JB, Culver DA, Hamzeh NY, Wijsenbeek MS, Albera C, Huizar I, Agarwal P, Brodmerkel C, Watt R, Barnathan ES. Safety and efficacy of ustekinumab or golimumab in patients with chronic sarcoidosis. Eur Respir J. 2014 Nov;44(5):1296-307. doi: 10.1183/09031936.00000914. Epub 2014 Jul 17.