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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02745145




Registration number
NCT02745145
Ethics application status
Date submitted
15/04/2016
Date registered
20/04/2016
Date last updated
18/06/2019

Titles & IDs
Public title
Abituzumab in SSc-ILD
Scientific title
A Phase II, Randomized, Double-blind, Placebo Controlled, Parallel-group, Multicenter Trial to Evaluate the Efficacy and Safety of Abituzumab in Subjects With Systemic Sclerosis-associated Interstitial Lung Disease (SSc-ILD)
Secondary ID [1] 0 0
2015-005023-11
Secondary ID [2] 0 0
EMR 200017-014
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Systemic Sclerosis-associated Interstitial Lung Disease 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Inflammatory and Immune System 0 0 0 0
Autoimmune diseases
Skin 0 0 0 0
Dermatological conditions
Skin 0 0 0 0
Other skin conditions

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Abituzumab 1500 mg
Treatment: Drugs - Abituzumab 500 mg
Treatment: Drugs - Placebo

Experimental: Abituzumab 1500 milligram (mg) -

Experimental: Abituzumab 500 mg -

Placebo comparator: Placebo -


Treatment: Drugs: Abituzumab 1500 mg
Participants received Abituzumab 1500 mg administered as an intravenous infusion for 1 hour every 4 weeks up to Week 64.

Treatment: Drugs: Abituzumab 500 mg
Participants received Abituzumab 500 mg administered as an intravenous infusion for 1 hour every 4 weeks up to Week 64.

Treatment: Drugs: Placebo
Participants received Placebo matched to Abituzumab administered as an intravenous infusion for 1 hour every 4 weeks up to Week 64.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change From Baseline in Absolute Forced Vital Capacity (FVC) at Week 52
Timepoint [1] 0 0
Baseline, Week 52
Secondary outcome [1] 0 0
Change From Baseline in Dyspnea as Measured by the Mahler's Transition Dyspnea Index (TDI) at Week 52
Timepoint [1] 0 0
Baseline, Week 52
Secondary outcome [2] 0 0
Absolute Change From Baseline in St. George Respiratory Questionnaire (SGRQ) Total Score at Week 52
Timepoint [2] 0 0
Baseline, Week 52
Secondary outcome [3] 0 0
Absolute Change From Baseline in Modified Rodnan Skin Score (mRSS) at Week 52 in Participants With Diffuse Cutaneous Skin Involvement at Baseline
Timepoint [3] 0 0
Baseline, Week 52
Secondary outcome [4] 0 0
Absolute Change From Baseline in Quantitative Lung Fibrosis (QLF) in the Region of Highest Baseline Severity at Week 52
Timepoint [4] 0 0
Baseline, Week 52
Secondary outcome [5] 0 0
Overall Survival (OS)
Timepoint [5] 0 0
Time from date of randomization until death, assessed up to 2 years
Secondary outcome [6] 0 0
Number of Participants With Clinically Meaningful Progression of Systemic Sclerosis (SSc) by Meeting Criterion 1 (Interstitial Lung Disease [ILD])
Timepoint [6] 0 0
upto Week 52
Secondary outcome [7] 0 0
Number of Participants With Clinically Meaningful Progression of Systemic Sclerosis (SSc) by Meeting Criterion 2 (SSc Progression Other Than ILD)
Timepoint [7] 0 0
upto Week 52
Secondary outcome [8] 0 0
Number of Participants With Clinically Meaningful Progression
Timepoint [8] 0 0
upto Week 52
Secondary outcome [9] 0 0
Number of Participants With Absolute Decrease From Baseline of FVC Percentage (%) Predicted Greater Than or Equal to (>=) 10% on 2 or More Consecutive Occasions at Least 4 Weeks Apart
Timepoint [9] 0 0
upto Week 52

Eligibility
Key inclusion criteria
* Participants were eligible for this trial if they fulfill all of the following inclusion criteria:
* Female or male participants aged between 18 and 75 years of age who provide informed written consent.
* Participants fulfilling the 2013 American College of Rheumatology (ACR) /European League Against Rheumatism criteria for classification of systemic sclerosis (SSc).
* Disease duration of less than (<) 7 years from first non-Raynaud's symptom.
* Participants who had been taking the same mycophenolate regimen (stable dose) in a range of 1.5 to 3 gram (g)/day of Mycophenolate mofetil (MMF) or 1080 to 2160 milligram/day (mg/day) of MPS for at least 2 months prior to the Screening Visit and continued through Day 1 of the Treatment Period, of the lung on HRCT according to central reading.
* According to central readings: Diffusion capacity of the lung for carbon monoxide (DLCO) greater than or equal to (>=) 30 percent (%) predicted, Forced vital capacity (FVC) 40% to 85% predicted, and a ratio of FVC % predicted to DLCO % predicted >=1.8 is acceptable if right heart catheterization within 3 months of screening revealed no pulmonary hypertension. If these criteria were met, then High-resolution computed tomography (HRCT) of lungs will be performed, and must show at least 5% fibrosis for participants to be eligible.
* Female participants of childbearing potential must use a highly effective method of contraception to prevent pregnancy for 4 weeks before randomization and must agree to continue to practice adequate contraception for the duration of their participation in the trial (up to the last Safety Follow-Up Visit). For the purposes of this trial, women of childbearing potential were defined as "All female participants after puberty unless they were post-menopausal for at least 2 years or weresurgically sterile." Highly effective contraception is defined as 2 barrier methods (eg, female diaphragm and male condoms); or 1 barrier method with at least one of the following: spermicide, a hormonal method, or an intrauterine device. Note that because mycophenolate affects the metabolism of oral contraceptives and may reduce their effectiveness, women receiving mycophenolate who were using oral contraceptives for birth control should employ an additional contraceptive method (for example, male or female barrier method).
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Any condition that in the Investigator's opinion constitutes an inappropriate risk or a contraindication for participation in the trial or that could interfere with the trial objectives, conduct, or evaluation.
* Renal impairment (glomerular filtration rate [GFR] <45 mL/minute (min)/1.73 square meter (m^2) as calculated by the Modification of Diet in Renal Disease equation) calculated as follows: GFR (mL/min per 1.73 m^2) = 175*(standardized serum creatinine)^-1.154 * (age)^-0.203 * 1.212 (if black) * 0.742 (if female)
* Urine dipstick with >=3 plus protein and urine protein:creatinine ratio more than (>)2 mg/mg.
* Known diagnosis of obstructive lung disease/emphysema (Forced Expiratory Volume [FEV1]/FVC ratio <0.65) and/or significant emphysematous change on screening HRCT.
* Other clinically significant abnormalities on HRCT not attributable to scleroderma or emphysema as defined above.
* Known diagnosis of other significant respiratory disorders.
* Pulmonary hypertension that fulfills at least one of the following:

* Current/planned treatment with systemic therapy targeted to Pulmonary arterial hypertension (PAH) or pulmonary hypertension;
* History of transthoracic echocardiography showing at least one of the following: tricuspid regurgitation jet >2.8 m/sec, right atrial enlargement (major dimension >53 mm), right ventricular enlargement (mid cavity dimension >35 mm), moderate to severe left ventricular dysfunction;
* N-terminal prohormone brain natriuretic peptide >3*Upper limit of normal (ULN)
* Considered by the investigator to require initiation of systemic targeted PAH therapy.
* Current clinical diagnosis of another inflammatory connective tissue disease (eg, systemic lupus erythematosus, rheumatoid arthritis, ankylosing spondylitis, or dermato/polymyositis). Concomitant scleroderma-associated myopathy, fibromyalgia, and secondary Sjögren's were allowed.
* Suspected/confirmed significant aspiration within the previous 6 months, for example.

* viral/bacterial/fungal infection
* infection requiring hospitalization
* Treatment with parenteral anti-infectives within 4 weeks prior/during Screening Period
* Completion of oral anti-infectives within 2 weeks of Screening
* Use of oral anti-infectives during Screening Period
* Vaginal candidiasis
* onychomycosis
* chronically suppressed oral herpes simplex virus
* Prophylaxis for Pneumocystis jiroveci pneumonia
* History of/positive Human immunodeficiency virus, hepatitis C antibody and/or polymerase chain reaction or Hepatitis B surface antigen and/or hepatitis B core antibody (total and/or Immunoglobulin M) antibody at screening.
* History of/current diagnosis of active tuberculosis (TB), or untreated latent TB infection (LTBI).
* Presence of uncontrolled or New York Heart Association Class 3 or 4 congestive heart failure.
* History of cancer, except adequately treated (ie, no evidence of recurrence within 5 years prior screening) basal cell/squamous cell carcinomas of the skin (=3 total in lifetime) or carcinoma in situ of the cervix.
* Known hypersensitivity to abituzumab DS or DP.
* Current smoker (incl. e-cigarettes) / smoking within 4 weeks of screening.
* Use of agents other than mycophenolate considered by the Investigator to have immunomodulating, immunosuppressive, or potential scleroderma disease-modifying properties within 2 months of screening visit is not allowed (or 5 months prior to the Screening Visit for cyclophosphamide). Hydroxychloroquine or chloroquine were permitted if dose has been stable for at least 4 weeks before the screening visit.
* Use of systemic corticosteroids above 10 mg/day prednisone equivalent within 4 weeks prior until last dose of study drug. Inhaled and topical corticosteroids were permitted.
* Use of any biologic agent within 12 weeks or 5 half-lives, whichever is longer, of screening.
* History of anti-CD20 B-cell depleting therapy, eg, rituximab or ocrelizumab within 6 months prior to screening visit.
* Use of anticoagulant or antiplatelet agent (aspirin =<350 mg daily is permitted).
* Clinically significant or predefined abnormalities in lab tests:

* Aspartate aminotransferase, Alanine aminotransferase or alkaline phosphatase level >2.5*ULN;
* Total bilirubin >1.5*ULN (other than that due to known Gilbert's disease);
* Hemoglobin <5.0 mmol/L (9 g/dL), white blood cell count <2.5*10^9/L, or platelets <100*10^9/L);
* International normalized ratio or partial thromboplastin time >2.0*ULN;
* Thyroid-stimulating hormone <0.01 or >=7.1 milli international units per litre (mIU/L).
* Inability to receive IV infusions.
* History of alcohol/drug abuse for 1 year prior screening.
* Pregnancy/breastfeeding/lactation within 3 months prior screening.
* History of thrombotic, thromboembolic, or abnormal bleeding events including concomitant antiphospholipid antibody syndrome. Participants with known lupus anticoagulant and/or anticardiolipin and/or anti-b2 glycoprotein antibodies alone should not be excluded.
* Legal incapacity/limited legal capacity.
* Receipt/planned live/attenuated vaccination within 12 weeks prior screening until 3 months after last dose of study drug. Seasonal influenza vaccination with inactivated vaccine formulation is permitted.
* Major surgery requiring hospitalization within 4 weeks prior screening, planned major surgery for the duration of the trial. Participants with lung resection.
* History of/planned major organ or hematopoietic stem cell/marrow transplant.
* Severe gastrointestinal disease requiring parenteral nutrition. Other protocol defined exclusion criteria could apply.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
31/05/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
30/05/2018
Sample size
Target
Accrual to date
Final
24
Recruitment in Australia
Recruitment state(s)
NSW,SA
Recruitment hospital [1] 0 0
Research site - Camperdown
Recruitment hospital [2] 0 0
Research site - Woodville South
Recruitment postcode(s) [1] 0 0
- Camperdown
Recruitment postcode(s) [2] 0 0
- Woodville South
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Connecticut
Country [3] 0 0
United States of America
State/province [3] 0 0
District of Columbia
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Massachusetts
Country [7] 0 0
United States of America
State/province [7] 0 0
Michigan
Country [8] 0 0
United States of America
State/province [8] 0 0
New Jersey
Country [9] 0 0
United States of America
State/province [9] 0 0
New York
Country [10] 0 0
United States of America
State/province [10] 0 0
Oregon
Country [11] 0 0
United States of America
State/province [11] 0 0
Tennessee
Country [12] 0 0
United States of America
State/province [12] 0 0
Texas
Country [13] 0 0
Argentina
State/province [13] 0 0
Buenos Aires
Country [14] 0 0
Argentina
State/province [14] 0 0
Tucuman
Country [15] 0 0
Argentina
State/province [15] 0 0
San Juan
Country [16] 0 0
Canada
State/province [16] 0 0
British Columbia
Country [17] 0 0
Canada
State/province [17] 0 0
Ontario
Country [18] 0 0
Israel
State/province [18] 0 0
Haifa
Country [19] 0 0
Israel
State/province [19] 0 0
Jerusalem
Country [20] 0 0
Israel
State/province [20] 0 0
Kfar- Saba
Country [21] 0 0
Israel
State/province [21] 0 0
Petach Tikva
Country [22] 0 0
Israel
State/province [22] 0 0
Ramat Gan
Country [23] 0 0
Israel
State/province [23] 0 0
Tel Aviv
Country [24] 0 0
Italy
State/province [24] 0 0
Ancona
Country [25] 0 0
Italy
State/province [25] 0 0
Milano
Country [26] 0 0
Italy
State/province [26] 0 0
Napoli
Country [27] 0 0
Italy
State/province [27] 0 0
Pisa
Country [28] 0 0
Italy
State/province [28] 0 0
Reggio Emilia
Country [29] 0 0
Italy
State/province [29] 0 0
Roma
Country [30] 0 0
Poland
State/province [30] 0 0
Gdansk
Country [31] 0 0
Poland
State/province [31] 0 0
Warszawa
Country [32] 0 0
Poland
State/province [32] 0 0
Lódz
Country [33] 0 0
Spain
State/province [33] 0 0
Madrid
Country [34] 0 0
Spain
State/province [34] 0 0
Valladolid
Country [35] 0 0
United Kingdom
State/province [35] 0 0
Cambridgeshire
Country [36] 0 0
United Kingdom
State/province [36] 0 0
Greater London
Country [37] 0 0
United Kingdom
State/province [37] 0 0
Staffordshire
Country [38] 0 0
United Kingdom
State/province [38] 0 0
Tayside Region
Country [39] 0 0
United Kingdom
State/province [39] 0 0
West Midlands

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
EMD Serono Research & Development Institute, Inc.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Merck KGaA, Darmstadt, Germany
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this trial was to compare two doses of abituzumab with placebo and determine whether abituzumab was more effective, safer, would be better tolerated and could provoke better immune response than placebo in the treatment of participants with SSc-ILD who already receive constant doses of mycophenolate.
Trial website
https://clinicaltrials.gov/study/NCT02745145
Trial related presentations / publications
Khanna D, Tashkin DP, Wells AU, Seibold JR, Wax S, Vazquez-Mateo C, Fleuranceau-Morel P, Damian D, Denton CP. STRATUS: A Phase II Study of Abituzumab in Patients With Systemic Sclerosis-associated Interstitial Lung Disease. J Rheumatol. 2021 Aug;48(8):1295-1298. doi: 10.3899/jrheum.191365. Epub 2020 Oct 1.
Public notes

Contacts
Principal investigator
Name 0 0
Medical Responsible
Address 0 0
EMD Serono Inc., a business of Merck KGaA, Darmstadt, Germany
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT02745145