Abituzumab in SSc-ILD

NCT ID: NCT02745145

Last Updated: 2019-06-18

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-05-31
• Study Completion Date: 2018-05-30

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.

Conditions

Systemic Sclerosis-associated Interstitial Lung Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Abituzumab 1500 milligram (mg)

Group Type: EXPERIMENTAL

Abituzumab 1500 mg

Intervention Type: DRUG

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

Abituzumab 500 mg

Group Type: EXPERIMENTAL

Abituzumab 500 mg

Intervention Type: DRUG

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

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Participants received Placebo matched to Abituzumab administered as an intravenous infusion for 1 hour every 4 weeks up to Week 64.

Interventions

Abituzumab 1500 mg

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

Intervention Type: DRUG

Abituzumab 500 mg

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

Intervention Type: DRUG

Placebo

Participants received Placebo matched to Abituzumab administered as an intravenous infusion for 1 hour every 4 weeks up to Week 64.

Intervention Type: DRUG

Eligibility Criteria

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).

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck KGaA, Darmstadt, Germany

INDUSTRY

Sponsor Role: collaborator

EMD Serono Research & Development Institute, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Responsible

Role: STUDY_DIRECTOR

EMD Serono Inc., a business of Merck KGaA, Darmstadt, Germany

Locations

Research site 1

Los Angeles, California, United States

Research site

Los Angeles, California, United States

Research site

Farmington, Connecticut, United States

Research site

Washington D.C., District of Columbia, United States

Research site

Orlando, Florida, United States

Research site

Weston, Florida, United States

Research site

Chicago, Illinois, United States

Research site 1

Boston, Massachusetts, United States

Research site 2

Boston, Massachusetts, United States

Research site

Ann Arbor, Michigan, United States

Research site

New Brunswick, New Jersey, United States

Research site

Great Neck, New York, United States

Research site 1

New York, New York, United States

Research site 2

New York, New York, United States

Research site

Portland, Oregon, United States

Research site

Nashville, Tennessee, United States

Research site

Dallas, Texas, United States

Research site

Houston, Texas, United States

Research site 1

Ciudad Autonoma Buenos Aires, Buenos Aires, Argentina

Research site 2

Ciudad Autonoma Buenos Aires, Buenos Aires, Argentina

Research site 3

Ciudad Autonoma Buenos Aires, Buenos Aires, Argentina

Research site

San Fernando, Buenos Aires, Argentina

Research site

San Miguel de Tucumán, Tucumán Province, Argentina

Research site

San Juan, , Argentina

Research site

Camperdown, New South Wales, Australia

Research site

Woodville South, South Australia, Australia

Research site

Vancouver, British Columbia, Canada

Research site

Toronto, Ontario, Canada

Research site

Haifa, , Israel

Research site

Jerusalem, , Israel

Research site

Kfar Saba, , Israel

Research site

Petah Tikva, , Israel

Research site

Ramat Gan, , Israel

Research site

Tel Aviv, , Israel

Research site

Torrette, Ancona, Italy

Research site

Rozzano, Milano, Italy

Research site 1

Milan, , Italy

Research site 2

Milan, , Italy

Research site

Napoli, , Italy

Research site

Pisa, , Italy

Research site

Reggio Emilia, , Italy

Research site 1

Roma, , Italy

Research site 2

Roma, , Italy

Research site

Gdansk, , Poland

Research site

Lodz, , Poland

Research site 1

Warsaw, , Poland

Research site 2

Warsaw, , Poland

Research site

Madrid, , Spain

Research site

Valladolid, , Spain

Research site

Cambridge, Cambridgeshire, United Kingdom

Research site

London, Greater London, United Kingdom

Research site

Cannock, Staffordshire, United Kingdom

Research site

Dundee, Tayside Region, United Kingdom

Research site

Birmingham, West Midlands, United Kingdom

Research site

Sheffield, West Midlands, United Kingdom

Countries

United States; Argentina; Australia; Canada; Israel; Italy; Poland; Spain; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 33004536 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2015-005023-11

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

EMR 200017-014

Identifier Type: -

Identifier Source: org_study_id