We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

Abituzumab in SSc-ILD

This study is currently recruiting participants.
Verified October 2017 by EMD Serono ( EMD Serono Research & Development Institute, Inc. )
Sponsor:
ClinicalTrials.gov Identifier:
NCT02745145
First Posted: April 20, 2016
Last Update Posted: October 17, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
Merck KGaA
Information provided by (Responsible Party):
EMD Serono ( EMD Serono Research & Development Institute, Inc. )
  Purpose
The purpose of this trial is to compare two doses of abituzumab with placebo and determine whether abituzumab is more effective, safer, will be better tolerated and can provoke better immune response than placebo in the treatment of patients with SSc-ILD who already receive constant doses of mycophenolate.

Condition Intervention Phase
Systemic Sclerosis-associated Interstitial Lung Disease Drug: Abituzumab 1500 mg Drug: Abituzumab 500 mg Drug: Placebo Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official 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)

Resource links provided by NLM:


Further study details as provided by EMD Serono ( EMD Serono Research & Development Institute, Inc. ):

Primary Outcome Measures:
  • Annual rate of absolute Forced vital capacity (FVC) change in volume (millilitre [mL]) [ Time Frame: Week 52 or prematurely discontinued from the trial, whichever occur first ]

Secondary Outcome Measures:
  • Change in dyspnea from baseline as measured by the Mahler Transition Dyspnea Index (TDI) [ Time Frame: at Week 52 ]
  • Absolute change from baseline in St. George Respiratory Questionnaire (SGRQ) total score [ Time Frame: at Week 52 ]
  • Absolute change from baseline in Modified Rodnan skin score (mRSS) at Week 52 in subjects with diffuse cutaneous skin involvement at baseline [ Time Frame: at Week 52 ]
  • Absolute change from baseline in Quantitative lung fibrosis (QLF) in the region of highest severity [ Time Frame: at Week 52 ]
  • Overall survival [ Time Frame: Time from date of randomization until death, assessed up to 5 years ]
    The OS is defined as the time from randomization to death due to any cause.

  • Proportion of subjects with clinically meaningful progression of Systemic sclerosis (SSc) by meeting Criterion 1 (Interstitial lung disease[ ILD]) [ Time Frame: by Week 52 and by Week 104 ]
    SSc-ILD is defined as one of the following (in the absence of causative intercurrent illness) on at least 2 occasions within approximately 4 weeks (per OMERACT criteria): Relative decrease from baseline in forced vital capacity (FVC) % predicted greater than or equal to (>=)10%; Relative decrease from baseline in FVC % predicted of >=5% to <10% and relative decrease from baseline in DLCO % predicted >=15%.

  • Proportion of subjects with clinically meaningful progression of SSc by meeting Criterion 2 (SSc progression other than ILD) [ Time Frame: by Week 52 and by Week 104 ]

    SSc progression other than ILD is defined as new onset of one or more of the following:

    Scleroderma renal crisis; Left ventricular failure (defined as ejection fraction <=45%); Pulmonary arterial hypertension requiring treatment.


  • Proportion of subjects with clinically meaningful progression [ Time Frame: by Week 52 and by Week 104 ]

    Subjects meeting one or both of the below criteria will be considered as having clinically meaningful disease progression: SSc-ILD is defined as one of the following (in the absence of causative intercurrent illness) on at least 2 occasions within approximately 4 weeks (per OMERACT criteria): Relative decrease from baseline in FVC % predicted ≥10%; Relative decrease from baseline in FVC % predicted of >=5% to <10% and relative decrease from baseline in DLCO % predicted >=15%.

    SSc progression other than ILD is defined as new onset of one or more of the following:

    Scleroderma renal crisis; Left ventricular failure (defined as ejection fraction =<45%); Pulmonary arterial hypertension requiring treatment


  • Proportion of subjects with absolute decrease from baseline of FVC % predicted >=10% on 2 or more consecutive occasions at least 4 weeks apart [ Time Frame: by Week 52 and by Week 104 ]
  • Time to first clinically meaningful progression [ Time Frame: At Week 52 and by Week 104 ]
  • Absolute change from baseline in FVC % predicted [ Time Frame: up to Week 104 ]
  • Absolute change from baseline in Diffusion capacity of the lung for carbon monoxide (DLCO) % predicted [ Time Frame: up to Week 104 ]
  • Absolute change from baseline in transfer coefficient of the lung for carbon monoxide (KCO) [ Time Frame: up to Week 104 ]
  • Absolute change from baseline in quantitative lung fibrosis (QLF) in the region of highest severity [ Time Frame: at Week 104 ]
  • Absolute change from baseline in quantitative High-resolution computed tomography (HRCT) analyses of extent of total ILD [ Time Frame: up to Week 104 ]

Estimated Enrollment: 175
Actual Study Start Date: May 31, 2016
Estimated Study Completion Date: December 17, 2019
Estimated Primary Completion Date: July 31, 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Abituzumab 1500 milligram (mg) Drug: Abituzumab 1500 mg
Abituzumab 1500 mg, intravenous infusion over approximately 1 hour every 4 weeks with last administration is at the Week 100 visit (2 years). Close observation of the subject is recommended for a period of at least 1 hour after administration of abituzumab.
Experimental: Abituzumab 500 mg Drug: Abituzumab 500 mg
Abituzumab 500 mg, intravenous infusion over approximately 1 hour every 4 weeks with last administration is at the Week 100 visit (2 years). Close observation of the subject is recommended for a period of at least 1 hour after administration of abituzumab.
Placebo Comparator: Placebo Drug: Placebo
Placebo, intravenous infusion over approximately 1 hour every 4 weeks with last administration is at the Week 100 visit (2 years). Close observation of the subject is recommended for a period of at least 1 hour after administration of placebo.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects are eligible for this trial if they fulfill all of the following inclusion criteria:
  • Female or male subjects aged between 18 and 75 years of age who provide informed written consent.
  • Subjects 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.
  • Subjects who have 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 are met, then High-resolution computed tomography (HRCT) of lungs will be performed, and must show at least 5% fibrosis for subjects to be eligible.
  • Female subjects 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 are defined as "All female subjects after puberty unless they are post-menopausal for at least 2 years or are surgically 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 are 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 are 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 are 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 are 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. Subjects 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. Subjects 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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02745145


Contacts
Contact: US Medical Information 888-275-7376
Contact: Merck KGaA Communication Center 49 6151 72 5200 service@merckgroup.com

  Show 55 Study Locations
Sponsors and Collaborators
EMD Serono Research & Development Institute, Inc.
Merck KGaA
Investigators
Study Director: Medical Responsible EMD Serono Inc., a business of Merck KGaA, Darmstadt, Germany
  More Information

Responsible Party: EMD Serono Research & Development Institute, Inc.
ClinicalTrials.gov Identifier: NCT02745145     History of Changes
Other Study ID Numbers: EMR 200017-014
2015-005023-11 ( EudraCT Number )
First Submitted: April 15, 2016
First Posted: April 20, 2016
Last Update Posted: October 17, 2017
Last Verified: October 2017

Keywords provided by EMD Serono ( EMD Serono Research & Development Institute, Inc. ):
Double-Blind Method
Interstitial Lung Diseases
Systemic Scleroderma
Abituzumab
Mycophenolate
Efficacy, Safety

Additional relevant MeSH terms:
Sclerosis
Lung Diseases
Scleroderma, Systemic
Scleroderma, Diffuse
Lung Diseases, Interstitial
Pathologic Processes
Respiratory Tract Diseases
Connective Tissue Diseases
Skin Diseases