Abituzumab in SSc-ILD

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02745145
• Date of registration: 15/04/2016
• Prospective Registration: Yes
• Primary sponsor: EMD Serono Research & Development Institute, Inc.
• 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)
• Date of first enrolment: May 31, 2016
• Target sample size: 24
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT02745145
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 2

Countries of recruitment

Argentina, Australia, Canada, Germany, Israel, Italy, Poland, Spain, Turkey, United Kingdom, United States

Contacts

• Name: Medical Responsible
• Affiliation: EMD Serono Inc., a business of Merck KGaA, Darmstadt, Germany

Key inclusion & exclusion criteria

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).

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


Age minimum: 18 Years
Age maximum: 75 Years
Gender: All

Health Condition(s) or Problem(s) studied

Systemic Sclerosis-associated Interstitial Lung Disease

Intervention(s)

Drug: Abituzumab 1500 mg

Drug: Abituzumab 500 mg

Drug: Placebo

Primary Outcome(s)

Change From Baseline in Absolute Forced Vital Capacity (FVC) at Week 52 [Time Frame: Baseline, Week 52]

Secondary Outcome(s)

Absolute Change From Baseline in Quantitative Lung Fibrosis (QLF) in the Region of Highest Baseline Severity at Week 52 [Time Frame: Baseline, Week 52]

Absolute Change From Baseline in St. George Respiratory Questionnaire (SGRQ) Total Score at Week 52 [Time Frame: Baseline, Week 52]

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 [Time Frame: upto Week 52]

Number of Participants With Clinically Meaningful Progression [Time Frame: upto Week 52]

Change From Baseline in Dyspnea as Measured by the Mahler's Transition Dyspnea Index (TDI) at Week 52 [Time Frame: Baseline, Week 52]

Absolute Change From Baseline in Modified Rodnan Skin Score (mRSS) at Week 52 in Participants With Diffuse Cutaneous Skin Involvement at Baseline [Time Frame: Baseline, Week 52]

Number of Participants With Clinically Meaningful Progression of Systemic Sclerosis (SSc) by Meeting Criterion 1 (Interstitial Lung Disease [ILD]) [Time Frame: upto Week 52]

Number of Participants With Clinically Meaningful Progression of Systemic Sclerosis (SSc) by Meeting Criterion 2 (SSc Progression Other Than ILD) [Time Frame: upto Week 52]

Overall Survival (OS) [Time Frame: Time from date of randomization until death, assessed up to 2 years]

Secondary ID(s)

EMR 200017-014

2015-005023-11

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Merck KGaA, Darmstadt, Germany

Results

• Results available: Yes
• Date Posted: 18/06/2019
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02745145