A Long Term Safety Study of Mavrilimumab in Adult Subjects With Rheumatoid Arthritis

NCT01712399 | Terminated Phase 2 Results DMC

• 2 other identifiers: CD-IA-CAM-3001-1109Earth Explorer X
• Study Type: interventional
• Target: 409
• Locations: 18 countries
• Sites: 51

Brief Summary

A clinical study to investigate the safety of mavrilimumab, an antibody being developed for the treatment of moderate to severe rheumatoid arthritis, an inflammatory condition that affects the joints.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (10)

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)

  An adverse event (AE) was any untoward medical occurrence attributed to study drug in a participant who received investigational product. A serious adverse event (SAE) was an AE resulting in any of following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs were defined as AEs with onset date after the first dose of mavrilimumab 100 mg.

  From the start of study drug administration up to 12 weeks after the last dose of study drug (approximately up to 3 years)

• Number of Participants With Clinical Laboratory Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs)

  Laboratory parameters included hematology, serum chemistry and urinalysis recorded as TEAEs. Clinical laboratory abnormalities recorded as TEAEs were reported.TEAEs were defined as AEs with onset date after the first dose of mavrilimumab 100 mg.

  From the start of study drug administration in the study up to 12 weeks after the last dose of study drug (approximately up to 3 years)

• Number of Participants With Vital Sign Abnormalities Reported as Treatment-Emergent Adverse Events (TEAEs)

  Vital sign assessments included blood pressure, pulse rate, temperature, weight and respiration rate. Vital sign abnormalities recorded as TEAEs were reported. TEAEs were defined as AEs with onset date after the first dose of mavrilimumab 100 mg.

  From the start of study drug administration in the study up to 12 weeks after the last dose of study drug (approximately up to 3 years)

• Number of Participants With Abnormal Electrocardiogram (ECG) Findings Reported as TEAEs

  The 12-lead ECG data were summarized and evaluated. TEAEs related to abnormal ECG findings were recorded and reported. TEAEs were defined as AEs with onset date after the first dose of mavrilimumab 100 mg.

  From the start of study drug administration in the study up to 12 weeks after the last dose of study drug (approximately up to 3 years)

• Number of Participants With Forced Expiratory Volume in 1 Second (FEV1) Outside Threshold Values

  Pulmonary function testing was performed by spirometry to assess forced expiratory volume in 1 second (FEV1). FEV1 was the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration.The percentage (%) of predicted values of these pulmonary function tests were calculated based on decrease from baseline and categorized as less than or equal to (=\<)15% reduction from baseline, greater than (\>)15% to =\<20% reduction from baseline, \>20% reduction from baseline and \>20% reduction to \<80%. The threshold values refer to baseline values for each participant.

  From Week 24 to Week 130 at specified time points

• Number of Participants With Forced Expiratory Volume in 6 Seconds (FEV6) Outside Threshold Values

  Pulmonary function testing was performed by spirometry to assess forced expiratory volume in 6 seconds (FEV6). FEV6 was the maximal volume of air exhaled in the six second of a forced expiration from a position of full inspiration. The percentage of predicted values of these pulmonary function tests were calculated based on decrease from baseline and categorized as =\<15% reduction from baseline, \>15% to =\<20% reduction from baseline, \>20% reduction from baseline and \>20% reduction to \<80%. The threshold values refer to baseline values for each participant.

  From Week 24 to Week 130 at specified time points

• Number of Participants With Forced Vital Capacity (FVC) Outside Threshold Values

  Pulmonary function testing was performed by spirometry to assess forced vital capacity (FVC). FVC was the volume of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. The percentage of predicted values of these pulmonary function tests were calculated based on decrease from baseline and categorized as =\<15% reduction from baseline, \>15% to =\<20% reduction from baseline, \>20% reduction from baseline and \>20% reduction to \<80%. The threshold values refer to baseline values for each participant.

  From Week 24 to Week 156 at specified time points

• Number of Participants With Clinically Meaningful Change in Borg Dyspnea Score Considered as an AE

  Borg dyspnea score was a validated participant reported outcome assessing participant's perceived difficulty in breathing (dyspnea). The score ranges from 0 (nothing at all) to 10 (maximal difficulty). Higher scores indicated greater difficulty in breathing.

  From Week 0 to Week 132 at specified time points

• Oxygen Saturation Levels by Pulse Oximetry

  Oxygen saturation measured by pulse oximetry which measures the concentration of oxygen in the blood.

  From Week 0 to Week 132 at specified time points

• Diffusing Capacity of the Lung for Carbon Monoxide (DLCO)

  DLCO is a pulmonary function testing that measures partial pressure difference between inspired and expired carbon monoxide.

  From Week 12 to Week 156 at specified time points

Study Arms (1)

Mavrilimumab 100 mg

EXPERIMENTAL

Participants will receive 100 mg mavrilimumab once in every 2 weeks (Q2W) subcutaneously for up to 3 years.

Biological: Mavrilimumab 100 mg

Interventions

Mavrilimumab 100 mg BIOLOGICAL

Participants will receive 100 mg mavrilimumab once in every 2 weeks (Q2W) subcutaneously for up to 3 years

Mavrilimumab 100 mg

Eligibility Criteria

• Age: 19 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects who have completed the treatment period of the qualifying study or will have failed to respond adequately to investigational product at a predefined time point in the qualifying study regardless of their initial randomization.
• No evidence of clinically uncontrolled respiratory disease to be confirmed by a local pulmonologist

You may not qualify if:

• Subjects who have been permanently discontinued from investigational product in previous qualifying study.
• Any new conditions or worsening of any pre-existing conditions as defined in the protocol.

Sponsors & Collaborators

• MedImmune LLC: lead

Study Sites (52)

Research Site

Ciudad Autonoma Buenos Aires, Argentina

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Ciudad Autonoma de Buenos Aire, Argentina

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Rosario, Argentina

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San Miguel de Tucumán, Argentina

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Plovdiv, Bulgaria

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Sofia, Bulgaria

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Santiago, Chile

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Viña del Mar, Chile

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Barranquilla, Colombia

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Bruntál, Czechia

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Jihlava, Czechia

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Ostrava - Trebovice, Czechia

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Prague, Czechia

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Uherské Hradiště, Czechia

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Zlín, Czechia

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Tallinn, Estonia

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Cologne, Germany

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Magdeburg, Germany

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Athens, Greece

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Larissa, Greece

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Baja, Hungary

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Balatonfüred, Hungary

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Budapest, Hungary

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Debrecen, Hungary

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Ashkelon, Israel

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Kfar Saba, Israel

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Petah Tikva, Israel

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Mérida, Mexico

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Gdynia, Poland

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Grodzisk Mazowiecki, Poland

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Katowice, Poland

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Krakow, Poland

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Wroclaw, Poland

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Barnaul, Russia

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Kazan', Russia

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Moscow, Russia

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Saint Petersburg, Russia

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Yaroslavl, Russia

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Belgrade, Serbia

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Niška Banja, Serbia

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Bratislava, Slovakia

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Durban, South Africa

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Barcelona, Spain

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Málaga, Spain

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Santiago de Compostela, Spain

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Donetsk, Ukraine

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Kharkiv, Ukraine

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Kiev, Ukraine

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Lutsk, Ukraine

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Vinnytsia, Ukraine

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Edinburgh, United Kingdom

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London, United Kingdom

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Related Publications (1)

• Burmester GR, McInnes IB, Kremer JM, Miranda P, Vencovsky J, Godwood A, Albulescu M, Michaels MA, Guo X, Close D, Weinblatt M. Mavrilimumab, a Fully Human Granulocyte-Macrophage Colony-Stimulating Factor Receptor alpha Monoclonal Antibody: Long-Term Safety and Efficacy in Patients With Rheumatoid Arthritis. Arthritis Rheumatol. 2018 May;70(5):679-689. doi: 10.1002/art.40420. Epub 2018 Mar 31.

  PMID: 29361199 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

mavrilimumab

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Limitations and Caveats

The study was terminated after approximately 3 years due to future clinical development plans, including ethical considerations.

Results Point of Contact

• Title: Marius Albulescu, MD
• Organization: MedImmune, LLC.

clinicaltrialenquiries@medimmune.com

301-398-0000

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 19, 2012
• First Posted: October 23, 2012
• Study Start: January 28, 2013
• Primary Completion: December 30, 2015
• Study Completion: December 30, 2015
• Last Updated: June 1, 2017
• Results First Posted: June 1, 2017

Record last verified: 2017-05

Locations

GR (2); ES (3); SL (1); IL (3); ZA (1); ME (1); AR (4); DE (2); CZ (6); UA (5); CO (1); SE (2); HU (4); GB (2); CL (2); PL (5); RU (5); BU (2)