Evaluate Safety and Biological Activity of ATYR1940 in Pa... | NCT02579239

ID	Type	Description	Link
2015-001910-88	EudraCT Number

Label	Type	Description	Intervention Names
Group A - FSHD	Experimental	Participants with FSHD will receive single dose of placebo intravenous (IV) infusion followed by ATYR1940 IV infusion at doses of 0.3 up to 1.0 milligrams/kilograms (mg/kg) once weekly for 8 weeks and then twice weekly for 4 weeks using intraparticipant dose escalation for up to 12 weeks.	Biological: ATYR1940 Biological: Placebo
Group B - LGMD2B and FSHD	Experimental	Participants with LGMD2B and FSHD will receive single dose of placebo IV infusion followed by ATYR1940 IV infusion at doses of 0.3 up to 1.0 and 3.0 mg/kg once weekly for 8 weeks and then twice weekly for 4 weeks using intraparticipant dose escalation for up to 12 weeks.	Biological: ATYR1940 Biological: Placebo

Name	Type	Description	Arm Group Labels	Other Names
ATYR1940	Biological	Concentrate for solution for infusion	Group A - FSHD Group B - LGMD2B and FSHD

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	TEAEs were defined as adverse events (AEs) with an onset following administration of the first dose of study drug. An AE was defined as any untoward medical occurrence in a participant administered study drug and that does not necessarily have a causal relationship with the study drug. Worsening of a pre-existing medical condition should have been considered an AE if there was either an increase in severity, frequency, or duration of the condition or an association with significantly worse outcomes. An SAE was defined as any AE that, in the view of either the Investigator or Sponsor, resulted in any of the following outcomes as fatal, life-threatening, required in-participant hospitalization or prolongation of existing hospitalization, in persistent or significant disability/incapacity, a congenital anomaly/birth defect, or an important medical event. A summary of all SAEs and Other AEs (nonserious) regardless of causality is located in 'Reported Adverse Events' Section.	Up to End of Study (up to Week 25)
Number of Participants With a Clinically Significant Electrocardiogram (ECG) Abnormality Leading to a TEAE	ECG parameters that were evaluated included heart rate, PR, and QR and QT intervals. A clinically significant ECG abnormality was based upon the Investigator's discretion. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.	Up to End of Study (up to Week 25)
Number of Participants With a Clinically Significant Pulmonary Function Event Resulting in a TEAE	Pulmonary evaluations included pulmonary function tests and pulse oximetry. Clinically significant changes were to be reported as adverse events. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.	Up to End of Study (up to Week 25)
Number of Participants With a Clinical Laboratory Abnormality Leading to an AE

Secondary Outcomes

Measure	Description	Time Frame
Percent Change From Baseline in Manual Muscle Testing (MMT) Score at Week 14	MMT (muscle strength) was graded on a scale from 0 (no contraction palpable) to 5 (normal strength). Decreased muscle strength was indicated by a decreased score.	Baseline, Week 14

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Provided informed consent.
Investigator's opinion, participant is willing and able to complete all study procedures and comply with the study visit schedule.

Participant with LGMD2B:

Established, genetically confirmed diagnosis of LGMD2B.
Either the presence of a short tau inversion recovery (STIR) positive muscle on lower extremity skeletal muscle magnetic resonance imaging (MRI), or, if no STIR positive muscles, meets muscle biomarker criteria.

Participant with FSHD:

Established, genetically confirmed diagnosis of FSHD.
The presence of a STIR positive muscle on lower extremity skeletal muscle MRI.

Exclusion Criteria:

Currently receiving treatment with an immunomodulatory agent, including targeted biological therapies within the 3 months before baseline; corticosteroids within 3 months before baseline; or high-dose non-steroidal anti-inflammatory agents within 2 weeks before baseline.
Currently receiving curcumin or albuterol; use of a product that putatively enhances muscle growth on a chronic basis within 30 days before baseline; statin treatment initiation or significant adjustment to statin regimen within 3 months before baseline (stable, chronic statin use is permissible).
Use of an investigational product or device within 30 days before baseline.
Evidence of an alternative diagnosis other than LGMD2B or FSHD or a coexisting myopathy or dystrophy, based on prior muscle biopsy or other available investigations.
History of severe restrictive or obstructive lung disease or evidence for interstitial lung disease on screening chest radiograph.
History of anti-synthetase syndrome, prior Jo-1 Ab-positivity, or a positive or equivocally positive Jo-1 Ab test result during screening.
Chronic infection, such as hepatitis B, hepatitis C, or human immunodeficiency virus or a history of tuberculosis.
Vaccination within 8 weeks before baseline or vaccination is planned during study participation.
Symptomatic cardiomyopathy or severe cardiac arrhythmia that may in the Investigator's opinion, limit the participant's ability to complete the study protocol.
Muscle biopsy within 30 days before baseline.

Facility	Status	City	State	ZIP	Country	Contacts
University of California, Irvine, ALS and Neuromuscular Center		Irvine	California	92697	United States

ID	Title	Description
FG000	Group A - FSHD	Participants with FSHD received single dose of placebo intravenous (IV) infusion followed by ATYR1940 IV infusion at doses of 0.3 up to 1.0 milligrams/kilograms (mg/kg) once weekly for 8 weeks and then twice weekly for 4 weeks using intraparticipant dose escalation for up to 12 weeks.
FG001

ID	Title	Description
BG000	Group A - FSHD	Participants with FSHD received single dose of placebo IV infusion followed by ATYR1940 IV infusion at doses of 0.3 up to 1.0 mg/kg once weekly for 8 weeks and then twice weekly for 4 weeks using intraparticipant dose escalation for up to 12 weeks.
BG001	Group B - LGMD2B and FSHD	Participants with LGMD2B and FSHD received single dose of placebo IV infusion followed by ATYR1940 IV infusion at doses of 0.3 up to 1.0 and 3.0 mg/kg once weekly for 8 weeks and then twice weekly for 4 weeks using intraparticipant dose escalation for up to 12 weeks.
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG0004 BG00114 BG00218

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

TEAEs were defined as adverse events (AEs) with an onset following administration of the first dose of study drug. An AE was defined as any untoward medical occurrence in a participant administered study drug and that does not necessarily have a causal relationship with the study drug. Worsening of a pre-existing medical condition should have been considered an AE if there was either an increase in severity, frequency, or duration of the condition or an association with significantly worse outcomes. An SAE was defined as any AE that, in the view of either the Investigator or Sponsor, resulted in any of the following outcomes as fatal, life-threatening, required in-participant hospitalization or prolongation of existing hospitalization, in persistent or significant disability/incapacity, a congenital anomaly/birth defect, or an important medical event. A summary of all SAEs and Other AEs (nonserious) regardless of causality is located in 'Reported Adverse Events' Section.

Safety population included all participants who received at least 1 full or partial dose of ATYR1940 and had a post-infusion safety observation.

Posted

Count of Participants

Participants

Up to End of Study (up to Week 25)

ID	Title	Description
OG000	Group A - FSHD	Participants with FSHD received single dose of placebo IV infusion followed by ATYR1940 IV infusion at doses of 0.3 up to 1.0 mg/kg once weekly for 8 weeks and then twice weekly for 4 weeks using intraparticipant dose escalation for up to 12 weeks.
OG001	Group B - LGMD2B and FSHD	Participants with LGMD2B and FSHD received single dose of placebo IV infusion followed by ATYR1940 IV infusion at doses of 0.3 up to 1.0 and 3.0 mg/kg once weekly for 8 weeks and then twice weekly for 4 weeks using intraparticipant dose escalation for up to 12 weeks.

Units	Counts
Participants	OG0004 OG00114

Title

Denominators

Categories

TEAEs

Title	Measurements
	OG0004 OG00114

SAEs

Title	Measurements
	OG000

Primary

Number of Participants With a Clinically Significant Electrocardiogram (ECG) Abnormality Leading to a TEAE

ECG parameters that were evaluated included heart rate, PR, and QR and QT intervals. A clinically significant ECG abnormality was based upon the Investigator's discretion. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.

Safety population included all participants who received at least 1 full or partial dose of ATYR1940 and had a post-infusion safety observation.

Posted

Count of Participants

Participants

Up to End of Study (up to Week 25)

ID	Title	Description
OG000	Group A - FSHD	Participants with FSHD received single dose of placebo IV infusion followed by ATYR1940 IV infusion at doses of 0.3 up to 1.0 mg/kg once weekly for 8 weeks and then twice weekly for 4 weeks using intraparticipant dose escalation for up to 12 weeks.
OG001	Group B - LGMD2B and FSHD	Participants with LGMD2B and FSHD received single dose of placebo IV infusion followed by ATYR1940 IV infusion at doses of 0.3 up to 1.0 and 3.0 mg/kg once weekly for 8 weeks and then twice weekly for 4 weeks using intraparticipant dose escalation for up to 12 weeks.

Primary

Number of Participants With a Clinically Significant Pulmonary Function Event Resulting in a TEAE

Pulmonary evaluations included pulmonary function tests and pulse oximetry. Clinically significant changes were to be reported as adverse events. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.

Safety population included all participants who received at least 1 full or partial dose of ATYR1940 and had a post-infusion safety observation.

Posted

Count of Participants

Participants

Up to End of Study (up to Week 25)

ID	Title	Description
OG000	Group A - FSHD	Participants with FSHD received single dose of placebo IV infusion followed by ATYR1940 IV infusion at doses of 0.3 up to 1.0 mg/kg once weekly for 8 weeks and then twice weekly for 4 weeks using intraparticipant dose escalation for up to 12 weeks.
OG001	Group B - LGMD2B and FSHD	Participants with LGMD2B and FSHD received single dose of placebo IV infusion followed by ATYR1940 IV infusion at doses of 0.3 up to 1.0 and 3.0 mg/kg once weekly for 8 weeks and then twice weekly for 4 weeks using intraparticipant dose escalation for up to 12 weeks.

Primary

Number of Participants With a Clinical Laboratory Abnormality Leading to an AE

Laboratory parameters included hematology (hematocrit, hemoglobin, red blood cell count, white blood cell count with differential [neutrophils, lymphocytes, monocytes, eosinophils, basophils], and platelet count); serum chemistries (blood urea nitrogen, creatinine, total bilirubin, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, alkaline phosphatase, total protein, sodium, potassium, bicarbonate, calcium, chloride, magnesium, inorganic phosphate, creatine kinase, lactate dehydrogenase, erythrocyte sedimentation rate, C-reactive protein, troponin, myoglobin, insulin-like growth factor 1, and cholesterol [(nonfasting]); urinalysis (color, pH, specific gravity, protein, glucose, ketones, and blood). Clinically significant laboratory abnormalities were based upon Investigator's discretion. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.

Safety population included all participants who received at least 1 full or partial dose of ATYR1940 and had a post-infusion safety observation.

Posted

Count of Participants

Participants

Up to End of Study (up to Week 25)

ID	Title	Description
OG000	Group A - FSHD	Participants with FSHD received single dose of placebo IV infusion followed by ATYR1940 IV infusion at doses of 0.3 up to 1.0 mg/kg once weekly for 8 weeks and then twice weekly for 4 weeks using intraparticipant dose escalation for up to 12 weeks.
OG001

Primary

Number of Participants With Vital Sign Abnormality Resulting in a TEAE

The vital sign parameters that were evaluated included heart rate, systolic and diastolic blood pressure, and respiration rate as well as temperature. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.

Safety population included all participants who received at least 1 full or partial dose of ATYR1940 and had a post-infusion safety observation.

Posted

Count of Participants

Participants

Up to End of Study (Up to Week 25)

ID	Title	Description
OG000	Group A - FSHD	Participants with FSHD received single dose of placebo IV infusion followed by ATYR1940 IV infusion at doses of 0.3 up to 1.0 mg/kg once weekly for 8 weeks and then twice weekly for 4 weeks using intraparticipant dose escalation for up to 12 weeks.
OG001	Group B - LGMD2B and FSHD	Participants with LGMD2B and FSHD received single dose of placebo IV infusion followed by ATYR1940 IV infusion at doses of 0.3 up to 1.0 and 3.0 mg/kg once weekly for 8 weeks and then twice weekly for 4 weeks using intraparticipant dose escalation for up to 12 weeks.

Units

Secondary

Percent Change From Baseline in Manual Muscle Testing (MMT) Score at Week 14

MMT (muscle strength) was graded on a scale from 0 (no contraction palpable) to 5 (normal strength). Decreased muscle strength was indicated by a decreased score.

Safety population included all participants who received at least 1 full or partial dose of ATYR1940 and had a post-infusion safety observation. Here, 'Overall Number of Participants Analyzed' (N) signifies number of participants evaluable for this outcome measure.

Posted

Mean

Standard Deviation

percent change

Baseline, Week 14

ID	Title	Description
OG000	Group A - FSHD	Participants with FSHD received single dose of placebo IV infusion followed by ATYR1940 IV infusion at doses of 0.3 up to 1.0 mg/kg once weekly for 8 weeks and then twice weekly for 4 weeks using intraparticipant dose escalation for up to 12 weeks.
OG001	Group B - LGMD2B and FSHD	Participants with LGMD2B and FSHD received single dose of placebo IV infusion followed by ATYR1940 IV infusion at doses of 0.3 up to 1.0 and 3.0 mg/kg once weekly for 8 weeks and then twice weekly for 4 weeks using intraparticipant dose escalation for up to 12 weeks.

Units	Counts

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Headache	Nervous system disorders	MedDRA 18.1	Non-systematic Assessment	EG0002 affected4 at risk EG0017 affected14 at risk
Presyncope	Nervous system disorders	MedDRA version 18.1	Non-systematic Assessment	EG0000 affected4 at risk EG0012 affected14 at risk
Asthenia	General disorders	MedDRA version 18.1	Non-systematic Assessment	EG0001 affected4 at risk EG0012 affected14 at risk
Fatigue	General disorders	MedDRA version 18.1	Non-systematic Assessment	EG0002 affected4 at risk EG0011 affected14 at risk
Pyrexia	General disorders	MedDRA version 18.1	Non-systematic Assessment	EG0000 affected4 at risk EG0012 affected14 at risk
Nasopharyngitis	Infections and infestations	MedDRA version 18.1	Non-systematic Assessment	EG0000 affected4 at risk EG0013 affected14 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA version 18.1	Non-systematic Assessment	EG0002 affected4 at risk EG0012 affected14 at risk
Nausea	Gastrointestinal disorders	MedDRA version 18.1	Non-systematic Assessment	EG0000 affected4 at risk EG0012 affected14 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA version 18.1	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected14 at risk
Fall	Injury, poisoning and procedural complications	MedDRA version 18.1	Non-systematic Assessment	EG0000 affected4 at risk EG0014 affected14 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA version 18.1	Non-systematic Assessment	EG0000 affected4 at risk EG0012 affected14 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA version 18.1	Non-systematic Assessment	EG0001 affected4 at risk EG0011 affected14 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA version 18.1	Non-systematic Assessment	EG0000 affected4 at risk EG0012 affected14 at risk
Burning sensation	Nervous system disorders	MedDRA version 18.1	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected14 at risk
Migraine	Nervous system disorders	MedDRA version 18.1	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected14 at risk
Muscle contractions involuntary	Nervous system disorders	MedDRA version 18.1	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected14 at risk
Paraesthesia	Nervous system disorders	MedDRA version 18.1	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected14 at risk
Feeling hot	General disorders	MedDRA version 18.1	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected14 at risk
Infusion site pain	General disorders	MedDRA version 18.1	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected14 at risk
Infusion site urticaria	General disorders	MedDRA version 18.1	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected14 at risk
Laryngitis	Infections and infestations	MedDRA version 18.1	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected14 at risk
Oral herpes	Infections and infestations	MedDRA version 18.1	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected14 at risk
Pharyngitis	Infections and infestations	MedDRA version 18.1	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected14 at risk
Pneumonia	Infections and infestations	MedDRA version 18.1	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected14 at risk
Sinusitis	Infections and infestations	MedDRA version 18.1	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected14 at risk
Tonsillitis	Infections and infestations	MedDRA version 18.1	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected14 at risk
Tracheitis	Infections and infestations	MedDRA version 18.1	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected14 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA version 18.1	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected14 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA version 18.1	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected14 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA version 18.1	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected14 at risk
Toothache	Gastrointestinal disorders	MedDRA version 18.1	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected14 at risk
Vomiting	Gastrointestinal disorders	MedDRA version 18.1	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected14 at risk
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA version 18.1	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected14 at risk
Tooth fracture	Injury, poisoning and procedural complications	MedDRA version 18.1	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected14 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA version 18.1	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected14 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA version 18.1	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected14 at risk
Blood potassium decreased	Investigations	MedDRA version 18.1	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected14 at risk
C-reactive protein increased	Investigations	MedDRA version 18.1	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected14 at risk
Insulin-like growth factor increased	Investigations	MedDRA version 18.1	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected14 at risk
Red blood cell sedimentation rate increased	Investigations	MedDRA version 18.1	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected14 at risk
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA version 18.1	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected14 at risk
Sneezing	Respiratory, thoracic and mediastinal disorders	MedDRA version 18.1	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected14 at risk
Acne	Skin and subcutaneous tissue disorders	MedDRA version 18.1	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected14 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA version 18.1	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected14 at risk
Petechiae	Skin and subcutaneous tissue disorders	MedDRA version 18.1	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected14 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA version 18.1	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected14 at risk
Insomnia	Psychiatric disorders	MedDRA version 18.1	Non-systematic Assessment	EG0000 affected4 at risk EG0012 affected14 at risk
Haematoma	Vascular disorders	MedDRA version 18.1	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected14 at risk
Hypotension	Vascular disorders	MedDRA version 18.1	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected14 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA version 18.1	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected14 at risk
Palpitations	Cardiac disorders	MedDRA version 18.1	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected14 at risk
Tinnitus	Ear and labyrinth disorders	MedDRA version 18.1	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected14 at risk
Cataract	Eye disorders	MedDRA version 18.1	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected14 at risk
Acidosis	Metabolism and nutrition disorders	MedDRA version 18.1	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected14 at risk

ID	Term
D049288	Muscular Dystrophies, Limb-Girdle
D020391	Muscular Dystrophy, Facioscapulohumeral
C535899	Limb-girdle muscular dystrophy, type 2B

ID	Term
D009136	Muscular Dystrophies
D020966	Muscular Disorders, Atrophic
D009135	Muscular Diseases
D009140	Musculoskeletal Diseases
D009468	Neuromuscular Diseases
D009422	Nervous System Diseases
D030342	Genetic Diseases, Inborn
D009358	Congenital, Hereditary, and Neonatal Diseases and Abnormalities

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Group A - FSHD	Participants with FSHD received single dose of placebo IV infusion followed by ATYR1940 IV infusion at doses of 0.3 up to 1.0 mg/kg once weekly for 8 weeks and then twice weekly for 4 weeks using intraparticipant dose escalation for up to 12 weeks.			0	4	4	4
EG001	Group B - LGMD2B and FSHD	Participants with LGMD2B and FSHD received single dose of placebo IV infusion followed by ATYR1940 IV infusion at doses of 0.3 up to 1.0 and 3.0 mg/kg once weekly for 8 weeks and then twice weekly for 4 weeks using intraparticipant dose escalation for up to 12 weeks.			0	14	14	14