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| Name | Class |
|---|---|
| Merck KGaA, Darmstadt, Germany | INDUSTRY |
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This was a double-blind, placebo-controlled, parallel-arm, multicentre, prospective dose-finding trial of the safety and efficacy of atacicept in subjects with active rheumatoid arthritis who had failed a three month therapeutic trial with a tumor necrosis factor alpha (TNFa) antagonist due to lack of efficacy.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Atacicept 25 mg | Experimental |
| |
| Atacicept 75 mg | Experimental |
| |
| Atacicept 150 mg | Experimental |
| |
| Placebo | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Atacicept | Drug | Atacicept was administered subcutaneously at a dose of 25 milligram (mg) twice a week for initial 4 weeks as loading dose, followed by 25 mg once a week for subsequent 21 weeks. |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants Achieving American College of Rheumatology 20 Response Based on C-reactive Protein (ACR20-CRP) at Week 26 | ACR20-CRP response is defined as greater than or equal to (>=) 20 percent (%) improvement in both tender joint counts (based on a total of 68 joints) and swollen joint counts (based on a total of 66 joints) together with >=20% improvement in at least 3 of the following 5 measures: 1) participant's assessment of pain; 2) participant's global assessment of disease activity; 3) physician's global assessment of disease activity; 4) participant's assessment of physical function; and 5) acute-phase marker (CRP). | Week 26 |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants Achieving American College of Rheumatology 50 Response Based on CRP (ACR50-CRP) at Week 26 | ACR50-CRP response is defined as >=50% improvement in both tender joint counts (based on a total of 68 joints) and swollen joint counts (based on a total of 66 joints) together with >=50% improvement in at least 3 of the following 5 measures: 1) participant's assessment of pain; 2) participant's global assessment of disease activity; 3) physician's global assessment of disease activity; 4) participant's assessment of physical function; and 5) acute-phase marker (CRP). |
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Inclusion Criteria:
Rheumatoid arthritis (RA) satisfying American College of Rheumatology (ACR) diagnostic criteria with a disease history of at least one year
Male or female greater than or equal to (>=)18-years of age at time of informed consent
Active RA as defined by:
Failure of at least one TNFa antagonist therapy (previously or at the time of screening) as specified in the protocol
Other protocol defined inclusion criteria could apply
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Responsible | EMD Serono, an affiliate of Merck KGaA, Darmstadt, Germany | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| EMD Serono | Rockland | Massachusetts | 02370 | United States | ||
| Merck/Serono |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 21452293 | Derived | Genovese MC, Kinnman N, de La Bourdonnaye G, Pena Rossi C, Tak PP. Atacicept in patients with rheumatoid arthritis and an inadequate response to tumor necrosis factor antagonist therapy: results of a phase II, randomized, placebo-controlled, dose-finding trial. Arthritis Rheum. 2011 Jul;63(7):1793-803. doi: 10.1002/art.30373. |
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A total of 456 subjects were screened, of whom 256 were enrolled and randomized of which 254 received the trial medication and included in Intention to Treat (ITT) population.
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | Placebo matched to atacicept was administered subcutaneously twice a week for initial 4 weeks, followed by once a week for subsequent 21 weeks. |
| FG001 | Atacicept 25 mg | Atacicept was administered subcutaneously at a dose of 25 milligram (mg) twice a week for initial 4 weeks as loading dose, followed by 25 mg once a week for subsequent 21 weeks. |
| FG002 | Atacicept 75 mg | Atacicept was administered subcutaneously at a dose of 75 mg twice a week for initial 4 weeks as loading dose, followed by 75 mg once a week for subsequent 21 weeks. |
| FG003 | Atacicept 150 mg | Atacicept was administered subcutaneously at a dose of 150 mg twice a week for initial 4 weeks as loading dose, followed by 150 mg once a week for subsequent 21 weeks. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Intention-to-treat (ITT) population included all randomized participants who received at least one treatment dose.
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | Placebo matched to atacicept was administered subcutaneously twice a week for initial 4 weeks, followed by once a week for subsequent 21 weeks. |
| BG001 | Atacicept 25 mg |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 | Percentage of Participants Achieving American College of Rheumatology 20 Response Based on C-reactive Protein (ACR20-CRP) at Week 26 | ACR20-CRP response is defined as greater than or equal to (>=) 20 percent (%) improvement in both tender joint counts (based on a total of 68 joints) and swollen joint counts (based on a total of 66 joints) together with >=20% improvement in at least 3 of the following 5 measures: 1) participant's assessment of pain; 2) participant's global assessment of disease activity; 3) physician's global assessment of disease activity; 4) participant's assessment of physical function; and 5) acute-phase marker (CRP). | ITT population included all randomized participants who received at least 1 treatment dose. | Posted | Number | percentage of participants | Week 26 |
|
Baseline up to Week 38
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Placebo matched to atacicept was administered subcutaneously twice a week for initial 4 weeks, followed by once a week for subsequent 21 weeks. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Rheumatoid arthritis | Musculoskeletal and connective tissue disorders | MedDRA (11.1) | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Upper respiratory tract infection | Infections and infestations | MedDRA (11.1) | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Merck KGaA Communication Center | Merck Healthcare, a business of Merck KGaA, Darmstadt, Germany | +49-6151-72-5200 | service@merckgroup.com |
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| ID | Term |
|---|---|
| D001172 | Arthritis, Rheumatoid |
| D001168 | Arthritis |
| ID | Term |
|---|---|
| D007592 | Joint Diseases |
| D009140 | Musculoskeletal Diseases |
| D012216 | Rheumatic Diseases |
| D003240 | Connective Tissue Diseases |
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| ID | Term |
|---|---|
| C524618 | TACI receptor-IgG Fc fragment fusion protein |
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| Atacicept | Drug | Atacicept was administered subcutaneously at a dose of 75 mg twice a week for initial 4 weeks as loading dose, followed by 75 mg once a week for subsequent 21 weeks. |
|
| Atacicept | Drug | Atacicept was administered subcutaneously at a dose of 150 mg twice a week for initial 4 weeks as loading dose, followed by 150 mg once a week for subsequent 21 weeks. |
|
| Placebo matched to atacicept | Drug | Placebo matched to atacicept was administered subcutaneously twice a week for initial 4 weeks, followed by once a week for subsequent 21 weeks. |
|
| Week 26 |
| Percentage of Participants Achieving American College of Rheumatology 70 Response Based on CRP (ACR70-CRP) at Week 26 | ACR70-CRP response is defined as >=70% improvement in both tender joint counts (based on a total of 68 joints) and swollen joint counts (based on a total of 66 joints) together with >=70% improvement in at least 3 of the following 5 measures: 1) participant's assessment of pain; 2) participant's global assessment of disease activity; 3) physician's global assessment of disease activity; 4) participant's assessment of physical function; and 5) acute-phase marker (CRP). | Week 26 |
| Percentage of Participants Achieving Disease Activity Score in 28 Joints (DAS28) Based on CRP (DAS28-CRP) of Less Than or Equal to (<=) 3.2 at Week 26 | DAS28-CRP incorporates non-graded joint counts for tenderness and swelling based on a total of 28 joints, CRP as a marker of inflammation, and a general health assessment using a 100-millimeter (mm) visual analog scale (the participant's global assessment of disease activity). DAS28 ranges between 0 and 10 representing current disease activity. A value above 5.1 represents high disease activity, a value below 3.2 represents low disease activity, and a value below 2.6 represents remission. | Week 26 |
| Percentage of Participants Achieving Disease Activity Score in 28 Joints (DAS28) Based on CRP (DAS28-CRP) of <=2.6 at Week 26 | DAS28-CRP incorporates non-graded joint counts for tenderness and swelling based on a total of 28 joints, CRP as a marker of inflammation, and a general health assessment using a 100 mm visual analog scale (the participant's global assessment of disease activity). DAS28 ranges between 0 and 10 representing current disease activity. A value above 5.1 represents high disease activity, a value below 3.2 represents low disease activity, and a value below 2.6 represents remission. | Week 26 |
| Percentage of Participants Achieving Improvement in Health Assessment Questionnaire Disability Index (HAQ-DI) of at Least 0.3 From Baseline at Week 26 | The HAQ-DI is a participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item was scored on 4-point scale from 0 to 3: 0 = no difficulty; 1 = some difficulty; 2 = much difficulty; 3 = unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range is 0 to 3 where 0 = least difficulty and 3 = extreme difficulty. Percentage of participants achieving improvement in HAQ-DI of at least 0.3 from baseline at Week 26 was reported. | Week 26 |
| Percentage of Participants With Good or Moderate European League Against Rheumatism (EULAR) Response at Week 26 | The EULAR response criteria evaluate change in DAS28 scores represented as "good response", "moderate response", or "no response" considering both the current DAS28 score and the observed improvement from baseline. Participants were considered to have "good" or "moderate" EULAR response if at the time of assessment, their DAS28 score was <=5.1 and the improvement from baseline in their DAS28 score was greater than (>) 0.6; or if at the time of assessment, their DAS28 score was >5.1 and improvement from baseline in their DAS28 score was >1.2. | Week 26 |
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | An AE was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. An SAE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect. | Baseline up to Week 38 |
| Canada |
| Canada |
| Death |
|
| Lost to Follow-up |
|
| Protocol Violation |
|
| Disease Progression |
|
| Other |
|
| Randomized but not Treated |
|
Atacicept was administered subcutaneously at a dose of 25 mg twice a week for initial 4 weeks as loading dose, followed by 25 mg once a week for subsequent 21 weeks.
| BG002 | Atacicept 75 mg | Atacicept was administered subcutaneously at a dose of 75 mg twice a week for initial 4 weeks as loading dose, followed by 75 mg once a week for subsequent 21 weeks. |
| BG003 | Atacicept 150 mg | Atacicept was administered subcutaneously at a dose of 150 mg twice a week for initial 4 weeks as loading dose, followed by 150 mg once a week for subsequent 21 weeks. |
| BG004 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| OG001 | Atacicept 25 mg | Atacicept was administered subcutaneously at a dose of 25 mg twice a week for initial 4 weeks as loading dose, followed by 25 mg once a week for subsequent 21 weeks. |
| OG002 | Atacicept 75 mg | Atacicept was administered subcutaneously at a dose of 75 mg twice a week for initial 4 weeks as loading dose, followed by 75 mg once a week for subsequent 21 weeks. |
| OG003 | Atacicept 150 mg | Atacicept was administered subcutaneously at a dose of 150 mg twice a week for initial 4 weeks as loading dose, followed by 150 mg once a week for subsequent 21 weeks. |
|
|
| Secondary | Percentage of Participants Achieving American College of Rheumatology 50 Response Based on CRP (ACR50-CRP) at Week 26 | ACR50-CRP response is defined as >=50% improvement in both tender joint counts (based on a total of 68 joints) and swollen joint counts (based on a total of 66 joints) together with >=50% improvement in at least 3 of the following 5 measures: 1) participant's assessment of pain; 2) participant's global assessment of disease activity; 3) physician's global assessment of disease activity; 4) participant's assessment of physical function; and 5) acute-phase marker (CRP). | ITT population included all randomized participants who received at least 1 treatment dose. | Posted | Number | percentage of participants | Week 26 |
|
|
|
| Secondary | Percentage of Participants Achieving American College of Rheumatology 70 Response Based on CRP (ACR70-CRP) at Week 26 | ACR70-CRP response is defined as >=70% improvement in both tender joint counts (based on a total of 68 joints) and swollen joint counts (based on a total of 66 joints) together with >=70% improvement in at least 3 of the following 5 measures: 1) participant's assessment of pain; 2) participant's global assessment of disease activity; 3) physician's global assessment of disease activity; 4) participant's assessment of physical function; and 5) acute-phase marker (CRP). | ITT population included all randomized participants who received at least 1 treatment dose. | Posted | Number | percentage of participants | Week 26 |
|
|
|
| Secondary | Percentage of Participants Achieving Disease Activity Score in 28 Joints (DAS28) Based on CRP (DAS28-CRP) of Less Than or Equal to (<=) 3.2 at Week 26 | DAS28-CRP incorporates non-graded joint counts for tenderness and swelling based on a total of 28 joints, CRP as a marker of inflammation, and a general health assessment using a 100-millimeter (mm) visual analog scale (the participant's global assessment of disease activity). DAS28 ranges between 0 and 10 representing current disease activity. A value above 5.1 represents high disease activity, a value below 3.2 represents low disease activity, and a value below 2.6 represents remission. | ITT population included all randomized participants who received at least 1 treatment dose. | Posted | Number | percentage of participants | Week 26 |
|
|
|
| Secondary | Percentage of Participants Achieving Disease Activity Score in 28 Joints (DAS28) Based on CRP (DAS28-CRP) of <=2.6 at Week 26 | DAS28-CRP incorporates non-graded joint counts for tenderness and swelling based on a total of 28 joints, CRP as a marker of inflammation, and a general health assessment using a 100 mm visual analog scale (the participant's global assessment of disease activity). DAS28 ranges between 0 and 10 representing current disease activity. A value above 5.1 represents high disease activity, a value below 3.2 represents low disease activity, and a value below 2.6 represents remission. | ITT population included all randomized participants who received at least 1 treatment dose. | Posted | Number | percentage of participants | Week 26 |
|
|
|
| Secondary | Percentage of Participants Achieving Improvement in Health Assessment Questionnaire Disability Index (HAQ-DI) of at Least 0.3 From Baseline at Week 26 | The HAQ-DI is a participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item was scored on 4-point scale from 0 to 3: 0 = no difficulty; 1 = some difficulty; 2 = much difficulty; 3 = unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range is 0 to 3 where 0 = least difficulty and 3 = extreme difficulty. Percentage of participants achieving improvement in HAQ-DI of at least 0.3 from baseline at Week 26 was reported. | ITT population included all randomized participants who received at least 1 treatment dose. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure. | Posted | Number | percentage of participants | Week 26 |
|
|
|
| Secondary | Percentage of Participants With Good or Moderate European League Against Rheumatism (EULAR) Response at Week 26 | The EULAR response criteria evaluate change in DAS28 scores represented as "good response", "moderate response", or "no response" considering both the current DAS28 score and the observed improvement from baseline. Participants were considered to have "good" or "moderate" EULAR response if at the time of assessment, their DAS28 score was <=5.1 and the improvement from baseline in their DAS28 score was greater than (>) 0.6; or if at the time of assessment, their DAS28 score was >5.1 and improvement from baseline in their DAS28 score was >1.2. | ITT population included all randomized participants who received at least 1 treatment dose. | Posted | Number | percentage of participants | Week 26 |
|
|
|
| Secondary | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | An AE was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. An SAE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect. | Safety population included all randomized participants who received at least 1 treatment dose and had safety data following their first dose. | Posted | Number | participants | Baseline up to Week 38 |
|
|
|
| 3 |
| 62 |
| 15 |
| 62 |
| EG001 | Atacicept 25 mg | Atacicept was administered subcutaneously at a dose of 25 mg twice a week for initial 4 weeks as loading dose, followed by 25 mg once a week for subsequent 21 weeks. | 9 | 66 | 25 | 66 |
| EG002 | Atacicept 75 mg | Atacicept was administered subcutaneously at a dose of 75 mg twice a week for initial 4 weeks as loading dose, followed by 75 mg once a week for subsequent 21 weeks. | 8 | 62 | 16 | 62 |
| EG003 | Atacicept 150 mg | Atacicept was administered subcutaneously at a dose of 150 mg twice a week for initial 4 weeks as loading dose, followed by 150 mg once a week for subsequent 21 weeks. | 5 | 64 | 26 | 64 |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (11.1) | Non-systematic Assessment |
|
| Osteonecrosis | Musculoskeletal and connective tissue disorders | MedDRA (11.1) | Non-systematic Assessment |
|
| Femur fracture | Injury, poisoning and procedural complications | MedDRA (11.1) | Non-systematic Assessment |
|
| Hip fracture | Injury, poisoning and procedural complications | MedDRA (11.1) | Non-systematic Assessment |
|
| Humerus fracture | Injury, poisoning and procedural complications | MedDRA (11.1) | Non-systematic Assessment |
|
| Pelvic fracture | Injury, poisoning and procedural complications | MedDRA (11.1) | Non-systematic Assessment |
|
| Upper limb fracture | Injury, poisoning and procedural complications | MedDRA (11.1) | Non-systematic Assessment |
|
| Acute myocardial infarction | Cardiac disorders | MedDRA (11.1) | Non-systematic Assessment |
|
| Angina pectoris | Cardiac disorders | MedDRA (11.1) | Non-systematic Assessment |
|
| Cardio-respiratory arrest | Cardiac disorders | MedDRA (11.1) | Non-systematic Assessment |
|
| Right ventricular failure | Cardiac disorders | MedDRA (11.1) | Non-systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA (11.1) | Non-systematic Assessment |
|
| Pyopneumothorax | Infections and infestations | MedDRA (11.1) | Non-systematic Assessment |
|
| Relapsing fever | Infections and infestations | MedDRA (11.1) | Non-systematic Assessment |
|
| Stenotrophomonas infection | Infections and infestations | MedDRA (11.1) | Non-systematic Assessment |
|
| Diverticular perforation | Gastrointestinal disorders | MedDRA (11.1) | Non-systematic Assessment |
|
| Inguinal hernia | Gastrointestinal disorders | MedDRA (11.1) | Non-systematic Assessment |
|
| Intestinal obstruction | Gastrointestinal disorders | MedDRA (11.1) | Non-systematic Assessment |
|
| Basedow's disease | Endocrine disorders | MedDRA (11.1) | Non-systematic Assessment |
|
| Hyperthyroidism | Endocrine disorders | MedDRA (11.1) | Non-systematic Assessment |
|
| Non-cardiac chest pain | General disorders | MedDRA (11.1) | Non-systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (11.1) | Non-systematic Assessment |
|
| Migraine | Nervous system disorders | MedDRA (11.1) | Non-systematic Assessment |
|
| Vasculitis cerebral | Nervous system disorders | MedDRA (11.1) | Non-systematic Assessment |
|
| Fibrin D dimer increased | Investigations | MedDRA (11.1) | Non-systematic Assessment |
|
| Gamma-glutamyltransferase increased | Investigations | MedDRA (11.1) | Non-systematic Assessment |
|
| Anaemia | Blood and lymphatic system disorders | MedDRA (11.1) | Non-systematic Assessment |
|
| Drug hypersensitivity | Immune system disorders | MedDRA (11.1) | Non-systematic Assessment |
|
| Abortion spontaneous | Pregnancy, puerperium and perinatal conditions | MedDRA (11.1) | Non-systematic Assessment |
|
| Fallopian tube cyst | Reproductive system and breast disorders | MedDRA (11.1) | Non-systematic Assessment |
|
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA (11.1) | Non-systematic Assessment |
|
| Angioedema | Skin and subcutaneous tissue disorders | MedDRA (11.1) | Non-systematic Assessment |
|
| Prostatic operation | Surgical and medical procedures | MedDRA (11.1) | Non-systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA (11.1) | Non-systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA (11.1) | Non-systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA (11.1) | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (11.1) | Non-systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA (11.1) | Non-systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (11.1) | Non-systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA (11.1) | Non-systematic Assessment |
|
| Iron deficiency anaemia | Blood and lymphatic system disorders | MedDRA (11.1) | Non-systematic Assessment |
|
Prior to publishing results, Institution and Principal Investigator (PI) must first provide Sponsor with a copy of proposed publication for review at least 30 days prior to submission. If Institution and PI do not agree to modification, they shall so notify Sponsor and postpone submission for additional 60 days to allow Sponsor to seek legal remedies or file patent applications. There is a need for coordinated approach to any publication of results from sites for any multi-site study.
| D017437 |
| Skin and Connective Tissue Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| SAEs |
|