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| Name | Class |
|---|---|
| Friedreich's Ataxia Research Alliance | OTHER |
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The purpose of this phase 3 multi-center, open-label extension study is to evaluate the long-term safety of ACTIMMUNE® (interferon-γ 1b) in participants with Friedreich's Ataxia.
Participants who complete 26 weeks of blinded treatment in HZNP-ACT-301 (NCT02415127), will be eligible to enter this 6-month study. All participants will receive ACTIMMUNE® 3 times a week (TIW) for 26 weeks. In order to maintain the study blind in HZNP-ACT-301 (NCT02415127), all participants in this open-label extension study will undergo ACTIMMUNE® titration, regardless if they received ACTIMMUNE® or placebo in HZNP-ACT-301 (NCT02415127). The Week 26 Visit from HZNP-ACT-301 (NCT02415127) will serve as the Baseline Visit (Day 1) for this study. During the treatment period, additional clinic visits are scheduled at Weeks 4, 13, and 26; in between clinic visits, participants (and/or caregivers) will be monitored via emails/phone calls on a weekly basis until participants reach their maximum tolerated dose, and on a monthly basis thereafter.
Study with completed results acquired from Horizon in 2024.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| interferon γ-1b | Experimental | Subcutaneous (SC) doses of ACTIMMUNE® TIW for a total of 26 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Interferon γ-1b | Drug | The study drug dose is planned to be escalated on a weekly basis over the first 4 weeks of treatment (from 10 µg/m² to 25, 50, and 100 µg/m²). The dose may be reduced, interrupted, or held based on tolerability. By Week 13, all participants are to be on a stable tolerated dose of study drug in order to continue study participation; the dose may not be further increased after Week 13, however, it may be reduced on a case-by-case basis to manage drug-related adverse events (AEs). |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs | An adverse event (AE) is any untoward medical occurrence, whether or not the event is considered related to the investigational product. A TEAE is any adverse change from the subject's baseline condition, including any laboratory test value abnormality judged as clinically significant by the investigator, that occurs on or after the date of the first dose of study drug administered at home and throughout the duration of the clinical study, whether the adverse event is considered related to the treatment or not. An SAE is an AE that results in death, is life-threatening, results in persistent or significant disability or incapacity, inpatient hospitalization or prolongation of an existing hospitalization, is a congenital anomaly or birth defect, or other medically important event. | Baseline/Day 1 (Week 26 of Study HZNP-ACT-301 [NCT02415127]) through Week 28 (follow-up safety visit) |
| Number of Participants With Positive/Negative Neutralizing Antibody (NAb) and Anti-Drug Antibody (ADA) Tests | NAb testing only for those participants with a positive ADA test. Baseline is defined as the last non-missing measurement/assessment on the date of Week 26 Visit from study HZNP-ACT-301 (NCT02415127). If this measurement was missing or otherwise unavailable, it was the last non-missing measurement/assessment on or prior to first dose in this study. If the participant discontinued the study, then premature withdrawal assessments were mapped to the nearest scheduled visit based on schedule of the assessment and the study day. If the mapped visit was already available then the visit was mapped to the next schedule visit. Last on study assessment is the last non-missing post-baseline assessment for each participant. | Baseline/Day 1 (Week 26 of Study HZNP-ACT-301 [NCT02415127]), Week 4, Week 13, Week 26, and Week 28 (follow-up safety visit) |
| Change From Baseline to Week 26 in the Friedreich's Ataxia Rating Scale (FARS)-mNeuro Score | The FARS assessment includes neurological signs that specifically reflect neural substrates affected in FA. Based on a neurological examination, bulbar, upper limb, lower limb, peripheral nerve, and upright stability/gait functions were assessed. The FARS-mNeuro score excludes the peripheral nervous system subscale score and the facial and tongue atrophy and fasciculations from the bulbar subscale score. Scores range from 0 (normal) to 93 (most impairment). A negative change from baseline is an improvement. |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline to Week 26 in Activities of Daily Living (ADL) Score | Participants and/or their caregivers rated 9 areas of daily living skills (speech, swallowing, cutting food and handling utensils, dressing, personal hygiene, falling, walking, quality of sitting position, and bladder function) on a 5-point scale (0=normal, 4=greatest loss of function) with allowable increments of 0.5 if the participant or caregiver strongly felt that a task falls between 2 scores. ADL scores can range from 0 (normal) to 36 (greatest loss of function). A negative change from baseline indicates improvement. |
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Inclusion Criteria:
Exclusion Criteria:
NOTE: Additional inclusion/exclusion criteria may apply.
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| Name | Affiliation | Role |
|---|---|---|
| MD | Amgen | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California, Los Angeles Neurology Clinic | Los Angeles | California | 90038 | United States | ||
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| ID | Title | Description |
|---|---|---|
| FG000 | Interferon γ-1b | Subcutaneous (SC) ACTIMMUNE® 3 times a week (TIW) for a total of 26 weeks. The study drug dose was escalated on a weekly basis over the first 4 weeks of treatment (from 10 μg/m² to 25, 50, and 100 μg/m²), based on tolerability, with all participants on a stable tolerated dose by Week 13. Dose may have been reduced, interrupted, or held based on tolerability thereafter. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Interferon γ-1b | SC ACTIMMUNE® TIW for a total of 26 weeks. The study drug dose was escalated on a weekly basis over the first 4 weeks of treatment (from 10 μg/m² to 25, 50, and 100 μg/m²), based on tolerability, with all participants on a stable tolerated dose by Week 13. Dose may have been reduced, interrupted, or held based on tolerability thereafter. |
| 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 | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs | An adverse event (AE) is any untoward medical occurrence, whether or not the event is considered related to the investigational product. A TEAE is any adverse change from the subject's baseline condition, including any laboratory test value abnormality judged as clinically significant by the investigator, that occurs on or after the date of the first dose of study drug administered at home and throughout the duration of the clinical study, whether the adverse event is considered related to the treatment or not. An SAE is an AE that results in death, is life-threatening, results in persistent or significant disability or incapacity, inpatient hospitalization or prolongation of an existing hospitalization, is a congenital anomaly or birth defect, or other medically important event. | Safety Population, defined as all participants who received at least 1 dose of open-label study drug after the Baseline Visit. | Posted | Number | participants | Baseline/Day 1 (Week 26 of Study HZNP-ACT-301 [NCT02415127]) through Week 28 (follow-up safety visit) |
Post-dose on Day 1 (Week 26 of Study HZNP-ACT-301 [NCT02415127]) through Week 28 (follow-up safety visit) for Serious TEAEs, and through the end of the study (Week 26) for nonserious TEAEs.
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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 | Interferon γ-1b | SC ACTIMMUNE® TIW for a total of 26 weeks. The study drug dose was escalated on a weekly basis over the first 4 weeks of treatment (from 10 μg/m² to 25, 50, and 100 μg/m²), based on tolerability, with all participants on a stable tolerated dose by Week 13. Dose may have been reduced, interrupted, or held based on tolerability thereafter. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Atrial fibrillation | Cardiac disorders | MedDRA 16.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Neutropenia | Blood and lymphatic system disorders | MedDRA 16.1 | Systematic Assessment |
This study was terminated early by the Sponsor because the development of ACTIMMUNE® for the treatment of Friedreich's Ataxia was discontinued after Study HZNP-ACT-301 (NCT02415127) failed to meet its primary efficacy endpoint.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Julie Ball, Executive Director, Clinical Development & Operations | Horizon Pharma Ireland, Ltd, Dublin Ireland | (224) 383-3000 | clinicaltrials@horizonpharma.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Sep 28, 2016 | Mar 21, 2018 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | May 22, 2017 | Mar 21, 2018 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D005621 | Friedreich Ataxia |
| ID | Term |
|---|---|
| D013132 | Spinocerebellar Degenerations |
| D002526 | Cerebellar Diseases |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
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| ID | Term |
|---|---|
| C554125 | interferon gamma-1b |
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|
|
| From Baseline to Week 26 for all participants and from Baseline of HZNP-ACT-301 (NCT02415127)to Week 26 of HZNP-ACT-302 (52-week treatment duration) for participants receiving active treatment in both studies. |
| From Baseline to Week 26 for all participants and from Baseline of HZNP-ACT-301 (NCT02415127)to Week 26 of HZNP-ACT-302 (52-week treatment duration) for participants receiving active treatment in both studies. |
| Change From Baseline at Week 26 in Timed 25-Foot Walk (T25FW) | The T25FW is a quantitative measure of lower extremity function. Participants are directed to 1 end of a clearly marked 25-foot course and instructed to walk 25 feet as quickly as possible, but safely. The task is immediately administered again by having the participant walk back the same distance, and the score for the test is the average of the 2 walks (after reciprocal transformation). Participants may use assistive devices when performing this task, with the same assistive device used at each assessment. A negative change from Baseline indicates improvement. | From Baseline to Week 26 for all participants and from Baseline of HZNP-ACT-301 (NCT02415127)to Week 26 of HZNP-ACT-302 (52-week treatment duration) for participants receiving active treatment in both studies. |
| Number of FARS-mNeuro Responders and Non-Responders at Week 26 | A participant was considered a responder if they had an improvement (decrease) of at least 3 points from Baseline at Week 26 for the FARS-mNeuro score. The FARS assessment includes neurological signs that specifically reflect neural substrates affected in FA. Based on a neurological examination, bulbar, upper limb, lower limb, peripheral nerve, and upright stability/gait functions were assessed. The FARS-mNeuro score excludes the peripheral nervous system subscale score and the facial and tongue atrophy and fasciculations from the bulbar subscale score. Scores range from 0 (normal) to 93 (most impairment). | Week 26 |
| Change From Baseline to Week 26 in Total Friedreich Ataxia Rating Scale Score (FARStot) | The FARS assessment includes neurological signs that specifically reflect neural substrates affected in FA. Based on a neurological examination, bulbar, upper limb, lower limb, peripheral nerve, and upright stability/gait functions are assessed. FARStot scores range from 0 (normal) to 125 (most impairment). A negative change from baseline indicates improvement. | From Baseline to Week 26 for all participants and from Baseline of HZNP-ACT-301 (NCT02415127)to Week 26 of HZNP-ACT-302 (52-week treatment duration) for participants receiving active treatment in both studies. |
| University of Florida - Clinical Research Center |
| Gainesville |
| Florida |
| 32603 |
| United States |
| University of Iowa Children's Hospital | Iowa City | Iowa | 52242 | United States |
| Children's Hospital of Philadelphia | Philadelphia | Pennsylvania | 19104 | United States |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| ID |
|---|
| Title |
|---|
| Description |
|---|
| OG000 | Interferon γ-1b | SC ACTIMMUNE® TIW for a total of 26 weeks. The study drug dose was escalated on a weekly basis over the first 4 weeks of treatment (from 10 μg/m² to 25, 50, and 100 μg/m²), based on tolerability, with all participants on a stable tolerated dose by Week 13. Dose may have been reduced, interrupted, or held based on tolerability thereafter. |
|
|
| Primary | Number of Participants With Positive/Negative Neutralizing Antibody (NAb) and Anti-Drug Antibody (ADA) Tests | NAb testing only for those participants with a positive ADA test. Baseline is defined as the last non-missing measurement/assessment on the date of Week 26 Visit from study HZNP-ACT-301 (NCT02415127). If this measurement was missing or otherwise unavailable, it was the last non-missing measurement/assessment on or prior to first dose in this study. If the participant discontinued the study, then premature withdrawal assessments were mapped to the nearest scheduled visit based on schedule of the assessment and the study day. If the mapped visit was already available then the visit was mapped to the next schedule visit. Last on study assessment is the last non-missing post-baseline assessment for each participant. | Safety Population, defined as all participants who received at least 1 dose of open-label study drug after the Baseline Visit. Participants with an assessment at each time point are presented. | Posted | Number | participants | Baseline/Day 1 (Week 26 of Study HZNP-ACT-301 [NCT02415127]), Week 4, Week 13, Week 26, and Week 28 (follow-up safety visit) |
|
|
|
| Primary | Change From Baseline to Week 26 in the Friedreich's Ataxia Rating Scale (FARS)-mNeuro Score | The FARS assessment includes neurological signs that specifically reflect neural substrates affected in FA. Based on a neurological examination, bulbar, upper limb, lower limb, peripheral nerve, and upright stability/gait functions were assessed. The FARS-mNeuro score excludes the peripheral nervous system subscale score and the facial and tongue atrophy and fasciculations from the bulbar subscale score. Scores range from 0 (normal) to 93 (most impairment). A negative change from baseline is an improvement. | Because the Sponsor discontinued the development of ACTIMMUNE® for the treatment of Friedreich's Ataxia, the planned analyses of the efficacy endpoints were not conducted. Any raw data collected for this endpoint exist as by-subject listings only, and are unanalyzed per protocol. | Posted | From Baseline to Week 26 for all participants and from Baseline of HZNP-ACT-301 (NCT02415127)to Week 26 of HZNP-ACT-302 (52-week treatment duration) for participants receiving active treatment in both studies. |
|
|
| Secondary | Change From Baseline to Week 26 in Activities of Daily Living (ADL) Score | Participants and/or their caregivers rated 9 areas of daily living skills (speech, swallowing, cutting food and handling utensils, dressing, personal hygiene, falling, walking, quality of sitting position, and bladder function) on a 5-point scale (0=normal, 4=greatest loss of function) with allowable increments of 0.5 if the participant or caregiver strongly felt that a task falls between 2 scores. ADL scores can range from 0 (normal) to 36 (greatest loss of function). A negative change from baseline indicates improvement. | Because the Sponsor discontinued the development of ACTIMMUNE® for the treatment of Friedreich's Ataxia, the planned analyses of the efficacy endpoints were not conducted. Any raw data collected for this endpoint exist as by-subject listings only, and are unanalyzed per protocol. | Posted | From Baseline to Week 26 for all participants and from Baseline of HZNP-ACT-301 (NCT02415127)to Week 26 of HZNP-ACT-302 (52-week treatment duration) for participants receiving active treatment in both studies. |
|
|
| Secondary | Change From Baseline at Week 26 in Timed 25-Foot Walk (T25FW) | The T25FW is a quantitative measure of lower extremity function. Participants are directed to 1 end of a clearly marked 25-foot course and instructed to walk 25 feet as quickly as possible, but safely. The task is immediately administered again by having the participant walk back the same distance, and the score for the test is the average of the 2 walks (after reciprocal transformation). Participants may use assistive devices when performing this task, with the same assistive device used at each assessment. A negative change from Baseline indicates improvement. | Because the Sponsor discontinued the development of ACTIMMUNE® for the treatment of Friedreich's Ataxia, the planned analyses of the efficacy endpoints were not conducted. Any raw data collected for this endpoint exist as by-subject listings only, and are unanalyzed per protocol. | Posted | From Baseline to Week 26 for all participants and from Baseline of HZNP-ACT-301 (NCT02415127)to Week 26 of HZNP-ACT-302 (52-week treatment duration) for participants receiving active treatment in both studies. |
|
|
| Secondary | Number of FARS-mNeuro Responders and Non-Responders at Week 26 | A participant was considered a responder if they had an improvement (decrease) of at least 3 points from Baseline at Week 26 for the FARS-mNeuro score. The FARS assessment includes neurological signs that specifically reflect neural substrates affected in FA. Based on a neurological examination, bulbar, upper limb, lower limb, peripheral nerve, and upright stability/gait functions were assessed. The FARS-mNeuro score excludes the peripheral nervous system subscale score and the facial and tongue atrophy and fasciculations from the bulbar subscale score. Scores range from 0 (normal) to 93 (most impairment). | Because the Sponsor discontinued the development of ACTIMMUNE® for the treatment of Friedreich's Ataxia, the planned analyses of the efficacy endpoints were not conducted. Any raw data collected for this endpoint exist as by-subject listings only, and are unanalyzed per protocol. | Posted | Week 26 |
|
|
| Secondary | Change From Baseline to Week 26 in Total Friedreich Ataxia Rating Scale Score (FARStot) | The FARS assessment includes neurological signs that specifically reflect neural substrates affected in FA. Based on a neurological examination, bulbar, upper limb, lower limb, peripheral nerve, and upright stability/gait functions are assessed. FARStot scores range from 0 (normal) to 125 (most impairment). A negative change from baseline indicates improvement. | Because the Sponsor discontinued the development of ACTIMMUNE® for the treatment of Friedreich's Ataxia, the planned analyses of the efficacy endpoints were not conducted. Any raw data collected for this endpoint exist as by-subject listings only, and are unanalyzed per protocol. | Posted | From Baseline to Week 26 for all participants and from Baseline of HZNP-ACT-301 (NCT02415127)to Week 26 of HZNP-ACT-302 (52-week treatment duration) for participants receiving active treatment in both studies. |
|
|
| 1 |
| 86 |
| 4 |
| 86 |
| 66 |
| 86 |
| Cardiogenic shock | Cardiac disorders | MedDRA 16.1 | Systematic Assessment |
|
| Eosinophilic myocarditis | Cardiac disorders | MedDRA 16.1 | Systematic Assessment |
|
| Chest pain | General disorders | MedDRA 16.1 | Systematic Assessment |
|
| Sepsis | Infections and infestations | MedDRA 16.1 | Systematic Assessment |
|
| Chest injury | Injury, poisoning and procedural complications | MedDRA 16.1 | Systematic Assessment |
|
| Heart rate increased | Investigations | MedDRA 16.1 | Systematic Assessment |
|
| Haemodynamic instability | Vascular disorders | MedDRA 16.1 | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 16.1 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 16.1 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 16.1 | Systematic Assessment |
|
| Chills | General disorders | MedDRA 16.1 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 16.1 | Systematic Assessment |
|
| Pain | General disorders | MedDRA 16.1 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 16.1 | Systematic Assessment |
|
| Gastroenteritis viral | Infections and infestations | MedDRA 16.1 | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA 16.1 | Systematic Assessment |
|
| Sinusitis | Infections and infestations | MedDRA 16.1 | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA 16.1 | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 16.1 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 16.1 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 16.1 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 16.1 | Systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 16.1 | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 16.1 | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA 16.1 | Systematic Assessment |
|
Horizon requests that any Investigator/institution that plans on presenting or publishing results provide written notification of their request a minimum of 60 days prior to presentation or publication. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsors' Intellectual Property rights .
| D009422 | Nervous System Diseases |
| D013118 | Spinal Cord Diseases |
| D020271 | Heredodegenerative Disorders, Nervous System |
| D019636 | Neurodegenerative Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D028361 | Mitochondrial Diseases |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
|
| Baseline NAb = negative |
|
|
| Baseline NAb = positive |
|
|
| Week 4 ADA = negative |
|
|
| Week 4 ADA = positive |
|
|
| Week 4 NAb = negative |
|
| Week 4 NAb = positive |
|
| Week 13 ADA = negative |
|
|
| Week 13 ADA = positive |
|
|
| Week 13 NAb = negative |
|
| Week 13 NAb = positive |
|
| Week 26 ADA = negative |
|
|
| Week 26 ADA = positive |
|
|
| Week 26 NAb = negative |
|
| Week 26 NAb = positive |
|
| Week 28 (Follow-up) ADA = negative |
|
|
| Week 28 (Follow-up) ADA = positive |
|
|
| Week 28 (Follow-up) NAb = negative |
|
| Week 28 (Follow-up) NAb = positive |
|
| Last On Study Assessment ADA = negative |
|
|
| Last On Study Assessment ADA = positive |
|
|
| Last On Study Assessment NAb = negative |
|
| Last On Study Assessment NAb = positive |
|