A Study to Evaluate the Efficacy and Safety of ABC008 for Inclusion Body Myositis

A Phase II/III Randomized, Double-blind, Placebo-controlled, Multicenter Study to Determine the Efficacy and Safety of ABC008 in the Treatment of Subjects with Inclusion Body Myositis Detailed Description: A Phase II/III Randomized, Double-blind, Placebo-controlled, Multicenter Study to Determine the Efficacy and Safety of ABC008 in the Treatment of Subjects with Inclusion Body Myositis Detailed Description: This is a Phase II/III randomized, double-blind, placebo-controlled, parallel multicenter study with 3 parts.

The study will include a sentinel cohort (Part A) of 30 subjects who will receive first three doses of the study drug. Safety data from subjects in the sentinel cohorts will be evaluated by a Data and Safety Monitoring Board (DSMB) before further dosing of the sentinel cohort, as well as initiation of enrollment in the double-blind safety and efficacy cohort (Part B). After completion of Part A or Part B, subjects have the option of enrolling in an open-label long-term extension study or progressing to the pharmacodynamics (PD) recovery cohort (Part C), to evaluate the recovery of the depletion of killer cell lectin-like receptor G1 (KLRG1)+ cells after the end of treatment with ABC008.

Efficacy, safety, HRQoL, and HRU assessments will be conducted. Blood samples will be obtained to evaluate the serum PK, PD, and immunogenicity of ABC008 throughout the study.

• ABC008 (Drug): Given by subcutaneous injection

Primary outcomes

• Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) [Up to Week 80]: An adverse event (AE) was defined as any untoward medical occurrence in any participant participating in a clinical investigation, regardless of the suspected cause. An AE was therefore any unfavorable and unintended sign, symptom, disease, concurrent illness, or clinically significant abnormal laboratory finding that emerged or worsened during the study. A TEAE was defined as an AE that first occurred or worsened after initiation of study drug.
• Part A: Number of Participants With TEAEs by Severity [Up to Week 80]: A TEAE was defined as an AE that first occurred or worsened after initiation of study drug and was graded by severity per protocol-specified Common Terminology Criteria for Adverse Events (CTCAE) criteria: Grade 1, Mild (asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated); Grade 2, Moderate (minimal, local, or noninvasive intervention indicated; limited age-appropriate instrumental activities of daily living (ADL)); Grade 3, Severe or medically significant (medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; or limiting self-care ADL); Grade 4, Life-threatening (threatening consequences; urgent intervention indicated); and Grade 5, Death (death related to an AE).
• Part A: Number of Participants With TEAEs Related to Study Drug [Up to Week 80]: An AE was defined as any untoward medical occurrence in any participant participating in a clinical investigation, regardless of the suspected cause. An AE was therefore can be any unfavorable and unintended sign, symptom, disease, concurrent illness, or clinically significant abnormal laboratory finding that emerged or worsened during the study. A TEAE was defined as an AE that first occurred or worsened after initiation of study drug. An AE with missing relationship to study drug was considered as related to study drug.
• Part A: Mean Change From Baseline in the Inclusion Body Myositis Functional Rating Scale (IBMFRS) Total Score at Week 76 [Baseline (Day 1) and at Week 76]: The IBMFRS was used as an ordinal rating scale to determine participant's assessments of their capabilities. It included 10 measures (swallowing, handwriting, cutting food and handling utensils, fine motor tasks, dressing, hygiene, turning in bed and adjusting covers, changing position from sitting to standing, walking, and climbing stairs) graded on a Likert scale (a psychometric tool) from 0 (being unable to perform) to 4 (normal). The sum of the 10 items provided a value between 0 and 40, with a higher score representing less functional limitation or better functional status. Baseline value was defined as the last non-missing valid value prior to first administration of study treatment (on Day 1). Change from Baseline was calculated as the data collected at post-randomization visits minus the Baseline.
• Part B: Number of Participants With TEAEs [Day 1 to Week 80]: An AE was defined as any untoward medical occurrence in any participant participating in a clinical investigation, regardless of the suspected cause. An AE was therefore can be any unfavorable and unintended sign, symptom, disease, concurrent illness, or clinically significant abnormal laboratory finding that emerged or worsened during the study. A TEAE was defined as an AE that first occurred or worsened after initiation of study drug.
• Part B: Number of Participants With TEAEs by Severity [Day 1 to Week 80]: A TEAE was defined as an AE that first occurred or worsened after initiation of study drug and was graded by severity per protocol-specified CTCAE criteria: Grade 1, Mild (asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated); Grade 2, Moderate (minimal, local, or noninvasive intervention indicated; limited age-appropriate instrumental ADL); Grade 3, Severe or medically significant (medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; or limiting self-care ADL); Grade 4, Life-threatening (threatening consequences; urgent intervention indicated); and Grade 5, Death (death related to an AE).
• Part B: Number of Participants With TEAEs Related to Study Drug [Day 1 to Week 80]: An AE was defined as any untoward medical occurrence in any participant participating in a clinical investigation, regardless of the suspected cause. An AE was therefore can be any unfavorable and unintended sign, symptom, disease, concurrent illness, or clinically significant abnormal laboratory finding that emerged or worsened during the study. A TEAE was defined as an AE that first occurred or worsened after initiation of study drug. An AE with missing relationship to study drug was considered as related to study drug.
• Part B: Mean Change From Baseline in the IBMFRS Total Score at Week 76 [Baseline (Day 1) and Up to Week 76]: The IBMFRS was used as an ordinal rating scale to determine participant's assessments of their capabilities. It included 10 measures (swallowing, handwriting, cutting food and handling utensils, fine motor tasks, dressing, hygiene, turning in bed and adjusting covers, changing position from sitting to standing, walking, and climbing stairs) graded on a Likert scale (a psychometric tool) from 0 (being unable to perform) to 4 (normal). The sum of the 10 items provided a value between 0 and 40, with a higher score representing less functional limitation or better functional status. Baseline value was defined as the last non-missing valid value prior to first administration of study treatment (on Day 1). Change from Baseline was calculated as the data collected at post-randomization visits minus the Baseline.
• Part C: Time to PD Recovery [Up to Week 24]: Recovery was defined as the return of KLRG1+ cell counts toward baseline levels during the PD follow-up period.

Secondary outcomes

• Part A and B: Number of Participants With Treatment-emergent Serious Adverse Events (TESAEs) [Up to Week 80]: A TESAE was defined as a serious AE that first occurred or worsened after initiation of study drug and met seriousness criteria per protocol (including death, life-threatening event, hospitalization or prolongation of hospitalization, persistent or significant disability/incapacity, congenital anomaly, or other medically important event).
• Part A and B: Number of Participants With TEAEs With Onset Within 24 Hours From the Start of Any Study Medication Administration [Within 24 hours following each dose, Up to Week 80]: A TEAE was defined as an AE that first occurred or worsened after initiation of study drug, with onset assessed within 24 hours following the dosing.
• Part A and B: Number of Participants With TEAEs Leading to Study Discontinuation [Up to Week 80]: A TEAE was defined as an AE that first occurred or worsened after initiation of study drug that led to discontinuation of study.
• Part A and B: Change From Baseline in Hematology Parameters - Absolute Neutrophil Count, Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, and Platelets [Baseline (Day 1) to Week 76]: Blood samples were collected for the analysis of hematology parameters: Absolute Neutrophil Count, Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, and Platelets. Baseline value was defined as the last non-missing valid value prior to first administration of study treatment (on Day 1). Change from Baseline was calculated as the data collected at post-randomization visits minus the Baseline.
• Part A and B: Change From Baseline in Hematology Parameter - Erythrocytes [Baseline (Day 1) to Week 76]: Blood samples were collected for the analysis of hematology parameter Erythrocytes. Baseline value was defined as the last non-missing valid value prior to first administration of study treatment (on Day 1). Change from Baseline was calculated as the data collected at post-randomization visits minus the Baseline.
• Part A and B: Change From Baseline in Hematology Parameters - Hemoglobin and Erythrocyte Mean Corpuscular Hemoglobin Concentration [Baseline (Day 1) to Week 76]: Blood samples were collected for the analysis of hematology parameters: Hemoglobin and Erythrocyte Mean Corpuscular Hemoglobin Concentration. Baseline value was defined as the last non-missing valid value prior to first administration of study treatment (on Day 1). Change from Baseline was calculated as the data collected at post-randomization visits minus the Baseline.
• Part A and B: Change From Baseline in Hematology Parameter - Erythrocyte Mean Corpuscular Hemoglobin [Baseline (Day 1) to Week 76]: Blood samples were collected for the analysis of hematology parameters: Hemoglobin and Erythrocyte Mean Corpuscular Hemoglobin. Baseline value was defined as the last non-missing valid value prior to first administration of study treatment (on Day 1). Change from Baseline was calculated as the data collected at post-randomization visits minus the Baseline.
• Part A and B: Change From Baseline in Hematology Parameters - Erythrocyte Mean Corpuscular Volume [Baseline (Day 1) to Week 76]: Blood samples were collected for the analysis of hematology parameter Erythrocyte Mean Corpuscular Volume. Baseline value was defined as the last non-missing valid value prior to first administration of study treatment (on Day 1). Change from Baseline was calculated as the data collected at post-randomization visits minus the Baseline.
• Part A and B: Change From Baseline in Hematology Parameters - Hematocrit [Baseline (Day 1) to Week 76]: Blood samples were collected for the analysis of hematology parameter Hematocrit. Baseline value was defined as the last non-missing valid value prior to first administration of study treatment (on Day 1). Change from Baseline was calculated as the data collected at post-randomization visits minus the Baseline.
• Part A and B: Change From Baseline in Blood Chemistry Parameters - Alanine Aminotransferase (ALT), Aldolase, Gamma Glutamyl Transferase (GGT), Lactate Dehydrogenase, Aspartate Aminotransferase (AST) [Baseline (Day 1) to Week 76]: Blood samples were collected for the analysis of blood chemistry parameters: ALT, Aldolase, AST, GGT and Lactate Dehydrogenase. Baseline value was defined as the last non-missing valid value prior to first administration of study treatment (on Day 1). Change from Baseline was calculated as the data collected at post-randomization visits minus the Baseline.
• Part A and B: Change From Baseline in Blood Chemistry Parameters - Albumin and Protein [Baseline (Day 1) to Week 76]: Blood samples were collected for the analysis of blood chemistry parameters Albumin and Protein. Baseline value was defined as the last non-missing valid value prior to first administration of study treatment (on Day 1). Change from Baseline was calculated as the data collected at post-randomization visits minus the Baseline.
• Part A and B: Change From Baseline in Blood Chemistry Parameters - Alkaline Phosphatase and Creatine Kinase (CK) [Baseline (Day 1) to Week 76]: Blood samples were collected for the analysis of blood chemistry parameters Alkaline Phosphatase and CK. Baseline value was defined as the last non-missing valid value prior to first administration of study treatment (on Day 1). Change from Baseline was calculated as the data collected at post-randomization visits minus the Baseline.
• Part A and B: Change From Baseline in Blood Chemistry Parameters - Bicarbonate, Calcium, Chloride, Glucose, Potassium, Sodium and Urea [Baseline (Day 1) to Week 76]: Blood samples were collected for the analysis of blood chemistry parameters: Bicarbonate, Calcium, Chloride, Glucose, Potassium, and Urea. Baseline value was defined as the last non-missing valid value prior to first administration of study treatment (on Day 1). Change from Baseline was calculated as the data collected at post-randomization visits minus the Baseline.
• Part A and B: Change From Baseline in Blood Chemistry Parameters - Bilirubin, Creatinine and Urate [Baseline (Day 1) to Week 76]: Blood samples were collected for the analysis of blood chemistry parameters: Bilirubin, Creatinine, and Urate. Baseline value was defined as the last non-missing valid value prior to first administration of study treatment (on Day 1). Change from Baseline was calculated as the data collected at post-randomization visits minus the Baseline.
• Part A and B: Change From Baseline in Urinalysis Parameter - pH [Baseline (Day 1) to Week 76]: Urine samples were collected for the analysis of Urinalysis parameter: pH. Baseline value was defined as the last non-missing valid value prior to first administration of study treatment (on Day 1). Change from Baseline was calculated as the data collected at post-randomization visits minus the Baseline.
• Part A and B: Change From Baseline in Urinalysis Parameter- Specific Gravity [Baseline (Day 1) to Week 76]: Urine samples were collected for the analysis of Urinalysis parameters- specific gravity. Baseline value was defined as the last non-missing valid value prior to first administration of study treatment (on Day 1). Change from Baseline was calculated as the data collected at post-randomization visits minus the Baseline.
• Part A and B: Change From Baseline in Complement Parameters - C3 and C4 [Baseline (Day 1) to Week 76]: Blood samples were collected for the analysis of complement parameters included C3 and C4. Baseline value was defined as the last non-missing valid value prior to first administration of study treatment (on Day 1). Change from Baseline was calculated as the data collected at post-randomization visits minus the Baseline.
• Part A and B: Change From Baseline in Complement Parameters - Hemolytic Complement Filtration (CH50) [Baseline (Day 1) to Week 76]: Blood samples were collected for the analysis of complement parameter- hemolytic complement filtration (CH50). Baseline value was defined as the last non-missing valid value prior to first administration of study treatment (on Day 1). Change from Baseline was calculated as the data collected at post-randomization visits minus the Baseline.
• Part A and B: Change From Baseline in C Reactive Protein (CRP) [Baseline (Day 1) to Week 76]: Blood samples were collected for the analysis of blood chemistry parameter- CRP. Baseline value was defined as the last non-missing valid value prior to first administration of study treatment (on Day 1). Change from Baseline was calculated as the data collected at post-randomization visits minus the Baseline.
• Part A and B: Number of Participants With Clinically Significant Changes in Vital Signs [Up to Week 76]: Vital signs were planned to be measured after 5 minutes of rest and taken in the same position throughout the study. Vital signs included blood pressure, pulse, temperature, and respiration rate. Clinically significant changes in vital signs were defined according to protocol-specified criteria for abnormal values (or clinically significant worsening from baseline) as determined by the Investigator.
• Part A and B: Change From Baseline in Electrocardiogram (ECG) Mean Heart Rate [Baseline (Day 1) to Week 76]: Triplicate 12-lead ECG was recorded with the participant in a supine position for at least 5 minutes. Changes in ECG parameters were defined according to protocol-specified criteria for change from baseline values as determined by the Investigator. Baseline value was defined as the last non-missing valid value prior to first administration of study treatment (on Day 1). Change from Baseline was calculated as the data collected at post-baseline visits minus the Baseline.
• Part A and B: Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval and Interval Corrected Using Fridericia's Formula (QTcF) Interval [Baseline (Day 1) to Week 76]: Triplicate 12-lead ECG was recorded with the participant in a supine position for at least 5 minutes. Changes in ECG parameters were defined according to protocol-specified criteria for change from baseline values as determined by the Investigator. Baseline value was defined as the last non-missing valid value prior to first administration of study treatment (on Day 1). Change from Baseline was calculated as the data collected at post-randomization visits minus the Baseline.
• Part A and B: Number of Participants With Treatment-emergent Adverse Events of Special Interest (AESI) [Up to Week 80]: An AE was defined as any untoward medical occurrence in any participant partaking in a clinical investigation, regardless of the suspected cause. An AE was therefore can be any unfavorable and unintended sign, symptom, disease, concurrent illness, or clinically significant abnormal laboratory finding that emerged or worsened during the study. AESIs included injection site reactions, systemic injection reactions (e.g., hypersensitivity, systemic inflammatory response), and infection.
• Part A and B: Mean Change From Baseline in the Manual Muscle Testing - 12 (MMT-12) Score at Week 76 [Baseline (Day 1) and up to Week 76]: Manual Muscle Testing - 12 assessed the muscle strength across the muscle groups that included neck flexion and both right and left shoulder abduction, elbow flexion, elbow extension, wrist extension, wrist flexion, flexor pollicis longus, hip flexors, hip abduction, hip extension, knee extension, and ankle dorsiflexion. Scores were calculated by summing the outcomes, with the Investigator providing the score, on a scale of 0 (no contraction) to 5 (normal strength), which is then converted by a standard procedure to a Kendall score equivalent on a scale of 0 to 10. Individual scores are summed to generate a total score ranging from 0 to 60. A higher score reflects better muscle strength. Baseline value was defined as the last non-missing valid value prior to first administration of study treatment (on Day 1). Change from Baseline was calculated as the data collected at post-randomization visits minus the Baseline.
• Part A and B: Mean Change From Baseline in the Hand Grip Strength Score by Dynamometry at Week 76 [Baseline (Day 1) and up to Week 76]: Grip strength was assessed using a handheld dynamometer which provided a precise measurement of the force that a muscle can exert and reflects muscle strength of the hand. Positive values indicated increased grip strength and negative values indicated decreased grip strength. Baseline value was defined as the last non-missing valid value prior to first administration of study treatment (on Day 1). Change from Baseline was calculated as the data collected at post-randomization visits minus the Baseline.
• Part A and B: Mean Change From Baseline in the Quadriceps Strength Score by Dynamometry at Week 76 [Baseline (Day 1) and up to Week 76]: Quadriceps strength was measured using a dynamometer which provided the applied force of leg extension and reflects muscle strength of the dominant leg. Positive values indicated increased strength and negative values indicated decreased strength. Baseline value was defined as the last non-missing valid value prior to first administration of study treatment (on Day 1). Change from Baseline was calculated as the data collected at post-randomization visits minus the Baseline.
• Part A and B: Mean Change From Baseline in Modified Timed Up and Go Test (mTUG) at Week 76 [Baseline (Day 1) and up to Week 76]: The mTUG assessed functional mobility by measuring the time required for a participant to rise from a standard armchair, walk 3 meters, turn around, walk back to the chair, and sit down (assistive devices permitted after standing, but no support from a caregiver, or a wall). Negative values indicated faster performance and positive values indicated slower performance. Baseline value was defined as the last non-missing valid value prior to first administration of study treatment (on Day 1). Change from Baseline was calculated as the data collected at post-randomization visits minus the Baseline.

Sex: All, ages: 40 Years to any

Inclusion Criteria:

* Adult males and females age >40 years at the time of the first dose of study medication;
* Weight >40 and <150 kg;
* Diagnosis of either clinico-pathologically defined IBM, clinically defined IBM, or probable IBM according to the European Neuromuscular Centre (ENMC) IBM 2011 research diagnostic criteria (Rose et al., 2013). Documented histopathology results must be available prior to Baseline (Day 1) to confirm eligibility;
* Able to arise from a chair (with armrests), with use of their arms but without support from another person or device (e.g., cane, walking stick), at Screening and Baseline (Day 1);
* Able to walk 3 meters, turn around, walk back to the chair, and sit down, with or without assistive device. Once arisen from the chair, subject may use any walking device but cannot be supported by another person, furniture, or a wall;

Exclusion Criteria:

* Any other form of myositis or myopathy other than IBM, e.g., metabolic or drug-induced myopathy, drug-induced myositis, anti-synthetase syndrome, polymyositis or dermatomyositis, cancer-associated myositis (myositis diagnosed within 3 years, either before or after), myositis in overlap with another autoimmune disease (e.g., systemic lupus, systemic sclerosis, rheumatoid arthritis), or muscular dystrophy;
* Any condition, e.g., severe degenerative arthritis with limited range of motion, which precludes the ability to quantitate muscle strength or perform functional assessments (e.g., mTUG), in the Investigator's opinion;.
* Presence of another autoimmune or autoinflammatory disease other than indication under study, e.g., rheumatoid arthritis, psoriatic arthritis, axial spondyloarthropathy, inflammatory bowel disease, systemic lupus erythematosus. Subjects with Sjogren's syndrome, T-cell large granular lymphocyte leukemia (T-LGLL), or well-controlled thyroid disease are permitted;

Participant flow

Outcome results

• Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) (Primary), Count of participants, Participants: Part A: Placebo 8; Part A: Ulviprubart 0.5 mg/kg 17; Part A: Ulviprubart 2.0 mg/kg 17
• Part A: Number of Participants With TEAEs by Severity (Primary), Count of participants, Participants: Part A: Placebo 2; Part A: Ulviprubart 0.5 mg/kg 3; Part A: Ulviprubart 2.0 mg/kg 4
• Part A: Number of Participants With TEAEs Related to Study Drug (Primary), Count of participants, Participants: Part A: Placebo 3; Part A: Ulviprubart 0.5 mg/kg 15; Part A: Ulviprubart 2.0 mg/kg 13
• Part A: Mean Change From Baseline in the Inclusion Body Myositis Functional Rating Scale (IBMFRS) Total Score at Week 76 (Primary), Least squares mean, score on a scale: Part A: Placebo -2.7 (-4.8 to -0.7); Part A: Ulviprubart 0.5 mg/kg -2.4 (-3.9 to -0.9); Part A: Ulviprubart 2.0 mg/kg -2.2 (-3.7 to -0.7) (p 0.7805)
• Part B: Number of Participants With TEAEs (Primary), Count of participants, Participants: Part B: Placebo 76; Part B: Ulviprubart 0.5 mg/kg 75; Part B: Ulviprubart 2.0 mg/kg 74
• Part B: Number of Participants With TEAEs by Severity (Primary), Count of participants, Participants: Part B: Placebo 20; Part B: Ulviprubart 0.5 mg/kg 32; Part B: Ulviprubart 2.0 mg/kg 16
• Part B: Number of Participants With TEAEs Related to Study Drug (Primary), Count of participants, Participants: Part B: Placebo 28; Part B: Ulviprubart 0.5 mg/kg 39; Part B: Ulviprubart 2.0 mg/kg 51
• Part B: Mean Change From Baseline in the IBMFRS Total Score at Week 76 (Primary), Least squares mean, score on a scale: Part B: Placebo -2.4 (-3.1 to -1.8); Part B: Ulviprubart 0.5 mg/kg -1.6 (-2.2 to -0.9); Part B: Ulviprubart 2.0 mg/kg -2.0 (-2.6 to -1.4) (p 0.0644)
• Part C: Time to PD Recovery (Primary), Median, hours: Part C: PD Recovery and Safety Follow-Up NA (NA to NA)
• Part A and B: Number of Participants With Treatment-emergent Serious Adverse Events (TESAEs) (Secondary), Count of participants, Participants: Part A: Placebo 2; Part A: Ulviprubart 0.5 mg/kg 2; Part A: Ulviprubart 2.0 mg/kg 3; Part B: Placebo 16; Part B: Ulviprubart 0.5 mg/kg 6; Part B: Ulviprubart 2.0 mg/kg 9
• Part A and B: Number of Participants With TEAEs With Onset Within 24 Hours From the Start of Any Study Medication Administration (Secondary), Count of participants, Participants: Part A: Placebo 2; Part A: Ulviprubart 0.5 mg/kg 10; Part A: Ulviprubart 2.0 mg/kg 12; Part B: Placebo 21; Part B: Ulviprubart 0.5 mg/kg 36; Part B: Ulviprubart 2.0 mg/kg 45
• Part A and B: Number of Participants With TEAEs Leading to Study Discontinuation (Secondary), Count of participants, Participants: Part A: Placebo 0; Part A: Ulviprubart 0.5 mg/kg 0; Part A: Ulviprubart 2.0 mg/kg 0; Part B: Placebo 2; Part B: Ulviprubart 0.5 mg/kg 0; Part B: Ulviprubart 2.0 mg/kg 0
• Part A and B: Change From Baseline in Hematology Parameters - Absolute Neutrophil Count, Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, and Platelets (Secondary), Mean, 10^9 cells per liter: Part A: Placebo -0.030 +/- 1.7759; Part A: Ulviprubart 0.5 mg/kg -0.995 +/- 1.9932; Part A: Ulviprubart 2.0 mg/kg -0.432 +/- 0.8482; Part B: Placebo -0.255 +/- 1.0776; Part B: Ulviprubart 0.5 mg/kg -0.537 +/- 1.5477; Part B: Ulviprubart 2.0 mg/kg -0.753 +/- 1.3915
• Part A and B: Change From Baseline in Hematology Parameter - Erythrocytes (Secondary), Mean, 10^12 cells per liter: Part A: Placebo 0.07 +/- 0.421; Part A: Ulviprubart 0.5 mg/kg -0.04 +/- 0.245; Part A: Ulviprubart 2.0 mg/kg -0.06 +/- 0.213; Part B: Placebo -0.02 +/- 0.261; Part B: Ulviprubart 0.5 mg/kg 0.05 +/- 0.291; Part B: Ulviprubart 2.0 mg/kg 0.00 +/- 0.245
• Part A and B: Change From Baseline in Hematology Parameters - Hemoglobin and Erythrocyte Mean Corpuscular Hemoglobin Concentration (Secondary), Mean, gram per liter (g/L): Part A: Placebo 2.1 +/- 10.43; Part A: Ulviprubart 0.5 mg/kg -2.3 +/- 7.11; Part A: Ulviprubart 2.0 mg/kg -1.4 +/- 6.16; Part B: Placebo -1.4 +/- 8.00; Part B: Ulviprubart 0.5 mg/kg 1.1 +/- 10.96; Part B: Ulviprubart 2.0 mg/kg 0.4 +/- 6.34
• Part A and B: Change From Baseline in Hematology Parameter - Erythrocyte Mean Corpuscular Hemoglobin (Secondary), Mean, picograms per cell: Part A: Placebo 0.1 +/- 0.93; Part A: Ulviprubart 0.5 mg/kg -0.1 +/- 0.99; Part A: Ulviprubart 2.0 mg/kg 0.2 +/- 0.66; Part B: Placebo -0.2 +/- 0.86; Part B: Ulviprubart 0.5 mg/kg -0.1 +/- 1.31; Part B: Ulviprubart 2.0 mg/kg 0.2 +/- 1.03
• Part A and B: Change From Baseline in Hematology Parameters - Erythrocyte Mean Corpuscular Volume (Secondary), Mean, femtoliter (fL): Part A: Placebo 1.9 +/- 4.08; Part A: Ulviprubart 0.5 mg/kg 0.6 +/- 2.69; Part A: Ulviprubart 2.0 mg/kg 0.4 +/- 1.67; Part B: Placebo -0.3 +/- 2.43; Part B: Ulviprubart 0.5 mg/kg 0.2 +/- 3.10; Part B: Ulviprubart 2.0 mg/kg -0.1 +/- 2.81
• Part A and B: Change From Baseline in Hematology Parameters - Hematocrit (Secondary), Mean, percent by volume [%(v/v)]: Part A: Placebo 0.017 +/- 0.0361; Part A: Ulviprubart 0.5 mg/kg -0.001 +/- 0.0237; Part A: Ulviprubart 2.0 mg/kg -0.004 +/- 0.0213; Part B: Placebo -0.003 +/- 0.0258; Part B: Ulviprubart 0.5 mg/kg 0.005 +/- 0.0318; Part B: Ulviprubart 2.0 mg/kg -0.002 +/- 0.0217
• Part A and B: Change From Baseline in Blood Chemistry Parameters - Alanine Aminotransferase (ALT), Aldolase, Gamma Glutamyl Transferase (GGT), Lactate Dehydrogenase, Aspartate Aminotransferase (AST) (Secondary), Mean, units per liter (U/L): Part A: Placebo -7.7 +/- 9.12; Part A: Ulviprubart 0.5 mg/kg -12.8 +/- 10.60; Part A: Ulviprubart 2.0 mg/kg -4.1 +/- 7.79; Part B: Placebo -5.7 +/- 11.55; Part B: Ulviprubart 0.5 mg/kg -1.2 +/- 12.40; Part B: Ulviprubart 2.0 mg/kg -4.0 +/- 11.29
• Part A and B: Change From Baseline in Blood Chemistry Parameters - Albumin and Protein (Secondary), Mean, gram per litre (g/L): Part A: Placebo -0.9 +/- 2.09; Part A: Ulviprubart 0.5 mg/kg -0.5 +/- 2.43; Part A: Ulviprubart 2.0 mg/kg -0.5 +/- 2.40; Part B: Placebo 0.1 +/- 2.27; Part B: Ulviprubart 0.5 mg/kg 0.4 +/- 2.40; Part B: Ulviprubart 2.0 mg/kg 0.8 +/- 1.88
• 16 more outcome measures not shown.

Adverse events

Time frame: Day 1 through Week 80

Serious adverse events by term

Other adverse events by term

103 more terms not shown.

• Study Protocol (PDF, 2025-12-01)
• Statistical Analysis Plan (PDF, 2026-01-13)