Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Nipocalimab, JNJ-80202135, JNJ-86507083
M281 · 17 trials · 12 indications
SLE SRI-4 composite response is a composite response of at least a 4 point reduction in SLE Disease Activity Index 2000 (SLEDAI-2K), no British Isles Lupus Assessment Group-2004 (BILAG-2004) worsening, defined as no new A or less than or equal to \<= 1 new B items compared to baseline, no worsening in Physician's Global Assessment (PGA \[greater than {\>} 10 percent {%} increase from baseline\]).
Average mean percent change from baseline in total IgG levels over Weeks 8 , 10 and 12 will be reported.
Outcome of fetus/neonate death or adjudicated severe bleeding up to the first week post birth or platelet count \<30\*10\^9/L will be reported.
ClinESSDAI is a validated tool used in clinical studies to measure the systemic disease activity in participants with SjD. The ClinESSDAI includes 11 domains divided into 3-4 activity levels, where zero represents no activity and low, medium, and high scores can vary in numerical value depending on the domain being measured. A higher score represents worse disease symptoms.
Percentage of pregnancies that did not result in fetal loss, IUT, hydrops fetalis, or neonatal death (during the neonatal period) will be reported. Hydrops fetalis is defined as the presence of greater than or equal to(\>=)2 abnormal fluid collections in the fetus or neonate, such as ascites, pleural effusions, pericardial effusion, and generalized skin edema (skin thickness greater (\>)5 millimeter \[mm\]). PMA is the time elapsed between the first day of the last menstrual period and birth (gestational age) plus the time elapsed after birth (chronological age).
Average change from baseline over multiple timepoints (Weeks 22, 23, and 24) was reported in this outcome measure. The MG-ADL provided a rapid assessment of the participant's MG symptom severity of eight functions (talking, chewing, swallowing, breathing, impairment of ability to brush teeth or comb hair, impairment of ability to arise from a chair, double vision, eyelid droop) rated on a 4-point scale ranging from 0 (normal) to 3 (severe). MG-ADL total score was sum of 8 individual items, which ranging from 0 to 24. A higher score indicated greater symptom severity. Baseline was defined as the average of the screening and Day 1 total scores.
Change from baseline in DAS28-CRP at Week 12 were reported. The DAS28 is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity, and C-reactive protein (CRP; in milligrams per liter \[mg/L\]). The set of 28 joint count was based on evaluation of the shoulder, elbow, wrist, metacarpophalangeal (MCP) MCP1 to MCP5, proximal interphalangeal (PIP) PIP1 to PIP5 joints of both the upper right extremity and the upper left extremity as well as the knee joints of lower right and lower left extremities. Score on the DAS28 ranged from 0 to 10, where higher scores indicated more disease activity. Negative changes from baseline indicated improvement of arthritis.
Stage B time to first occurrence of a relapse event will be reported.
Change from baseline in total serum IgG levels were reported.
Number of participants with infectious AEs will be reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.
Number of participants with SAEs will be reported. A SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect, is suspected transmission of any infectious agent via a medicinal product, is medically important to prevent one of the outcomes listed above.
Number of participants with AESIs will be reported. Treatment-emergent AEs associated with the following situations are considered an AESI: a) infections that are severe or require intravenous (IV) anti-infective or operative/invasive intervention; b) hypoalbuminemia with albumin less than (\<)20 grams per liter (g/L) \[\<\] 2.0 grams per deciliter \[g/dL\]) c) opportunistic infections and d) Serious and non-serious deep-vein thrombosis (DVT) and/or pulmonary embolism (PE). Any AE occurring at or after the initial administration of study intervention through end of study is treatment emergent.
Number of participants with abnormalities in clinical laboratory tests (including chemistry, hematology, coagulation, and urinalysis) will be reported.
Number of participants with abnormalities in vital signs including sitting pulse/heart rate, sitting systolic and diastolic blood pressure, and oral temperature (degrees Celsius) will be reported.
Number of participants with abnormalities in physical examinations including height, weight, assessments of the skin, head, eyes, ears, nose, throat, neck, thyroid, lungs, heart, abdomen, lymph nodes and extremities will be reported.
Serum samples will be analyzed to determine concentrations of nipocalimab using a validated, specific, and sensitive immunoassay method.
CL is defined as the volume of serum from which nipocalimab is completely removed per unit time.
V is defined as the representation of nipocalimab's propensity to either remain in the serum or redistribute to other tissue compartments.
t1/2 is defined as the time it takes for nipocalimab's active substance in the body to reduce by half.
Cpeak,ss is defined as the peak serum concentration of nipocalimab at steady state.
Ctrough,ss will be reported. It is defined as the observed serum concentration of nipocalimab just prior to the beginning of a dosing interval at steady state.
AUCss is defined as the area under the curve for nipocalimab at steady state.
Percentage of participants who achieve at least minimal improvement (\>=20) in IMACS TIS at Week 52 and on \<=5 mg/day of oral prednisone (or equivalent) from Week 44 through Week 52 will be reported. International Myositis Assessment and Clinical Studies Total Improvement Score (IMACS TIS) is a standardized clinical response criteria to assess minimal, moderate and major clinical improvement in adult participants with idiopathic inflammatory myopathies (IIM). Minimal improvement is defined as IMACS TIS greater than or equal to (\>=) 20 in participants with IIM. The criteria use the 6 IMACS core set measures: physicians' global activity, patient global activity (PtGA), manual muscle testing (MMT)-8, muscle enzymes, myositis disease activity assessment tool (MDAAT), and health assessment questionnaire-disability index (HAQ-DI). The absolute percentage change in each measure with varying weights is combined to obtain a TIS on a scale of 0 to 100. Higher score indicates greater improvement.
The clinESSDAI is a validated tool used in clinical studies to measure the systemic disease activity in participants with primary Sjogren's syndrome. The clinESSDAI includes 11 domains divided into 3-4 activity levels, where zero represents no activity and low, medium, and high scores can vary in numerical value depending on the domain.
SLE SRI-4 composite response is a composite of at least 4-point improvement in SLE Disease Activity Index 2000(SLEDAI-2K), no worsening in British Isles Lupus Assessment Group (BILAG), no worsening in Physician's Global Assessment of Disease Activity score (PGA) and not meeting study treatment failure criteria.
An AE was any unfavorable and unintended sign (example, an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality. TEAE was defined as any event occurring after the initiation of the first infusion of nipocalimab.
An AE was any unfavorable and unintended sign (example, an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
SAE was defined as any untoward medical occurrence that resulted in death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect. An AE was any unfavorable and unintended sign (example, an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality. TESAEs were any SAEs occurring after the initiation of the first infusion of nipocalimab.
SAE was defined as any untoward medical occurrence that resulted in death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect. An AE was any unfavorable and unintended sign (example, an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.
Number of maternal participants with TEAESIs were reported. An AE was any unfavorable and unintended sign (example, an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality. All infections requiring anti-infective (that is, oral or intravenous antibacterial, antiviral, or antifungal) treatment and with hypoalbuminemia greater than or equal to (\>=) Grade 3 (less than \[\<\]20 gram per liter \[g/L\] by National Cancer Institute of Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0 criteria were considered an AESI for maternal participants. TEAE was defined as any event occurring after the initiation of the first infusion of nipocalimab.
Number of neonates/infants with TEAESIs were reported. An AE was any unfavorable and unintended sign (example, an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality. All infections requiring anti-infective (that is, oral or intravenous antibacterial, antiviral, or antifungal) treatment, unexpected/unusual childhood illnesses and Immunoglobulin G (IgG) concentrations \<200 milligrams per deciliter (mg/dL) at Week 24 through Week 47 or \<300 mg/dL at Week 48 through Week 96 were considered an AESI for neonates and infants.
Absolute value of ECG parameter - mean ventricular rate at baseline in maternal participants was reported. Electrocardiogram assessments included comments on whether the tracings were normal or abnormal, rhythm, presence of arrhythmia or conduction defects, morphology, any evidence of myocardial infarction, or ST segment, T Wave, and U Wave abnormalities.
Absolute value of ECG parameter - mean ventricular rate at GA Week 36 in maternal participants was reported. Electrocardiogram assessments included comments on whether the tracings were normal or abnormal, rhythm, presence of arrhythmia or conduction defects, morphology, any evidence of myocardial infarction, or ST segment, T Wave, and U Wave abnormalities.
Change from baseline in ECG parameter- mean ventricular rate in maternal participants was reported. Electrocardiogram assessments included comments on whether the tracings were normal or abnormal, rhythm, presence of arrhythmia or conduction defects, morphology, any evidence of myocardial infarction, or ST segment, T Wave, and U Wave abnormalities.
Laboratory parameters included hematology, chemistry, blood Lipids panel, and Immunoglobulin G (IgG) parameters. TEAE was defined as any event occurring after the initiation of the first infusion of nipocalimab. Here, HDL: high-density lipoprotein, LDL: low-density lipoprotein. The during-pregnancy value of albumin \<20 g/L was from a local laboratory and was \>=20 g/L when analyzed at the central laboratory for the same time point.
Laboratory parameters included total bilirubin and biomarker included immunoglobulin G (IgG).
Absolute value of vital signs - body temperature at baseline in maternal participants was reported.
Absolute value of vital signs - body temperature at GA Week 36 in maternal participants was reported.
Absolute value of vital signs - body temperature at PP Week 24 in maternal participants was reported.
Change from baseline in vital signs- body temperature in maternal participants was reported.
Absolute value of vital signs -respiratory rate at baseline in maternal participants was reported.
Absolute value of vital signs -respiratory rate at GA Week 36 in maternal participants was reported.
Absolute value of vital signs - respiratory rate at PP Week 24 in maternal participants was reported.
Change from baseline in vital signs- respiratory rate in maternal participants was reported.
Absolute value of vital signs - pulse rate at baseline in maternal participants was reported.
Absolute value of vital signs -pulse rate at GA Week 36 in maternal participants was reported.
Absolute value of vital signs -pulse rate at PP Week 24 in maternal participants was reported.
Change from baseline in vital signs -pulse rate in maternal participants was reported.
Absolute value of vital signs - SBP and DBP at baseline in maternal participants was reported.
Absolute value of vital signs -SBP and DBP at GA Week 36 in maternal participants was reported.
Absolute value of vital signs - SBP and DBP at PP Week 24 in maternal participants was reported.
Change from baseline in vital signs -SBP and DBP in maternal participants were reported.
Absolute value of vital signs - body weight at baseline in maternal participants was reported.
Absolute value of vital signs -body weight at GA Week 36 in maternal participants was reported.
Absolute value of vital signs included body weight at PP Week 24 in maternal participants was reported.
Change from baseline in vital signs- body weight in maternal participants was reported.
Absolute value in vital signs parameter -body temperature at baseline was reported for all neonates/infants.
Absolute value of vital signs parameter -body temperature at PP Week 1 was reported for all neonates/infants.
Absolute value in vital signs parameter - body temperature at PP Week 4 was reported for all neonates/infants.
Absolute value in vital signs parameter -body temperature at PP Week 24 was reported for all neonates/infants.
Change from baseline in vital signs- body temperature were reported for all neonates/infants.
Absolute value of vital signs parameter- body weight at baseline was reported for all neonates/infants.
Absolute value of vital signs parameter - body weight at PP Week 1 was reported for all neonates/infants.
Absolute value of vital signs parameter - body weight at PP Week 4 was reported for all neonates/infants.
Absolute value of vital signs parameter - body weight at PP Week 24 was reported for all neonates/infants.
Change from baseline in vital signs - body weight were reported for all neonates/infants.
Absolute value of vital signs parameter -respiratory rate at baseline was reported for all neonates/infants.
Absolute value of vital signs parameter - respiratory rate at PP Week 1 was reported for all neonates/infants.
Absolute value of vital signs parameter - respiratory rate at PP Week 4 was reported for all neonates/infants.
Absolute value of vital signs parameter- respiratory rate at PP Week 24 was reported for all neonates/infants.
Change from baseline in vital signs -respiratory rate was reported for all neonates/infants.
Absolute value of vital signs parameter - SBP and DBP at baseline were reported for all neonates/infants.
Absolute value of vital signs parameter - SBP and DBP at PP Week 1 were reported for all neonates/infants.
Absolute value of vital signs parameter -SBP and DBP at PP Week 4 were reported for all neonates/infants.
Absolute value of vital signs parameter -SBP and DBP at PP Week 24 were reported for all neonates/infants.
Change from baseline in vital signs- SBP and DBP were reported for all neonates/infants.
Percentage of maternal participants with intrauterine growth restriction (IUGR) based on ultrasound assessments and guidelines from American College of Obstetricians and Gynecologists, and Society for Maternal-Fetal Medicine was reported. This outcome measure provided the incidence of with IUGR at delivery. IUGR is defined as weight below the 10th percentile for gestational age based on the World Health Organization (WHO) fetal growth curve.
Percentage of maternal participants with abnormal amniotic fluid values: amniotic fluid index (AFI) at baseline was reported. The amniotic fluid volume abnormality was categorized as an AFI \<5 centimeter (cm) or \>24 cm.
Percentage of maternal participants with abnormal amniotic fluid values: AFI at GA Week 26 was reported. The amniotic fluid volume abnormality was categorized as an AFI \<5 cm or \>24 cm.
Percentage of maternal participants with abnormal amniotic fluid values: AFI at GA Week 36 was reported. The amniotic fluid volume abnormality was categorized as an AFI \<5 cm or \>24 cm.
Percentage of maternal participants with abnormal amniotic fluid values: maximum vertical pocket (MVP) at baseline was reported. The amniotic fluid volume abnormality was categorized as MVP \<2 cm or \>8 cm.
Percentage of maternal participants with abnormal amniotic fluid values: MVP at GA Week 18 was reported. The amniotic fluid volume abnormality was categorized as MVP \<2 cm or \>8 cm.
Percentage of maternal participants with abnormal amniotic fluid values: MVP at GA Week 22 was reported. The amniotic fluid volume abnormality was categorized as MVP \<2 cm or \>8 cm.
Number of neonates/infants with Apgar score from 1 to 10 minutes of life were reported. The system provided a standardized assessment for infants after delivery. The Apgar score comprises five components: 1) color, 2) heart rate, 3) reflexes, 4) muscle tone, and 5) respiration, each of which is given a score of 0, 1, or 2. The score is reported at 1 minute and 5 minutes after birth for all infants, and at 5-minute intervals thereafter until 20 minutes for infants with a score less than 7. This is using an Apgar scale which ranges from minimum total score of 0 and maximum total score of 10, with higher score representing a better outcome.
Number of maternal participants with concomitant medications and therapies were reported.
Number of neonates/infants with concomitant medications and therapies were reported.
Percentage of maternal participants with live birth at or after GA Week 32 and without an IUT throughout their entire pregnancies were reported.
| Arm | Type | Description |
|---|---|---|
| Nipocalimab | EXPERIMENTAL | Participants will receive nipocalimab up to Week 52 in the double blind treatment period along with standard of care treatments. At Week 52, eligible participants from both studies will have the option to enter an open-label long-term extension (OLE) period, where they will continue to receive nipocalimab until Week 156 or until the study intervention is discontinued. |
| Placebo | PLACEBO_COMPARATOR | Participants will receive placebo up to Week 52 in the double blind treatment period along with standard of care treatment. At Week 52, eligible participants from both studies will have the option to enter an OLE period, where they will continue to receive nipocalimab until Week 156 or until the study intervention is discontinued. |
| Arm 1: Nipocalimab | EXPERIMENTAL | Participants will receive nipocalimab intravenously (IV), at a loading dose on Day 1 followed by maintenance dosing once every 2 weeks (q2w) until Week 12. |
| Arm 2: Efgartigimod | ACTIVE_COMPARATOR | Participants will receive efgartigimod IV, once a week for 4 weeks starting from Day 1. Eligible participants will be given the option to switch to Arm 3 between Week 4 and Week 12. |
| Arm 3: Treatment Switch (Nipocalimab) | EXPERIMENTAL | Participants previously treated with efgartigimod, who are directly enrolled in this arm, and eligible participants switching from Arm 2 will receive nipocalimab IV at a loading dose on Switch Day 1 followed by maintenance dosing q2w until Switch Week 12. |
| Arm 2: Intravenous Immunoglobins (IVIG) | EXPERIMENTAL | Maternal participants with alloantibodies against HPA-1a and/or HPA-5b will be randomized to receive IVIG from GA week 12 for high-risk pregnancies or GA week 20 for standard-risk pregnancies. Additionally, prednisone will be added per study protocol. Participants will be gradually tapered off prednisone after delivery as per investigator judgement or maternal participant tolerance. |
| Nipocalimab Subcutaneous (SC) | EXPERIMENTAL | OLE Phase: Participants from Cohort 1 will receive nipocalimab subcutaneous liquid in vial (SC-LIV) qw until Week 8. Participants with gMG from Cohort 2 who have not received nipocalimab previously, will receive nipocalimab SC-LIV until Week 8. Participants who complete the 8-week treatment period will have the opportunity to continue receiving nipocalimab SC-LIV qw in the Long term extension (LTE) period. |
| Certolizumab + Placebo | ACTIVE_COMPARATOR | Participants will receive placebo intravenously (IV) and certolizumab dose 1 subcutaneously at Week 0, 2, and 4 followed by placebo IV and certolizumab dose 2 subcutaneously at Weeks 6 to 22. |
| Certolizumab + Nipocalimab | EXPERIMENTAL | Participants will receive nipocalimab IV and certolizumab dose 1 subcutaneously at Week 0, 2, and 4 followed by nipocalimab IV and certolizumab dose 2 subcutaneously at Weeks 6 to 22. |
| Group 1: Placebo | PLACEBO_COMPARATOR | Participants will receive placebo intravenously (IV) every 2 weeks (q2w) through Week 10 along with standard-of-care background therapy. |
| Group 2: Nipocalimab | EXPERIMENTAL | Participants will receive nipocalimab IV q2w through Week 10 along with standard-of-care background therapy. |
| Group 2: Nipocalimab Dose 1 | EXPERIMENTAL | Participants will receive nipocalimab dose 1 IV q2w through Week 22 along with standard of care treatments (\[including ophthalmic drops, artificial tears and saliva, punctum plugs, and secretagogues\], and/or one immunomodulator with or without low-dose glucocorticosteroids). |
| Group 3: Nipocalimab Dose 2 | EXPERIMENTAL | Participants will receive nipocalimab dose 2 IV q2w through Week 22 along with standard of care treatments (\[including ophthalmic drops, artificial tears and saliva, punctum plugs, and secretagogues\], and/or one immunomodulator with or without low-dose glucocorticosteroids). |
| M281 administered every 4 weeks (double-blind period) | EXPERIMENTAL | Participants will receive M281 administered every 4 weeks alternating with placebo every 4 weeks during the 24 weeks double-blind period. |
| M281 administered every 2 weeks (double-blind period) | EXPERIMENTAL | Participants will receive M281 administered every 2 weeks during the 24 weeks double-blind period. |
| Placebo administered every 2 weeks (double-blind period) | EXPERIMENTAL | Participants will receive M281 matching placebo administered every 2 weeks during the 24 weeks double-blind period. |
| M281 administered every 4 weeks (open-label extension period) | EXPERIMENTAL | Participants will receive M281 administered every 4 weeks during the 144 weeks open-label extension period. |
| M281 administered every 2 weeks (open-label extension period) | EXPERIMENTAL | Participants will receive M281 administered every 2 weeks during the 144 weeks open-label extension period. |
| M281 | EXPERIMENTAL | - |
| Name | Type | Description |
|---|---|---|
| Nipocalimab | DRUG | Nipocalimab will be administered. |
| Placebo | DRUG | Placebo will be administered. |
| Standard of care treatment | DRUG | Protocol-defined topical and systemic standard of care background treatments. |
| Efgartigimod | DRUG | Efgartigimod will be administered intravenously. |
| Intravenous immunoglobulins (IVIG) | DRUG | IVIG will be administered intravenously. |
| Prednisone | DRUG | Prednisone will be administered orally. |
| Nipocalimab SC-LIV | DRUG | Nipocalimab will be administered subcutaneously. |
| M281 | DRUG | M281 administered as IV infusion |
| Certolizumab | DRUG | Certolizumab will be administered subcutaneously. |
| Glucocorticoids | DRUG | Prednisone or equivalent will be administered orally as Glucocorticoid. |
| Standard-of-care treatment | DRUG | Standard-of-care treatment including immunomodulators, antimalarial drugs and GCs will be administered orally. |
Inclusion Criteria:- * Medically stable on the basis of physical examination, medical history, vital signs and 12-lead electrocardiogram (ECG) performed at screening * Clinical diagnosis of systemic lupus erythematosus (SLE) for more than or equal to (\>=) 24 weeks prior to screening and meeting eu...
M281 is an investigational drug being studied for generalized myasthenia gravis, hemolytic disease of the fetus and newborn, and warm autoimmune hemolytic anemia. It is in Phase 2 clinical development and has not been approved for any indication. Johnson & Johnson is the developer.
M281 targets the neonatal Fc receptor, also known as FcRn, a protein involved in recycling immunoglobulin G antibodies. By binding to FcRn, M281 is designed to reduce levels of pathogenic IgG antibodies, which are implicated in autoimmune conditions such as generalized myasthenia gravis and warm autoimmune hemolytic anemia.
M281 is being developed by Johnson & Johnson, which trades on the New York Stock Exchange under the ticker symbol JNJ. The company is responsible for the clinical development program across the studied indications.
M281 is in Phase 2 clinical development. It is an investigational therapy and has not received FDA approval. The Phase 2 program includes studies in generalized myasthenia gravis, hemolytic disease of the fetus and newborn, and warm autoimmune hemolytic anemia.
M281 has been studied in three Phase 2 trials: NCT04119050 in warm autoimmune hemolytic anemia, NCT03842189 in hemolytic disease of the fetus and newborn, and NCT03772587 in generalized myasthenia gravis. The warm autoimmune hemolytic anemia trial is active but not recruiting, while the other two are completed.
Yes, M281 is also known as nipocalimab. Both names refer to the same investigational FcRn-targeting therapy developed by Johnson & Johnson for autoimmune and alloimmune conditions.