Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Crovalimab · 8 trials · 4 indications
A Generalized Estimating Equation (GEE) was used to estimate the population-average percentage of the participants with hemolysis control (measured by lactate dehydrogenase (LDH) ≤1.5 x upper limit of normal (ULN)) from Week 5 to Week 25 taking account of the intra-patient and inter-patient correlation between LDH control statuses across visits. The dependent variable was the binary indicator for hemolysis control. Independent variables are categorical effects of visits, continuous baseline LDH.
TA was defined as participants who were packed red blood cell (pRBC) transfusion-free and did not require transfusion per protocol-specified guidelines. TA within 24 weeks prior to screening was based on the pRBC transfusion history in the medical records. Reported in this outcome measure is the difference in the percentage of participants between "baseline through Week 25" and "within 24 weeks prior to screening". 95% Confidence Interval (CI) for the difference between the percentage of participants with transfusion avoidance between Pre-screening and Post-baseline is calculated using the Newcombe method. Screening= Day -28 to Day -1 and Baseline= Day 1.
TA is defined as participants who are packed red blood cell (pRBC) transfusion-free and do not require transfusion per protocol-specified guidelines. 95% Confidence Interval (CI) for percentage of participants with TA was calculated using the Wilson's method with continuity correction. Participants who withdrew before Week 25 were deemed to have had a transfusion. Percentages are rounded off to the nearest single decimal.
A Generalized Estimating Equation (GEE) was used to estimate the population-average percentage of the participants with hemolysis control (measured by LDH ≤1.5 x upper limit of normal (ULN)) from Week 5 to Week 25 taking account of the intra-patient and inter-patient correlation between LDH control statuses across visits. Percentages are rounded off to the nearest single decimal.
Severity determined according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events, Version 5 (CTCAE v5).
| Arm | Type | Description |
|---|---|---|
| Crovalimab | EXPERIMENTAL | Participants will be enrolled in three cohorts: \[1\] Naive Cohort - participants who have not been previously treated with complement inhibitor therapy; \[2\] Switch Cohort - participants who switch to crovalimab from another C5 inhibitor and \[3\] Pretreated Cohort (includes C5 SNP (Single Nucleotide Polymorphism) participants) - participants who received treatment with another C5 inhibitor and subsequently discontinued it. |
| Arm A (Crovalimab) | EXPERIMENTAL | Crovalimab will be administered at an initial loading dose of 1000 milligrams (mg) (for participants with body weight between 40 and 100 kilograms \[kg\]) or 1500 mg (for participants with body weight ≥ 100 kg), as intravenous (IV) injection on Day 1 of Week 1 followed by four weekly subcutaneous (SC) injections of 340 mg starting on Day 2 of Week 1 and then once weekly (QW) at Weeks 2,3 and 4. Thereafter crovalimab will be administered, as SC injection, at a maintenance dose of 680 mg (for participants with body weight between 40 and 100 kg) or 1020 mg (for participants with body weight ≥ 100 kg) once every 4 weeks (Q4W) from Week 5 for a total of 24 weeks of study treatment. Participants may continue to receive crovalimab after 24 weeks of treatment up to maximum of 5 years. |
| Arm B (Eculizumab) | ACTIVE_COMPARATOR | Participants will receive loading dose of eculizumab 600 mg on Days 1, 8, 15, and 22, followed by maintenance dose of 900 mg on Day 29 and every 2 weeks (Q2W) thereafter until 24 weeks. Participants may switch to receive crovalimab after 24 weeks of eculizumab treatment. |
| Arm C (Crovalimab) (Exploratory) | EXPERIMENTAL | Participants with a body weight ≥ 5 to \<12 kg will receive a loading series of crovalimab doses comprised of an IV dose on Day 1 of Week 1, followed by crovalimab SC dose on Day 2 Week 1. Maintenance doses will begin at Week 3 and will be administered Q2W, thereafter. Participants with a body weight ≥ 12 to \< 20 kg and ≥ 20 kg will receive a loading series of crovalimab doses comprised of an IV dose on Day 1 of Week 1, followed by weekly crovalimab SC doses for 4 weeks at Week 1 (Day 2) and then at Weeks 2, 3, and 4. Maintenance doses will begin at Week 5 and will be administered Q2W thereafter, for participants with a body weight ≥ 12 to \< 20 kg and Q4W thereafter, for participants with a body weight \> 20 kg. After 24 weeks of crovalimab treatment, participants who derive benefit from the drug may continue to receive crovalimab. |
| Placebo | PLACEBO_COMPARATOR | Participants will receive matching Placebo administered by IV infusion and SC injection over the same duration as Crovalimab, for a total of 48 weeks of treatment. |
| Part 1 (Healthy Volunteers): Crovalimab | EXPERIMENTAL | Healthy participants will receive a single dose of crovalimab in each dose-escalation cohort of Part 1. Crovalimab will be administered at a starting dose of 75 milligrams (mg) intravenous (IV) infusion. Doses are planned to be escalated up to Cohort 5. |
| Part 1 (Healthy Volunteers): Placebo | PLACEBO_COMPARATOR | Healthy participants will receive a single dose of crovalimab matching placebo in each dose-escalation cohort of Part 1. |
| Part 2 (PNH Participants): Crovalimab | EXPERIMENTAL | PNH participants will receive 3 single ascending doses (375 mg IV, 500 mg IV, 1000 mg IV of crovalimab) on Days 1, 8, and 22 followed by weekly crovalimab administrations up to a maximum of 5 months. Weekly crovalimab administrations will start no earlier than Day 36. The starting dose of Part 2 is based on data from Part 1 of the study. |
| Part 3 (PNH Participants): Crovalimab QW | EXPERIMENTAL | Participants will receive crovalimab at a dose of 1000 mg on Day 1 and 170 mg weekly (QW) starting on Day 8 for a maximum treatment duration of 5 months. |
| Part 3 (PNH Participants): Crovalimab Q2W | EXPERIMENTAL | Participants will receive crovalimab at a dose of 1000 mg on Day 1 and 340 mg every 2 weeks (Q2W) for a maximum treatment duration of 5 months. |
| Part 3 (PNH Participants): Crovalimab Q4W | EXPERIMENTAL | Participants will receive crovalimab at a dose of 1000 mg on Day 1 and 680 mg every 4 weeks (Q4W) starting on Day 8 for a maximum treatment duration of 5 months. |
| Part 4 (eculizumab pretreated PNH Participants): Crovalimab | EXPERIMENTAL | PNH Participants pretreated with eculizumab will receive crovalimab: Participants \>/= 100 kilograms (kg): loading dose of 1500 mg IV on Day 1; Participants \< 100 kg: loading dose of 1000 mg IV on Day 1. In all Participants, the remainder of the loading series schedule will be 340 mg subcutaneous (SC) on Days 2, 8, 15, and 22. For Participants \>/= 100 kg, maintenance dosing will be 1020 mg SC on week 5 and then Q4W thereafter. Patients \< 100 kg will receive a maintenance dose of 680 mg SC on the same schedule. |
| Part 4 (treatment naïve PNH Participants): Crovalimab | EXPERIMENTAL | Treatment naïve PNH Participants will receive: Participants \>/= 100 kg: loading dose of 1500 mg IV on day 1; Participants \< 100 kg: loading dose of 1000 mg IV on day 1. In all Participants, the remainder of the loading series schedule will be 340 mg SC on Days 2, 8, 15, and 22. For Participants \>/= 100 kg, maintenance dosing will be 1020 mg SC on week 5 and then Q4W thereafter. Patients \< 100 kg will receive a maintenance dose of 680 mg SC on the same schedule. |
| OLE (PNH Participants): Crovalimab | EXPERIMENTAL | PNH Participants who participated in Parts 2, 3 and 4 and who derive clinical benefit from crovalimab may enroll into OLE. Participants will either receive 680 mg SC Q4W (body weight \>/= 40 kg to \< 100 kg) or 1020 mg SC Q4W (body weight \>/= 100 kg) for up to a maximum treatment duration of ten years from entry into OLE. |
| Name | Type | Description |
|---|---|---|
| Crovalimab | DRUG | Crovalimab will be administered at a dose of 1000 mg intravenously (IV) (for participants weighing =\> 40 to \<100 kg) or 1500 mg IV (for participants weighing \>=100 kg) on Week 1 Day 1. On Week 1 Day 2 and on Weeks 2, 3 and 4, crovalimab will be administered at a dose of 340 mg subcutaneously (SC). On Week 5 and Q4W thereafter, it will be administered at a dose of 680 mg SC (for participants weighing =\> 40 to \<100 kg) or 1020 mg SC (for participants weighing \>=100 kg). Enrollment of participants weighing \<40 kg will be staggered using two weight-based dose confirmation groups (Group 1 participants weighing \>=20 kg to \<40 kg, followed by Group 2 participants weighing \>=5 kg to \<20 kg). All participants will receive an initial IV loading dose, which will be followed by SC dosing at either Q2W or Q4W intervals (depending on body weight), until study completion. |
| Eculizumab | DRUG | Eculizumab will be administered as specified in the respective arm. |
| Placebo | DRUG | Matching Placebo will be administered with the same dosing schedule and equivalent IV and SC volume as weight-based Crovalimab. |
Inclusion Criteria: * Body weight \>= 5 kg at screening. * Vaccination against Neisseria meningitis serotypes A, C, W, and Y; vaccination against serotype B, according to national vaccination recommendations. * Vaccination against Haemophilus influenzae type B and Streptococcus pneumoniae, accordin...
Crovalimab is an investigational drug being studied for paroxysmal nocturnal hemoglobinuria, sickle cell disease, and atypical hemolytic uremic syndrome. It is in Phase 3 clinical development for atypical hemolytic uremic syndrome and paroxysmal nocturnal hemoglobinuria, with additional studies in sickle cell disease.
Crovalimab is a monoclonal antibody, indicated by its -mab suffix. It is designed to target components of the complement system, which is involved in the diseases it treats. The specific molecular target is not disclosed in available information.
Crovalimab is being developed by Roche Holding AG, which trades under the ticker RHHBY. Roche is conducting multiple clinical trials for the drug across various countries.
Crovalimab is in Phase 3 clinical development. It has active Phase 3 trials for atypical hemolytic uremic syndrome in adults, adolescents, and pediatric patients. Earlier phase studies for sickle cell disease have been completed.
Crovalimab is being studied in several trials. NCT04861259 is a Phase 3 trial in atypical hemolytic uremic syndrome with 83 participants. NCT04958265 is a Phase 3 pediatric trial for the same condition with 41 participants. NCT05075824, a Phase 2 trial for sickle cell disease, has been completed.
Crovalimab is a distinct investigational monoclonal antibody. No alternative names for Crovalimab have been reported in the available clinical trial information.