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Active, not recruitingNCT04958265COMMUTE-pUpdated Oct 1, 2026Results posted

A Study Evaluating the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of Crovalimab in Pediatric Participants With Atypical Hemolytic Uremic Syndrome (aHUS)

A Phase 3 interventional study of Crovalimab in Atypical Hemolytic Uremic Syndrome, sponsored by Hoffmann-La Roche. Active, not recruiting at 20 sites in 10 countries. Open to participants aged 28 Days to 17 Years. Per ClinicalTrials.gov, last updated 2026-10-01.

Sponsored by Hoffmann-La Roche · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
41
Allocation
Not applicable
Ages
28 Days to 17 Years
Sex
All
01

Study summary

This study aims to evaluate the efficacy and safety of crovalimab in pediatric participants with aHUS.

02

Conditions studied

  • Atypical Hemolytic Uremic Syndrome
03

In context

Atypical Hemolytic Uremic Syndrome

42 studies on the registry are indexed under Atypical Hemolytic Uremic Syndrome; 12 are open to participants now.

This study's enrollment of 41 is above the median of 34 across 23 interventional studies indexed under Atypical Hemolytic Uremic Syndrome.

Browse Atypical Hemolytic Uremic Syndrome studies →

Lead sponsor

Hoffmann-La Roche is the lead sponsor of 2,061 studies on the registry; 85 are open to participants now.

Of its 319 completed or terminated interventional studies of FDA-regulated products, 239 (75%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
28 Days to 17 Years
Sexes eligible
All
Accepts healthy volunteers
No

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, according to national vaccination recommendations.
  • For patients continuing to receive other therapies concomitantly with crovalimab (e.g., immunosuppressants, corticosteroids, mammalian target of rapamycin inhibitor (mTORi), or calcineurin inhibitors): stable dose for >=28 days prior to screening and up to the first crovalimab administration.
  • For female participants of childbearing potential: an agreement to remain abstinent or use contraception.
  • Participants with a prior kidney transplant are eligible if they have a known history of complement-mediated aHUS prior to the kidney transplant.
  • Onset of initial TMA presentation within 28 days prior to the first dose of crovalimab (for Naive Cohort only).
  • Documented treatment with either eculizumab or ravulizumab (for Switch Cohort only).
  • Clinical evidence of response to a C5 inhibitor (for Switch Cohort only).
  • Poorly controlled TMA following treatment with another C5 inhibitor (for C5 SNP participants in the Pretreated Cohort only).
  • Known C5 polymorphism (for C5 SNP participants in the Pretreated Cohort only).

Exclusion criteria

Exclusion Criteria:

  • TMA associated with non-aHUS related renal disease.
  • Positive direct Coombs test.
  • Chronic dialysis within 90 days prior to first crovalimab administration , and /or end stage renal disease
  • Identified drug exposure-related TMA.
  • Presence or history of a condition that could trigger TMA, such as malignancy, bone marrow or organ transplant (other than kidney transplant) or autoimmune disease.
  • History of a kidney disease, other than aHUS.
  • History of Neisseria meningitidis infection within 6 months of study enrollment.
  • Known or suspected immune deficiency (e.g., history of frequent recurrent infections).
  • Positive HIV test.
  • Active systemic bacterial, viral, or fungal infection within 14 days before first crovalimab administration.
  • Presence of fever (>= 38°C) before the first crovalimab administration (If fevers are solely due to the underlying aHUS pathology, and there is no evidence or suspicion of a systemic infection, participants may enroll).
  • Multi-system organ dysfunction or failure.
  • Recent intravenous immunoglobulin (IVIg) treatment.
  • Pregnant or breastfeeding or intending to become pregnant.
  • Participation in another interventional treatment study with an investigational agent or use of any experimental therapy within 28 days of screening or within five half lives of that investigational product, whichever is greater.
  • Recent use of tranexamic acid.
  • Current or previous treatment with a complement inhibitor (for Naive Cohort only).
  • First initiation of plasma exchange/plasma infusions (PE/PI) should not be more than 28 days prior to first crovalimab administration (for Naive Cohort only).
  • Last PE/PI completed less than 2 hours prior to first crovalimab administration (for Naive Cohort only).
  • Receiving PE/PI within 8 weeks of the first crovalimab administration (Switch Cohort only).
  • Normalization of serum creatinine values at baseline (\<97.5th percentile for age), (for Naive Cohort only).
  • Positive for active Hepatitis B and/or C infections (HBV/HCV) (for Switch Cohort and switching C5 SNP Pretreated Cohort participants who recently received C5 inhibitor treatment).
  • Cryoglobulinemia at screening (for Switch Cohort and C5 SNP Cohort participants who recently received C5 inhibitor treatment).
  • Diagnosis of a condition leading to non-aHUS TMA: Thrombotic Thrombocytopenic Purpura (TTP), Shiga Toxin producing Escherichia Coli (STEC)-TMA, Pneumococcal HUS, TMA secondary to cobalamin C defect (as demonstrated by either increased total blood homocysteine levels or MMACHC gene mutation) and TMA related to Diacylglycerol kinase ε (DGKE) nephropathy.
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
41 participants (actual)

Study arms

  • Experimental
    Crovalimab

    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.

    Drug: Crovalimab

Interventions

  • DrugCrovalimab

    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.

06

What researchers measure

Primary outcomes

  1. Naïve Cohort: Percentage of Participants With Complete Thrombotic Microangiopathy Response (cTMAr) Anytime From Baseline to Week 25 (After 24 Weeks on Treatment)

    cTMAr was defined by meeting all of the following criteria at two separate assessments, obtained at least 4 weeks (a minimum of 26 days) apart, and any measurement in between: Platelet count ≥ lower limit of normal (LLN); Lactate dehydrogenase (LDH) ≤ upper limit of normal (ULN); and ≥ 25% decrease in serum creatinine from baseline. Participants with normalized creatinine (i.e., LLN ≤ creatinine ≤ ULN) at baseline were excluded from analysis. 95% confidence interval (CI) was calculated using Wilson's score method. Percentage has been rounded off.

    Time frame: From baseline up to Week 25

Secondary outcomes

  1. Naïve and Switch Cohorts: Percentage of Participants Requiring Dialysis at Baseline or Week 25 and Who Completed 24 Weeks of Treatment

    Participants were considered to be on dialysis at baseline or at Week 25 if dialysis occurred within 5 days prior to the first crovalimab administration or prior to the end date of the primary treatment period, respectively. The percentage of participants who required dialysis at baseline and Week 25 has been reported here. Percentages have been rounded off.

    Time frame: Baseline and Week 25

  2. Naïve and Switch Cohorts: Percentage of Participants With Change From Baseline to Week 25 (After 24 Weeks on Treatment) on Dialysis Status (Yes/No)

    Participants were considered as being on dialysis at baseline or at Week 25 if dialysis occurred within 5 days prior to the first crovalimab administration or prior to the end date of the primary treatment period, respectively. Percentages have been rounded off.

    Time frame: From baseline up to Week 25

  3. Naïve and Switch Cohorts: Observed Value of Estimated Glomerular Filtration Rate (eGFR), as Calculated From Central Serum Creatinine

    GFR is an index of kidney function that describes the flow rate of filtered fluid through the kidneys. It was categorized according to chronic kidney disease (CKD) staging criteria. eGFR was calculated using the creatinine-based bedside Schwartz equation. eGFR (milliliters per minute per 1.73 square meter \[mL/min/1.73 m\^2\])=0.413\*(height \[ht\]/serum creatinine \[sCr\]), if height is expressed in centimeters, or 41.3\*(ht/sCr), if height is expressed in meters.

    Time frame: Baseline, Weeks 2, 3, 4, 5, 7, 9, 11, 13, 17, 21, and 25

  4. Naïve and Switch Cohorts: Change From Baseline to Week 25 in eGFR, as Calculated From Central Serum Creatinine

    GFR is an index of kidney function that describes the flow rate of filtered fluid through the kidneys. It was categorized according to CKD staging criteria. eGFR was calculated using the creatinine-based bedside Schwartz equation. eGFR (mL/min/1.73 m\^2\])=0.413\*(ht/sCr), if height is expressed in centimeters, or 41.3\*(ht/sCr), if height is expressed in meters.

    Time frame: Baseline, Weeks 2, 3, 4, 5, 7, 9, 11, 13, 17, 21, and 25

  5. Naïve and Switch Cohorts: Percentage of Participants With Change From Baseline to Week 25 (After 24 Weeks on Treatment) in CKD Stage, as Assessed Based on eGFR Calculated From Central Serum Creatinine

    CKD stage was assessed using eGFR, calculated from central serum creatinine using Creatinine-based bedside Schwartz equation \& classified according to National Kidney Foundation CKD staging criteria as follows: G1 (≥90 mL/min/1.73 m²; normal or high kidney function), G2 (60-89 mL/min/1.73 m²; mildly decreased kidney function), G3a (45-59 mL/min/1.73 m²; mildly to moderately decreased kidney function), G3b (30-44 mL/min/1.73 m²; moderately to severely decreased kidney function), G4 (15-29 mL/min/1.73 m²; severely decreased kidney function), \& G5 (\<15 mL/min/1.73 m²; kidney failure). Change in CKD stage from baseline to Week 25 was categorized as improved (participants who improved in CKD stage from Baseline to Week 25 were based on the number of participants who completed 24 weeks and were not Stage 1 at baseline), stable (no change), or worsened (participants with CKD Stage 1 to 4 at baseline) among participants who completed 24 weeks of treatment. Percentages have been rounded off.

    Time frame: From baseline up to Week 25

  6. Naïve and Switch Cohorts: Observed Value of Platelet Count

    Time frame: Baseline and Week 25

  7. Naïve and Switch Cohorts: Observed Value of LDH

    Time frame: Baseline and Week 25

  8. Naïve and Switch Cohorts: Observed Value of Hemoglobin (Hb)

    Time frame: Baseline and Week 25

  9. Naïve and Switch Cohorts: Change From Baseline to Week 25 (After 24 Weeks on Treatment) in Platelet Count

    Time frame: Baseline and Week 25

  10. Naïve and Switch Cohorts: Change From Baseline to Week 25 (After 24 Weeks on Treatment) in LDH

    Time frame: Baseline and Week 25

  11. Naïve and Switch Cohorts: Change From Baseline to Week 25 (After 24 Weeks on Treatment) in Hb

    Time frame: Baseline and Week 25

  12. Naïve Cohort: Percentage of Participants With Platelet Count ≥ LLN at Two Separate Assessments, Obtained at Least 4 Weeks Apart (Minimum of 26 Days), by Week 25 (After 24 Weeks on Treatment)

    This event was confirmed at two separate assessments obtained at least 4 weeks (a minimum of 26 days) apart and any measurement in between.

    Time frame: From baseline up to Week 25

  13. Naïve Cohort: Percentage of Participants With LDH Normalization (i.e., ≤ ULN) at Two Separate Assessments, Obtained at Least 4 Weeks Apart (Minimum of 26 Days), by Week 25 (After 24 Weeks on Treatment)

    Percentage has been rounded off.

    Time frame: From baseline up to Week 25

  14. Naïve Cohort: Percentage of Participants With ≥ 25% Decrease in Serum Creatinine From Baseline, Confirmed at Two Separate Assessments, Obtained at Least 4 Weeks Apart (Minimum of 26 Days), by Week 25 (After 24 Weeks on Treatment)

    Percentage has been rounded off.

    Time frame: From baseline up to Week 25

  15. Naïve Cohort: Time to cTMAr

    cTMAr was defined by meeting all of the following criteria at two separate assessments, obtained at least 4 weeks (a minimum of 26 days) apart, and any measurement in between: Platelet count ≥ LLN; LDH ≤ ULN; and ≥ 25% decrease in serum creatinine from baseline. Kalpan-Meier (K-M) method was used to estimate median time to cTMAr. Data for participants who did not reach cTMAr during PTP were censored at the date of their last visit when cTMAr was assessed during the primary treatment period or prior to the treatment discontinuation, whichever was earlier. Data for participants who received a prohibited therapy during the PTP were censored at the date of the first received prohibited therapy during the primary treatment period or prior to the treatment discontinuation, whichever was earlier.

    Time frame: From baseline up to Week 25

  16. Naïve Cohort: Duration of cTMAr, Among Participants Who Achieved cTMAr

    cTMAr=meeting following criteria at 2 separate assessments, obtained at least 4 weeks (minimum of 26 days) apart \& any measurement in between: Platelet count ≥LLN; LDH ≤ULN; \& ≥25% decrease in serum creatinine from baseline. Duration of cTMAr was calculated as time from start of cTMAr to end of cTMAr. End of cTMAr=when all of following criteria were met during same visit \& confirmed at assessment that took place at least 4 weeks (minimum of 26 days) later: Platelet count \<LLN; LDH \>ULN; \& ≥25% increase in serum creatinine from baseline \& ULN. K-M method was used to estimate the median duration of cTMAr. Data for participants with no observed end of cTMAr at CCOD were censored at the date of their last visit when cTMAr was assessed before CCOD or before treatment discontinuation, whichever was earlier. Data for participants who received prohibited therapy before CCOD were censored at date of first receiving prohibited therapy or before treatment discontinuation, whichever was earlier.

    Time frame: From baseline up to primary CCOD (up to 190 weeks)

  17. Naïve Cohort: Percentage of Participants With cTMAr Ongoing at Week 25

    cTMAr at Week 25 was defined by meeting all of the three cTMAr criteria at Week 25: Platelet count ≥ LLN; LDH ≤ ULN; and ≥ 25% decrease in serum creatinine from baseline. Percentage has been rounded off.

    Time frame: At Week 25

  18. Switch Cohort: Percentage of Participants With Maintained Thrombotic Microangiopathy Response Control (mTMAc) From Baseline Through Week 25 (After 24 Weeks on Treatment)

    mTMAc was considered not maintained if all of the following criteria were met during one of the visits between baseline and Week 25, and were confirmed at an assessment that took place at least 4 weeks (a minimum of 26 days) later: Platelet count \< LLN; LDH \> ULN; and 25% increase in serum creatinine from baseline.

    Time frame: From baseline up to Week 25

  19. All Cohorts: Number of Participants With Adverse Events (AEs)

    An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.

    Time frame: Up to approximately 8 years

  20. All Cohorts: Number of Participants With Injection-site Reactions, Infusion-related Reactions, Hypersensitivity, Malignant Hypertension (Including Malignant Renal Hypertension), and Infections (Including Meningococcal Meningitis)

    An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.

    Time frame: Up to approximately 8 years

  21. All Cohorts: Number of Participants With AEs Leading to Study Drug Discontinuation

    An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.

    Time frame: Up to approximately 8 years

  22. Switch Cohort: Number of Participants With Clinical Manifestations of Drug-target-drug Complexes (DTDCs)

    Crovalimab and eculizumab bind distinct epitopes on complement component C5, and formation of DTDCs comprising crovalimab, eculizumab, and C5 are formed when participants switch treatment. DTDCs will be characterized using size exclusion chromatography (SEC) coupled with enzyme-linked immunosorbent assay (ELISA).

    Time frame: Up to approximately 8 years

  23. All Cohorts: Serum Concentrations of Crovalimab Over Time

    Time frame: Up to approximately 8 years

  24. All Cohorts: Number of Participants With Anti-drug Antibodies (ADAs) to Crovalimab

    Participants will be considered to be ADA positive if they were ADA negative at baseline but developed an ADA response following stuy drug exposure (treatment-induced ADA response), or if they were ADA positive at baseline and the titer of one or more post-baseline samples is at least 4-fold greater than the titer of the baseline sample (treatment-enhanced ADA response).

    Time frame: Up to approximately 8 years

  25. All Cohorts: Observed Value of Total Complement Activity 50 (CH50), as Measured by Liposome Immunoassay (LIA)

    Time frame: Up to approximately 8 years

  26. All Cohorts: Change From Baseline in CH50 Over Time, as Measured by LIA

    Time frame: Up to approximately 8 years

  27. All Cohorts: Observed Value of Free Complement Component 5 (C5) Concentrations in Crovalimab-treated Participants

    Time frame: Up to approximately 8 years

  28. All Cohorts: Change From Baseline in Free C5 Concentrations Over Time in Crovalimab-treated Participants

    Time frame: Up to approximately 8 years

  29. All Cohorts: Observed Value of Total C5 Concentrations in Crovalimab-treated Participants

    Time frame: Up to approximately 8 years

  30. All Cohorts: Change From Baseline in Total C5 Concentrations Over Time in Crovalimab-treated Participants

    Time frame: Up to approximately 8 years

07

Results

Posted Sep 9, 2026

Participant flow

A total of 41 pediatric participants with hemolytic uremic syndrome (aHUS), took part in the study at 19 investigative sites across 10 countries. Participants were planned to be enrolled in 3 parallel cohorts, based on their previous exposure \& response to complement inhibitor therapy: Naïve, Switch, \& Pretreated cohorts. No participants were enrolled in the pre-treated cohort.

Primary Treatment Period
Participant flow — Primary Treatment Period
MilestoneCrovalimab Naïve CohortCrovalimab Switch Cohort
Started2120
Completed1920
Not completed20
Withdrew: Reason not specified10
Withdrew: Non ahus diagnosis10
Crovalimab Continuation Period
Participant flow — Crovalimab Continuation Period
MilestoneCrovalimab Naïve CohortCrovalimab Switch Cohort
Started1120
Completed00
Not completed1120
Withdrew: Maintained tma remission21
Withdrew: Ongoing in study919
Safety Follow-up Period
Participant flow — Safety Follow-up Period
MilestoneCrovalimab Naïve CohortCrovalimab Switch Cohort
Started101
Completed11
Not completed90
Withdrew: Ongoing in study90

Outcome measures

SecondaryNaïve and Switch Cohorts: Percentage of Participants Requiring Dialysis at Baseline or Week 25 and Who Completed 24 Weeks of Treatment

Participants were considered to be on dialysis at baseline or at Week 25 if dialysis occurred within 5 days prior to the first crovalimab administration or prior to the end date of the primary treatment period, respectively. The percentage of participants who required dialysis at baseline and Week 25 has been reported here. Percentages have been rounded off.

Time frame:
Baseline and Week 25
Reported as:
Number · percentage of participants
Naïve and Switch Cohorts: Percentage of Participants Requiring Dialysis at Baseline or Week 25 and Who Completed 24 Weeks of Treatment
percentage of participantsCrovalimab Naïve CohortCrovalimab Switch Cohort
Baseline37.5 (18.48 to 61.36)0 (0.00 to 16.11)
Week 250 (0.00 to 19.36)0 (0.00 to 16.11)
SecondaryNaïve and Switch Cohorts: Percentage of Participants With Change From Baseline to Week 25 (After 24 Weeks on Treatment) on Dialysis Status (Yes/No)

Participants were considered as being on dialysis at baseline or at Week 25 if dialysis occurred within 5 days prior to the first crovalimab administration or prior to the end date of the primary treatment period, respectively. Percentages have been rounded off.

Time frame:
From baseline up to Week 25
Reported as:
Number · percentage of participants
Naïve and Switch Cohorts: Percentage of Participants With Change From Baseline to Week 25 (After 24 Weeks on Treatment) on Dialysis Status (Yes/No)
percentage of participantsCrovalimab Naïve CohortCrovalimab Switch Cohort
Initiated Dialysis at any Timepoint00
Discontinued dialysis37.50
Remained on Dialysis00
Remained Dialysis-free Throughout62.5100
SecondaryNaïve and Switch Cohorts: Observed Value of Estimated Glomerular Filtration Rate (eGFR), as Calculated From Central Serum Creatinine

GFR is an index of kidney function that describes the flow rate of filtered fluid through the kidneys. It was categorized according to chronic kidney disease (CKD) staging criteria. eGFR was calculated using the creatinine-based bedside Schwartz equation. eGFR (milliliters per minute per 1.73 square meter \[mL/min/1.73 m\^2\])=0.413\*(height \[ht\]/serum creatinine \[sCr\]), if height is expressed in centimeters, or 41.3\*(ht/sCr), if height is expressed in meters.

Time frame:
Baseline, Weeks 2, 3, 4, 5, 7, 9, 11, 13, 17, 21, and 25
Reported as:
Mean · mL/min/1.73 m^2
Naïve and Switch Cohorts: Observed Value of Estimated Glomerular Filtration Rate (eGFR), as Calculated From Central Serum Creatinine
mL/min/1.73 m^2Crovalimab Naïve CohortCrovalimab Switch Cohort
Baseline31.62 ± 18.9998.14 ± 26.30
Week 247.36 ± 24.6095.93 ± 26.05
Week 366.12 ± 20.3894.12 ± 26.18
Week 472.55 ± 25.4493.81 ± 25.06
Week 580.72 ± 26.7593.24 ± 24.32
Week 780.09 ± 23.9393.10 ± 24.91
Week 981.10 ± 25.12100.99 ± 22.08
Week 1181.19 ± 34.9575.83 ± 38.48
Week 1383.24 ± 23.3895.39 ± 23.33
Week 1785.77 ± 18.1996.44 ± 22.40
Week 2188.41 ± 16.9897.90 ± 22.93
Week 2590.00 ± 18.7899.56 ± 22.63
SecondaryNaïve and Switch Cohorts: Change From Baseline to Week 25 in eGFR, as Calculated From Central Serum Creatinine

GFR is an index of kidney function that describes the flow rate of filtered fluid through the kidneys. It was categorized according to CKD staging criteria. eGFR was calculated using the creatinine-based bedside Schwartz equation. eGFR (mL/min/1.73 m\^2\])=0.413\*(ht/sCr), if height is expressed in centimeters, or 41.3\*(ht/sCr), if height is expressed in meters.

Time frame:
Baseline, Weeks 2, 3, 4, 5, 7, 9, 11, 13, 17, 21, and 25
Reported as:
Mean · mL/min/1.73 m^2
Naïve and Switch Cohorts: Change From Baseline to Week 25 in eGFR, as Calculated From Central Serum Creatinine
mL/min/1.73 m^2Crovalimab Naïve CohortCrovalimab Switch Cohort
Change at Week 224.07 ± 19.15-1.74 ± 4.74
Change at Week 333.90 ± 21.68-1.84 ± 6.66
Change at Week 439.63 ± 24.25-3.87 ± 8.98
Change at Week 548.14 ± 27.02-4.43 ± 8.12
Change at Week 748.47 ± 23.54-6.40 ± 8.52
Change at Week 948.20 ± 24.38-2.43 ± 6.87
Change at Week 1143.21 ± 13.41-1.09 ± 3.99
Change at Week 1351.26 ± 26.34-2.75 ± 9.92
Change at Week 1756.90 ± 23.41-4.00 ± 8.00
Change at Week 2159.53 ± 17.28-4.68 ± 9.22
Change at Week 2557.73 ± 23.81-3.86 ± 7.50
SecondaryNaïve and Switch Cohorts: Percentage of Participants With Change From Baseline to Week 25 (After 24 Weeks on Treatment) in CKD Stage, as Assessed Based on eGFR Calculated From Central Serum Creatinine

CKD stage was assessed using eGFR, calculated from central serum creatinine using Creatinine-based bedside Schwartz equation \& classified according to National Kidney Foundation CKD staging criteria as follows: G1 (≥90 mL/min/1.73 m²; normal or high kidney function), G2 (60-89 mL/min/1.73 m²; mildly decreased kidney function), G3a (45-59 mL/min/1.73 m²; mildly to moderately decreased kidney function), G3b (30-44 mL/min/1.73 m²; moderately to severely decreased kidney function), G4 (15-29 mL/min/1.73 m²; severely decreased kidney function), \& G5 (\<15 mL/min/1.73 m²; kidney failure). Change in CKD stage from baseline to Week 25 was categorized as improved (participants who improved in CKD stage from Baseline to Week 25 were based on the number of participants who completed 24 weeks and were not Stage 1 at baseline), stable (no change), or worsened (participants with CKD Stage 1 to 4 at baseline) among participants who completed 24 weeks of treatment. Percentages have been rounded off.

Time frame:
From baseline up to Week 25
Reported as:
Number · percentage of participants
Naïve and Switch Cohorts: Percentage of Participants With Change From Baseline to Week 25 (After 24 Weeks on Treatment) in CKD Stage, as Assessed Based on eGFR Calculated From Central Serum Creatinine
percentage of participantsCrovalimab Naïve CohortCrovalimab Switch Cohort
Improved92.3 (66.69 to 98.63)0 (0.00 to 43.45)
Stable (no Change)0 (0.00 to 19.36)75.0 (53.13 to 88.81)
Worsened0 (0.00 to 27.75)15.0 (5.24 to 36.04)
SecondaryNaïve and Switch Cohorts: Observed Value of Platelet Count
Time frame:
Baseline and Week 25
Reported as:
Mean · cells*10^9 per liter (cells*10^9/L)
Naïve and Switch Cohorts: Observed Value of Platelet Count
cells*10^9 per liter (cells*10^9/L)Crovalimab Naïve CohortCrovalimab Switch Cohort
Baseline133.1 ± 90.6301.5 ± 74.2
Week 25298.2 ± 93.3306.2 ± 72.7
SecondaryNaïve and Switch Cohorts: Observed Value of LDH
Time frame:
Baseline and Week 25
Reported as:
Mean · units per liter (U/L)
Naïve and Switch Cohorts: Observed Value of LDH
units per liter (U/L)Crovalimab Naïve CohortCrovalimab Switch Cohort
Baseline595.7 ± 526.8146.1 ± 36.0
Week 25142.3 ± 25.8142.2 ± 35.9
PrimaryNaïve Cohort: Percentage of Participants With Complete Thrombotic Microangiopathy Response (cTMAr) Anytime From Baseline to Week 25 (After 24 Weeks on Treatment)

cTMAr was defined by meeting all of the following criteria at two separate assessments, obtained at least 4 weeks (a minimum of 26 days) apart, and any measurement in between: Platelet count ≥ lower limit of normal (LLN); Lactate dehydrogenase (LDH) ≤ upper limit of normal (ULN); and ≥ 25% decrease in serum creatinine from baseline. Participants with normalized creatinine (i.e., LLN ≤ creatinine ≤ ULN) at baseline were excluded from analysis. 95% confidence interval (CI) was calculated using Wilson's score method. Percentage has been rounded off.

Time frame:
From baseline up to Week 25
Reported as:
Number · percentage of participants
Naïve Cohort: Percentage of Participants With Complete Thrombotic Microangiopathy Response (cTMAr) Anytime From Baseline to Week 25 (After 24 Weeks on Treatment)
percentage of participantsCrovalimab Naïve Cohort
Naïve Cohort: Percentage of Participants With Complete Thrombotic Microangiopathy Response (cTMAr) Anytime From Baseline to Week 25 (After 24 Weeks on Treatment)70.6 (46.87 to 86.72)
SecondaryNaïve and Switch Cohorts: Observed Value of Hemoglobin (Hb)
Time frame:
Baseline and Week 25
Reported as:
Mean · grams per liter (g/L)
Naïve and Switch Cohorts: Observed Value of Hemoglobin (Hb)
grams per liter (g/L)Crovalimab Naïve CohortCrovalimab Switch Cohort
Baseline85.2 ± 16.5134.8 ± 13.7
Week 25125.8 ± 16.6136.8 ± 13.3
SecondaryNaïve and Switch Cohorts: Change From Baseline to Week 25 (After 24 Weeks on Treatment) in Platelet Count
Time frame:
Baseline and Week 25
Reported as:
Mean · cells*10^9/L
Naïve and Switch Cohorts: Change From Baseline to Week 25 (After 24 Weeks on Treatment) in Platelet Count
cells*10^9/LCrovalimab Naïve CohortCrovalimab Switch Cohort
Naïve and Switch Cohorts: Change From Baseline to Week 25 (After 24 Weeks on Treatment) in Platelet Count158.6 ± 111.34.7 ± 60.1
SecondaryNaïve and Switch Cohorts: Change From Baseline to Week 25 (After 24 Weeks on Treatment) in LDH
Time frame:
Baseline and Week 25
Reported as:
Mean · U/L
Naïve and Switch Cohorts: Change From Baseline to Week 25 (After 24 Weeks on Treatment) in LDH
U/LCrovalimab Naïve CohortCrovalimab Switch Cohort
Naïve and Switch Cohorts: Change From Baseline to Week 25 (After 24 Weeks on Treatment) in LDH-406.3 ± 515.3-9.2 ± 28.6
SecondaryNaïve and Switch Cohorts: Change From Baseline to Week 25 (After 24 Weeks on Treatment) in Hb
Time frame:
Baseline and Week 25
Reported as:
Mean · g/L
Naïve and Switch Cohorts: Change From Baseline to Week 25 (After 24 Weeks on Treatment) in Hb
g/LCrovalimab Naïve CohortCrovalimab Switch Cohort
Naïve and Switch Cohorts: Change From Baseline to Week 25 (After 24 Weeks on Treatment) in Hb39.9 ± 20.42.0 ± 5.6
SecondaryNaïve Cohort: Percentage of Participants With Platelet Count ≥ LLN at Two Separate Assessments, Obtained at Least 4 Weeks Apart (Minimum of 26 Days), by Week 25 (After 24 Weeks on Treatment)

This event was confirmed at two separate assessments obtained at least 4 weeks (a minimum of 26 days) apart and any measurement in between.

Time frame:
From baseline up to Week 25
Reported as:
Number · percentage of participants
Naïve Cohort: Percentage of Participants With Platelet Count ≥ LLN at Two Separate Assessments, Obtained at Least 4 Weeks Apart (Minimum of 26 Days), by Week 25 (After 24 Weeks on Treatment)
percentage of participantsCrovalimab Naïve Cohort
Naïve Cohort: Percentage of Participants With Platelet Count ≥ LLN at Two Separate Assessments, Obtained at Least 4 Weeks Apart (Minimum of 26 Days), by Week 25 (After 24 Weeks on Treatment)100.0 (81.57 to 100.00)
SecondaryNaïve Cohort: Percentage of Participants With LDH Normalization (i.e., ≤ ULN) at Two Separate Assessments, Obtained at Least 4 Weeks Apart (Minimum of 26 Days), by Week 25 (After 24 Weeks on Treatment)

Percentage has been rounded off.

Time frame:
From baseline up to Week 25
Reported as:
Number · percentage of participants
Naïve Cohort: Percentage of Participants With LDH Normalization (i.e., ≤ ULN) at Two Separate Assessments, Obtained at Least 4 Weeks Apart (Minimum of 26 Days), by Week 25 (After 24 Weeks on Treatment)
percentage of participantsCrovalimab Naïve Cohort
Naïve Cohort: Percentage of Participants With LDH Normalization (i.e., ≤ ULN) at Two Separate Assessments, Obtained at Least 4 Weeks Apart (Minimum of 26 Days), by Week 25 (After 24 Weeks on Treatment)76.5 (52.74 to 90.44)
SecondaryNaïve Cohort: Percentage of Participants With ≥ 25% Decrease in Serum Creatinine From Baseline, Confirmed at Two Separate Assessments, Obtained at Least 4 Weeks Apart (Minimum of 26 Days), by Week 25 (After 24 Weeks on Treatment)

Percentage has been rounded off.

Time frame:
From baseline up to Week 25
Reported as:
Number · percentage of participants
Naïve Cohort: Percentage of Participants With ≥ 25% Decrease in Serum Creatinine From Baseline, Confirmed at Two Separate Assessments, Obtained at Least 4 Weeks Apart (Minimum of 26 Days), by Week 25 (After 24 Weeks on Treatment)
percentage of participantsCrovalimab Naïve Cohort
Naïve Cohort: Percentage of Participants With ≥ 25% Decrease in Serum Creatinine From Baseline, Confirmed at Two Separate Assessments, Obtained at Least 4 Weeks Apart (Minimum of 26 Days), by Week 25 (After 24 Weeks on Treatment)94.1 (73.02 to 98.95)
SecondaryNaïve Cohort: Time to cTMAr

cTMAr was defined by meeting all of the following criteria at two separate assessments, obtained at least 4 weeks (a minimum of 26 days) apart, and any measurement in between: Platelet count ≥ LLN; LDH ≤ ULN; and ≥ 25% decrease in serum creatinine from baseline. Kalpan-Meier (K-M) method was used to estimate median time to cTMAr. Data for participants who did not reach cTMAr during PTP were censored at the date of their last visit when cTMAr was assessed during the primary treatment period or prior to the treatment discontinuation, whichever was earlier. Data for participants who received a prohibited therapy during the PTP were censored at the date of the first received prohibited therapy during the primary treatment period or prior to the treatment discontinuation, whichever was earlier.

Time frame:
From baseline up to Week 25
Reported as:
Median · weeks
Naïve Cohort: Time to cTMAr
weeksCrovalimab Naïve Cohort
Naïve Cohort: Time to cTMAr8.7 (5.9 to 16.1)
SecondaryNaïve Cohort: Duration of cTMAr, Among Participants Who Achieved cTMAr

cTMAr=meeting following criteria at 2 separate assessments, obtained at least 4 weeks (minimum of 26 days) apart \& any measurement in between: Platelet count ≥LLN; LDH ≤ULN; \& ≥25% decrease in serum creatinine from baseline. Duration of cTMAr was calculated as time from start of cTMAr to end of cTMAr. End of cTMAr=when all of following criteria were met during same visit \& confirmed at assessment that took place at least 4 weeks (minimum of 26 days) later: Platelet count \<LLN; LDH \>ULN; \& ≥25% increase in serum creatinine from baseline \& ULN. K-M method was used to estimate the median duration of cTMAr. Data for participants with no observed end of cTMAr at CCOD were censored at the date of their last visit when cTMAr was assessed before CCOD or before treatment discontinuation, whichever was earlier. Data for participants who received prohibited therapy before CCOD were censored at date of first receiving prohibited therapy or before treatment discontinuation, whichever was earlier.

Time frame:
From baseline up to primary CCOD (up to 190 weeks)
Reported as:
Median · weeks
Naïve Cohort: Duration of cTMAr, Among Participants Who Achieved cTMAr
weeksCrovalimab Naïve Cohort
Naïve Cohort: Duration of cTMAr, Among Participants Who Achieved cTMArNA (NA to NA)
SecondaryNaïve Cohort: Percentage of Participants With cTMAr Ongoing at Week 25

cTMAr at Week 25 was defined by meeting all of the three cTMAr criteria at Week 25: Platelet count ≥ LLN; LDH ≤ ULN; and ≥ 25% decrease in serum creatinine from baseline. Percentage has been rounded off.

Time frame:
At Week 25
Reported as:
Number · percentage of participants
Naïve Cohort: Percentage of Participants With cTMAr Ongoing at Week 25
percentage of participantsCrovalimab Naïve Cohort
Naïve Cohort: Percentage of Participants With cTMAr Ongoing at Week 2570.6 (46.87 to 86.72)
SecondarySwitch Cohort: Percentage of Participants With Maintained Thrombotic Microangiopathy Response Control (mTMAc) From Baseline Through Week 25 (After 24 Weeks on Treatment)

mTMAc was considered not maintained if all of the following criteria were met during one of the visits between baseline and Week 25, and were confirmed at an assessment that took place at least 4 weeks (a minimum of 26 days) later: Platelet count \< LLN; LDH \> ULN; and 25% increase in serum creatinine from baseline.

Time frame:
From baseline up to Week 25
Reported as:
Number · percentage of participants
Switch Cohort: Percentage of Participants With Maintained Thrombotic Microangiopathy Response Control (mTMAc) From Baseline Through Week 25 (After 24 Weeks on Treatment)
percentage of participantsCrovalimab Switch Cohort
Switch Cohort: Percentage of Participants With Maintained Thrombotic Microangiopathy Response Control (mTMAc) From Baseline Through Week 25 (After 24 Weeks on Treatment)100.0 (83.89 to 100.00)
SecondaryAll Cohorts: Number of Participants With Adverse Events (AEs)

An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.

Time frame:
Up to approximately 8 years

Results for this outcome have not been posted.

SecondaryAll Cohorts: Number of Participants With Injection-site Reactions, Infusion-related Reactions, Hypersensitivity, Malignant Hypertension (Including Malignant Renal Hypertension), and Infections (Including Meningococcal Meningitis)

An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.

Time frame:
Up to approximately 8 years

Results for this outcome have not been posted.

SecondaryAll Cohorts: Number of Participants With AEs Leading to Study Drug Discontinuation

An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.

Time frame:
Up to approximately 8 years

Results for this outcome have not been posted.

SecondarySwitch Cohort: Number of Participants With Clinical Manifestations of Drug-target-drug Complexes (DTDCs)

Crovalimab and eculizumab bind distinct epitopes on complement component C5, and formation of DTDCs comprising crovalimab, eculizumab, and C5 are formed when participants switch treatment. DTDCs will be characterized using size exclusion chromatography (SEC) coupled with enzyme-linked immunosorbent assay (ELISA).

Time frame:
Up to approximately 8 years

Results for this outcome have not been posted.

SecondaryAll Cohorts: Serum Concentrations of Crovalimab Over Time
Time frame:
Up to approximately 8 years

Results for this outcome have not been posted.

SecondaryAll Cohorts: Number of Participants With Anti-drug Antibodies (ADAs) to Crovalimab

Participants will be considered to be ADA positive if they were ADA negative at baseline but developed an ADA response following stuy drug exposure (treatment-induced ADA response), or if they were ADA positive at baseline and the titer of one or more post-baseline samples is at least 4-fold greater than the titer of the baseline sample (treatment-enhanced ADA response).

Time frame:
Up to approximately 8 years

Results for this outcome have not been posted.

SecondaryAll Cohorts: Observed Value of Total Complement Activity 50 (CH50), as Measured by Liposome Immunoassay (LIA)
Time frame:
Up to approximately 8 years

Results for this outcome have not been posted.

SecondaryAll Cohorts: Change From Baseline in CH50 Over Time, as Measured by LIA
Time frame:
Up to approximately 8 years

Results for this outcome have not been posted.

SecondaryAll Cohorts: Observed Value of Free Complement Component 5 (C5) Concentrations in Crovalimab-treated Participants
Time frame:
Up to approximately 8 years

Results for this outcome have not been posted.

SecondaryAll Cohorts: Change From Baseline in Free C5 Concentrations Over Time in Crovalimab-treated Participants
Time frame:
Up to approximately 8 years

Results for this outcome have not been posted.

SecondaryAll Cohorts: Observed Value of Total C5 Concentrations in Crovalimab-treated Participants
Time frame:
Up to approximately 8 years

Results for this outcome have not been posted.

SecondaryAll Cohorts: Change From Baseline in Total C5 Concentrations Over Time in Crovalimab-treated Participants
Time frame:
Up to approximately 8 years

Results for this outcome have not been posted.

Adverse events

Collected over Up to approximately 190 weeks. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Crovalimab Naïve Cohort0/21 (0%)8/21 (38.1%)15/21 (71.4%)
Crovalimab Switch Cohort0/20 (0%)4/20 (20%)19/20 (95%)
Most frequent serious events
Showing 10 of 17
Most frequent serious events
EventCrovalimab Naïve CohortCrovalimab Switch Cohort
COVID-19Infections and infestations2/210/20
AppendicitisInfections and infestations0/211/20
InfluenzaInfections and infestations1/211/20
Meningitis meningococcalInfections and infestations0/211/20
MyelitisInfections and infestations0/211/20
PharyngitisInfections and infestations0/211/20
Thrombotic microangiopathyBlood and lymphatic system disorders1/210/20
Bacterial sepsisInfections and infestations1/210/20
PneumoniaInfections and infestations1/210/20
Pneumonia viralInfections and infestations1/210/20
Most frequent other events
Showing 10 of 113
Most frequent other events
EventCrovalimab Naïve CohortCrovalimab Switch Cohort
NasopharyngitisInfections and infestations1/217/20
HeadacheNervous system disorders2/217/20
Upper respiratory tract infectionInfections and infestations6/214/20
PyrexiaGeneral disorders5/215/20
ContusionInjury, poisoning and procedural complications0/215/20
Viral infectionInfections and infestations0/214/20
ConstipationGastrointestinal disorders4/212/20
DiarrhoeaGastrointestinal disorders2/213/20
NauseaGastrointestinal disorders1/213/20
Injection site reactionGeneral disorders2/213/20

Baseline characteristics

All patients population included all 41 enrolled participants.

Age, Continuous
Age, Continuous(years)Crovalimab Naïve CohortCrovalimab Switch CohortTotal
Mean6.8 ± 3.99.8 ± 4.08.2 ± 4.2
Sex: Female, Male
Sex: Female, Male(Participants)Crovalimab Naïve CohortCrovalimab Switch CohortTotal
Female9918
Male121123
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Crovalimab Naïve CohortCrovalimab Switch CohortTotal
Hispanic or Latino314
Not Hispanic or Latino61218
Unknown or Not Reported12719
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Crovalimab Naïve CohortCrovalimab Switch CohortTotal
American Indian or Alaska Native000
Asian11314
Native Hawaiian or Other Pacific Islander000
Black or African American000
White51419
More than one race000
Unknown or Not Reported538
08

Study locations

20 sites
  • Children's Hospital Colorado
    Aurora, Colorado 80045, United States
  • University of Nebraska
    Omaha, Nebraska 68198, United States
  • Hackensack University Medical Center
    Hackensack, New Jersey 07601, United States
  • UZ Gent
    Ghent, 9000, Belgium
  • UZ Leuven Gasthuisberg
    Leuven, 3000, Belgium
  • Inst. Da Criança- Faculdade de Medicina Usp
    São Paulo, São Paulo 05403-900, Brazil
  • CHU Sainte-Justine
    Montreal, Quebec H3T 1C5, Canada
  • Peking University First Hospital
    Beijing, 100034, China
  • Beijing Children's Hospital, Capital Medical University
    Beijing, 100045, China
  • The children's hospital , Zhejiang university school of medicine
    Hangzhou, 310051, China
  • Hôpital Arnaud de Villeneuve
    Montpellier, 34295, France
  • Gh Necker Enfants Malades
    Paris, 75743, France
  • Institute of Kidney Diseases and Research Centre
    Ahmedabad, Gujarat 380016, India
  • Medanta-The Medicity
    Gurgaon, Haryana 122001, India
  • All India Institute Of Medical Sciences (AIIMS)
    New Delhi, National Capital Territory of Delhi 110029, India
  • Aichi Children?s Health and Medical Center
    Aichi, 474-8710, Japan
  • Chiba Children's Hospital
    Chibashi, Chibaken, 266-0007, Japan
  • Hospital de Especialidades Puerta de Hierro S.A de C.V.
    Zapopan, 45116, Mexico
  • Uniwersyteckie Centrum Kliniczne
    Gdansk, 80-294, Poland
  • Instytut ?Centrum Zdrowia Matki Polki
    Lodz, 93-338, Poland
09

References and documents

Study documents

  • Study protocol · Jul 1, 2024
  • Statistical analysis plan · Dec 4, 2023

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data\_sharing

10

Updates

1 registry update since Sep 25, 2026
Minor edits
Nothing that changes what the study is or who can join. Edited: verification date
1 update, last Oct 1, 2026
Show all 1 update
  1. Oct 1, 2026
    Minor edits only
    + 1 other change: verification date

From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗

11

Registry details

Key details

Study ID
NCT04958265
Lead sponsor
Hoffmann-La Roche
Collaborators
Chugai Pharmaceutical
Responsible party
Sponsor
First posted
Jul 12, 2021
Start date
Nov 17, 2021
Primary completion
Jul 4, 2025
Completion
May 19, 2029 (estimated)
Results posted
Sep 9, 2026
Last update
Oct 1, 2026

Study contacts

Clinical Trials
study director · Hoffmann-La Roche

Oversight

FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is active, not recruiting, as verified in Sep 2026. You cannot join it, but the record below documents what was studied.

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