Trial Outcomes & Findings for A Study Evaluating the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of Crovalimab in Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH) Not Previously Treated With Complement Inhibition (NCT NCT04654468)

Results Overview

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.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE3

Target enrollment

51 participants

Primary outcome timeframe

From Week 5 up to Week 25

Results posted on

2025-11-17

Participant Flow

Participants took part in the study at 5 investigative sites in China.

A total of 51 participants with a diagnosis of paroxysmal nocturnal hemoglobinuria (PNH) were enrolled in the study and received at least 1 dose of crovalimab.

Participant milestones

Participant milestones
Measure	Crovalimab Crovalimab was administered at an initial loading dose of 1000 milligrams (mg) (for participants with body weight between 40 and 100 kg) or 1500 mg (for participants with body weight \>=100kg), 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 was administered, as SC injection, at a maintenance dose of 680 mg (for participants with body weight between 40 and 100kg) or 1020 mg (for participants with body weight \>=100kg) once every 4 weeks (Q4W) from Week 5 for a total of 24 weeks of study treatment. Participants who derive benefit from the drug after 24 weeks of treatment may continue to receive crovalimab Q4W.
Overall Study STARTED	51
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	51

Reasons for withdrawal

Reasons for withdrawal
Measure	Crovalimab Crovalimab was administered at an initial loading dose of 1000 milligrams (mg) (for participants with body weight between 40 and 100 kg) or 1500 mg (for participants with body weight \>=100kg), 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 was administered, as SC injection, at a maintenance dose of 680 mg (for participants with body weight between 40 and 100kg) or 1020 mg (for participants with body weight \>=100kg) once every 4 weeks (Q4W) from Week 5 for a total of 24 weeks of study treatment. Participants who derive benefit from the drug after 24 weeks of treatment may continue to receive crovalimab Q4W.
Overall Study Death	1
Overall Study Ongoing in the Study	50

Baseline Characteristics

A Study Evaluating the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of Crovalimab in Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH) Not Previously Treated With Complement Inhibition

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Crovalimab n=51 Participants Crovalimab was administered at an initial loading dose of 1000 mg (for participants with body weight between 40 and 100) kg or 1500 mg (for participants with body weight \>=100kg), as IV injection on Day 1 of Week 1 followed by four weekly SC injections of 340 mg starting on Day 2 of Week 1 and then QW at Weeks 2,3 and 4. Thereafter crovalimab was administered, as SC injection, at a maintenance dose of 680 mg (for participants with body weight between 40 and 100kg) or 1020 mg (for participants with body weight \>=100kg) Q4W from Week 5 for a total of 24 weeks of study treatment. Participants who derive benefit from the drug after 24 weeks of treatment may continue to receive crovalimab.
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=202 Participants
Age, Continuous	33.0 Years STANDARD_DEVIATION 9.4 • n=202 Participants
Sex: Female, Male Female	29 Participants n=202 Participants
Sex: Female, Male Male	22 Participants n=202 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=202 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	51 Participants n=202 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=202 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=202 Participants
Race (NIH/OMB) Asian	51 Participants n=202 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=202 Participants
Race (NIH/OMB) Black or African American	0 Participants n=202 Participants
Race (NIH/OMB) White	0 Participants n=202 Participants
Race (NIH/OMB) More than one race	0 Participants n=202 Participants

PRIMARY outcome

Timeframe: From Week 5 up to Week 25

Population: Primary Analysis Population (PAP) included all enrolled participants who received at least one dose of crovalimab and had at least one central LDH level assessment after the first IV infusion.

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.

Outcome measures

Outcome measures
Measure	Crovalimab n=51 Participants Crovalimab was administered at an initial loading dose of 1000 mg (for participants with body weight between 40 and 100) kg or 1500 mg (for participants with body weight \>=100kg), as IV injection on Day 1 of Week 1 followed by four weekly SC injections of 340 mg starting on Day 2 of Week 1 and then QW at Weeks 2,3 and 4. Thereafter crovalimab was administered, as SC injection, at a maintenance dose of 680 mg (for participants with body weight between 40 and 100kg) or 1020 mg (for participants with body weight \>=100kg) Q4W from Week 5 for a total of 24 weeks of study treatment. Participants who derive benefit from the drug after 24 weeks of treatment may continue to receive crovalimab.
Mean Percentage of Participants With Hemolysis Control	78.66 mean percentage of participants Interval 67.78 to 86.59

PRIMARY outcome

Timeframe: 24 Weeks Prior to Screening, Baseline to Week 25

Population: PAP included all enrolled participants who received at least one dose of crovalimab and had at least one central LDH level assessment after the first IV infusion.

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.

Outcome measures

Outcome measures
Measure	Crovalimab n=51 Participants Crovalimab was administered at an initial loading dose of 1000 mg (for participants with body weight between 40 and 100) kg or 1500 mg (for participants with body weight \>=100kg), as IV injection on Day 1 of Week 1 followed by four weekly SC injections of 340 mg starting on Day 2 of Week 1 and then QW at Weeks 2,3 and 4. Thereafter crovalimab was administered, as SC injection, at a maintenance dose of 680 mg (for participants with body weight between 40 and 100kg) or 1020 mg (for participants with body weight \>=100kg) Q4W from Week 5 for a total of 24 weeks of study treatment. Participants who derive benefit from the drug after 24 weeks of treatment may continue to receive crovalimab.
Difference in Percentage of Participants With Transfusion Avoidance (TA) From Baseline Through Week 25 and Within 24 Weeks Prior to Screening	50.98 percentage of participants Interval 34.3 to 65.05

SECONDARY outcome

Timeframe: Baseline, Week 25

Population: PAP included all enrolled participants who received at least one dose of crovalimab and had at least one central LDH level assessment after the first IV infusion.

BTH was defined as at least one new or worsening symptom or sign of intravascular hemolysis (fatigue, hemoglobinuria, abdominal pain, shortness of breath \[dyspnea\], anemia \[hemoglobin \< 10 grams per deciliter (g/dL)\], major adverse vascular event \[MAVE, including thrombosis\], dysphagia, or erectile dysfunction) in the presence of elevated LDH ≥2xULN after a prior LDH reduction to ≤1.5xULN from the start of study treatment. As pre-specified in the SAP participants withdrawing before Week 25 were deemed to have experienced a BTH event. Percentages have been rounded off to the first decimal point.

Outcome measures

Outcome measures
Measure	Crovalimab n=51 Participants Crovalimab was administered at an initial loading dose of 1000 mg (for participants with body weight between 40 and 100) kg or 1500 mg (for participants with body weight \>=100kg), as IV injection on Day 1 of Week 1 followed by four weekly SC injections of 340 mg starting on Day 2 of Week 1 and then QW at Weeks 2,3 and 4. Thereafter crovalimab was administered, as SC injection, at a maintenance dose of 680 mg (for participants with body weight between 40 and 100kg) or 1020 mg (for participants with body weight \>=100kg) Q4W from Week 5 for a total of 24 weeks of study treatment. Participants who derive benefit from the drug after 24 weeks of treatment may continue to receive crovalimab.
Percentage of Participants With Breakthrough Hemolysis (BTH)	3.9 percentage of participants Interval 0.68 to 14.59

SECONDARY outcome

Timeframe: Baseline, Week 25

Population: PAP included all enrolled participants who received at least one dose of crovalimab and had at least one central LDH level assessment after the first IV infusion.

Stabilized hemoglobin was defined as avoidance of a ≥2 g/dL decrease in hemoglobin level from baseline, in the absence of transfusion. As pre-specified in the SAP participants withdrawing before Week 25 were deemed to not have hemoglobin stabilization.

Outcome measures

Outcome measures
Measure	Crovalimab n=51 Participants Crovalimab was administered at an initial loading dose of 1000 mg (for participants with body weight between 40 and 100) kg or 1500 mg (for participants with body weight \>=100kg), as IV injection on Day 1 of Week 1 followed by four weekly SC injections of 340 mg starting on Day 2 of Week 1 and then QW at Weeks 2,3 and 4. Thereafter crovalimab was administered, as SC injection, at a maintenance dose of 680 mg (for participants with body weight between 40 and 100kg) or 1020 mg (for participants with body weight \>=100kg) Q4W from Week 5 for a total of 24 weeks of study treatment. Participants who derive benefit from the drug after 24 weeks of treatment may continue to receive crovalimab.
Percentage of Participants With Stabilized Hemoglobin	51.0 percentage of participants Interval 36.77 to 65.05

SECONDARY outcome

Timeframe: Baseline, Week 2, Week 5, Week 9, Week 17, Week 25

Population: PAP included all enrolled participants who received at least one dose of crovalimab and had at least one central LDH level assessment after the first IV infusion. Overall number analyzed is the number of participants ≥18 years with data available for analysis.

Fatigue was assessed using functional assessment of chronic illness therapy-fatigue (FACIT-F) scale. FACIT-F is a self-assessment questionnaire with a 7-day recall period and 13 items evaluating fatigue and its impact on daily life activities. Items are scored on a response scale that ranges from 0 ("not at all") to 4 ("very much so"). Relevant items are reverse scored, and all the items are summed to create a total score range from 0 to 52, with 0 being the worst possible score and 52 being the best possible score. A higher score indicates low fatigue severity. A positive mean change indicates improvement. FACIT-F was assessed in adult participants only. FACIT-F assessment was unintentionally missed in the Schedule of Activities (SoA) table, which site used to guide the assessments at each timepoint. Therefore, data were not collected at Week 25.

Outcome measures

Outcome measures
Measure	Crovalimab n=48 Participants Crovalimab was administered at an initial loading dose of 1000 mg (for participants with body weight between 40 and 100) kg or 1500 mg (for participants with body weight \>=100kg), as IV injection on Day 1 of Week 1 followed by four weekly SC injections of 340 mg starting on Day 2 of Week 1 and then QW at Weeks 2,3 and 4. Thereafter crovalimab was administered, as SC injection, at a maintenance dose of 680 mg (for participants with body weight between 40 and 100kg) or 1020 mg (for participants with body weight \>=100kg) Q4W from Week 5 for a total of 24 weeks of study treatment. Participants who derive benefit from the drug after 24 weeks of treatment may continue to receive crovalimab.
Change From Baseline in Fatigue in Adults Aged >=18 Years Baseline	31.77 score on a scale Standard Deviation 8.53
Change From Baseline in Fatigue in Adults Aged >=18 Years Change from Baseline at Week 2	6.67 score on a scale Standard Deviation 8.02
Change From Baseline in Fatigue in Adults Aged >=18 Years Change from Baseline at Week 5	8.08 score on a scale Standard Deviation 9.28
Change From Baseline in Fatigue in Adults Aged >=18 Years Change from Baseline at Week 9	8.15 score on a scale Standard Deviation 10.61
Change From Baseline in Fatigue in Adults Aged >=18 Years Change from Baseline at Week 17	8.77 score on a scale Standard Deviation 9.63

SECONDARY outcome

Timeframe: Baseline, Week 25

Population: Safety population included all enrolled participants who received at least one dose of crovalimab. Number of participants analyzed is the number of participants with data available for analysis at the specified timepoints.

Outcome measures

Outcome measures
Measure	Crovalimab n=44 Participants Crovalimab was administered at an initial loading dose of 1000 mg (for participants with body weight between 40 and 100) kg or 1500 mg (for participants with body weight \>=100kg), as IV injection on Day 1 of Week 1 followed by four weekly SC injections of 340 mg starting on Day 2 of Week 1 and then QW at Weeks 2,3 and 4. Thereafter crovalimab was administered, as SC injection, at a maintenance dose of 680 mg (for participants with body weight between 40 and 100kg) or 1020 mg (for participants with body weight \>=100kg) Q4W from Week 5 for a total of 24 weeks of study treatment. Participants who derive benefit from the drug after 24 weeks of treatment may continue to receive crovalimab.
Percent Change From Baseline in Absolute Reticulocyte Count	40.9411 percent change Standard Deviation 66.0292

SECONDARY outcome

Timeframe: Baseline, Week 25

Population: Safety population included all enrolled participants who received at least one dose of crovalimab. Number of participants analyzed is the number of participants with data available for analysis at the specified timepoints.

Outcome measures

Outcome measures
Measure	Crovalimab n=37 Participants Crovalimab was administered at an initial loading dose of 1000 mg (for participants with body weight between 40 and 100) kg or 1500 mg (for participants with body weight \>=100kg), as IV injection on Day 1 of Week 1 followed by four weekly SC injections of 340 mg starting on Day 2 of Week 1 and then QW at Weeks 2,3 and 4. Thereafter crovalimab was administered, as SC injection, at a maintenance dose of 680 mg (for participants with body weight between 40 and 100kg) or 1020 mg (for participants with body weight \>=100kg) Q4W from Week 5 for a total of 24 weeks of study treatment. Participants who derive benefit from the drug after 24 weeks of treatment may continue to receive crovalimab.
Percent Change From Baseline in Free Hemoglobin	-45.6180 percent change Standard Deviation 51.8421

SECONDARY outcome

Timeframe: Baseline, Week 25

Population: Safety population included all enrolled participants who received at least one dose of crovalimab. Number of participants analyzed is the number of participants with data available for analysis at the specified timepoints.

Outcome measures

Outcome measures
Measure	Crovalimab n=37 Participants Crovalimab was administered at an initial loading dose of 1000 mg (for participants with body weight between 40 and 100) kg or 1500 mg (for participants with body weight \>=100kg), as IV injection on Day 1 of Week 1 followed by four weekly SC injections of 340 mg starting on Day 2 of Week 1 and then QW at Weeks 2,3 and 4. Thereafter crovalimab was administered, as SC injection, at a maintenance dose of 680 mg (for participants with body weight between 40 and 100kg) or 1020 mg (for participants with body weight \>=100kg) Q4W from Week 5 for a total of 24 weeks of study treatment. Participants who derive benefit from the drug after 24 weeks of treatment may continue to receive crovalimab.
Percent Change From Baseline in Haptoglobin	295.1351 percent change Standard Deviation 1735.4180

Adverse Events

CROVALIMAB

Serious events: 4 serious events

Other events: 46 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	CROVALIMAB n=51 participants at risk Crovalimab was administered at an initial loading dose of 1000 mg (for participants with body weight between 40 and 100) kg or 1500 mg (for participants with body weight \>=100kg), as IV injection on Day 1 of Week 1 followed by four weekly SC injections of 340 mg starting on Day 2 of Week 1 and then QW at Weeks 2,3 and 4. Thereafter crovalimab was administered, as SC injection, at a maintenance dose of 680 mg (for participants with body weight between 40 and 100kg) or 1020 mg (for participants with body weight \>=100kg) Q4W from Week 5 for a total of 24 weeks of study treatment. Participants who derive benefit from the drug after 24 weeks of treatment may continue to receive crovalimab.
Blood and lymphatic system disorders Thrombocytopenia	2.0% 1/51 • Number of events 1 • From enrollment until primary completion date cutoff (up to approximately 25 weeks) Safety population included all enrolled participants who received at least one dose of crovalimab.
Gastrointestinal disorders Abdominal wall mass	2.0% 1/51 • Number of events 1 • From enrollment until primary completion date cutoff (up to approximately 25 weeks) Safety population included all enrolled participants who received at least one dose of crovalimab.
Hepatobiliary disorders Bile duct stone	2.0% 1/51 • Number of events 1 • From enrollment until primary completion date cutoff (up to approximately 25 weeks) Safety population included all enrolled participants who received at least one dose of crovalimab.
Infections and infestations Bacteraemia	2.0% 1/51 • Number of events 1 • From enrollment until primary completion date cutoff (up to approximately 25 weeks) Safety population included all enrolled participants who received at least one dose of crovalimab.
Injury, poisoning and procedural complications Subdural haematoma	2.0% 1/51 • Number of events 1 • From enrollment until primary completion date cutoff (up to approximately 25 weeks) Safety population included all enrolled participants who received at least one dose of crovalimab.
Investigations Platelet count decreased	2.0% 1/51 • Number of events 1 • From enrollment until primary completion date cutoff (up to approximately 25 weeks) Safety population included all enrolled participants who received at least one dose of crovalimab.

Other adverse events

Other adverse events
Measure	CROVALIMAB n=51 participants at risk Crovalimab was administered at an initial loading dose of 1000 mg (for participants with body weight between 40 and 100) kg or 1500 mg (for participants with body weight \>=100kg), as IV injection on Day 1 of Week 1 followed by four weekly SC injections of 340 mg starting on Day 2 of Week 1 and then QW at Weeks 2,3 and 4. Thereafter crovalimab was administered, as SC injection, at a maintenance dose of 680 mg (for participants with body weight between 40 and 100kg) or 1020 mg (for participants with body weight \>=100kg) Q4W from Week 5 for a total of 24 weeks of study treatment. Participants who derive benefit from the drug after 24 weeks of treatment may continue to receive crovalimab.
Blood and lymphatic system disorders Neutropenia	13.7% 7/51 • Number of events 8 • From enrollment until primary completion date cutoff (up to approximately 25 weeks) Safety population included all enrolled participants who received at least one dose of crovalimab.
Gastrointestinal disorders Gingival swelling	5.9% 3/51 • Number of events 3 • From enrollment until primary completion date cutoff (up to approximately 25 weeks) Safety population included all enrolled participants who received at least one dose of crovalimab.
Infections and infestations Upper respiratory tract infection	47.1% 24/51 • Number of events 26 • From enrollment until primary completion date cutoff (up to approximately 25 weeks) Safety population included all enrolled participants who received at least one dose of crovalimab.
Infections and infestations Urinary tract infection	5.9% 3/51 • Number of events 4 • From enrollment until primary completion date cutoff (up to approximately 25 weeks) Safety population included all enrolled participants who received at least one dose of crovalimab.
Investigations Alanine aminotransferase increased	21.6% 11/51 • Number of events 15 • From enrollment until primary completion date cutoff (up to approximately 25 weeks) Safety population included all enrolled participants who received at least one dose of crovalimab.
Investigations Alpha hydroxybutyrate dehydrogenase increased	15.7% 8/51 • Number of events 8 • From enrollment until primary completion date cutoff (up to approximately 25 weeks) Safety population included all enrolled participants who received at least one dose of crovalimab.
Investigations Bilirubin conjugated increased	29.4% 15/51 • Number of events 27 • From enrollment until primary completion date cutoff (up to approximately 25 weeks) Safety population included all enrolled participants who received at least one dose of crovalimab.
Investigations Blood alkaline phosphatase increased	17.6% 9/51 • Number of events 12 • From enrollment until primary completion date cutoff (up to approximately 25 weeks) Safety population included all enrolled participants who received at least one dose of crovalimab.
Investigations Blood bilirubin increased	17.6% 9/51 • Number of events 10 • From enrollment until primary completion date cutoff (up to approximately 25 weeks) Safety population included all enrolled participants who received at least one dose of crovalimab.
Investigations Blood bilirubin unconjugated increased	23.5% 12/51 • Number of events 13 • From enrollment until primary completion date cutoff (up to approximately 25 weeks) Safety population included all enrolled participants who received at least one dose of crovalimab.
Investigations Gamma-glutamyltransferase increased	11.8% 6/51 • Number of events 9 • From enrollment until primary completion date cutoff (up to approximately 25 weeks) Safety population included all enrolled participants who received at least one dose of crovalimab.
Investigations Lymphocyte count decreased	15.7% 8/51 • Number of events 15 • From enrollment until primary completion date cutoff (up to approximately 25 weeks) Safety population included all enrolled participants who received at least one dose of crovalimab.
Investigations Neutrophil count decreased	25.5% 13/51 • Number of events 25 • From enrollment until primary completion date cutoff (up to approximately 25 weeks) Safety population included all enrolled participants who received at least one dose of crovalimab.
Investigations Platelet count decreased	9.8% 5/51 • Number of events 10 • From enrollment until primary completion date cutoff (up to approximately 25 weeks) Safety population included all enrolled participants who received at least one dose of crovalimab.
Investigations Weight increased	11.8% 6/51 • Number of events 6 • From enrollment until primary completion date cutoff (up to approximately 25 weeks) Safety population included all enrolled participants who received at least one dose of crovalimab.
Investigations White blood cell count decreased	23.5% 12/51 • Number of events 29 • From enrollment until primary completion date cutoff (up to approximately 25 weeks) Safety population included all enrolled participants who received at least one dose of crovalimab.
Metabolism and nutrition disorders Hypercholesterolaemia	5.9% 3/51 • Number of events 5 • From enrollment until primary completion date cutoff (up to approximately 25 weeks) Safety population included all enrolled participants who received at least one dose of crovalimab.
Metabolism and nutrition disorders Hypertriglyceridaemia	9.8% 5/51 • Number of events 16 • From enrollment until primary completion date cutoff (up to approximately 25 weeks) Safety population included all enrolled participants who received at least one dose of crovalimab.
Metabolism and nutrition disorders Hyperuricaemia	9.8% 5/51 • Number of events 7 • From enrollment until primary completion date cutoff (up to approximately 25 weeks) Safety population included all enrolled participants who received at least one dose of crovalimab.

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 800 821-8590

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER