Trial · NCT04654468

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

NCT04654468, Phase 3, Active not recruiting, Hoffmann-La Roche; results first posted 2023-06-05

3 sourcestrials-2026-11-12-0.5.0

Cite this record

ConductScience Library. A Study Evaluating the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of Crovalimab in Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH) Not Previously Treated With Complement Inhibition. Trials, record NCT04654468. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT04654468

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Trial

As registered on ClinicalTrials.gov, in the graph's capture of the registry.

Title: 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 number: NCT04654468
Status: Active not recruiting
Phases: Phase 3
Enrollment: 51 participants, actual
Lead sponsor: Hoffmann-La Roche
Conditions: Paroxysmal Nocturnal Hemoglobinuria
Interventions: Crovalimab
First posted: 2020-12-04
Last updated: 2026-11-09
Results first posted: 2023-06-05

Source ClinicalTrials.gov

Registered outcomes19

Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.

List	Outcome	Time frame	Description
Primary	Mean Percentage of Participants With Hemolysis Control	From Week 5 up to Week 25	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.
Primary	Difference in Percentage of Participants With Transfusion Avoidance (TA) From Baseline Through Week 25 and Within 24 Weeks Prior to Screening	24 Weeks Prior to Screening, Baseline to Week 25	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.
Secondary	Percentage of Participants With Breakthrough Hemolysis (BTH)	Baseline, Week 25	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.
Secondary	Percentage of Participants With Stabilized Hemoglobin	Baseline, Week 25	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.
Secondary	Change From Baseline in Fatigue in Adults Aged >=18 Years	Baseline, Week 2, Week 5, Week 9, Week 17, Week 25	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.
Secondary	Percentage of Participants With Adverse Events (AEs)	Up to 7 years
Secondary	Percentage of Participants With Injection-Site Reactions, Infusion-Related Reactions, Hypersensitivity, and Infections (Including Meningococcal Meningitis)	Up to 7 years
Secondary	Percentage of Participants With Adverse Events (AEs) Leading to Study Drug Discontinuation	Up to 7 years
Secondary	Trough Serum Concentration of Crovalimab Over Time	Up to 7 years
Secondary	Serum Concentrations of Crovalimab	Up to 7 years

1 to 10 of 19Source ClinicalTrials.gov

See all 19 registered outcomes

Outcomes19

Each outcome the trial posted results for, in ClinicalTrials.gov's words.

Type	Outcome	Time frame	Population	Units	Measured as
PRIMARY	Mean Percentage of Participants With Hemolysis Control	From Week 5 up to Week 25	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.	mean percentage of participants	LEAST_SQUARES_MEAN
PRIMARY	Difference in Percentage of Participants With Transfusion Avoidance (TA) From Baseline Through Week 25 and Within 24 Weeks Prior to Screening	24 Weeks Prior to Screening, Baseline to Week 25	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.	percentage of participants	NUMBER
SECONDARY	Percentage of Participants With Breakthrough Hemolysis (BTH)	Baseline, Week 25	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.	percentage of participants	NUMBER
SECONDARY	Percentage of Participants With Stabilized Hemoglobin	Baseline, Week 25	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.	percentage of participants	NUMBER
SECONDARY	Change From Baseline in Fatigue in Adults Aged >=18 Years	Baseline, Week 2, Week 5, Week 9, Week 17, Week 25	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.	score on a scale	MEAN
SECONDARY	Percentage of Participants With Adverse Events (AEs)	Up to 7 years
SECONDARY	Percentage of Participants With Injection-Site Reactions, Infusion-Related Reactions, Hypersensitivity, and Infections (Including Meningococcal Meningitis)	Up to 7 years
SECONDARY	Percentage of Participants With Adverse Events (AEs) Leading to Study Drug Discontinuation	Up to 7 years
SECONDARY	Trough Serum Concentration of Crovalimab Over Time	Up to 7 years
SECONDARY	Serum Concentrations of Crovalimab	Up to 7 years

1 to 10 of 19Source ClinicalTrials.gov

See all 19 outcomes

Results by group12

Each measurement the trial posted, group by group, in the words and numbers it posted.

Outcome	Group	Category	Value	Spread	Units
Mean Percentage of Participants With Hemolysis Control	Crovalimab		78.66	95% Confidence Interval 67.78 to 86.59	mean percentage of participants
Difference in Percentage of Participants With Transfusion Avoidance (TA) From Baseline Through Week 25 and Within 24 Weeks Prior to Screening	Crovalimab		50.98	95% Confidence Interval 34.30 to 65.05	percentage of participants
Percentage of Participants With Breakthrough Hemolysis (BTH)	Crovalimab		3.9	95% Confidence Interval 0.68 to 14.59	percentage of participants
Percentage of Participants With Stabilized Hemoglobin	Crovalimab		51.0	95% Confidence Interval 36.77 to 65.05	percentage of participants
Change From Baseline in Fatigue in Adults Aged >=18 Years	Crovalimab	Baseline	31.77	Standard Deviation 8.53	score on a scale
Change From Baseline in Fatigue in Adults Aged >=18 Years	Crovalimab	Change from Baseline at Week 2	6.67	Standard Deviation 8.02	score on a scale
Change From Baseline in Fatigue in Adults Aged >=18 Years	Crovalimab	Change from Baseline at Week 5	8.08	Standard Deviation 9.28	score on a scale
Change From Baseline in Fatigue in Adults Aged >=18 Years	Crovalimab	Change from Baseline at Week 9	8.15	Standard Deviation 10.61	score on a scale
Change From Baseline in Fatigue in Adults Aged >=18 Years	Crovalimab	Change from Baseline at Week 17	8.77	Standard Deviation 9.63	score on a scale
Percent Change From Baseline in Absolute Reticulocyte Count	Crovalimab		40.9411	Standard Deviation 66.0292	percent change

1 to 10 of 12Source ClinicalTrials.gov

See all 12 results by group

Participant flow3

How many started, completed or left each group, period by period.

Period	Milestone	Group	Participants
Overall Study	STARTED	Crovalimab	51
Overall Study	COMPLETED	Crovalimab	0
Overall Study	NOT COMPLETED	Crovalimab	51

Source ClinicalTrials.gov

Adverse events25

Each adverse event the trial posted, group by group: the participants affected out of those at risk.

Type	Event	Organ system	Group	Affected	At risk	Events
other	Neutropenia	Blood and lymphatic system disorders	CROVALIMAB	7	51	8
other	Gingival swelling	Gastrointestinal disorders	CROVALIMAB	3	51	3
other	Upper respiratory tract infection	Infections and infestations	CROVALIMAB	24	51	26
other	Urinary tract infection	Infections and infestations	CROVALIMAB	3	51	4
other	Alanine aminotransferase increased	Investigations	CROVALIMAB	11	51	15
other	Alpha hydroxybutyrate dehydrogenase increased	Investigations	CROVALIMAB	8	51	8
other	Bilirubin conjugated increased	Investigations	CROVALIMAB	15	51	27
other	Blood alkaline phosphatase increased	Investigations	CROVALIMAB	9	51	12
other	Blood bilirubin increased	Investigations	CROVALIMAB	9	51	10
other	Blood bilirubin unconjugated increased	Investigations	CROVALIMAB	12	51	13

1 to 10 of 25Source ClinicalTrials.gov

See all 25 adverse events

Adverse event totals3

The totals the trial posted for each group.

Total	Group	Affected	At risk
Total, all-cause mortality	CROVALIMAB	1	51
Total, other adverse events	CROVALIMAB	46	51
Total, serious adverse events	CROVALIMAB	4	51

Source ClinicalTrials.gov

Papers2

The papers the trial lists on ClinicalTrials.gov.

PMID	Listed as	Source
37421604	DERIVED	PubMed
39535306	DERIVED	PubMed

Grants0

The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.

None in this release.

Trial comparisons0

Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.

None in this release.

Tests0

The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.

None in this release.

Data dates

The day each source was copied for this release.

ClinicalTrials.gov: 2026-11-12; ClinicalTrials.gov
Results, from AACT: 2026-03-23; AACT
NIH grant links: 2026-11-13; NIH RePORTER

Sources 3

ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
ClinicalTrials.govNo license stated
NIH RePORTER's clinical studies and project filesPublic domain

Each source's terms

ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
ClinicalTrials.govnone stated
NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)

ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.

For software

Read this trial from software.

The record and each of its lists are JSON, twenty rows a page. No key.

GET https://conductscience.org/api/trials/v1/NCT04654468

GET https://conductscience.org/api/trials/v1/NCT04654468/events?page=2

API reference For AI assistants