A Study Evaluating the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of Crovalimab in Pediatric Participants With Atypical Hemolytic Uremic Syndrome (aHUS) (COMMUTE-p)
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| ClinicalTrials.gov Identifier: NCT04958265 |
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Recruitment Status :
Recruiting
First Posted : July 12, 2021
Last Update Posted : May 10, 2024
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Sponsor:
Hoffmann-La Roche
Collaborator:
Chugai Pharmaceutical
Information provided by (Responsible Party):
Hoffmann-La Roche
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Brief Summary:
This study aims to evaluate the efficacy and safety of crovalimab in pediatric participants with aHUS.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Atypical Hemolytic Uremic Syndrome | Drug: Crovalimab | Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 45 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase III, Multicenter, Single-Arm Study Evaluating the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Crovalimab in Pediatric Patients With Atypical Hemolytic Uremic Syndrome (aHUS) |
| Actual Study Start Date : | November 17, 2021 |
| Estimated Primary Completion Date : | December 12, 2025 |
| Estimated Study Completion Date : | September 16, 2029 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Atypical hemolytic-uremic syndrome
| Arm | Intervention/treatment |
|---|---|
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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.
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Drug: Crovalimab
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. |
Primary Outcome Measures :
- Percentage of Participants with complete TMA response (cTMAr) (Naive Cohort only) [ Time Frame: Baseline up to Week 25 ]
Secondary Outcome Measures :
- Change from Baseline in Dialysis Status [ Time Frame: Baseline up to Week 25 ]
- Change in Estimated Glomerular Filtration Rate (eGFR) (Naive and Switch Cohorts) [ Time Frame: Baseline up to Week 25 ]
- Percentage of Participants with Change from Baseline in Chronic Kidney Disease (CKD) stage (Naive and Switch Cohorts) [ Time Frame: Baseline up to Week 25 ]
- Observed Value in Platelet Count (Naive and Switch Cohorts) [ Time Frame: Baseline up to Week 25 ]
- Observed Value in Lactate Dehydrogenase (LDH) (mg/dL) (Naive and Switch Cohorts) [ Time Frame: Baseline up to Week 25 ]
- Observed Value in Hemoglobin (mg/dL) (Naive and Switch Cohorts) [ Time Frame: Baseline up to Week 25 ]
- Change from Baseline in Platelet Count (Naive and Switch Cohorts) [ Time Frame: Baseline up to Week 25 ]
- Change from Baseline in Lactate Dehydrogenase (LDH) (mg/dL) (Naive and Switch Cohorts) [ Time Frame: Baseline up to Week 25 ]
- Change from Baseline in Hemoglobin (mg/dL) (Naive and Switch Cohorts) [ Time Frame: Baseline up to Week 25 ]
- Percentage of Participants with Platelet Count >= LLN (Naive Cohort only) [ Time Frame: Baseline up to Week 25 ]
- Percentage of Participants with Normalisation of LDH (i.e., =< Upper Limit Normal (ULN)) (Naive Cohort only) [ Time Frame: Baseline up to Week 25 ]
- Percentage of Participants with >=25% decrease in Serum Creatinine (Naive Cohort only) [ Time Frame: Baseline up to Week 25 ]
- Time to complete TMA response (cTMAr) (Naive Cohort only) [ Time Frame: Up to 8 years ]
- Duration of complete TMA response (cTMAr) (Naive Cohort only) [ Time Frame: Up to 8 years ]
- Percentage of Participants with complete TMA response (cTMAr) (Naive Cohort only) [ Time Frame: Week 25 ]
- Percentage of Participants with maintained TMA control (mTMAc) (Switch Cohort only) [ Time Frame: Baseline through Week 25 ]
- Percentage of Participants with Adverse Events (AEs) [ Time Frame: Up to 8 years ]
- Percentage of Participants with Injection-Site Reactions, Infusion-Related Reactions, Hypersensitivity, Malignant Hypertension (including malignant renal hypertension) and Infections (including meningococcal meningitis) [ Time Frame: Up to 8 years ]
- Percentage of Participants with Adverse Events (AEs) leading to Study Drug Discontinuation [ Time Frame: Up to 8 years ]
- Percentage of Participants with Clinical Manifestations of Drug-Target-Drug Complex (DTDC) formation amongst participants who switched to crovalimab treatment from eculizumab/ravulizumab treatment (Switch Cohort and switching Pretreated participants) [ Time Frame: Up to Week 25 ]
- Serum Concentrations of Crovalimab over time [ Time Frame: Up to 8 years ]
- Percentage of Participants with Anti-Crovalimab Antibodies [ Time Frame: Up to 8 years ]
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| Ages Eligible for Study: | 28 Days to 17 Years (Child) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
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:
- 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) within 7 days before the first crovalimab administration.
- 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).
- 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).
- Documented 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 and TMA related to Diacylglycerol kinase ε (DGKE) nephropathy.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04958265
Contacts
| Contact: Reference Study ID Number: BO42354 https://forpatients.roche.com/ | 888-662-6728 (U.S. and Canada) | global-roche-genentech-trials@gene.com |
Locations
Show 40 study locations
Sponsors and Collaborators
Hoffmann-La Roche
Chugai Pharmaceutical
Investigators
| Study Director: | Clinical Trials | Hoffmann-La Roche |
| Responsible Party: | Hoffmann-La Roche |
| ClinicalTrials.gov Identifier: | NCT04958265 |
| Other Study ID Numbers: |
BO42354 2020-002437-15 ( EudraCT Number ) |
| First Posted: | July 12, 2021 Key Record Dates |
| Last Update Posted: | May 10, 2024 |
| Last Verified: | May 2024 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm). |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
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Azotemia Hemolytic-Uremic Syndrome Atypical Hemolytic Uremic Syndrome Syndrome Hemolysis Disease Pathologic Processes Uremia Kidney Diseases Urologic Diseases Female Urogenital Diseases |
Female Urogenital Diseases and Pregnancy Complications Urogenital Diseases Male Urogenital Diseases Anemia, Hemolytic Anemia Hematologic Diseases Thrombotic Microangiopathies Thrombocytopenia Blood Platelet Disorders Cytopenia |