A clinical trial to compare how safe and effective crovalimab is in people with paroxysmal nocturnal hemoglobinuria (PNH) currently treated with complement inhibitors.

A Study Evaluating The Efficacy And Safety Of Crovalimab Versus Eculizumab In Participants With Paroxysmal Nocturnal Hemoglobinuria (PNH) Currently Treated With Complement Inhibitors.

  • Autoimmune Disorder
  • Paroxysmal Nocturnal Hemoglobinuria
Please note that the recruitment status of the trial at your site may differ from the overall study status because some study sites may recruit earlier than others.
Trial Status:

Recruiting

This trial runs in
Cities
  • Aachen
  • Amsterdam
  • Ankara
  • Athens
  • Aveiro
  • Avellino
  • Badalona
  • Barcelona
  • Bilbo
  • Bruxelles
  • Budapest
  • Bydgoszcz
  • Catania
  • Ceará
  • Chaidari
  • Changhua County
  • Charlotte
  • Columbus
  • Cáceres
  • Detroit
  • Distrito Federal
  • Dublin 8
  • Esplugues de Llobregat
  • Essen
  • Fort Worth
  • Gdańsk
  • Hlavní město Praha
  • Isehara
  • İstanbul
  • İzmir
  • Las Palmas de Gran Canaria
  • Lille
  • London
  • Los Angeles
  • Lublin
  • Lévis
  • Madrid
  • Marseille
  • Milano
  • Málaga
  • Nagasaki
  • New Territories
  • Okayama
  • Oviedo
  • Paraná
  • Porto
  • Rennes
  • Ribeirao Preto
  • Riesa
  • Rio Grande do Sul
  • Riyadh
  • Roeselare
  • Roma
  • Salamanca
  • Samsun
  • Santa Catarina
  • Santiago de Compostela
  • sasebo
  • Seoul
  • Sevilla
  • Shinagawa City
  • Singapore
  • skorzewo
  • Suita
  • São Paulo
  • Taipei City
  • takasago
  • Tallinn
  • Toledo
  • Torino
  • toyama
  • Toyoake
  • Tsu
  • Ulm
  • Ulsan
  • Uppsala län
  • València
  • Warszawa
  • Yvoir
  • Zaragoza
  • 横浜市
Trial Identifier:

NCT04432584 2020-000597-26 BO42161

      Show trial locations

      The source of the below information is public registry websites such as ClinicalTrials.gov, EuClinicalTrials.eu, ISRCTN.com, etc.. It has been summarised and edited into simpler language. For more information about this clinical trial see the For Expert tab on the specific ForPatients page or follow these links to https://clinicaltrials.gov and/or https://euclinicaltrials.eu and/or https://www.isrctn.com.

      The below information is taken directly from public registry websites such as ClinicalTrials.gov, EuClinicalTrials.eu, ISRCTN.com, etc., and has not been edited.

      Results Disclaimer

      Trial Summary

      A study designed to evaluate the safety of crovalimab with eculizumab in participants with PNH currently treated with complement inhibitors. This study will enroll approximately 190 participants.

      Hoffmann-La Roche Sponsor
      Phase 3 Phase
      NCT04432584,BO42161,2020-000597-26 Trial Identifier
      All Gender
      No Healthy Volunteers

      1. Why is the COMMODORE 1 clinical trial needed?

      Paroxysmal nocturnal hemoglobinuria (PNH) is a genetic blood disorder that leads to the breakdown of red blood cells (‘haemolysis’) causing anaemia (low levels of haemoglobin).This can lead to symptoms like tiredness, headaches, trouble breathing, less appetite, difficulty exercising or concentrating, and stomach or chest pain. If haemolysis destroys too many red blood cells, a person may need to receive blood from a donor (a blood transfusion). People with PNH also have a higher risk of blood clots. PNH is currently treated with medicines called C5 inhibitors (eculizumab or ravulizumab), which reduce the destruction of blood cells. However, this treatment means life-long drip infusions into a vein. Only some people benefit from this treatment, and better treatment options are needed. Crovalimab is also a C5 inhibitor, but it is given as injection under the skin (subcutaneous injection) every four weeks. Crovalimab can be self-administered or given by a caregiver at home, or can be given by your doctor. Crovalimab is an experimental drug, which means it has not been approved by health authorities for treating PNH. This clinical trial aims to compare how safe and effective crovalimab is against eculizumab in people with PNH currently treated with C5 inhibitors.

      2. How does the COMMODORE 1 clinical trial work?

      This clinical trial is recruiting people with PNH. The trial has 3 groups – groups A, B, and C. Enrollment to groups A and B has now finished. People newly joining this clinical trial (participants) will join Group C and be given the clinical trial treatment crovalimab for 6 months. The clinical trial doctor will see them regularly. These hospital visits will include checks to see how the participant responds to crovalimab treatment and any side effects they may have. After the 6-month treatment period, there may be the opportunity to continue crovalimab treatment for an extension period of up to 5 years, or maybe longer if the clinical trial doctor thinks it is in the participant’s best interest. The total time of participation in the clinical trial will be up to about 6 and a half years including a safety follow-up. Participants can stop trial treatment and leave the clinical trial at any time, the trial doctor will advise how this can be done safely.

      3. What are the main endpoints of the COMMODORE 1 clinical trial?

      The main clinical trial endpoints (the main results measured in the trial to see if the drug has worked) are the number and seriousness of any side effects.

      The other clinical trial endpoints include:

      • The number of participants who do not need a blood transfusion after 6 months of treatment
      • The number of participants who have controlled red blood cell breakdown during treatment
      • How the body processes crovalimab, eculizumab and ravulizumab
      • How crovalimab affects the immune system
      • Any change in certain molecules (biomarkers) in the blood

      4. Who can take part in this clinical trial?

      People can take part in this trial if they have been diagnosed with PNH, weigh at least 40kg and have been treated with eculizumab for a certain period of time, or have been treated with ravulizumab for a certain period of time, or have a specific variation of PNH (known as C5 polymorphism), or if they are younger than 18. People may not be able to take part in this trial if they have not previously had certain vaccinations or have had certain other medical conditions including certain types of cancer in the last 5 years, certain infections, or are pregnant or breastfeeding.

      5. What treatment will participants be given in this clinical trial?

      Previously, everyone in this clinical trial joined 1 of the following groups depending on prior treatment, age, and a variation in a specific gene (known as C5 polymorphism) and were given either:

      • Group A: crovalimab, as an infusion (into the vein) on Day 1 of the trial, then from Day 2 as an injection under the skin (subcutaneous) once every week for four weeks. From Week 5, crovalimab was given as a subcutaneous injection once every four weeks for a total of 6 months and may have been self-administered (or by a caregiver) from Week 9
      • OR Group B: eculizumab, as an infusion (into the vein) on Day 1 of the trial, then once every two weeks for a total of 6 months

      Groups A and B are no longer open to new participants. New participants will join Group C and will be given:

      • Group C: crovalimab, as an infusion (into the vein) once on Day 1 of the trial, then from Day 2 as a subcutaneous injection once every week for four weeks. After four weeks, crovalimab was given as a subcutaneous injection once every four weeks for 6 months and may have been self-administered (or by a caregiver) from Week 9.

      This is an open-label trial, which means everyone involved, including the participant and the clinical trial doctor, will know the clinical trial treatment the participant has been given.

      6. Are there any risks or benefits in taking part in this clinical trial?

      The safety or effectiveness of the experimental treatment or use may not be fully known at the time of the trial. Most trials involve some risks to the participant. However, it may not be greater than the risks related to routine medical care or the natural progression of the health condition. People who would like to participate will be told about any risks and benefits of taking part in the clinical trial, as well as any additional procedures, tests, or assessments they will be asked to undergo. All of these will be described in an informed consent document (a document that provides people with the information they need to decide to volunteer for the clinical trial).

      Risks associated with the clinical trial drug

      Participants may have side effects (an unwanted effect of a drug or medical treatment) from the drug used in this clinical trial. Side effects can be mild to severe, even life-threatening, and vary from person to person. Participants will be closely monitored during the clinical trial; safety assessments will be performed regularly. Participants will be told about the known side effects of crovalimab and eculizumab, and possible side effects based on human and laboratory studies or knowledge of similar drugs. Crovalimab and eculizumab will be given as infusions and/or subcutaneous injections. Participants will be told about any known side effects of infusion and subcutaneous injections.

      Potential benefits associated with the clinical trial

      Participants' health may or may not improve from participation in the clinical trial. Still, the information collected may help other people with similar medical conditions in the future.

      Trial Summary

      A study designed to evaluate the safety of crovalimab with eculizumab in participants with PNH currently treated with complement inhibitors. This study will enroll approximately 190 participants.

      Hoffmann-La Roche Sponsor
      Phase 3 Phase
      NCT04432584,BO42161,2020-000597-26 Trial Identifier
      Crovalimab, Eculizumab Treatments
      Paroxysmal Nocturnal Hemoglobinuria Condition
      Official Title

      A phase III, randomized, open-label, active-controlled, multicenter study evaluating the safety, pharmacokinetics, pharmacodynamics, and efficacy of crovalimab versus eculizumab in patients with paroxysmal nocturnal hemoglobinuria (PNH) currently treated with complement inhibitors

      Eligibility Criteria

      All Gender
      No Healthy Volunteers
      Inclusion Criteria
      • Body weight >= 40 kg at screening.
      • Treated with eculizumab or ravulizumab for PNH for at least 3 months prior to Day 1.
      • Lactate Dehydrogenase Levels =< 2x the upper limit of normal (ULN) at screening.
      • Willingness and ability to comply with all study visits and procedures.
      • Documented diagnosis of PNH, confirmed by high sensitivity flow cytometry.
      • Vaccination against Neisseria meningitidis serotypes A, C, W, and Y < 3 years prior to initiation of study treatment; or, if not previously done, vaccination administered no later than one week after the first drug administration.
      • Women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception during the treatment period and for 10.5 months after the final dose of crovalimab or for 3 months after the final dose of eculizumab (or longer if required by the local product label).
      Exclusion Criteria
      • History of allogeneic bone marrow transplantation.
      • History of myelodysplastic syndrome with Revised International Prognostic Scoring System (IPSS-R) prognostic risk categories of intermediate, high and very high.
      • Pregnant or breastfeeding, or intending to become pregnant during the study, within 10.5 months after the final dose of crovalimab, or 3 months after the final dose of eculizumab (or longer if required by the local product label).
      • Participation in another interventional treatment study with an investigational agent or use of any experimental therapy within 28 days of screening or within 5 half-lives of that investigational product, whichever was greater: participants enrolled in an eculizumab or ravulizumab interventional study are eligible provided they fulfill eligibility (e.g., are willing and able to comply with the study assessments) and stop their participation in current trial before randomisation/enrolment.
      • Positive for Active Hepatitis B and C infection (HBV/HCV).
      • Concurrent disease, treatment, procedure, or surgery or abnormality in clinical laboratory tests that could interfere with the conduct of the study, may pose any additional risk for the participant, or would, in the opinion of the investigator, preclude the participant's safe participation in and completion of the study.
      • History of or ongoing cryoglobulinemia at screening.

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