Paroxysmal Nocturnal HemoglobinuriaPhase 4NCT03866681
Sirolimus Combined With Low-dose Warfarin for the Treatment of Refractory PNH
A Phase 4 study testing sirolimus in people with Paroxysmal Nocturnal Hemoglobinuria, run by Peking Union Medical College Hospital at 1 site in China.
Trial summary
Classical paroxysmal nocturnal hemoglobinuria(PNH) is mainly characterized by hemolysis and thrombosis, which reduced patients ' quality of life(QoL) greatly and even lead to death. Glucocorticoids and symptomatic supportive therapy are traditional treatments and the response rate is far from satisfactory. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Paroxysmal Nocturnal Hemoglobinuria
- What is being tested?
- sirolimus
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteChina
- Study dates
- 1 Apr 2019to 1 Apr 2022
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- age 18-70 years
- diagnosed with PNH and no thrombosis
- ineffective, relapsed or intolerant to conventional treatment (eg glucocorticoids, • • iron, folic acid, androgen, etc.)
- not available for hematopoietic stem cell transplantation
- ECOG≤2
- agreed to sign the consent forms
Who cannot join
- severe heart, liver and kidney dysfunction
- combined with thrombotic complications
- people who are pregnant and breastfeeding
- history of other immunosuppressive agents in recent 3 months
- Patients who are not eligible to participate in this trial due to any reason based • • • on the consideration of investigator
Trial locations and contacts
1 site in 1 country.
China1 site
Peking union medical college hospital
Beijing
Bing Han, Doctor, +86-010-69155760, hanbing_li@sina.com
About this study
Official title: Sirolimus Combined With Low-dose Warfarin for the Treatment of Refractory Classic Paroxysmal Nocturnal Hemoglobinuria ,a Prospective Study
Classical paroxysmal nocturnal hemoglobinuria(PNH) is mainly characterized by hemolysis and thrombosis, which reduced patients ' quality of life(QoL) greatly and even lead to death. Glucocorticoids and symptomatic supportive therapy are traditional treatments and the response rate is far from satisfactory. Eculizumab is an effective therapy but it is expensive and not available in China mainland.The investigators aim to explore the efficacy and safety of sirolimus for refractory classic PNH.
Read the detailed description
Classical paroxysmal nocturnal hemoglobinuria(PNH) is mainly characterized by hemolysis and thrombosis, which reduced patients ' quality of life(QoL) greatly and even lead to death. There is no ideal therapy except for eculizumab, expensive and not available in China mainland. Glucocorticoids and symptomatic supportive therapy are traditional treatments. The response rate is 30%, far from satisfactory. In recent years, T lymphocyte-mediated destruction of normal hematopoietic stem cells have been reported to involve the pathogenesis of PNH, making immunomodulatory drugs be potential effective treatments.
Sirolimus (rapamycin), produced by the bacterium Streptomyces hygroscopicus, is a mammalian target of Rapamycin (mTOR) inhibitor. mTOR is a serine/threonine kinase that regulates cell growth, proliferation, metabolism and survival. It has two interacting complex, mTORC1 and mTORC2. Sirolimus primarily inhibits mTORC1, has been demonstrated for its immunomodulatory effects and ability to improve hematopoietic stem cell function. Recently, sirolimus has been reported to be effective and well tolerated in the treatment of immune-mediated cytopenias, even in multi-immunosuppressants resistant patients. In addition, classical PNH patients have a higher risk of thrombosis especially in refractory ones and it is reasonable to use low-dose warfarin in the management of patients with classic refractory PNH.
In this study, it is anticipated to evaluate the effect of sirolimus combined with low-dose warfarin on patients with refractory classic PNH. The adverse effects and QoL on different time points were documented.
- Conditions
- Paroxysmal Nocturnal Hemoglobinuria
- Being tested
- sirolimus
- Medical subject headings
- Hemoglobinuria, Paroxysmal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sirolimusDrug
Also called warfarin
The dose of sirolimus is adjusted according to monitored serum concentration, maintain Rapamycin concentration ranging from 4 to 10ng/ml.Warfarin was administered orally at a dose of 1mg per day for a year,then gradually reduced to stop.
| Study group | Role | What they receive |
|---|---|---|
| Patients cohort | Experimental | A total of 40 patients with refractory classic PNH will be included and will be intervened by a combined therapy including sirolimus and low-dose warfarin Receives: Drug: sirolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hemoglobin
Hemoglobin in g/L
Measured: 2 years
Secondary outcomes (1)
Short Form 36 items(SF-36) questionnaire
SF-36 questionnaire in scores
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Mar 2019
- Study start1 Apr 2019 (estimated)
- Primary completion1 Mar 2021 (estimated)
- Study completion1 Apr 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Paroxysmal Nocturnal HemoglobinuriaStudies of the same condition, open and under way.
- More trials run by Peking Union Medical College HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Peking Union Medical College Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Bing Han, Peking Union Medical College Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03866681
- Sponsor's protocol ID
- hanb
- Status last verified
- Mar 2019
- First submitted
- 28 Feb 2019
- Last updated
- 8 Mar 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sirolimus Combined With Low-dose Warfarin for the Treatment of Refractory Classic Paroxysmal Nocturnal Hemoglobinuria ,a Prospective Study
- ClinicalTrials.gov ID
- NCT03866681
- Acronym / sponsor ID
- hanb
- Conditions
- Paroxysmal Nocturnal Hemoglobinuria
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Peking Union Medical College HospitalUniversity, hospital or other
- Study start
- 1 Apr 2019 (estimated)
- Primary completion
- 1 Mar 2021 (estimated)
- Study completion
- 1 Apr 2022 (estimated)
- First posted
- 7 Mar 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Classical paroxysmal nocturnal hemoglobinuria(PNH) is mainly characterized by hemolysis and thrombosis, which reduced patients ' quality of life(QoL) greatly and even lead to death. Glucocorticoids and symptomatic supportive therapy are traditional treatments and the response rate is far from satisfactory. Eculizumab is an effective therapy but it is expensive and not available in China mainland.The investigators aim to explore the efficacy and safety of sirolimus for refractory classic PNH.
Detailed description
Classical paroxysmal nocturnal hemoglobinuria(PNH) is mainly characterized by hemolysis and thrombosis, which reduced patients ' quality of life(QoL) greatly and even lead to death. There is no ideal therapy except for eculizumab, expensive and not available in China mainland. Glucocorticoids and symptomatic supportive therapy are traditional treatments. The response rate is 30%, far from satisfactory. In recent years, T lymphocyte-mediated destruction of normal hematopoietic stem cells have been reported to involve the pathogenesis of PNH, making immunomodulatory drugs be potential effective treatments.
Sirolimus (rapamycin), produced by the bacterium Streptomyces hygroscopicus, is a mammalian target of Rapamycin (mTOR) inhibitor. mTOR is a serine/threonine kinase that regulates cell growth, proliferation, metabolism and survival. It has two interacting complex, mTORC1 and mTORC2. Sirolimus primarily inhibits mTORC1, has been demonstrated for its immunomodulatory effects and ability to improve hematopoietic stem cell function. Recently, sirolimus has been reported to be effective and well tolerated in the treatment of immune-mediated cytopenias, even in multi-immunosuppressants resistant patients. In addition, classical PNH patients have a higher risk of thrombosis especially in refractory ones and it is reasonable to use low-dose warfarin in the management of patients with classic refractory PNH.
In this study, it is anticipated to evaluate the effect of sirolimus combined with low-dose warfarin on patients with refractory classic PNH. The adverse effects and QoL on different time points were documented.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients cohort | Experimental | Drug: sirolimusA total of 40 patients with refractory classic PNH will be included and will be intervened by a combined therapy including sirolimus and low-dose warfarin |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- age 18-70 years
- diagnosed with PNH and no thrombosis
- ineffective, relapsed or intolerant to conventional treatment (eg glucocorticoids, • • iron, folic acid, androgen, etc.)
- not available for hematopoietic stem cell transplantation
- ECOG≤2
Key exclusion criteria (5 listed)
- severe heart, liver and kidney dysfunction
- combined with thrombotic complications
- people who are pregnant and breastfeeding
- history of other immunosuppressive agents in recent 3 months
- Patients who are not eligible to participate in this trial due to any reason based • • • on the consideration of investigator
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| sirolimusAlso: warfarinThe dose of sirolimus is adjusted according to monitored serum concentration, maintain Rapamycin concentration ranging from 4 to 10ng/ml.Warfarin was administered orally at a dose of 1mg per day for a year,then gradually reduced to stop. | Drug | Patients cohort |
Primary outcome
Hemoglobin
Time frame: 2 years
Hemoglobin in g/L
1 secondary outcome
Short Form 36 items(SF-36) questionnaire
Time frame: 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Mar 2019.
- Individual participant dataSharing planned: No
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A Study of Efficacy and Safety of FXS6837 in Anti-C5 Treated PNH Patients.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing sirolimus in people with Paroxysmal Nocturnal Hemoglobinuria, run by Peking Union Medical College Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 8 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Hemoglobin (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Mar 2019.