HemophiliaPhase 1/2NCT05920512
Combination Regimen With Sodium Valproate for Severe Hemophilia: a Single-arm, Phase 1, Pilot Trial.
A Phase 1/2 study testing Sodium valproate extended-release tablets in people with Hemophilia, run by Xue-chun Lu at 1 site in China.
Trial summary
The goal of this clinical trial is to determine the clinical efficacy and toxic effects of sodium valproate, sirolimus and calcitriol in the treatment of severe haemophilia in participants with severe haemophilia . Read more about this study
- Who is it for?
- Ages 14 to 85 years
- Conditions the study is for
- Hemophilia
- What is being tested?
- Sodium valproate extended-release tablets
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteChina
- Study dates
- 1 Apr 2022to 1 Apr 2025
- Phase
- Phase 1/2
- 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 14 to 85 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients with clinically confirmed severe haemophilia;
- Expected survival of ≥ 24 weeks with an ECOG score of 0-2;
- Not having participated in another clinical trial within four weeks;
- Informed consent signed by the patient or an immediate family member.
Who cannot join
- Those with other types of blood disorders diagnosed at the morphological or molecular level of the bone marrow;
- Significantly abnormal cardiopulmonary function;
- Hepatic or renal insufficiency;
- Pregnancy or lactation, or inability to use contraception during the trial and for three months before the test and one year after administration
- Persons who are allergic to the drugs likely to be used or where there is a contraindication to their use;
- Those with severe uncontrollable infectious diseases or uncontrolled hypertension, malignancy, etc.;
- Inability to cooperate with a regular follow-up due to psychological, social, family and other geographical circumstances;
- Any other condition that, in the investigator's opinion, makes participation in this trial inappropriate.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
PLA General Hospital
Beijing, 100853
Jundong ZHANG, 15536032300, drzjd123@163.com
About this study
Official title: PLA General Hospital
The goal of this clinical trial is to determine the clinical efficacy and toxic effects of sodium valproate, sirolimus and calcitriol in the treatment of severe haemophilia in participants with severe haemophilia . The main questions it aims to answer are the possibility of adding a combination regimen to primary treatment for severe haemophilia . Patients will receive oral sodium valproate extended-release tablets 0.5g/day, sirolimus tablets 1mg/day and osteopontin capsules 0.25μg/day.
- Conditions
- Hemophilia
- Being tested
- Sodium valproate extended-release tablets
- Keywords
- Hemophilia, Sodium valproate, Sirolimus, Calcitriol
- Medical subject headings
- Hemophilia A
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sodium valproate extended-release tabletsDrug
Also called sirolimus tablets, calcitriol capsules
Sodium valproate extended-release tablets 0.5g/day; sirolimus tablets 1mg/day and calcitriol capsules 0.25μg/day.
| Study group | Role | What they receive |
|---|---|---|
| Patients with severe haemophilia | Experimental | confirmed as hemophilia and FVIII/FIX activity <1% Receives: Drug: Sodium valproate extended-release tablets |
What is being measured
The primary outcome is the main question the study is designed to answer.
FVIII/FIX Activity
FVIII/FIX activity in peripheral blood
Measured: through study completion, an average of 1 month
FVIII/ FIX inhibitor concentration
FVIII/ FIX inhibitor concentration in peripheral blood
Measured: through study completion, an average of 1 month
Secondary outcomes (2)
frequency of joint bleeding
Record the number of joint bleeds each month
Measured: through study completion, an average of 1 month
Activated Partial Thromboplastin Time
activated partial thromboplastin time in peripheral blood
Measured: through study completion, an average of 1 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jun 2023
- Study start1 Apr 2022
- Primary completion1 Apr 2025 (estimated)
- Study completion1 Apr 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (18)Papers the sponsor has linked to this study.
- Other trials for HemophiliaStudies of the same condition, open and under way.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Xue-chun Lu
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Xue-chun Lu, Chinese PLA General Hospital
- Investigators
- Xuechun Lu, M.D., Principal investigator, Department of Hematology, the Second Medical Center of PLA General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05920512
- Sponsor's protocol ID
- S2023-261-02
- Status last verified
- Feb 2024
- First submitted
- 6 Jun 2023
- Last updated
- 29 Feb 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Leissinger C. Another Victory for Patients with Hemophilia. N Engl J Med. 2023 Jan 26;388(4):372-373. doi: 10.1056/NEJMe2216176. No abstract available.
PubMed 36720139Den Uijl IE, Mauser Bunschoten EP, Roosendaal G, Schutgens RE, Biesma DH, Grobbee DE, Fischer K. Clinical severity of haemophilia A: does the classification of the 1950s still stand? Haemophilia. 2011 Nov;17(6):849-53. doi: 10.1111/j.1365-2516.2011.02539.x. Epub 2011 May 5.
PubMed 21545376DiMichele D. Inhibitor development in haemophilia B: an orphan disease in need of attention. Br J Haematol. 2007 Aug;138(3):305-15. doi: 10.1111/j.1365-2141.2007.06657.x.
PubMed 17614818Jankowska KI, McGill J, Pezeshkpoor B, Oldenburg J, Atreya CD, Sauna ZE. Clinical manifestation of hemophilia A in the absence of mutations in the F8 gene that encodes FVIII: role of microRNAs. Transfusion. 2020 Feb;60(2):401-413. doi: 10.1111/trf.15605. Epub 2019 Nov 29.
PubMed 31785023Marchesini E, Morfini M, Valentino L. Recent Advances in the Treatment of Hemophilia: A Review. Biologics. 2021 Jun 15;15:221-235. doi: 10.2147/BTT.S252580. eCollection 2021.
PubMed 34163136Lu P, Yan M, He L, Li J, Ji Y, Ji J. Crosstalk between Epigenetic Modulations in Valproic Acid Deactivated Hepatic Stellate Cells: An Integrated Protein and miRNA Profiling Study. Int J Biol Sci. 2019 Jan 6;15(1):93-104. doi: 10.7150/ijbs.28642. eCollection 2019.
PubMed 30662350Moghimi B, Sack BK, Nayak S, Markusic DM, Mah CS, Herzog RW. Induction of tolerance to factor VIII by transient co-administration with rapamycin. J Thromb Haemost. 2011 Aug;9(8):1524-33. doi: 10.1111/j.1538-7836.2011.04351.x.
PubMed 21585650Johannessen SI, Landmark CJ. Antiepileptic drug interactions - principles and clinical implications. Curr Neuropharmacol. 2010 Sep;8(3):254-67. doi: 10.2174/157015910792246254.
PubMed 21358975Mintzer S, Mattson RT. Should enzyme-inducing antiepileptic drugs be considered first-line agents? Epilepsia. 2009 Sep;50 Suppl 8:42-50. doi: 10.1111/j.1528-1167.2009.02235.x.
PubMed 19702733Verrotti A, Coppola G, Parisi P, Mohn A, Chiarelli F. Bone and calcium metabolism and antiepileptic drugs. Clin Neurol Neurosurg. 2010 Jan;112(1):1-10. doi: 10.1016/j.clineuro.2009.10.011. Epub 2009 Nov 12.
PubMed 19913352Stanford S, Pink R, Creagh D, Clark A, Lowe G, Curry N, Pasi J, Perry D, Fong S, Hayes G, Chandrakumaran K, Rangarajan S. Adenovirus-associated antibodies in UK cohort of hemophilia patients: A seroprevalence study of the presence of adenovirus-associated virus vector-serotypes AAV5 and AAV8 neutralizing activity and antibodies in patients with hemophilia A. Res Pract Thromb Haemost. 2019 Jan 25;3(2):261-267. doi: 10.1002/rth2.12177. eCollection 2019 Apr.
PubMed 31011710Nathwani AC, Gray JT, McIntosh J, Ng CY, Zhou J, Spence Y, Cochrane M, Gray E, Tuddenham EG, Davidoff AM. Safe and efficient transduction of the liver after peripheral vein infusion of self-complementary AAV vector results in stable therapeutic expression of human FIX in nonhuman primates. Blood. 2007 Feb 15;109(4):1414-21. doi: 10.1182/blood-2006-03-010181. Epub 2006 Nov 7.
PubMed 17090654Mingozzi F, Anguela XM, Pavani G, Chen Y, Davidson RJ, Hui DJ, Yazicioglu M, Elkouby L, Hinderer CJ, Faella A, Howard C, Tai A, Podsakoff GM, Zhou S, Basner-Tschakarjan E, Wright JF, High KA. Overcoming preexisting humoral immunity to AAV using capsid decoys. Sci Transl Med. 2013 Jul 17;5(194):194ra92. doi: 10.1126/scitranslmed.3005795.
PubMed 23863832Puetz J, Soucie JM, Kempton CL, Monahan PE; Hemophilia Treatment Center Network (HTCN) Investigators. Prevalent inhibitors in haemophilia B subjects enrolled in the Universal Data Collection database. Haemophilia. 2014 Jan;20(1):25-31. doi: 10.1111/hae.12229. Epub 2013 Jul 16.
PubMed 23855900Rocca A, Minucci S, Tosti G, Croci D, Contegno F, Ballarini M, Nole F, Munzone E, Salmaggi A, Goldhirsch A, Pelicci PG, Testori A. A phase I-II study of the histone deacetylase inhibitor valproic acid plus chemoimmunotherapy in patients with advanced melanoma. Br J Cancer. 2009 Jan 13;100(1):28-36. doi: 10.1038/sj.bjc.6604817.
PubMed 19127265
Study at a glance
From the registry record, last updated by the sponsor on 29 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PLA General Hospital
- ClinicalTrials.gov ID
- NCT05920512
- Acronym / sponsor ID
- S2023-261-02
- Conditions
- Hemophilia
- Keywords
- Hemophilia, Sodium valproate, Sirolimus, Calcitriol
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- Xue-chun LuUniversity, hospital or other
- Study start
- 1 Apr 2022 (actual)
- Primary completion
- 1 Apr 2025 (estimated)
- Study completion
- 1 Apr 2025 (estimated)
- First posted
- 27 Jun 2023 (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.
The goal of this clinical trial is to determine the clinical efficacy and toxic effects of sodium valproate, sirolimus and calcitriol in the treatment of severe haemophilia in participants with severe haemophilia . The main questions it aims to answer are the possibility of adding a combination regimen to primary treatment for severe haemophilia . Patients will receive oral sodium valproate extended-release tablets 0.5g/day, sirolimus tablets 1mg/day and osteopontin capsules 0.25μg/day.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients with severe haemophilia | Experimental | Drug: Sodium valproate extended-release tabletsconfirmed as hemophilia and FVIII/FIX activity <1% |
Who may qualify
- Ages
- 14 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- Patients with clinically confirmed severe haemophilia;
- Expected survival of ≥ 24 weeks with an ECOG score of 0-2;
- Not having participated in another clinical trial within four weeks;
- Informed consent signed by the patient or an immediate family member.
Key exclusion criteria (8 listed)
- Those with other types of blood disorders diagnosed at the morphological or molecular level of the bone marrow;
- Significantly abnormal cardiopulmonary function;
- Hepatic or renal insufficiency;
- Pregnancy or lactation, or inability to use contraception during the trial and for three months before the test and one year after administration
- Persons who are allergic to the drugs likely to be used or where there is a contraindication to their use;
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 |
|---|---|---|
| Sodium valproate extended-release tabletsAlso: sirolimus tablets, calcitriol capsulesSodium valproate extended-release tablets 0.5g/day; sirolimus tablets 1mg/day and calcitriol capsules 0.25μg/day. | Drug | Patients with severe haemophilia |
Primary outcome
FVIII/FIX Activity
Time frame: through study completion, an average of 1 month
FVIII/FIX activity in peripheral blood
FVIII/ FIX inhibitor concentration
Time frame: through study completion, an average of 1 month
FVIII/ FIX inhibitor concentration in peripheral blood
2 secondary outcomes
frequency of joint bleeding
Time frame: through study completion, an average of 1 month
Activated Partial Thromboplastin Time
Time frame: through study completion, an average of 1 month
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Feb 2024.
- Background: PubMed 36720139Leissinger C. Another Victory for Patients with Hemophilia. N Engl J Med. 2023 Jan 26;388(4):372-373. doi: 10.1056/NEJMe2216176. No abstract available.
- Background: PubMed 21545376Den Uijl IE, Mauser Bunschoten EP, Roosendaal G, Schutgens RE, Biesma DH, Grobbee DE, Fischer K. Clinical severity of haemophilia A: does the classification of the 1950s still stand? Haemophilia. 2011 Nov;17(6):849-53. doi: 10.1111/j.1365-2516.2011.02539.x. Epub 2011 May 5.
- Background: PubMed 17614818DiMichele D. Inhibitor development in haemophilia B: an orphan disease in need of attention. Br J Haematol. 2007 Aug;138(3):305-15. doi: 10.1111/j.1365-2141.2007.06657.x.
- Background: PubMed 31785023Jankowska KI, McGill J, Pezeshkpoor B, Oldenburg J, Atreya CD, Sauna ZE. Clinical manifestation of hemophilia A in the absence of mutations in the F8 gene that encodes FVIII: role of microRNAs. Transfusion. 2020 Feb;60(2):401-413. doi: 10.1111/trf.15605. Epub 2019 Nov 29.
- Background: PubMed 34163136Marchesini E, Morfini M, Valentino L. Recent Advances in the Treatment of Hemophilia: A Review. Biologics. 2021 Jun 15;15:221-235. doi: 10.2147/BTT.S252580. eCollection 2021.
- Background: PubMed 30662350Lu P, Yan M, He L, Li J, Ji Y, Ji J. Crosstalk between Epigenetic Modulations in Valproic Acid Deactivated Hepatic Stellate Cells: An Integrated Protein and miRNA Profiling Study. Int J Biol Sci. 2019 Jan 6;15(1):93-104. doi: 10.7150/ijbs.28642. eCollection 2019.
- Background: PubMed 21585650Moghimi B, Sack BK, Nayak S, Markusic DM, Mah CS, Herzog RW. Induction of tolerance to factor VIII by transient co-administration with rapamycin. J Thromb Haemost. 2011 Aug;9(8):1524-33. doi: 10.1111/j.1538-7836.2011.04351.x.
- Background: PubMed 21358975Johannessen SI, Landmark CJ. Antiepileptic drug interactions - principles and clinical implications. Curr Neuropharmacol. 2010 Sep;8(3):254-67. doi: 10.2174/157015910792246254.
- Background: PubMed 19702733Mintzer S, Mattson RT. Should enzyme-inducing antiepileptic drugs be considered first-line agents? Epilepsia. 2009 Sep;50 Suppl 8:42-50. doi: 10.1111/j.1528-1167.2009.02235.x.
- Background: PubMed 19913352Verrotti A, Coppola G, Parisi P, Mohn A, Chiarelli F. Bone and calcium metabolism and antiepileptic drugs. Clin Neurol Neurosurg. 2010 Jan;112(1):1-10. doi: 10.1016/j.clineuro.2009.10.011. Epub 2009 Nov 12.
- Results publication: PubMed 31011710Stanford S, Pink R, Creagh D, Clark A, Lowe G, Curry N, Pasi J, Perry D, Fong S, Hayes G, Chandrakumaran K, Rangarajan S. Adenovirus-associated antibodies in UK cohort of hemophilia patients: A seroprevalence study of the presence of adenovirus-associated virus vector-serotypes AAV5 and AAV8 neutralizing activity and antibodies in patients with hemophilia A. Res Pract Thromb Haemost. 2019 Jan 25;3(2):261-267. doi: 10.1002/rth2.12177. eCollection 2019 Apr.
- Results publication: PubMed 17090654Nathwani AC, Gray JT, McIntosh J, Ng CY, Zhou J, Spence Y, Cochrane M, Gray E, Tuddenham EG, Davidoff AM. Safe and efficient transduction of the liver after peripheral vein infusion of self-complementary AAV vector results in stable therapeutic expression of human FIX in nonhuman primates. Blood. 2007 Feb 15;109(4):1414-21. doi: 10.1182/blood-2006-03-010181. Epub 2006 Nov 7.
- Individual participant dataSharing planned: No
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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.
Xuechun Lu, M.D. principal investigator
Department of Hematology, the Second Medical Center of PLA General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Sodium valproate extended-release tablets in people with Hemophilia, run by Xue-chun Lu 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 4 inclusion and 8 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 29 Feb 2024. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Contact Xuechun Lu, M.D. (13241892863, luxuechun@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
FVIII/FIX Activity (time frame: through study completion, an average of 1 month). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05920512, which also lists 18 linked publications.
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 29 Feb 2024.