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Trial details
An open-label, dose-escalation, dose-finding, and proof-of-concept trial of SP-420 in subjects with transfusion-dependent β-thalassemia
Current status:
Approved
|
Date registered:
07/03/2024
Trial version(s)
Current: 13/12/2022
Click here to view the tips and fields' descriptions
Main Information
Primary registry identifying number
LBCTR2023045220
Protocol number
P-SP420-THAL-01
MOH registration number
Trial already registered with the MoPH
Study registered at the country of origin
Type of registration
Prospective
Date of registration in national regulatory agency
13/12/2022
Primary sponsor
Pharmacosmos A/S
Primary sponsor: Country of origin
Denmark
Public title
An open-label, dose-escalation, dose-finding, and proof-of-concept trial of SP-420 in subjects with transfusion-dependent β-thalassemia
Acronym
Scientific title
An open-label, dose-escalation, dose-finding, and proof-of-concept trial of SP-420 in subjects with transfusion-dependent β-thalassemia
Acronym
Brief summary of the study: English
The trial is an open-label, dose-escalation, dose-finding, and proof-of-concept multi-centre trial evaluating the iron clearing efficacy, safety, tolerability, and pharmacokinetic (PK) properties of SP-420 (Pharmacosmos A/S, Holbæk, Denmark) administered 3 times per week to subjects with transfusion-dependent β-thalassemia for 48 weeks. Approximately 90 subjects will be enrolled in 3 dose cohorts of approximately 30 subjects each. Dosing will start with 6 subjects in each cohort (cohort 1a-3a) in a dose-escalating manner, and if no safety issues are identified, inclusion of additional 24 subjects is allowed in each cohort (cohort 1b-3b). Extensive electrocardiography (ECG) measurements and PK assessments will be performed in the 18 subjects in cohort 1a-3a. The trial consists of 2 parts: part 1 with a fixed dosing regimen and part 2 with an adjustable dosing regimen.
Brief summary of the study: Arabic
التجربة عبارة عن تجربة متعددة المراكز مفتوحة التسمية ، وتصعيد الجرعة ، وإيجاد الجرعة ، وإثبات صحة المفهوم لتقييم فعالية إزالة الحديد ، والسلامة ، والتحمل ، وخصائص الحرائك الدوائية (PK) لـ SP-420 (Pharmacosmos A / S ، Holbæk ، الدنمارك) 3 مرات في الأسبوع للأشخاص الذين يعانون من ثلاسيميا بيتا المعتمد على نقل الدم لمدة 48 أسبوعًا. سيتم تسجيل ما يقرب من 90 مريضا في 3 مجموعات جرعة من حوالي 30 مريضا لكل منها. ستبدأ الجرعات بـ 6 مريضا في كل مجموعة (مجموعة 1 أ -3 أ) بطريقة تصعيد الجرعة ، وإذا لم يتم تحديد مشكلات تتعلق بالسلامة ، يُسمح بإدراج 24مريضا إضافيًا في كل مجموعة (مجموعة 1 ب -3 ب). سيتم إجراء قياسات شاملة لتخطيط القلب (ECG) وتقييمات PK في 18 شخصًا في الفوج 1a-3a. تتكون التجربة من جزأين: الجزء الأول بنظام الجرعات الثابت والجزء الثاني بنظام الجرعات القابل للتعديل.
Health conditions/problem studied: Specify
Transfusion-dependent β-thalassemia
Interventions: Specify
A minimum of 90 subjects with transfusion-dependent β-thalassemia will be recruited, and they will be allocated to 1 the following treatment groups: • Cohort 1a+b (N=30): SP-420 initially at 28 mg/kg PO 3 times per week • Cohort 2a+b (N=30): SP-420 initially at 56 mg/kg (or a lower dose as suggested by the DMC) PO 3 times per week • Cohort 3a+b (N=30): SP-420 initially at 84 mg/kg (or a lower dose as suggested by the DMC) PO 3 times per week
Key inclusion and exclusion criteria: Inclusion criteria
1. Women and men aged ≥18 years 2. Transfusion-dependent β-thalassemia including HbE/β-thalassemia requiring iron chelation therapy (β-thalassemia with mutation and/or multiplication of α-globin is allowed) 3. On a stable dose of iron chelation for at least 4 weeks prior to screening 4. Weight ≥35 kg at screening 5. Willing to discontinue current iron chelation therapy 7 days (± 3 days) prior to the first dose of SP-420 and for the duration of the trial 6. Transfusion iron overload defined as LIC ≥5 and ≤20 mg/g dw on the R2-MRI obtained within 2 weeks prior to baseline 7. Subject has been treated and followed for at least the past 6 months in a specialised centre that maintained detailed medical records, including transfusion and iron chelation histories 8. Willingness to participate and signing the informed consent form
Key inclusion and exclusion criteria: Gender
Both
Key inclusion and exclusion criteria: Age minimum
18
Key inclusion and exclusion criteria: Age maximum
99
Key inclusion and exclusion criteria: Exclusion criteria
1. β-thalassemia with the structural Hb variants HbS and HbC 2. Cardiac MRI-T2* score <10 msec obtained within 2 weeks prior to baseline 3. S-ferritin <500 or >4000 ng/mL* 4. Current malignancy with the exceptions of localised basal cell or squamous cell skin cancer or localised prostate cancer or is receiving immunotherapy, chemotherapy, or radiation therapy for a malignancy 5. Current myelodysplastic syndrome 6. Current biliary disorder 7. ALAT >4 times the upper limit of normal, decompensated cirrhosis, or ascites at screening 8. Past or ongoing history of clinically significant kidney disease 9. Creatinine greater than the upper limit of normal at screening 10. Estimated glomerular filtration rate eGFR <60 mL/min/1.73 m2 11. Urine protein to creatinine ratio >0.5 mg/mg at screening 12. Heart failure grade II, III and IV by NYHA 13. LVEF on MRI <56 % (echocardiography allowed if MRI not available) 14. A QTcF >450 ms, 2nd or 3rd degree atrioventricular block, or incomplete left hemiblock, or the presence of clinically significant abnormalities as determined by the Investigator at screening 15. Hypertransfused defined as more than 6 units/month in average for the last 6 months prior to screening 16. Ongoing symptoms of neuropathy, including peripheral sensory neuropathy, peripheral motor neuropathy, or paresthesia at screening 17. Platelet count <100×109/L at screening 18. History of hypersensitivity to an iron chelator (investigational or marketed) or excipients 19. Documented history of non-compliance to chelation therapy within past 2 years 20. Received another investigational drug within 30 days or investigational antibody within 90 days before screening 21. Treatment with prohibited medication: iron, aluminium containing antacid therapies, systemic corticosteroids (topical and pulmonary corticosteroids are allowed), oral bisphosphonates, chronic use of high dose NSAIDs (as needed and low dose acetylsalicylic acid are allowed), drugs with known renal toxicity, drugs with known QTc prolongation, potent UGT inducers (e.g. rifampicin, phenytoin, phenobarbital, ritonavir) within 7 days prior to baseline 22. Initiation of treatment with luspatercept within 6 months prior to screening (luspatercept is allowed if initiated and dose is stable at least 6 months prior to screening) 23. Subject unable to undergo trial assessments including MRI, e.g. who are claustrophobic to MRI, have a cardiac pacemaker, ferromagnetic metal implants other than those approved as safe for use in MR scanners (e.g. some types of aneurysm clips, and shrapnel), and subjects who are obese (exceeding the equipment limits) 24. Pregnant or nursing women. In order to avoid pregnancy, women of childbearing potential (premenopausal and not surgically sterile) have to use highly efficient contraception (e.g. intrauterine devices, hormonal contraceptives (contraceptive pills, implants, transdermal patches, hormonal vaginal devices or injections with prolonged release)) during the whole trial period and 4 weeks post-dosing. A sterile sole partner or sexual abstinence is also considered acceptable provided it reflects the usual and preferred lifestyle of the participant 25. Men, even if surgically sterilised, (i.e. status post vasectomy), who do not agree to practice effective barrier contraception during the entire trial period, or agrees to completely abstain from heterosexual intercourse 26. Any other laboratory abnormality, medical condition, or psychiatric disorder which, in the opinion of the Investigator, will put the subject’s disease management at risk or may result in the subject being unable to comply with the trial requirements *If s-ferritin is slightly >4000 ng/mL at the screening, a second blood sample may be taken after at least 7 days for re-assessment of eligibility. This will not be considered a re-screening. If the second sample fulfils enrolment criteria, the subject may be enrolled. The results should be available at the baseline visit at the latest, i.e. max 4 weeks after the screening visit.
Type of Study
Type
Interventional
Type of intervention
Pharmaceutical
Trial scope
Therapy
Trial scope: Specify scope
Study design: Allocation
Non-randomized controlled trial
Study design: Masking
Open (masking not used)
Study design: Control
Dose comparison
Study phase
2
Study design: Purpose
Treatment
Study design: Assignment
Other
Study design: Specify assignment
Cohort design
IMP has market authorization
No
Name of IMP
SP-420
Type of IMP
Others
Type of IMP: Specify
Iron Chelator
Pharmaceutical class
SP-420((S)-4,5-dihydro-2-[2-hydroxy-4-(3,6-dioxaheptyloxy) phenyl]-4-methyl-4-thiazolecarboxylic acid) is a small molecule, tridentate iron chelator of the desferrithiocin class that chelates iron with a stoichiometry of 2:1 SP-420:Fe(III).
Therapeutic indication
Treatment of patients with Transfusion-dependent β-thalassemia
Therapeutic benefit
An ideal iron chelator would have high iron chelating efficiency with oral dosing, high penetration into all organs adversely affected by iron overload (e.g. liver, heart, pancreas, and kidney), and minimal toxicity, particularly to the renal, hepatic, and gastrointestinal systems, and an easy to use, palatable formulation. The ambition with SP-420 is to develop an efficacious iron chelator with a favourable safety profile and dosing regimen.
Biospecimen retention
None retained
Biospecimen description
NA
Target sample size
90
Actual enrollment target size
Date of first enrollment: Type
Anticipated
Date of first enrollment: Date
24/04/2023
Date of study closure: Type
Anticipated
Date of study closure: Date
20/12/2024
Recruitment status
Pending
Date of completion
IPD sharing statement plan
Yes
IPD sharing statement description
The trial will be registered in public registries (e.g. EudraCT, clinicaltrials.gov, or other national registries, if applicable). When part 1 of the trial is final it will be reported as a statistical report. When part 2 of the trial is final, all endpoints will be reported in a CSR. The CSR will be prepared by Pharmacosmos or its designee and reviewed and approved by Pharmacosmos. The CSR or a summary of the CSR should be sent to the IRB/IEC and Competent Authorities according to local legislation. The results of the trial, positive as well as negative, will be published by the end of the trial. Any publication or disclosure must comply with all applicable regulations and must be limited to scientific findings and must not constitute promotion under the applicable regulations. No data from the clinical trial may be published, presented, or communicated, except to Competent Authorities, prior to the release of the CSR, unless approved by Pharmacosmos in writing. The data and results from all sites participating in the trial shall be aggregated and analysed for publication in a primary publication. When and where the full results will be published will be decided on by Pharmacosmos. The Investigator and the site agree that they shall not publish any results (own data or aggregated data) until the primary publication has been published.
Additional data URL
Summary Results
Secondary Identifying Numbers
Full name of issuing authority
Secondary identifying number
Sources of Monetary or Material Support
Name
Secondary Sponsors
Name
Contact for Public/Scientific Queries
Contact type
First name
Last name
Address
Country
Telephone
Email
Affiliation
Public
Aziz
Zoghbi
MCT-CRO,Berytech Technology and Health,5th Floor Damascus Road,Beirut,Lebanon
Lebanon
009611612 500
aziz.zoghbi@mct-cro.com
Regional Manager
Scientific
Ali
Taher
Chronic Care Center, Hazmieh, Lebanon
Lebanon
009613755 669
ataher@aub.edu.lb
Principal Investigator
Centers/Hospitals Involved in the Study
Center/Hospital name
Name of principles investigator
Principles investigator speciality
Ethical approval
Chronic Care Center
Dr. Ali Taher
MD Hematology
Approved
Ethics Review
Ethics approval obtained
Approval date
Contact name
Contact email
Contact phone
Chronic Care Center
30/01/2023
Michelle Abi Saad
cccmas@chroniccare.org.lb
9615455101
American University of Beirut Medical Center
27/02/2023
Abeer Dakik
irb@aub.edu.lb
961350000 ext 5445
Countries of Recruitment
Name
Denmark
United Arab Emirates
Canada
Health Conditions or Problems Studied
Condition
Code
Keyword
Transfusion dependent beta-thalassemia
Thalassaemia (D56)
TDT
Interventions
Intervention
Description
Keyword
SP-420 – 28 mg/kg
28 mg/kg, oral dosing 3 times per week, Monday, Wednesday, and Friday
SP-420
SP-420 – 56 mg/kg
56 mg/kg, oral dosing 3 times per week, Monday, Wednesday, and Friday
SP-420
SP-420 – 84 mg/kg
84 mg/kg, oral dosing 3 times per week, Monday, Wednesday, and Friday
SP-420
Primary Outcomes
Name
Time points
Measure
dose-response relationship of SP-420 for 24 weeks
from baseline to week 24
Total body iron removed by SP-420
Key Secondary Outcomes
Name
Time points
Measure
clearing iron from the liver
from baseline to week 24
liver iron concentration (LIC)measured by R2-MRI
clearing iron from the liver after 12 and 48 weeks
from baseline to week 12 and week 48
LIC measured by R2-MRI
total body iron removal after 12 and 48 weeks
from baseline to week 12 and week 48, and from week 24 to week 48
Total body iron removed by SP-420
serum (s-) ferritin
from baseline to weeks 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48
s-ferritin
safety and tolerability
NA
adverse events (AEs)/physical examination (including auditory and ophthalmologic examinations), height, vital signs, ECG, and safety laboratory parameters (including urinalysis)/extensive ECG measurement will be performed in the 18 subjects in cohort 1a-3a
Trial Results
Summary results in Lebanon
Study results globally
Date of posting of results summaries
Date of first journal publication of results
Results URL link
Baseline characteristics
Participant flow
Adverse events
Outcome measures
URL to protocol files
Link(s) to publications related to the study
Changes History
Change
Date
Download as PDF
Save a PDF copy of the summary of the trial