Diamond Blackfan AnemiaPhase 1/2ACE-011-DBANCT01464164
Safety and Efficacy Study of Sotatercept in Adults With Transfusion Dependent Diamond Blackfan Anemia
A Phase 1/2 study testing Sotatercept and Sotatercept with prednisone boost in people with Diamond Blackfan Anemia, run by Northwell Health at 1 site in United States.
Trial summary
The purpose of this study is to determine the safety and dosing of drug Sotatercept, as a subcutaneous injection, to stimulate production of red blood cell production. To be given every 28 days for up to four doses. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diamond Blackfan Anemia
- What is being tested?
- Sotatercept and Sotatercept with prednisone boost
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2012to 13 Apr 2021
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- >/= 18 years of age
- DBA diagnosed
- RBC transfusion- dependence (defined as >/= 10 cc/kg of RBC per 28 days average)
- Karnofsky performance scale >/= 70
- Females of childbearing potential are to use birth control during study participation and for 112 days following the last dose of sotatercept
- Males must agree to use a latex condom during any sexual contact with females of childbearing potential while participating in the study and for 112 days following the last dose of sotatercept
- Agreement to adhere to the study visit schedule, understand and comply with all protocol requirements
- Understand and sign a written informed consent
Who cannot join
- Creatinine clearance < 30 ml/min
- SGOT > 3x upper limit of normal, SGPT > 3x upper limit normal, or bilirubin >3x upper limit normal
- Heart disease (NY Heart Association classification of >/= 3
- History of hypertension
- Subjects currently responsive to corticosteroids for treatment of Diamond Blackfan anemia
- Treatment with another investigational drug or device <56 days pre-study entry
- Pregnant or lactating females
- Cancer
Trial locations and contacts
1 site in 1 country.
United States1 site
North Shore- LIJ campus of The Feinstein Institute for Medical Research
Manhasset, New York, 11030
About this study
Official title: Phase I/II, Open-Label Study to Determine Safety and Efficacy of Sotatercept (ACE-011) in Adults With Red Blood Cell Transfusion- Dependent Diamond Blackfan Anemia
The purpose of this study is to determine the safety and dosing of drug Sotatercept, as a subcutaneous injection, to stimulate production of red blood cell production. To be given every 28 days for up to four doses.
Read the detailed description
This study is for adult patients with Diamond Blackfan Anemia who are currently being transfused every 3- 4 weeks.
The drug will be given as a subcutaneous injection within one of three dose levels. The first dose level (0.1 mg/kg) will include 3 subjects who will receive the same dose of the drug monthly for a total of 4 doses, as long as there are no dose- limiting toxicities (DLTs). A Dose limiting toxicity is defined as inability to deliver the scheduled doses because of toxicity >/= Grade 3, according to NCI Toxicity Grading Scale.
Once all 3 subjects have received and tolerated the low dose level, the next level will open (0.3 mg/kg)to 3 new subjects. Subjects will be monitored closely for response and side effects.
If more than 2 subjects have a dose limiting toxicity in the first dose level, then dose level -1 (0.05 mg/kg)will open, enrolling 3 more subjects. If more than 2 subjects at dose level -1, have dose limiting toxicities, the study will be discontinued. If there are no additional dose limiting toxicities, dose level -1 will be the maximum tolerated dose.
There are a total of 3 dose levels, not including dose level -1. Once the maximum tolerated dose has been reached, up to a total of 10 additional subjects will be enrolled.
Protocol Amendment: The protocol has been amended to include an additional enrollment of 20 subjects with two additional dose levels of Sotatercept (0.075 mg/kg and 0.100 mg/kg ) to be given with or without a prednisone boost.
Efficacy will be measured by response. A complete response will be determined if the subject no longer requires transfusion, while on study drug. A partial response will be measured by a reduction by 50% in need for transfusion.
Treatment modifications will be made based on evidence of side effects. Dose- escalation will be performed only if no side effects are reported and no efficacy is evidenced. Treatment will be stopped if hemoglobin is >12 gm/dl and/ or any >/+ grade 3 adverse event is related to sotatercept.
Study assessments will include:
- Physical exam (height, weight, vital signs and blood pressure)at screening, day 1 of each cycle and monthly for 3 months of follow up period as well as at study discontinuation.
- Additional blood pressure monitoring at day 1 of each cycle and weekly there after through cycle 4, monthly in follow up period and at study discontinuation.
- Karnofsky performance status at screening, day 1 of cycle 2 and day 1 of monthly follow up period for 3 months and study discontinuation.
- CBC reticulocyte count and ANC will be collected at day 1 of each cycle and weekly there after through cycle 4, monthly in follow up period and at study discontinuation.
- Blood chemistry, liver and kidney function will be assessed at screening, day 1 and 15 of cycle 1, day 1 of cycle 2, 3, 4 month 1 in follow up and at study discontinuation.
- Blood for iron status (serum iron, transferrin and %, ferritin) will be collected during the screening period, and at month 1 of the follow-up period as well as study discontinuation.
- Folate and B12 levels will be assessed during the screening period at day 1 of cycle 3 and again at study discontinuation.
- Urinalysis (creatinine, protein),at screening, day 15 of cycle 1, day 1 of cycles 2, 3, and 4 monthly during follow-up and at study discontinuation.
- Serum erythropoietin at screening, day 15 of cycle 1, day 1 of cycle 3, monthly during follow-up and at study discontinuation.
- FSH \& LH (everyone), DHEA \& testosterone (males only), estrogen \& estradiol (females only)at screening, day 1 of cycles 2, 3, and 4, monthly during follow- up period and at study discontinuation.
- EKG \& ECHO at screening, day 1 of cycle 3 first month of follow-up period and at study discontinuation
- Dexa Scan at screening, day 1 of monthly follow-up period and at study discontinuation
- Transfusion assessment at screening, day 1, 8, 15 and 22 of cycle 1, day 1 and 15 of cycles 2, 3, and 4, monthly during follow-up period and at study discontinuation.
- Response assessment at day 8, 15, 22 of cycle 1, day 1 and 15 of cycles2, 3, and 4, monthly for 3 months during follow-up period and at study discontinuation
- Adverse events, concomitant therapies to be assessed at day 1, 8, 15, and 22 of cycle 1, day 1 and 15 of cycles 2, 3, and 4, monthly during follow-up period and at study discontinuation
- Drug administration day 1 of cycles 1, 2, 3, and 4.
- Conditions
- Diamond Blackfan Anemia
- Being tested
- Sotatercept, Sotatercept with prednisone boost
- Keywords
- Diamond Blackfan anemia, DBA, Blackfan Diamond anemia, Congenital pure red cell aplasia, Aase-Smith II Syndrome, Aase Syndrome, Anemia, Congenital Pure Red Cell, Aplasia, Congenital Pure Red Cell, BDA, Congenital Hypoplastic Anemia, Erythrogenesis Imperfecta, Hypoplastic Congenital Anemia, Inherited Erythroblastopenia, pure red cell aplasia, bone marrow failure syndrome
- Medical subject headings
- Anemia, Diamond-Blackfan, Anemia, Hypoplastic, Congenital, Aase Smith syndrome 2, Red-Cell Aplasia, Pure, Bone Marrow Failure Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SotaterceptDrug
Also called ACE-011
Cohort 4a: 3 patients on Sotatercept 0.75 mg/kg every 3 weeks. If the patients have no untoward events in the Patients in Dose Level 4 by the end of 3 of the 6 doses, then additional patients (Dose Level 5) will be enrolled at the next dose level:
Cohort 5a: 3 patients on Sotatercept 1 mg/kg every 3 weeks
Sotatercept with prednisone boostDrug
Also called ACE-011 and Prednisone
Cohort 4b: 3 patients on Sotatercept 0.75 mg/kg every 3 weeks with a three week prednisone boost of 1 mg/kg/day (max 60 mg). If the patients have no untoward events in the Patients in Dose Level 4 by the end of 3 of the 6 doses, then additional patients (Dose Level 5) will be enrolled at the next dose level:
Cohort 5b: 3 patients on Sotatercept 1 mg/kg every 3 weeks with a 3 week prednisone boost of 1 mg/kg/day (max 60 mg).
| Study group | Role | What they receive |
|---|---|---|
| Sotatercept | Experimental | Sotatercept to be given as a subcutaneous injection once a month for 4 consecutive months, using a dose escalation scale among 3 cohorts. *Protocol Amendment: Two additional cohorts will be given Sotatercept 0.75mg/kg and 1 mg/kg as a subcutaneous injection once every 3 weeks. Receives: Drug: Sotatercept |
| Sotatercept with prednisone boost | Experimental | Protocol Amendment: Two additional cohorts will be given Sotatercept 0.75mg/kg and 1 mg/kg as a subcutaneous injection once every 3 weeks along with a prednisone boost of 1 mg/kg daily for 3 weeks (max of 60 mg). Receives: Drug: Sotatercept with prednisone boost |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Complete Response and Partial Response
Complete response is transfusion independence with hemoglobin >9 gm/dl; partial response is transfusion dependence with hemoglobin < 9gm/dl with an increase in reticulocyte count over baseline
Measured: 9 months
Secondary outcomes (1)
Severe Adverse Events Attributable to Study Drug
Assess severity of adverse events and relationship to sotatercept according to the currently active minor version of the NCI Common Terminology for Adverse Events version 4.0
Measured: 9 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Nov 2011 (estimated)
- Study startJan 2012
- Primary completion13 Apr 2021
- Study completion13 Apr 2021
Why it stopped: Supporter terminated the study due to no active patients (secondary to travel restrictions due to COVID).
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (30)Papers the sponsor has linked to this study.
- Other trials for Diamond Blackfan AnemiaStudies of the same condition, open and under way.
- More trials run by Northwell HealthThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Northwell Health
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Adrianna Vlachos, MD, Northwell Health
- Investigators
- Adrianna Vlachos, MD, Principal investigator, Northwell Health/Feinstein Institute for Medical Research
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01464164
- Sponsor's protocol ID
- 11-02-199 - 06A
- Acronym
- ACE-011-DBA
- Status last verified
- Feb 2023
- First submitted
- 31 Oct 2011
- Last updated
- 17 Mar 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Abkowitz JL, Schaison G, Boulad F, Brown DL, Buchanan GR, Johnson CA, Murray JC, Sabo KM. Response of Diamond-Blackfan anemia to metoclopramide: evidence for a role for prolactin in erythropoiesis. Blood. 2002 Oct 15;100(8):2687-91. doi: 10.1182/blood.V100.8.2687.
PubMed 12351372Diamond LK, Wang WC, Alter BP. Congenital hypoplastic anemia. Adv Pediatr. 1976;22:349-78.
PubMed 773132Ball SE, McGuckin CP, Jenkins G, Gordon-Smith EC. Diamond-Blackfan anaemia in the U.K.: analysis of 80 cases from a 20-year birth cohort. Br J Haematol. 1996 Sep;94(4):645-53. doi: 10.1046/j.1365-2141.1996.d01-1839.x.
PubMed 8826887Bastion Y, Bordigoni P, Debre M, Girault D, Leblanc T, Tchernia G, Ball S, McGuckin C, Gordon-Smith EC, Bekassy A, et al. Sustained response after recombinant interleukin-3 in diamond blackfan anemia. Blood. 1994 Jan 15;83(2):617-8. No abstract available.
PubMed 8286756Cmejla R, Cmejlova J, Handrkova H, Petrak J, Pospisilova D. Ribosomal protein S17 gene (RPS17) is mutated in Diamond-Blackfan anemia. Hum Mutat. 2007 Dec;28(12):1178-82. doi: 10.1002/humu.20608.
PubMed 17647292Da Costa L, Moniz H, Simansour M, Tchernia G, Mohandas N, Leblanc T. Diamond-Blackfan anemia, ribosome and erythropoiesis. Transfus Clin Biol. 2010 Sep;17(3):112-9. doi: 10.1016/j.tracli.2010.06.001. Epub 2010 Jul 23.
PubMed 20655265Doherty L, Sheen MR, Vlachos A, Choesmel V, O'Donohue MF, Clinton C, Schneider HE, Sieff CA, Newburger PE, Ball SE, Niewiadomska E, Matysiak M, Glader B, Arceci RJ, Farrar JE, Atsidaftos E, Lipton JM, Gleizes PE, Gazda HT. Ribosomal protein genes RPS10 and RPS26 are commonly mutated in Diamond-Blackfan anemia. Am J Hum Genet. 2010 Feb 12;86(2):222-8. doi: 10.1016/j.ajhg.2009.12.015. Epub 2010 Jan 28.
PubMed 20116044Draptchinskaia N, Gustavsson P, Andersson B, Pettersson M, Willig TN, Dianzani I, Ball S, Tchernia G, Klar J, Matsson H, Tentler D, Mohandas N, Carlsson B, Dahl N. The gene encoding ribosomal protein S19 is mutated in Diamond-Blackfan anaemia. Nat Genet. 1999 Feb;21(2):169-75. doi: 10.1038/5951.
PubMed 9988267Farrar JE, Nater M, Caywood E, McDevitt MA, Kowalski J, Takemoto CM, Talbot CC Jr, Meltzer P, Esposito D, Beggs AH, Schneider HE, Grabowska A, Ball SE, Niewiadomska E, Sieff CA, Vlachos A, Atsidaftos E, Ellis SR, Lipton JM, Gazda HT, Arceci RJ. Abnormalities of the large ribosomal subunit protein, Rpl35a, in Diamond-Blackfan anemia. Blood. 2008 Sep 1;112(5):1582-92. doi: 10.1182/blood-2008-02-140012. Epub 2008 Jun 5.
PubMed 18535205Gale RP, Barosi G, Barbui T, Cervantes F, Dohner K, Dupriez B, Gupta V, Harrison C, Hoffman R, Kiladjian JJ, Mesa R, Mc Mullin MF, Passamonti F, Ribrag V, Roboz G, Saglio G, Vannucchi A, Verstovsek S. What are RBC-transfusion-dependence and -independence? Leuk Res. 2011 Jan;35(1):8-11. doi: 10.1016/j.leukres.2010.07.015. Epub 2010 Aug 7.
PubMed 20692036Gazda HT, Grabowska A, Merida-Long LB, Latawiec E, Schneider HE, Lipton JM, Vlachos A, Atsidaftos E, Ball SE, Orfali KA, Niewiadomska E, Da Costa L, Tchernia G, Niemeyer C, Meerpohl JJ, Stahl J, Schratt G, Glader B, Backer K, Wong C, Nathan DG, Beggs AH, Sieff CA. Ribosomal protein S24 gene is mutated in Diamond-Blackfan anemia. Am J Hum Genet. 2006 Dec;79(6):1110-8. doi: 10.1086/510020. Epub 2006 Nov 2.
PubMed 17186470Gazda HT, Sheen MR, Vlachos A, Choesmel V, O'Donohue MF, Schneider H, Darras N, Hasman C, Sieff CA, Newburger PE, Ball SE, Niewiadomska E, Matysiak M, Zaucha JM, Glader B, Niemeyer C, Meerpohl JJ, Atsidaftos E, Lipton JM, Gleizes PE, Beggs AH. Ribosomal protein L5 and L11 mutations are associated with cleft palate and abnormal thumbs in Diamond-Blackfan anemia patients. Am J Hum Genet. 2008 Dec;83(6):769-80. doi: 10.1016/j.ajhg.2008.11.004.
PubMed 19061985Glader BE, Backer K, Diamond LK. Elevated erythrocyte adenosine deaminase activity in congenital hypoplastic anemia. N Engl J Med. 1983 Dec 15;309(24):1486-90. doi: 10.1056/NEJM198312153092404.
PubMed 6646173Gustavsson P, Skeppner G, Johansson B, Berg T, Gordon L, Kreuger A, Dahl N. Diamond-Blackfan anaemia in a girl with a de novo balanced reciprocal X;19 translocation. J Med Genet. 1997 Sep;34(9):779-82. doi: 10.1136/jmg.34.9.779.
PubMed 9321770Leblanc TM, Da Costa L, Marie I, Demolis P, Tchernia G. Metoclopramide treatment in DBA patients: no complete response in a French prospective study. Blood. 2007 Mar 1;109(5):2266-7. doi: 10.1182/blood-2006-08-039545. No abstract available.
PubMed 17312003
Study at a glance
From the registry record, last updated by the sponsor on 17 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II, Open-Label Study to Determine Safety and Efficacy of Sotatercept (ACE-011) in Adults With Red Blood Cell Transfusion- Dependent Diamond Blackfan Anemia
- ClinicalTrials.gov ID
- NCT01464164
- Acronym / sponsor ID
- ACE-011-DBA / 11-02-199 - 06A
- Conditions
- Diamond Blackfan Anemia
- Keywords
- Diamond Blackfan anemia, DBA, Blackfan Diamond anemia, Congenital pure red cell aplasia, Aase-Smith II Syndrome, Aase Syndrome, Anemia, Congenital Pure Red Cell, Aplasia, Congenital Pure Red Cell
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Supporter terminated the study due to no active patients (secondary to travel restrictions due to COVID).
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Northwell HealthUniversity, hospital or other
- Study start
- Jan 2012 (actual)
- Primary completion
- 13 Apr 2021 (actual)
- Study completion
- 13 Apr 2021 (actual)
- First posted
- 3 Nov 2011 (estimated)
- Results
- Posted 21 Dec 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine the safety and dosing of drug Sotatercept, as a subcutaneous injection, to stimulate production of red blood cell production. To be given every 28 days for up to four doses.
Detailed description
This study is for adult patients with Diamond Blackfan Anemia who are currently being transfused every 3- 4 weeks.
The drug will be given as a subcutaneous injection within one of three dose levels. The first dose level (0.1 mg/kg) will include 3 subjects who will receive the same dose of the drug monthly for a total of 4 doses, as long as there are no dose- limiting toxicities (DLTs). A Dose limiting toxicity is defined as inability to deliver the scheduled doses because of toxicity >/= Grade 3, according to NCI Toxicity Grading Scale.
Once all 3 subjects have received and tolerated the low dose level, the next level will open (0.3 mg/kg)to 3 new subjects. Subjects will be monitored closely for response and side effects.
If more than 2 subjects have a dose limiting toxicity in the first dose level, then dose level -1 (0.05 mg/kg)will open, enrolling 3 more subjects. If more than 2 subjects at dose level -1, have dose limiting toxicities, the study will be discontinued. If there are no additional dose limiting toxicities, dose level -1 will be the maximum tolerated dose.
There are a total of 3 dose levels, not including dose level -1. Once the maximum tolerated dose has been reached, up to a total of 10 additional subjects will be enrolled.
Protocol Amendment: The protocol has been amended to include an additional enrollment of 20 subjects with two additional dose levels of Sotatercept (0.075 mg/kg and 0.100 mg/kg ) to be given with or without a prednisone boost.
Efficacy will be measured by response. A complete response will be determined if the subject no longer requires transfusion, while on study drug. A partial response will be measured by a reduction by 50% in need for transfusion.
Treatment modifications will be made based on evidence of side effects. Dose- escalation will be performed only if no side effects are reported and no efficacy is evidenced. Treatment will be stopped if hemoglobin is >12 gm/dl and/ or any >/+ grade 3 adverse event is related to sotatercept.
Study assessments will include:
- Physical exam (height, weight, vital signs and blood pressure)at screening, day 1 of each cycle and monthly for 3 months of follow up period as well as at study discontinuation.
- Additional blood pressure monitoring at day 1 of each cycle and weekly there after through cycle 4, monthly in follow up period and at study discontinuation.
- Karnofsky performance status at screening, day 1 of cycle 2 and day 1 of monthly follow up period for 3 months and study discontinuation.
- CBC reticulocyte count and ANC will be collected at day 1 of each cycle and weekly there after through cycle 4, monthly in follow up period and at study discontinuation.
- Blood chemistry, liver and kidney function will be assessed at screening, day 1 and 15 of cycle 1, day 1 of cycle 2, 3, 4 month 1 in follow up and at study discontinuation.
- Blood for iron status (serum iron, transferrin and %, ferritin) will be collected during the screening period, and at month 1 of the follow-up period as well as study discontinuation.
- Folate and B12 levels will be assessed during the screening period at day 1 of cycle 3 and again at study discontinuation.
- Urinalysis (creatinine, protein),at screening, day 15 of cycle 1, day 1 of cycles 2, 3, and 4 monthly during follow-up and at study discontinuation.
- Serum erythropoietin at screening, day 15 of cycle 1, day 1 of cycle 3, monthly during follow-up and at study discontinuation.
- FSH \& LH (everyone), DHEA \& testosterone (males only), estrogen \& estradiol (females only)at screening, day 1 of cycles 2, 3, and 4, monthly during follow- up period and at study discontinuation.
- EKG \& ECHO at screening, day 1 of cycle 3 first month of follow-up period and at study discontinuation
- Dexa Scan at screening, day 1 of monthly follow-up period and at study discontinuation
- Transfusion assessment at screening, day 1, 8, 15 and 22 of cycle 1, day 1 and 15 of cycles 2, 3, and 4, monthly during follow-up period and at study discontinuation.
- Response assessment at day 8, 15, 22 of cycle 1, day 1 and 15 of cycles2, 3, and 4, monthly for 3 months during follow-up period and at study discontinuation
- Adverse events, concomitant therapies to be assessed at day 1, 8, 15, and 22 of cycle 1, day 1 and 15 of cycles 2, 3, and 4, monthly during follow-up period and at study discontinuation
- Drug administration day 1 of cycles 1, 2, 3, and 4.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sotatercept | Experimental | Drug: SotaterceptSotatercept to be given as a subcutaneous injection once a month for 4 consecutive months, using a dose escalation scale among 3 cohorts. *Protocol Amendment: Two additional cohorts will be given Sotatercept 0.75mg/kg and 1 mg/kg as a subcutaneous injection once every 3 weeks. |
| Sotatercept with prednisone boost | Experimental | Drug: Sotatercept with prednisone boostProtocol Amendment: Two additional cohorts will be given Sotatercept 0.75mg/kg and 1 mg/kg as a subcutaneous injection once every 3 weeks along with a prednisone boost of 1 mg/kg daily for 3 weeks (max of 60 mg). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- >/= 18 years of age
- DBA diagnosed
- RBC transfusion- dependence (defined as >/= 10 cc/kg of RBC per 28 days average)
- Karnofsky performance scale >/= 70
- Females of childbearing potential are to use birth control during study participation and for 112 days following the last dose of sotatercept
Key exclusion criteria (8 listed)
- Creatinine clearance < 30 ml/min
- SGOT > 3x upper limit of normal, SGPT > 3x upper limit normal, or bilirubin >3x upper limit normal
- Heart disease (NY Heart Association classification of >/= 3
- History of hypertension
- Subjects currently responsive to corticosteroids for treatment of Diamond Blackfan anemia
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 |
|---|---|---|
| SotaterceptAlso: ACE-011Cohort 4a: 3 patients on Sotatercept 0.75 mg/kg every 3 weeks. If the patients have no untoward events in the Patients in Dose Level 4 by the end of 3 of the 6 doses, then additional patients (Dose Level 5) will be enrolled at the next dose level: Cohort 5a: 3 patients on Sotatercept 1 mg/kg every 3 weeks | Drug | Sotatercept |
| Sotatercept with prednisone boostAlso: ACE-011 and PrednisoneCohort 4b: 3 patients on Sotatercept 0.75 mg/kg every 3 weeks with a three week prednisone boost of 1 mg/kg/day (max 60 mg). If the patients have no untoward events in the Patients in Dose Level 4 by the end of 3 of the 6 doses, then additional patients (Dose Level 5) will be enrolled at the next dose level: Cohort 5b: 3 patients on Sotatercept 1 mg/kg every 3 weeks with a 3 week prednisone boost of 1 mg/kg/day (max 60 mg). | Drug | Sotatercept with prednisone boost |
Primary outcome
Number of Participants With Complete Response and Partial Response
Time frame: 9 months
Complete response is transfusion independence with hemoglobin >9 gm/dl; partial response is transfusion dependence with hemoglobin < 9gm/dl with an increase in reticulocyte count over baseline
1 secondary outcome
Severe Adverse Events Attributable to Study Drug
Time frame: 9 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Mar 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 12351372Abkowitz JL, Schaison G, Boulad F, Brown DL, Buchanan GR, Johnson CA, Murray JC, Sabo KM. Response of Diamond-Blackfan anemia to metoclopramide: evidence for a role for prolactin in erythropoiesis. Blood. 2002 Oct 15;100(8):2687-91. doi: 10.1182/blood.V100.8.2687.
- Background: PubMed 773132Diamond LK, Wang WC, Alter BP. Congenital hypoplastic anemia. Adv Pediatr. 1976;22:349-78.
- Background: PubMed 8826887Ball SE, McGuckin CP, Jenkins G, Gordon-Smith EC. Diamond-Blackfan anaemia in the U.K.: analysis of 80 cases from a 20-year birth cohort. Br J Haematol. 1996 Sep;94(4):645-53. doi: 10.1046/j.1365-2141.1996.d01-1839.x.
- Background: PubMed 8286756Bastion Y, Bordigoni P, Debre M, Girault D, Leblanc T, Tchernia G, Ball S, McGuckin C, Gordon-Smith EC, Bekassy A, et al. Sustained response after recombinant interleukin-3 in diamond blackfan anemia. Blood. 1994 Jan 15;83(2):617-8. No abstract available.
- Background: PubMed 17647292Cmejla R, Cmejlova J, Handrkova H, Petrak J, Pospisilova D. Ribosomal protein S17 gene (RPS17) is mutated in Diamond-Blackfan anemia. Hum Mutat. 2007 Dec;28(12):1178-82. doi: 10.1002/humu.20608.
- Background: PubMed 20655265Da Costa L, Moniz H, Simansour M, Tchernia G, Mohandas N, Leblanc T. Diamond-Blackfan anemia, ribosome and erythropoiesis. Transfus Clin Biol. 2010 Sep;17(3):112-9. doi: 10.1016/j.tracli.2010.06.001. Epub 2010 Jul 23.
- Background: PubMed 20116044Doherty L, Sheen MR, Vlachos A, Choesmel V, O'Donohue MF, Clinton C, Schneider HE, Sieff CA, Newburger PE, Ball SE, Niewiadomska E, Matysiak M, Glader B, Arceci RJ, Farrar JE, Atsidaftos E, Lipton JM, Gleizes PE, Gazda HT. Ribosomal protein genes RPS10 and RPS26 are commonly mutated in Diamond-Blackfan anemia. Am J Hum Genet. 2010 Feb 12;86(2):222-8. doi: 10.1016/j.ajhg.2009.12.015. Epub 2010 Jan 28.
- Background: PubMed 9988267Draptchinskaia N, Gustavsson P, Andersson B, Pettersson M, Willig TN, Dianzani I, Ball S, Tchernia G, Klar J, Matsson H, Tentler D, Mohandas N, Carlsson B, Dahl N. The gene encoding ribosomal protein S19 is mutated in Diamond-Blackfan anaemia. Nat Genet. 1999 Feb;21(2):169-75. doi: 10.1038/5951.
- Background: PubMed 18535205Farrar JE, Nater M, Caywood E, McDevitt MA, Kowalski J, Takemoto CM, Talbot CC Jr, Meltzer P, Esposito D, Beggs AH, Schneider HE, Grabowska A, Ball SE, Niewiadomska E, Sieff CA, Vlachos A, Atsidaftos E, Ellis SR, Lipton JM, Gazda HT, Arceci RJ. Abnormalities of the large ribosomal subunit protein, Rpl35a, in Diamond-Blackfan anemia. Blood. 2008 Sep 1;112(5):1582-92. doi: 10.1182/blood-2008-02-140012. Epub 2008 Jun 5.
- Background: PubMed 20692036Gale RP, Barosi G, Barbui T, Cervantes F, Dohner K, Dupriez B, Gupta V, Harrison C, Hoffman R, Kiladjian JJ, Mesa R, Mc Mullin MF, Passamonti F, Ribrag V, Roboz G, Saglio G, Vannucchi A, Verstovsek S. What are RBC-transfusion-dependence and -independence? Leuk Res. 2011 Jan;35(1):8-11. doi: 10.1016/j.leukres.2010.07.015. Epub 2010 Aug 7.
- Background: PubMed 17186470Gazda HT, Grabowska A, Merida-Long LB, Latawiec E, Schneider HE, Lipton JM, Vlachos A, Atsidaftos E, Ball SE, Orfali KA, Niewiadomska E, Da Costa L, Tchernia G, Niemeyer C, Meerpohl JJ, Stahl J, Schratt G, Glader B, Backer K, Wong C, Nathan DG, Beggs AH, Sieff CA. Ribosomal protein S24 gene is mutated in Diamond-Blackfan anemia. Am J Hum Genet. 2006 Dec;79(6):1110-8. doi: 10.1086/510020. Epub 2006 Nov 2.
- Background: PubMed 19061985Gazda HT, Sheen MR, Vlachos A, Choesmel V, O'Donohue MF, Schneider H, Darras N, Hasman C, Sieff CA, Newburger PE, Ball SE, Niewiadomska E, Matysiak M, Zaucha JM, Glader B, Niemeyer C, Meerpohl JJ, Atsidaftos E, Lipton JM, Gleizes PE, Beggs AH. Ribosomal protein L5 and L11 mutations are associated with cleft palate and abnormal thumbs in Diamond-Blackfan anemia patients. Am J Hum Genet. 2008 Dec;83(6):769-80. doi: 10.1016/j.ajhg.2008.11.004.
- 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.
Adrianna Vlachos, MD principal investigator
Northwell Health/Feinstein Institute for Medical Research
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 Sotatercept and Sotatercept with prednisone boost in people with Diamond Blackfan Anemia, run by Northwell Health at 1 site in United States.
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 8 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: stopped early, as of the sponsor's last update on 17 Mar 2023. 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 United States. 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?
Yes. Results are posted in the registry (first posted 21 Dec 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Complete Response and Partial Response (time frame: 9 months). 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 NCT01464164, which also lists 30 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 17 Mar 2023.