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REGN7257 in Adult Patients With Severe Aplastic Anemia That Is Refractory to or Relapsed on Immunosuppressive Therapy

Phase 1
Suspended
Conditions
Severe Aplastic Anemia (SAA)
Interventions
Registration Number
NCT04409080
Lead Sponsor
Regeneron Pharmaceuticals
Brief Summary

This study is researching an experimental drug called REGN7257 (called "study drug"). The study is focused on patients who have severe aplastic anemia (SAA), a disease of the bone marrow resulting in an impairment of the production of blood cells.

The main purpose of this two-part study (Part A and Part B) is to test how safe and tolerable REGN7257 is in patients with SAA in which other Immunosuppressive therapies (ISTs) have not worked well.

The study is looking at several other research questions to better understand the following properties of REGN7257:

* Side effects that may be experienced by participants taking REGN7257

* How REGN7257 works in the body

* How much REGN7257 is present in blood after dosing

* If REGN7257 works to raise levels of certain blood counts after treatment

* How quickly REGN7257 works to raise levels of certain blood counts

* In patients for whom REGN7257 works to raise levels of certain blood counts after treatment, how many continue to show such a response throughout the study

* If REGN7257 works to lower the number of platelet and red blood cell transfusions needed

* How REGN7257 changes immune cell counts and composition

* How the body reacts to REGN7257 and if it produces proteins that bind to REGN7257 (this would be called the formation of anti-drug antibodies \[ADA\])

Detailed Description

Not available

Recruitment & Eligibility

Status
SUSPENDED
Sex
All
Target Recruitment
33
Inclusion Criteria
  1. Part A: SAA that is IST-refractory or IST-relapsed, as defined in the protocol
  2. Part B: SAA that is IST-relapsed, as defined in the protocol
  3. Hematopoietic stem cell transplantation (HSCT) is not available or suitable as a treatment option or has been refused by the patient
  4. Adequate hepatic and renal function as defined in the protocol

Key

Exclusion Criteria
  1. Diagnosis of Fanconi anemia or other congenital bone marrow failure syndrome as defined in the protocol
  2. Evidence of myelodysplastic syndrome as defined in the protocol
  3. Paroxysmal nocturnal hemoglobinuria (PNH) with evidence of clinically significant hemolysis (eg, treatment indicated) or history of PNH-associated thrombosis
  4. Treatment with a T cell-depleting agent (eg, ATG or alemtuzumab) within 6 months prior to dosing
  5. Treatment with a calcineurin inhibitor (eg, cyclosporine) within 4 weeks prior to dosing for patients enrolled in Part A
  6. Treatment with eltrombopag or investigational thrombopoietin receptor agonist, Granulocyte Colony-Stimulating Factor (G-CSF), or an androgen (eg, danazol), within 2 weeks prior to dosing
  7. HIV, hepatitis B or hepatitis C positive by serological testing at the screening visit as defined in the protocol
  8. Active tuberculosis, latent tuberculosis infection (LTBI) or history incompletely-treated tuberculosis or LTBI
  9. Active infection as defined in the protocol

Note: Other protocol-defined inclusion/ exclusion criteria apply

Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
Part AREGN7257Part A: Single ascending dose (SAD) escalation cohorts
Part BREGN7257Part B: Multiple REGN7257 dosages.
Primary Outcome Measures
NameTimeMethod
Incidence of serious adverse events (SAEs)Through the end of study visit, approximately 78 weeks

Part B

Incidence and severity of treatment-emergent adverse events (TEAEs)Through the end of study visit, approximately 78 weeks

Part B

Overall response rate (ORR)At 6 months, approximately 26 weeks

Part B

Incidence of adverse events (AEs)12 months post-treatment, approximately 52 weeks

Part A

Secondary Outcome Measures
NameTimeMethod
Time to best responseUp to 18 months

Part B

Any clinical responseUntil the end of study, approximately week 78

Part B

Changes in platelet cell countsUp to 18 months

Part B

Incidence of treatment-emergent anti-drug antibody (ADA) over timeUp to 12 months

Part A

ORRAt 3 months, approximately 12 weeks

Parts A and B

Platelet transfusions per month over timeUp to 18 months

Part B

Changes in the whole blood immune cell subsets (T cells)Up to 18 months

Part B

Changes in the whole blood immune cell subsets (B cells)Up to 18 months

Part B

Changes in the whole blood immune cell subsets (NK cells)Up to 18 months

Part B

Partial response (PR)At 3 months, approximately 12 weeks

Parts A and B

Time to first responseUp to 18 months

Part B

Red blood cell transfusions per month over timeUp to 18 months

Part B

Changes in reticulocyte cell countsUp to 18 months

Part B

Changes in the whole blood immune cell subsets [Natural killer (NK) cells]Up to 12 months

Part A

Complete response (CR)At 3 months, approximately 12 weeks

Parts A and B

Changes in neutrophil cell countsUp to 18 months

Part B

Changes in hemoglobin cell countsUp to 18 months

Part B

Changes in lymphocyte cell countsUp to 18 months

Part B

Drug concentrations in serum over timeUp to 18 months

Part B

Incidence of treatment-emergent ADA over timeUp to 18 months

Part B

Trial Locations

Locations (10)

Cleveland Clinic Foundation

🇺🇸

Cleveland, Ohio, United States

The University of Texas MD Anderson Cancer Center

🇺🇸

Houston, Texas, United States

Hopital Saint-Louis - APHP

🇫🇷

Paris, Ile-de-France, France

Gachon University Gil Hospital

🇰🇷

Incheon, Gyeonggi, Korea, Republic of

Seoul National University Hospital

🇰🇷

Seoul, Seoul Capital Area, Korea, Republic of

Samsung Medical Center

🇰🇷

Seoul, Seoul Capital Area, Korea, Republic of

The Catholic University of Korea, Seoul St. Marys Hospital

🇰🇷

Seoul, Seoul Capital Area, Korea, Republic of

Ewha Womans University Medical Centre

🇰🇷

Seoul, Seoul Capital Area, Korea, Republic of

St James's University Hospital

🇬🇧

Leeds, West Yorkshire, United Kingdom

King's College Hospital, London

🇬🇧

London, United Kingdom

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