A Study to Test the Safety, Tolerability, and Efficacy of an Antibody, REGN7999, Injected Under the Skin for the Treatment of Iron Overload in Adult Participants With Non-Transfusion Dependent β-thalassemia, Using MRI Scans to Measure Iron Levels in the Body (FERVENT-1)

A PHASE 2, TWO-PART, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTICENTER STUDY TO EVALUATE THE EFFICACY, SAFETY, AND TOLERABILITY OF SUBCUTANEOUSLY ADMINISTERED REGN7999 (AN INHIBITOR OF TMPRSS6) IN PARTICIPANTS WITH IRON OVERLOAD DUE TO NON-TRANSFUSION DEPENDENT β-THALASSEMIA

This study is researching an experimental drug called REGN7999 (called "study drug"). The study is focused on patients with non-transfusion dependent beta-thalassemia. The aim of the study is to see how safe and effective the study drug is.

The study is looking at several other research questions, including:

• Whether the study drug lowers extra iron levels in the body
• What side effects may happen from taking the study drug
• How much study drug is in the blood at different times
• Whether the body makes antibodies against the study drug (which could make the drug less effective or could lead to side effects)

Study Overview

• Status: Recruiting
• Conditions: Non-Transfusion Dependent Beta-Thalassemia (NTDT)
• Intervention / Treatment: Drug: Placebo; Drug: REGN7999

• Study Type: Interventional
• Enrollment (Estimated): 95
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Clinical Trials Administrator; Phone Number: 844-734-6643; Email: clinicaltrials@regeneron.com

Study Locations

• Georgia
  • Tbilisi, Georgia, 0159
    • Recruiting
    • K Eristavi National Center of Experimental and Clinical Surgery
  • Tbilisi, Georgia, 0160
    • Recruiting
    • Medinvest Institute of Hematology and Transfusiology Limited
• Greece
  • Ioannina, Greece, 45110
    • Recruiting
    • University Hospital of Ioannina
  • Attica
    • Athens, Attica, Greece, 11527
      • Recruiting
      • Laiko General Hospital of Athens
    • Athens, Attica, Greece, 11521
      • Recruiting
      • Children's Hospital Agia Sophia
• India
  • Gujarat
    • Ahmedabad, Gujarat, India, 380009
      • Recruiting
      • Hemato-Oncology Clinic Ahmedabad PVT. LTD.
    • Surat, Gujarat, India, 395002
      • Recruiting
      • Nirmal Hospital Pvt. Ltd - Surat
  • Kerala
    • Kochi, Kerala, India, 682041
      • Recruiting
      • Amrita Institute of Medical Sciences and Research Centre (AIMS)
  • Maharashtra
    • Mumbai, Maharashtra, India, 400022
      • Recruiting
      • K J Somaiya Super Specialty Hospital & Research Centre
  • National Capital Territory of Delhi
    • New Delhi, National Capital Territory of Delhi, India, 110029
      • Recruiting
      • All India Institute of Medical Sciences, New Delhi
    • New Delhi, National Capital Territory of Delhi, India, 110048
      • Recruiting
      • Indraprastha Apollo Hospitals
  • Rajasthan
    • Jaipur, Rajasthan, India, 302004
      • Recruiting
      • JK Lon Hospital
• Italy
  • Ferrara, Italy, 44124
    • Recruiting
    • Day Hospital Thalassemia and Haemoglobinopathies (DHTE); A.O.U S.Anna
• Malaysia
  • Kuala Lumpur, Malaysia, 56000
    • Recruiting
    • Hospital Tunku Ampuan Besar Tuanku Aishah Rohani (HPKK UKM)
  • Sabah
    • Kota Kinabalu, Sabah, Malaysia, 88586
      • Recruiting
      • Hospital Queen Elizabeth
  • Sarawak
    • Kuching, Sarawak, Malaysia, 93586
      • Recruiting
      • Sarawak General Hospital
  • Selangor
    • Ampang, Selangor, Malaysia, 68000
      • Recruiting
      • Hospital Ampang
• Thailand
  • Bangkok, Thailand, 10400
    • Recruiting
    • Phramongkutklao Hospital
  • Bangkok, Thailand, 10330
    • Recruiting
    • Chulalongkorn University
  • Chiang Mai, Thailand, 50200
    • Recruiting
    • Chiang Mai University
  • Khon Kaen, Thailand, 40000
    • Recruiting
    • Srinagarind Hospital
  • Changwat Songkhla
    • Hat Yai, Changwat Songkhla, Thailand, 90110
      • Recruiting
      • Songklanagarind Hospital, Prince of Songkla University
• Turkey (Türkiye)
  • Ankara, Turkey (Türkiye), 06100
    • Recruiting
    • Hacettepe University
• United Kingdom
  • London, United Kingdom, W12 0HS
    • Recruiting
    • Imperial College Healthcare NHS Trust
  • London, United Kingdom, NW1 2PG
    • Recruiting
    • University College London Hospitals NHS Trust
• United States
  • New York
    • New York, New York, United States, 10065
      • Recruiting
      • Weill Cornell Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. Clinical diagnosis of NTDT as described in the protocol
2. IOL, defined as LIC ≥ 5 mg Fe/g DW as measured by R2* MRI at screening
3. Serum ferritin ≥ 300 ng/mL as described in the protocol

Key Exclusion Criteria:

1. Hemoglobin ≤ 8 g/dL at screening
2. Any RBC transfusion within 12 weeks of visit 3
3. For Part A only: Any Iron Chelation Therapy (ICT) use in approximately 12 weeks prior to screening as described in the protocol
4. For Part B only: If on ICT, any change in ICT dose in approximately 12 weeks prior to screening as described in the protocol
5. Any use of luspatercept or mitapivat in 6 months prior to screening as described in the protocol
6. Absolute contraindication to MRI
7. Diagnosis of cirrhosis of the liver
8. Diagnosis of Chronic kidney disease (CKD) stage 4 or higher

Note: Other protocol-defined Inclusion/ Exclusion Criteria apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A High Dose; Randomized 2:2:1	Drug: REGN7999; Administered subcutaneous (SC)
Experimental: Part A Low Dose; Randomized 2:2:1	Drug: REGN7999; Administered subcutaneous (SC)
Placebo Comparator: Part A Placebo; Randomized 2:2:1	Drug: Placebo; Administered SC
Experimental: Part B High Dose; Randomized 2:2:1	Drug: REGN7999; Administered subcutaneous (SC)
Experimental: Part B Low Dose; Randomized 2:2:1	Drug: REGN7999; Administered subcutaneous (SC)
Placebo Comparator: Part B Placebo; Randomized 2:2:1	Drug: Placebo; Administered SC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in Liver Iron Concentration (LIC) by R2* Magnetic Resonance Imaging (MRI)	At week 24
Incidence of Treatment-Emergent Adverse Events (TEAEs)	Up to week 72
Severity of TEAEs	Up to week 72

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in hemoglobin over time	Up to week 56
Number of RBC transfusions required	Baseline to week 72
Achievement of transfusion independence	Baseline to week 72
Change in RBC counts over time	Baseline to week 56
Concentrations of REGN7999 in serum over time	Up to week 56
Achievement of ≥20% reduction from baseline in LIC by R2* MRI	Through week 52
Change from baseline in hemoglobin	To week 24
Change from baseline in LIC by R2* MRI	At week 52
Percent change from baseline in LIC by R2* MRI	To week 24 and week 52
Achievement of ≥20% reduction from baseline in LIC by R2* MRI	Through week 24
Achievement of ≥1.5 g/dL increase in hemoglobin for two consecutive assessments in the absence of Red Blood Cell (RBC) transfusions	Baseline to week 56
Incidence of Anti-Drug Antibody (ADA) to REGN7999 over time	Up to week 56
Magnitude of ADA to REGN7999 over time	Up to week 56

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals
• Investigators: Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2024
• Primary Completion (Estimated): January 24, 2028
• Study Completion (Estimated): January 24, 2028

Study Registration Dates

• First Submitted: May 14, 2024
• First Submitted That Met QC Criteria: May 14, 2024
• First Posted (Actual): May 20, 2024

Study Record Updates

• Last Update Posted (Actual): March 18, 2026
• Last Update Submitted That Met QC Criteria: March 16, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Beta-Thalassemia; Resultant Iron Overload (IOL)
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemoglobinopathies; Thalassemia; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemic and Lymphatic Diseases; beta-Thalassemia; Substandard Drugs; Pharmaceutical Preparations; Counterfeit Drugs
• Other Study ID Numbers: R7999-BThal-2350; 2023-508604-37-00 (Ctis: EU CT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing.

IPD Sharing Time Frame

When Regeneron has:

• received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc.) for the product and indication or has globally discontinued development of the product for all indications on or after April 2020 and has no plans for future development
• made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry)
• the legal authority to share the data, and
• ensured the ability to protect participant privacy

• IPD Sharing Access Criteria: Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No