A Trial to Learn if REGN7999 is Safe and Well Tolerated, and How it Works in the Body of Healthy Participants

Study Overview
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Brief Summary
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The primary objective of the study is to evaluate the safety and tolerability of single ascending intravenous (IV) and subcutaneous (SC) doses of REGN7999 in healthy adult participants. The secondary objectives of the study are: To characterize the drug concentration profile of single doses of IV or SC REGN7999 To assess the immunogenicity of single ascending SC or IV doses of REGN7999

Official Title
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A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single Center Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Ascending Doses of REGN7999, a TMPRSS6 Antagonist, in Healthy Adult Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: REGN7999
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Has a body mass index between 18 and 32 kg/m2, inclusive Is judged by the investigator to be in good health based on medical history, physical examination, vital sign measurements, and electrocardiogram (ECG)s performed at screening and/or prior to administration of initial dose of study drug Is in good health based on laboratory safety testing obtained at the screening and baseline visits per the protocol Hemoglobin, serum iron, transferrin, serum ferritin, and transferrin saturation, equal to or above the lower limit of the reference range for the participant's age and sex at the local labs, at screening, repeatable once during screening period White blood cell (WBC) count, platelet count, red blood cell (RBC) count, hematocrit, and RBC hemoglobin not clinically significantly outside of the reference range in the judgment of the investigator at screening and baseline visits Key Exclusion Criteria: Pregnant or breastfeeding women Consistent with Clinical Trial Facilitation Group (CTFG) guidance, women of childbearing potential (WOCBP) who are unwilling to practice highly effective contraception, during the study through the end of study (EOS) visit. Highly effective contraceptive measures include: stable use of combined (estrogen and progestogen containing) hormonal contraception (oral, intravaginal, transdermal) or progestogen-only hormonal contraception (oral, injectable, implantable) associated with inhibition of ovulation initiated 2 or more menstrual cycles prior to screening; intra-uterine device (IUD); intra-uterine hormone-releasing system; bilateral tubal ligation or tubal occlusion; vasectomized partner (provided that the male vasectomized partner is the sole sexual partner of the WOCBP study participant and that the vasectomized partner has obtained medical assessment of surgical success for the procedure); and/or sexual abstinence as described in the protocol In addition, premenopausal women whose method(s) of birth control is/are associated with ongoing menstruation (eg, combined hormonal contraceptive regimens associated with withdrawal bleeding, non-hormone-releasing IUD, bilateral tubal ligation, bilateral salpingectomy, vasectomized partner, sexual abstinence). Female participants must not be menstruating during the trial, due to being postmenopausal or due to permanent sterilization via hysterectomy, and/or bilateral oophorectomy, or amenorrheic due to use of hormone-releasing IUD, implantable device, or intake of continuous hormonal contraception Sexually active male participants with WOCBP partners who are unwilling to use the following forms of medically acceptable birth control during the study through the EOS visit: vasectomy with medical assessment of surgical success OR consistent use of a condom History of clinically significant cardiovascular (including congestive heart failure and angina), respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, infectious, autoimmune, oncologic, psychiatric or neurological disease, as assessed by the investigator, that may confound the results of the study or poses an additional risk to the participant by study participation. History of chronic anemia, at any time in the past History of RBC transfusion reaction Whole blood donation within the previous 56 days or plasma donation within the previous 7 days prior to screening. Planning on whole blood or plasma donation at any time point during the study. Has a history of significant multiple and/or severe allergies (eg, latex gloves), or has had an anaphylactic reaction to prescription or nonprescription drugs or food Note: Other protocol-defined Inclusion and Exclusion Criteria apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IV Cohort 1<br>Single dose REGN7999 or Placebo; randomized 3:1 | Drug: REGN7999<br>* Ascending IV or SC dose administered per protocol<br>Drug: Placebo<br>* Ascending IV or SC dose administered per protocol<br>|
| Experimental: IV Cohort 2<br>Single dose REGN7999 or Placebo; randomized 3:1 | Drug: REGN7999<br>* Ascending IV or SC dose administered per protocol<br>Drug: Placebo<br>* Ascending IV or SC dose administered per protocol<br>|
| Experimental: IV Cohort 3<br>Single dose REGN7999 or Placebo; randomized 3:1 | Drug: REGN7999<br>* Ascending IV or SC dose administered per protocol<br>Drug: Placebo<br>* Ascending IV or SC dose administered per protocol<br>|
| Experimental: IV Cohort 4<br>Single dose REGN7999 or Placebo; randomized 3:1 | Drug: REGN7999<br>* Ascending IV or SC dose administered per protocol<br>Drug: Placebo<br>* Ascending IV or SC dose administered per protocol<br>|
| Experimental: IV Cohort 5<br>Single dose REGN7999 or Placebo; randomized 3:1 | Drug: REGN7999<br>* Ascending IV or SC dose administered per protocol<br>Drug: Placebo<br>* Ascending IV or SC dose administered per protocol<br>|
| Experimental: SC Cohort 1<br>Single dose REGN7999 or Placebo; randomized 3:1 | Drug: REGN7999<br>* Ascending IV or SC dose administered per protocol<br>Drug: Placebo<br>* Ascending IV or SC dose administered per protocol<br>|
| Experimental: SC Cohort 2<br>Single dose REGN7999 or Placebo; randomized 3:1 | Drug: REGN7999<br>* Ascending IV or SC dose administered per protocol<br>Drug: Placebo<br>* Ascending IV or SC dose administered per protocol<br>|
| Experimental: SC Cohort 3<br>Single dose REGN7999 or Placebo; randomized 3:1 | Drug: REGN7999<br>* Ascending IV or SC dose administered per protocol<br>Drug: Placebo<br>* Ascending IV or SC dose administered per protocol<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of treatment emergent adverse events (TEAEs) in participants treated with REGN7999 or placebo | IV cohorts 1 to 4 SC cohorts 1 and 2 | Through the end of study visit, week 20 | 
| Incidence and severity of TEAEs in participants treated with REGN7999 or placebo | IV cohort 5 and SC cohort 3 | Through the end of study visit, week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentrations of REGN7999 in serum | IV cohorts 1 to 4 for SC cohorts 1 and 2 | Through the end of study visit, week 20 | 
| Concentrations of REGN7999 in serum | IV cohort 5 and SC cohort 3 | Through the end of study visit, week 26 | 
| Incidences of anti-drug antibodies (ADA) to REGN7999 over time | IV cohorts 1 to 4 for SC cohorts 1 and 2 | Through the end of study visit, week 20 | 
| Incidences of anti-drug antibodies (ADA) to REGN7999 over time | IV cohort 5 and SC cohort 3 | Through the end of study visit, week 26 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-menstruating, Transmembrane protease, serine 6 (TMPRSS6) antagonist, First in Human (FIH), Human monoclonal antibody (mAb)