Celldex CDX0159-09

03 Sep Celldex CDX0159-09

The purpose of this research study is to test barzolvolimab (also known as CDX-0159) and to understand the following in approximately 10 healthy male volunteers:

• If it stops or slows down the way your body makes new sperm cells and how quickly this occurs
• If and how fast new sperm cells start being made again after study drug is stopped

This study is being conducted due to observations from male monkey testing, where high doses of barzolvolimab (study drug) resulted in a significant decrease in sperm count, which fully recovered within 12 months after discontinuing barzolvolimab.

If you are 40 years of age or older, no longer planning on having any future children naturally, and have passed a medical evaluation, you may be able to participate in this study.

Participant Eligibility

INCLUSION:
1. Read, understood, and provided written informed consent, and Health Insurance Portability
and Accountability Act (HIPAA) authorization
2. Healthy male ≥ 40 years of age at the time of signing the informed consent, who have affirmed
that they do not wish to have children at any time in the future and are in generally good health
and without significant medical conditions, based upon medical history, physical examination,
vital signs, electrocardiogram (ECG), and laboratory tests.
4. Normal spermatogenesis, as assessed by normal sperm counts, concentrations, motility and
morphology (in accordance with accepted 5th percentile values of the sixth edition of the WHO
reference value) as measured by semen analysis on two occasions separated by 1 week, as
follows:
– Sperm concentration ≥ 15 million/mL
– Total sperm ≥ 35 million per ejaculate
– Semen volume ≥ 1.3 mL
– Total sperm motility ≥ 40%
– Normal forms ≥ 3.9
4. Hemoglobin, white blood count (WBC), absolute neutrophil count (ANC), and platelets above
the lower limit of normal (LLN) and less than 1.5 X the upper limit of normal (ULN) provided
the values between ULN and 1.5 X ULN are deemed to be not clinically significant by the
investigator, at the Screening Visit*.
5. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) each ≤ 2 x ULN, and
total bilirubin ≤ ULN (unless elevated bilirubin is related to Gilbert’s Syndrome), at the
Screening Visit*.
NOTE* For 4 and 5 above, if test results do not meet the above criteria, one repeat test may be
performed to establish eligibility.
6. Must agree that while participating in the study through End of Study and at least 5 months
post last dose, will use highly effective methods of contraception with female partners of
childbearing potential, and will not donate sperm.
7. Willing and able to comply with all study requirements and procedures.

EXCLUSION:
1. Known genetic infertility (e.g., Klinefelter syndrome or Y-chromosome microdeletions).
2. Hypogonadotropic hypogonadism.
3. Receipt of a live vaccine within 2 months prior to the Baseline (Day 1) Visit (participants must
agree to avoid live vaccination during study treatment and within 3 months thereafter).
Examples of live vaccines include, but are not limited to, the following: measles, mumps,
rubella, varicella-zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG),
and typhoid vaccine. Seasonal influenza vaccines for injection are generally inactivated virus
vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live
attenuated vaccines and are not allowed. Currently authorized COVID-19 vaccines are
allowed.
4. Planned or anticipated use of any prohibited medications during screening, Open Label
Treatment Phase, and Post Treatment Phase. These include use of sex hormones for treatment,
testosterone, anabolic steroids, retinoic acid (e.g., Accutane®), vitamin A, other drugs known
to inhibit spermatogenesis, opioids, cocaine, methamphetamine, and/or the consumption of >4
alcoholic beverages daily.
5. History of idiopathic anaphylaxis or other severe allergic reactions that in the opinion of the
investigator, could increase the participant’s risk for systemic hypersensitivity reactions; or any
known contraindications or hypersensitivity to any component of study treatments, or drugs of
similar chemical classes (i.e., to murine, chimeric or human antibodies).
6. Severe or uncontrolled chronic diseases (e.g., chronic hepatic or renal disease, diabetes
mellitus) that might interfere with the evaluation of the clinical effect or safety of study
treatment.
7. Participants with moderate-to-severe pulmonary or cardiovascular diseases (see Appendix 5
for guidelines). Note: participants with symptomatic cardiovascular or pulmonary disease that
requires medication should be carefully assessed and discussed with the medical monitor to
assure their cardiovascular and/or pulmonary status does not increase their risk of study
participation.
8. Participants with contraindications for use of epinephrine (e.g., history of closed angle
glaucoma, significant arrhythmias, myocardial infarction, or cardiomyopathy) or are taking
medications that might interfere with the pharmacodynamic actions of epinephrine (e.g., beta
blockers).
9. Known active hepatitis B, hepatitis C, human immunodeficiency virus (HIV), or COVID-19
infection.
10. History of malignancy within 5 years before the Screening Visit, except fully treated and
resolved non-metastatic squamous or basal cell carcinoma of the skin.
11. Other screening laboratory or electrocardiogram (ECG) findings that are considered clinically
significant.
12. Known active chronic or acute infection requiring treatment with systemic antibiotics,
antivirals, antifungals, antiparasitics or antiprotozoals during the Screening period.
13. Score of > 15 on the Patient Health Questionnaire-9 (PHQ-9).
14. Any other acute or chronic medical or psychiatric condition or laboratory abnormality that
could increase the risk associated with study participation in the judgment of the investigator,
would make the participant inappropriate for entry into the study.
15. Procedures requiring general or epidural anesthesia within 4 weeks prior to study treatment,
minor procedures (e.g., dental) within 14 days prior to study treatment, or anticipation of
procedures requiring general anesthesia during study participation.
16. Prior receipt of barzolvolimab.
17. Participation in another investigational clinical trial within the last 90 days or within 5 halflives
of investigational product, whichever is longer, prior to Screening Visit 1.
18. Participants who live in detention on court order or on regulatory action.
19. Sponsor or contract research organization (CRO) staff directly involved in the conduct of the
study, site staff supervised by the investigator, and their respective family members.

Contact

Kathy Winter
(206) 616-0484