XVIE to Treat Androgenetic Alopecia (AGA)

This Phase I/II randomized, double-blind, placebo-controlled trial evaluates the safety and preliminary efficacy of XVIE (decellularized allogeneic human amniotic fluid) administered via intradermal scalp injection in adults with androgenetic alopecia (AGA).

XVIE is manufactured by Nova Vita Laboratories, LLC under cGMP-aligned conditions. It contains naturally occurring soluble proteins, extracellular vesicles (nanoparticles 50-200 nm), and hyaluronic acid derived from full-term human amniotic fluid. Cellular components are removed by centrifugation and sterile filtration. Each lot is released against a 7-parameter specification panel including nanoparticle concentration, size, total protein, sterility, endotoxin, mycoplasma, and appearance.

Thirty adults (ages 18-70) with AGA will be randomized 1:1 to XVIE or placebo (0.9% saline). Both are supplied in identical 2.0 mL vials. Treatment is administered intradermally across 20 scalp injection sites (0.1 mL per site, 4-5 mm depth, 30-gauge needle) at Day 0 and Day 90. Final assessment occurs at Day 180 with no treatment administered.

Safety assessments include incidence, severity, and relatedness of treatment-emergent adverse events (TE-AEs) and serious adverse events (TE-SAEs), graded per CTCAE v5.0. Adverse events of special interest include scalp-specific events such as new-onset alopecia in previously unaffected areas, a decrease of 15% or greater in Total Area Hair Count within the injection zone, and scarring alopecia not consistent with natural AGA progression.

Efficacy assessments include Total Area Hair Count and hair density measured by Canfield HairMetrix imaging, global scalp coverage by SoCAI Global HairMap, Investigator and Subject Global Assessments (7-point scale), and quality of life via the Dermatology Life Quality Index (DLQI).

Male subjects must be Norwood-Hamilton Stage III-IVa; female subjects must be Ludwig Stage I-II. The study is conducted at two U.S. clinical sites: Advanced Dermatology and Cosmetic Surgery in Orlando, FL and Kindred Hair & Skin Center in Marriottsville, MD.

An independent Data Safety Monitoring Board (DSMB) will oversee participant safety throughout the trial. Enrollment will not begin until the DSMB is fully constituted and the DSMB Charter has been executed.

Inclusion criteria

• Male or female, aged 18 to 70 years (inclusive) at the time of informed consent
• Able to understand and voluntarily provide written informed consent
• Willing and able to comply with study procedures, including all scheduled visits and assessments
• In good general health as determined by the Investigator based on medical history and screening assessments
• Clinical diagnosis of androgenetic alopecia (AGA) with documented hair loss for at least 6 months prior to screening
• Stable pattern of hair loss (no rapid progression) for at least 6 months prior to screening
• Male subjects: Norwood-Hamilton Classification Stage III, IIIa, IIIv, IV, or IVa
• Female subjects: Ludwig Classification Stage I or II
• Normal thyroid function (TSH within normal limits) at screening, or stable on thyroid replacement therapy for at least 6 months
• Ferritin level within normal limits at screening, or documented adequate iron stores
• No clinically significant abnormalities on CBC with differential or comprehensive metabolic panel (CMP) at screening outside protocol-defined eligibility thresholds
• Female subjects of childbearing potential must have a negative urine pregnancy test at screening and agree to use an effective method of contraception throughout the study and for 30 days after the last treatment
• Female subjects who are postmenopausal (no menses for at least 12 months) or surgically sterile are not required to use contraception

Exclusion criteria

• Use of topical or oral minoxidil within 3 months prior to screening
• Use of oral finasteride or dutasteride within 6 months prior to screening
• Use of topical finasteride within 3 months prior to screening
• Platelet-rich plasma (PRP), exosome, or other regenerative scalp injections within 6 months prior to screening
• Hair transplant surgery within 12 months prior to screening
• Low-level laser therapy (LLLT) or other light-based hair treatments within 3 months prior to screening
• Scalp microneedling within 3 months prior to screening
• Use of drugs with anti-androgenic properties (e.g., spironolactone, cyproterone acetate, flutamide) within 6 months prior to screening
• Systemic corticosteroids within 2 weeks prior to screening, or corticosteroid scalp injections within 1 month prior to screening
• Chronic daily NSAID use (defined as daily use for 14 or more consecutive days), other than low-dose aspirin (81 mg/day or less) for cardiovascular prophylaxis
• Diagnosis or history of alopecia areata, cicatricial (scarring) alopecia, telogen effluvium, traction alopecia, or other non-AGA hair loss conditions
• Norwood-Hamilton Stage V, VI, or VII (male subjects); Ludwig Stage III (female subjects)
• Active or history of malignancy within 5 years prior to screening, except adequately treated non-melanoma skin cancer or carcinoma in situ of the cervix
• Known or suspected autoimmune disease (e.g., lupus, rheumatoid arthritis, psoriasis with scalp involvement)
• Known or newly identified immunodeficiency or immunocompromised state, including HIV infection identified at screening
• Positive for hepatitis B surface antigen (HBsAg) or hepatitis C antibody (anti-HCV) at screening
• Platelet count less than 100,000/µL, bleeding disorder, or hemoglobin less than 10 g/dL at screening
• Current use of anticoagulant therapy (e.g., warfarin, heparin, direct oral anticoagulants), P2Y12 receptor inhibitors (e.g., clopidogrel, prasugrel, ticagrelor), phosphodiesterase inhibitor antiplatelet agents (e.g., cilostazol, dipyridamole), or dual antiplatelet therapy
• Uncontrolled thyroid disease or thyroid dysfunction not adequately managed on stable therapy
• Uncontrolled diabetes (HbA1c greater than 9%) or other significant metabolic disorder
• Active scalp infection, inflammation, or dermatological condition in the treatment area
• Open wounds, abrasions, or abnormalities on the scalp in the intended treatment area
• History of keloid formation or propensity for keloids
• Hair weaving or use of hair pieces that cannot be removed for study assessments
• Known hypersensitivity or allergy to any component of XVIE or human-derived biological products
• Known allergy to lidocaine or other local anesthetics
• Women who are pregnant, breastfeeding, or planning to become pregnant during the study period
• Positive urine pregnancy test at screening or Day 0
• Participation in another interventional clinical trial within 30 days prior to screening or concurrent participation in another clinical study
• History of drug or alcohol abuse within 12 months prior to screening
• Use of systemic immunosuppressive therapy within 5 half-lives or 30 days prior to screening, whichever is longer, including biologic agents, conventional DMARDs, JAK inhibitors, and calcineurin inhibitors
• Use of topical JAK inhibitors applied to the scalp within 30 days prior to screening
• Any condition that, in the Investigator's judgment, would make the subject unsuitable for study participation