A Study of Gene Therapy for Classic Congenital Adrenal Hyperplasia (CAH)

Study Overview
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Brief Summary
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This study is designed to evaluate the safety, tolerability, and efficacy of AAV5 based BBP-631 in adult participants diagnosed with classic congenital adrenal hyperplasia.

Detailed Description
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Participants will receive a single dose of AAV5 based intravenous (IV) BBP-631 and will be followed for safety and efficacy for at least 5 years after the date of treatment with BBP-631.

Official Title
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A Phase 1/2, First-in-Human, Open-Label, Dose-Escalation Study of the Safety and Efficacy of Gene Therapy for Congenital Adrenal Hyperplasia Through Administration of an Adeno-Associated Virus (AAV) Serotype 5-Based Recombinant Vector Encoding the Human CYP21A2 Gene

Conditions
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Congenital Adrenal Hyperplasia

Intervention / Treatment
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* Biological: AAV BBP-631


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria Adult male and non-pregnant females with classic CAH (simple virilizing or salt-wasting) due to 21-OHD Screening/baseline 17-OHP levels > 5-10 × ULN and < 40 × ULN (upper limit of normal) Stable oral hydrocortisone (HC) regimen as the only glucocorticoid (GC) maintenance therapy Naïve to prior gene therapy or AAV-mediated therapy Key Exclusion Criteria Positive for anti-AAV5 (Adeno-Associated Virus Type 5) antibodies History of adrenalectomy and/or significant liver disease

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Participants will be assigned sequentially to one of 3 dose levels depending on the date of determination of eligibility.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Level 1<br>BBP-631 lowest dose, administered once, intravenously (IV) | Biological: AAV BBP-631<br>* intravenous<br>|
| Experimental: Dose Level 2<br>BBP-631 middle dose, administered once, IV | Biological: AAV BBP-631<br>* intravenous<br>|
| Experimental: Dose Level 3<br>BBP-631, highest dose, administered once, IV | Biological: AAV BBP-631<br>* intravenous<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with Treatment-emergent Adverse Events that Led to Study Discontinuation |  | up to 3 years | 
| To select the optimum dose or dose range of BBP 631 for future studies |  | up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in 17-OHP (hydroxyprogesterone) levels |  | Baseline, Week 52 | 
| Change from Baseline in endogenous cortisol levels |  | Baseline, Week 52 | 
| Change from Baseline in androstenedione (A4) levels |  | Baseline, Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CAH, Gene therapy, AAV, AAV5