Gene Therapy for Congenital Adrenal Hyperplasia

Recruiting at 8 trial locations

Overseen By Patient Advocacy

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Adrenas Therapeutics Inc

Must be taking: Glucocorticoids

Disqualifiers: Anti-AAV5 antibodies, Adrenalectomy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 1 day

8 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires participants to be on a stable oral hydrocortisone regimen as their only glucocorticoid maintenance therapy. If you are taking other medications, you may need to adjust your treatment to meet this requirement.

What data supports the effectiveness of the treatment AAV BBP-631 for congenital adrenal hyperplasia?

Research shows that similar gene therapy using adeno-associated virus (AAV) vectors can temporarily restore normal hormone production in mice with congenital adrenal hyperplasia, although the effects may not last long without further modifications. ^{1 2 3 4 5}

Is gene therapy using AAV BBP-631 generally safe in humans?

Research on gene therapy using adeno-associated virus (AAV) vectors, like AAV BBP-631, has shown that it can temporarily restore normal function in mice with congenital adrenal hyperplasia without causing an immune response. However, the effects were short-lived, and more research is needed to ensure long-term safety and effectiveness in humans. ^{1 2 3 6 7}

How is the gene therapy AAV BBP-631 different from other treatments for congenital adrenal hyperplasia?

AAV BBP-631 is a gene therapy that uses a virus to deliver a functional copy of the mutated gene directly to the adrenal gland, aiming to restore normal hormone production. Unlike lifelong oral steroid treatments, this approach targets the root genetic cause of the condition, although its effects may be temporary due to the renewal of adrenal cells. ^{1 2 7 8 9}

What is the purpose of this trial?

This trial tests a new gene therapy called BBP-631, delivered by a virus through an IV, in adults with classic congenital adrenal hyperplasia. The goal is to see if it is safe and effective over several years. BBP-631 is a gene therapy delivered by a virus, similar to other gene therapies that have shown promise in treating adrenal disorders.

Eligibility Criteria

Adults with classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, who haven't had gene therapy before and are on a stable dose of hydrocortisone. Pregnant women, those with previous adrenalectomy or significant liver disease, or immunity against AAV5 cannot participate.

Inclusion Criteria

I have never received gene therapy or AAV-mediated therapy.

I am on a stable dose of oral hydrocortisone as my only steroid treatment.

Your 17-OHP levels are too high or too low during the screening test.

Exclusion Criteria

I have had surgery to remove my adrenal gland or have significant liver disease.

You have antibodies against the AAV5 virus.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of AAV5 based intravenous (IV) BBP-631

1 day

Follow-up

Participants are monitored for safety and efficacy for at least 5 years after treatment

5 years

Treatment Details

Interventions

• AAV BBP-631

Trial Overview The trial is testing the safety and effectiveness of a gene therapy called AAV BBP-631 in adults with CAH. It aims to see if this treatment can manage the condition better than current therapies.

Participant Groups

Group I: Dose Level 4 Experimental Treatment 1 Intervention

BBP-631, highest dose, administered once, IV

Group II: Dose Level 3 Experimental Treatment 1 Intervention

BBP-631, high dose, administered once, IV

Group III: Dose Level 2 Experimental Treatment 1 Intervention

BBP-631 middle dose, administered once, IV

Group IV: Dose Level 1 Experimental Treatment 1 Intervention

BBP-631 lowest dose, administered once, intravenously (IV)

Who Is Running the Clinical Trial?

Adrenas Therapeutics Inc

Lead Sponsor

Trials

2

Recruited

70+

Findings from Research

In a 6-month study involving 122 adult patients with congenital adrenal hyperplasia (CAH), modified-release hydrocortisone (MR-HC) showed improved biochemical control of androgen levels compared to standard glucocorticoid therapy, with a significant increase in the percentage of patients achieving controlled serum 17-hydroxyprogesterone levels.

MR-HC not only reduced the need for higher steroid doses over time but also led to positive patient-reported outcomes, including restoration of menstrual cycles and successful pregnancies, highlighting its potential benefits beyond just biochemical control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modified-Release Hydrocortisone in Congenital Adrenal Hyperplasia. Merke, DP., Mallappa, A., Arlt, W., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Biology of the Adrenal Gland Cortex Obviates Effective Use of Adeno-Associated Virus Vectors to Treat Hereditary Adrenal Disorders. [2019]

2. England pubmed.ncbi.nlm.nih.gov

Restoration of adrenal steroidogenesis by adenovirus-mediated transfer of human cytochromeP450 21-hydroxylase into the adrenal gland of21-hydroxylase-deficient mice. [2016]

3. England pubmed.ncbi.nlm.nih.gov

An AAVrh10-CAG-CYP21-HA vector allows persistent correction of 21-hydroxylase deficiency in a Cyp21-/- mouse model. [2018]

4. England pubmed.ncbi.nlm.nih.gov

Classic congenital adrenal hyperplasia and puberty. [2019]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Models of Congenital Adrenal Hyperplasia for Gene Therapies Testing. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Modified-Release Hydrocortisone in Congenital Adrenal Hyperplasia. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

A Phase 2 Study of Continuous Subcutaneous Hydrocortisone Infusion in Adults With Congenital Adrenal Hyperplasia. [2019]

8. Germany pubmed.ncbi.nlm.nih.gov

Continuous subcutaneous hydrocortisone infusion (CSHI) in a young adolescent with congenital adrenal hyperplasia (CAH). [2019]

9. England pubmed.ncbi.nlm.nih.gov

Glucocorticoid replacement regimens for treating congenital adrenal hyperplasia. [2022]