This study is NOT currently recruiting participants.
Number
000310-CH
Sponsoring Institute
National Institute of Child Health and Human Development (NICHD)
Recruitment Detail
Type: No longer recruiting/follow-up only Gender: Male & Female Min Age: 18 Years Max Age: 99 Years
Referral Letter Required
No
Population Exclusion(s)
Children
Keywords
Excess Androgens; Glucocorticoid; 17-Ohp; Androstendione
Recruitment Keyword(s)
None
Condition(s)
Congenital Adrenal Hyperplasia; Adrenal Insufficiency
Investigational Drug(s)
BBP-631
Investigational Device(s)
Intervention(s)
Biological/Vaccine: BBP-631
Supporting Site
National Institute of Child Health and Human Development
Congenital adrenal hyperplasia (CAH) is an inherited disease that affects the adrenal glands. People with CAH do not have a working copy of a specific gene, so their bodies cannot produce certain hormones. They must take steroid medications throughout their life. Therapy that gives these people a working copy of the missing or defective gene may help.
Objective:
To test a gene therapy product (BBP-631) in people with severe CAH.
Eligibility:
People aged 18 years or older diagnosed with severe CAH.
Design:
This study will last 14 to 15 months. Participants will then be expected to join a follow-up study that will last 4 years.
A screening period will take up to 6 weeks. Participants will have a complete physical exam. They will provide blood and urine samples. They will have a test to measure their heart function.
To receive gene therapy, participants will stay overnight in the NIH clinic a total of 5 nights in a row. They will receive BBP-631 through a tube attached to a needle placed in a vein in the arm. The treatment may take up to 5 hours. This is the only time participants will receive BBP-631.
For the remainder of the study, participants will have additional visits including:
2 more 4-night stays in the NIH clinic
Up to 6 more 1-night stays in the NIH clinic
12 visits of 2 to 3 hours. These visits may be either in-home or at the NIH clinic.
Participants will have blood drawn during all of these visits.
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INCLUSION CRITERIA: A participant must meet all of the following criteria to be eligible for this study: 1. Is a male or female 18 years of age and older, inclusive. 2. Is able to understand and provide informed consent. 3. Has stable health in the opinion of the Investigator and as confirmed by medical history, which includes (but is not limited to) no acute hematologic, renal, neurologic, liver, or psychiatric disease within 1 year (12 months) of the first Eligibility visit during Screening. 4. Has CAH diagnosis: a. Group 1: Diagnosis of classic CAH (simple virilizing or salt-wasting) due to 21-OHD since childhood based on documented mutations in the CYP21A2 gene and clinical evidence including CAH historical data (ie, medical history, longitudinal laboratory values, and medication history) b. Group 2: Diagnosis of classic, salt-wasting CAH due to 21-OHD since childhood based on documented mutations in the CYP21A2 gene and clinical evidence including CAH historical data (ie, medical history, longitudinal laboratory values, and medication history) 5. Meets threshold 17-OHP levels during Screening (with upper limit of the normal range [ULN] based on gender and menopausal status): a. Group 1: 17-OHP levels >= 10 x ULN b. Group 2: 17-OHP levels >= 5 x ULN 6. Has been on a stable regimen of oral hydrocortisone as the only glucocorticoid maintenance therapy for at least 30 days before the first Eligibility visit during Screening at the following total daily doses: a. Group 1: <= 30 mg/day hydrocortisone for treatment of CAH b. Group 2: > 30 mg/day hydrocortisone for treatment of CAH Note: Participants who do not meet this oral hydrocortisone requirement will not have HPA-axis hormones measured as part of Screening until this 1-month requirement is met. 7. If already taking mineralocorticoid agonist therapy, then has a documented history of requiring mineralocorticoid agonist therapy (eg, fludrocortisone) and on stable dose of this mineralocorticoid agonist for at least one month before the first Eligibility visit during Screening. 8. Is up to date on all immunizations according to geographically applicable guidelines (eg, Centers for Disease Control, World Health Organization) and the participant s consent to administration of standard as well as study-specific immunizations as required over the course of the study. 9. For postmenopausal women on HRT, is willing to remain on a stable regimen of therapy for 12 months after treatment with BBP-631. For postmenopausal women not on HRT, willingness to remain off HRT for 12 months after treatment with BBP-631. 10. Is willing and able to participate in the study and to comply with all study requirements, including concomitant medication and other treatment restrictions. 11. Is willing to abstain from alcohol consumption for 12 months after treatment with BBP-631. 12. If a female participant of childbearing potential, then has a negative serum pregnancy test at Screening. Females of childbearing potential must be taking a stable oral contraceptive or using a contraceptive barrier method with a male sexual partner who is willing to use a condom and spermicide (if available). A female of childbearing potential is defined as a sexually mature woman who either: a. has had menses at any time in the preceding 24 consecutive months and has a Screening follicle stimulating hormone (FSH) level < 30 mIU/mL (30 IU/L) OR b. has not undergone a hysterectomy or bilateral oophorectomy 13. If the participant is a female who has been using an oral contraceptive for >= 3 months (ie, stable use), then the participant agrees to continue using the oral contraceptive for 12 months after treatment with BBP-631. 14. If the participant is a male with a female sexual partner who is of childbearing potential, then the couple is willing to use 2 highly effective methods of birth control for 12 months after treatment with BBP-631. The 2 forms of birth control authorized are defined as the use of a barrier method of contraception (condom and spermicide [if available]) in association with one of the methods of birth control listed in Inclusion Criterion 12. 15. If the participant is a sexually active male or female, then the participant is willing to use a barrier method of contraception during any sexual contact involving penetration or fluid exchange until vector shedding plateaus (ie, 3 consecutive measurements that are below the limit of detection of the assay). EXCLUSION CRITERIA: A participant who meets any of the following criteria will be excluded from this study: 1. Is a female participant who is pregnant, lactating, breastfeeding, or planning to become pregnant within 12 months after treatment with BBP-631 or before vector shedding plateaus (ie, 3 consecutive measurements that are below the limit of detection of the assay). 2. Has a body mass index (BMI) > 35 kg/m^2 3. Had prior treatment as follows: a. Participant received prior gene therapy or other treatment (including vaccination) with an adeno-associated virus (AAV) b. Participant received high-dose therapy with immunosuppressants within 1 year (12 months) of the first Eligibility visit during Screening (excluding glucocorticoids for replacement therapy for CAH and adrenal crises and prior chemotherapy related to malignancy treatment) 4. Has had an adrenalectomy 5. Tests positive for anti-AAV5 total antibodies (> 1:20) as determined by enzyme-linked immunosorbent assay within 6 weeks before dosing with BBP-631. 6. Has pre-existing auto-antibodies to 21-hydroxylase (21-OH) 7. Has a history of liver disease (including, but not limited to, cirrhosis, hepatic steatosis, and biliary disease) or active liver dysfunction as evidenced by the following laboratory test results anytime during the Screening Period: a. Alanine aminotransferase (ALT) > 1.5 x ULN b. Total bilirubin above ULN c. Alkaline phosphatase (ALP) > 1.5 x ULN NOTE: LFTs may be repeated during the Screening Period. 8. Is positive for presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, ie, coronavirus disease-2019 [COVID-19]) antigen. (A history of SARS-CoV-2 infection is not exclusionary as long as the participant had a full clinical recovery and 2 subsequent negative polymerase chain reaction [PCR] tests, which may include results from Screening.) 9. Is positive for current or past presence of human immunodeficiency virus type 1 or 2 (HIV-1 and HIV-2), hepatitis B or C, or tuberculosis. 10. Has a history of invasive fungal or nontuberculous mycobacterial infection. 11. Has a history of malignancy within 5 years (60 months) of the first Eligibility visit during Screening. Note: An allowance for time may be made after discussion between the Investigator and Sponsor. 12. Is currently participating in a clinical study or completed another clinical study with an investigational drug or device within 30 days or 5 half-lives (whichever is longer) of the first Eligibility visit during Screening. 13. Has a current or past history of alcohol abuse. 14. Has a current or past medical condition or illness (ie, active infection, liver disease, or immunosuppressive disorder) that, in the opinion of the Investigator, would compromise their safety during the study or confound study results. 15. Is a female of childbearing potential with a history of pregnancy-induced hypertension. 16. Has a history of hypersensitivity to any of the excipients of BBP-631. 17. Has a history of hypersensitivity to tacrolimus or any excipients of tacrolimus. 18. Sentinel Participants Only: Has known null mutations of CYP21A2 on both alleles. 19. Group 1 Only: At any time during the Screening Period has cortisol levels >= 7 micrograms/dL (193.2 nmol/L) with concurrent ACTH levels >= 225 pg/mL (0.49 pmol/L) 20. Is unwilling to participate in the rigorous follow-up procedures required for evaluation of long-term safety, including a follow-up period of at least 5 years after the date of treatment with BBP-631.
A participant must meet all of the following criteria to be eligible for this study:
1. Is a male or female 18 years of age and older, inclusive.
2. Is able to understand and provide informed consent.
3. Has stable health in the opinion of the Investigator and as confirmed by medical history, which includes (but is not limited to) no acute hematologic, renal, neurologic, liver, or psychiatric disease within 1 year (12 months) of the first Eligibility visit during Screening.
4. Has CAH diagnosis:
a. Group 1: Diagnosis of classic CAH (simple virilizing or salt-wasting) due to 21-OHD since childhood based on documented mutations in the CYP21A2 gene and clinical evidence including CAH historical data (ie, medical history, longitudinal laboratory values, and medication history)
b. Group 2: Diagnosis of classic, salt-wasting CAH due to 21-OHD since childhood based on documented mutations in the CYP21A2 gene and clinical evidence including CAH historical data (ie, medical history, longitudinal laboratory values, and medication history)
5. Meets threshold 17-OHP levels during Screening (with upper limit of the normal range [ULN] based on gender and menopausal status):
a. Group 1: 17-OHP levels >= 10 x ULN
b. Group 2: 17-OHP levels >= 5 x ULN
6. Has been on a stable regimen of oral hydrocortisone as the only glucocorticoid maintenance therapy for at least 30 days before the first Eligibility visit during Screening at the following total daily doses:
a. Group 1: <= 30 mg/day hydrocortisone for treatment of CAH
b. Group 2: > 30 mg/day hydrocortisone for treatment of CAH
Note: Participants who do not meet this oral hydrocortisone requirement will not have HPA-axis hormones measured as part of Screening until this 1-month requirement is met.
7. If already taking mineralocorticoid agonist therapy, then has a documented history of requiring mineralocorticoid agonist therapy (eg, fludrocortisone) and on stable dose of this mineralocorticoid agonist for at least one month before the first Eligibility visit during Screening.
8. Is up to date on all immunizations according to geographically applicable guidelines (eg, Centers for Disease Control, World Health Organization) and the participant s consent to administration of standard as well as study-specific immunizations as required over the course of the study.
9. For postmenopausal women on HRT, is willing to remain on a stable regimen of therapy for 12 months after treatment with BBP-631. For postmenopausal women not on HRT, willingness to remain off HRT for 12 months after treatment with BBP-631.
10. Is willing and able to participate in the study and to comply with all study requirements, including concomitant medication and other treatment restrictions.
11. Is willing to abstain from alcohol consumption for 12 months after treatment with BBP-631.
12. If a female participant of childbearing potential, then has a negative serum pregnancy test at Screening. Females of childbearing potential must be taking a stable oral contraceptive or using a contraceptive barrier method with a male sexual partner who is willing to use a condom and spermicide (if available). A female of childbearing potential is defined as a sexually mature woman who either:
a. has had menses at any time in the preceding 24 consecutive months and has a Screening follicle stimulating hormone (FSH) level < 30 mIU/mL (30 IU/L)
OR
b. has not undergone a hysterectomy or bilateral oophorectomy
13. If the participant is a female who has been using an oral contraceptive for >= 3 months (ie, stable use), then the participant agrees to continue using the oral contraceptive for 12 months after treatment with BBP-631.
14. If the participant is a male with a female sexual partner who is of childbearing potential, then the couple is willing to use 2 highly effective methods of birth control for 12 months after treatment with BBP-631. The 2 forms of birth control authorized are defined as the use of a barrier method of contraception (condom and spermicide [if available]) in association with one of the methods of birth control listed in Inclusion Criterion 12.
15. If the participant is a sexually active male or female, then the participant is willing to use a barrier method of contraception during any sexual contact involving penetration or fluid exchange until vector shedding plateaus (ie, 3 consecutive measurements that are below the limit of detection of the assay).
EXCLUSION CRITERIA:
A participant who meets any of the following criteria will be excluded from this study:
1. Is a female participant who is pregnant, lactating, breastfeeding, or planning to become pregnant within 12 months after treatment with BBP-631 or before vector shedding plateaus (ie, 3 consecutive measurements that are below the limit of detection of the assay).
2. Has a body mass index (BMI) > 35 kg/m^2
3. Had prior treatment as follows:
a. Participant received prior gene therapy or other treatment (including vaccination) with an adeno-associated virus (AAV)
b. Participant received high-dose therapy with immunosuppressants within 1 year (12 months) of the first Eligibility visit during Screening (excluding glucocorticoids for replacement therapy for CAH and adrenal crises and prior chemotherapy related to malignancy treatment)
4. Has had an adrenalectomy
5. Tests positive for anti-AAV5 total antibodies (> 1:20) as determined by enzyme-linked immunosorbent assay within 6 weeks before dosing with BBP-631.
6. Has pre-existing auto-antibodies to 21-hydroxylase (21-OH)
7. Has a history of liver disease (including, but not limited to, cirrhosis, hepatic steatosis, and biliary disease) or active liver dysfunction as evidenced by the following laboratory test results anytime during the Screening Period:
a. Alanine aminotransferase (ALT) > 1.5 x ULN
b. Total bilirubin above ULN
c. Alkaline phosphatase (ALP) > 1.5 x ULN
NOTE: LFTs may be repeated during the Screening Period.
8. Is positive for presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, ie, coronavirus disease-2019 [COVID-19]) antigen. (A history of SARS-CoV-2 infection is not exclusionary as long as the participant had a full clinical recovery and 2 subsequent negative polymerase chain reaction [PCR] tests, which may include results from Screening.)
9. Is positive for current or past presence of human immunodeficiency virus type 1 or 2 (HIV-1 and HIV-2), hepatitis B or C, or tuberculosis.
10. Has a history of invasive fungal or nontuberculous mycobacterial infection.
11. Has a history of malignancy within 5 years (60 months) of the first Eligibility visit during Screening.
Note: An allowance for time may be made after discussion between the Investigator and Sponsor.
12. Is currently participating in a clinical study or completed another clinical study with an investigational drug or device within 30 days or 5 half-lives (whichever is longer) of the first Eligibility visit during Screening.
13. Has a current or past history of alcohol abuse.
14. Has a current or past medical condition or illness (ie, active infection, liver disease, or immunosuppressive disorder) that, in the opinion of the Investigator, would compromise their safety during the study or confound study results.
15. Is a female of childbearing potential with a history of pregnancy-induced hypertension.
16. Has a history of hypersensitivity to any of the excipients of BBP-631.
17. Has a history of hypersensitivity to tacrolimus or any excipients of tacrolimus.
18. Sentinel Participants Only: Has known null mutations of CYP21A2 on both alleles.
19. Group 1 Only: At any time during the Screening Period has cortisol levels >= 7 micrograms/dL (193.2 nmol/L) with concurrent ACTH levels >= 225 pg/mL (0.49 pmol/L)
20. Is unwilling to participate in the rigorous follow-up procedures required for evaluation of long-term safety, including a follow-up period of at least 5 years after the date of treatment with BBP-631.
Principal Investigator
Referral Contact
For more information: