RECRUITING

Study of AT-02 in Healthy Volunteers and Subjects With Systemic Amyloidosis

Conditions

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This is a multicenter, international, three-part, Phase 1 study designed to evaluate the safety, tolerability, and PK of rising single doses of AT-02 in healthy volunteers and in subjects with systemic amyloidosis and to assess the safety, tolerability, and PK of multiple doses of AT-02 in subjects with systemic amyloidosis.

Official Title

A Three-part, Phase 1, Single-ascending, and Multiple-ascending Dose Escalation Study in Healthy Volunteers and Subjects With Systemic Amyloidosis to Assess the Safety, Tolerability, and Pharmacokinetics of AT-02

Quick Facts

Study Start:2022-09-01

Study Completion:2025-03-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05521022

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:Yes

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Understands the study procedures and can give signed informed consent 2. Male or female between \>18 and \<56 years of age. 3. Willing and able to comply with this protocol and informed consent and be available for the entire duration of the study. 4. Willing to abstain from alcohol and strenuous physical activity (i.e., strenuous or unaccustomed weightlifting, running, bicycling, etc.) from 48 hours prior to study treatment administration until discharge from the clinical unit and prior to each outpatient visit. 5. In good general health, determined by no clinically significant findings in the opinion of the Investigator from medical history, physical examination, 12-lead electrocardiogram (ECG), clinical laboratory findings, and vital signs at Screening and Phase 1 unit Check-in. 6. Has body mass index (BMI) of 18 to 32 kg/m2, inclusive. 7. Women of childbearing potential (WOCBP) 1. WOCBP must have a negative serum or urine pregnancy test within 24 hours prior to the start of study drug. 2. Must not be breastfeeding, lactating, or planning a pregnancy during the study period. 3. WOCBP who are not exclusively in same-sex relationships must agree to remain abstinent (complete avoidance of heterosexual intercourse) or use adequate contraceptive methods, defined as use of a condom by the male partner combined with use of a highly effective method of contraception by the female partner, during the treatment period and for at least 105 days after the last dose of study intervention. 8. Postmenopausal females: 9. Women of non-childbearing potential (WONCBP) and female participants with vasectomized male partners: 10. Male participants: 1. Male participants must inform their female sexual partners who are WOCBP of the contraceptive requirements of the protocol and are expected to adhere to using contraception with their partner. 2. Male participants with female sexual partners who are WOCBP must agree to remain abstinent (complete avoidance of heterosexual intercourse) or use adequate contraceptive methods, defined as use of a condom by the male partner combined with use of a highly effective method of contraception by the female partner, during the treatment period and for at least 165 days after the last dose of study intervention. 3. Male participants must not donate sperm for at least 165 days after the last dose of study intervention. 4. Male participants with potentially postmenopausal partners who are under the age of 55 years must use condoms unless their partner's postmenopausal status has been confirmed by FSH level. 5. Male participants in same-sex relationships or in relationships with WONCBP must agree to remain abstinent (complete avoidance of intercourse) or use a condom to prevent exposure of the partner to study intervention through ejaculate/seminal fluid during the treatment period and for at least 165 days after the last dose of study intervention. 1. Understands the study procedures and can give signed informed consent 2. Male or female ≥18 and ≤80 years of age. 3. Mini Mental Status Exam (MMSE) score \>27 (subjects \>55 years of age only). 4. Has a confirmed diagnosis of AL, ATTR, or other form of systemic amyloidosis, based on any one of the following: 1. A histologic confirmation with a biopsy containing deposits of apple-green birefringent, Congophilic material or other amyloid staining (i.e., thioflavin T or sulfated alcian blue) with confirmatory immunohistochemistry, mass spectrometry or identification of an amyloidogenic genetic variant; 2. Genetic screening with presence of amyloid-related pathology; or 3. Amyloid-specific imaging study (e.g., bone scintigraphy and echocardiogram/CMR consistent with ATTR cardiac amyloid). 5. Subjects with AL systemic amyloidosis must have achieved a hematologic very good partial response (VGPR) or complete response (CR) based on their most recent assessment (e.g., difference in free light chains \<40 mg/L) and within 12 months of Screening and may be receiving maintenance daratumumab. 6. Subjects with ATTR systemic amyloidosis may be receiving a TTR silencer (e.g., inotersen, vutrisiran, or patisiran) or a stabilizer (e.g., tafamadis or diflunisal), but not both. 7. Women of childbearing potential (WOCBP): 1. WOCBP must have a negative serum or urine pregnancy test within 24 hours prior to the start of study treatment. 2. Must not be breastfeeding, lactating, or planning a pregnancy during the study period. 3. WOCBP who are not exclusively in same-sex relationships must agree to remain abstinent (complete avoidance of heterosexual intercourse) or use adequate contraceptive methods, defined as use of a condom by the male partner combined with use of a highly effective method of contraception by the female partner, during the treatment period and for at least 105 days after the last dose of study intervention. 8. Women of non-childbearing potential (WONCBP), and female participants with vasectomized male partners: 1. WONCBP must agree to remain abstinent (complete avoidance of intercourse) or the male partners of WONCBP participants must wear a condom to protect against the transfer of study intervention through bodily fluids during the treatment period and for at least 105 days after the last dose of study intervention. 2. Postmenopausal females must have a documented serum FSH level \>40 mIU/mL at Screening to confirm menopause. 9. Male participants: 1. Male participants must inform their female sexual partners who are WOCBP of the contraceptive requirements of the protocol and are expected to adhere to using contraception with their partner. 2. Male participants with female sexual partners who are WOCBP must agree to remain abstinent (complete avoidance of heterosexual intercourse) or use adequate contraceptive methods, defined as use of a condom by the male partner combined with use of a highly effective method of contraception by the female partner, during the treatment period and for at least 165 days after the last dose of study intervention. 3. Male participants must not donate sperm for at least 165 days after the last dose of study intervention. 4. Male participants in same-sex relationships or in relationships with WONCBP, must agree to remain abstinent (complete avoidance of intercourse) or use a condom to prevent exposure of the partner to study intervention through ejaculate/seminal fluid during the treatment period and for at least 165 days after the last dose of study intervention. 1. Understands the study procedures and can give signed informed consent. 2. Male or female ≥18 and ≤85 years of age. 3. Has a confirmed diagnosis of ATTR cardiomyopathy (ATTR-CM), AL, or other form of systemic amyloidosis 4. Imaging evidence of organ amyloid deposits. 5. For ATTR cardiomyopathy subjects, genetic testing confirming wild type ATTR or identification of an amyloidogenic genetic variant is required. If genetic testing has not been performed prior to screening, then the test may be ordered during screening 6. Subjects with ATTR cardiomyopathy may be receiving a TTR silencer (e.g., inotersen, vutrisiran, or patisiran) or a stabilizer (e.g., tafamadis or diflunisal), but not both. 7. Subjects with AL systemic amyloidosis may be receiving maintenance daratumumab and must have 1. Achieved a hematologic very good partial response (VGPR) or complete response (CR) based on their most recent assessment (e.g., difference in free light chains \<40 mg/L) within 12 months of Screening or 2. Achieved a partial hematologic response, is in stable condition (defined as \>6 months without clonal or amyloidotic organ progression), is not receiving plasma cell directed (PCD) therapy and is not expected to require PCD therapy for the duration of the study. 8. Women of childbearing potential (WOCBP): 1. WOCBP must have a negative serum or urine pregnancy test within 24 hours prior to the start of study treatment. 2. Must not be breastfeeding, lactating, or planning a pregnancy during the study period. 3. WOCBP who are not exclusively in same-sex relationships must agree to remain abstinent (complete avoidance of heterosexual intercourse) or use adequate contraceptive methods, defined as use of a condom by the male partner combined with use of a highly effective method of contraception by the female partner, during the treatment period and for at least 105 days after the last dose of study intervention. 9. Women of non-childbearing potential (WONCBP), and female participants with vasectomized male partners: 1. WONCBP must agree to remain abstinent (complete avoidance of intercourse) or the male partners of WONCBP participants must wear a condom to protect against the transfer of study intervention through bodily fluids during the treatment period and for at least 105 days after the last dose of study intervention. 2. Postmenopausal females must have a documented serum FSH level \>40 mIU/mL at Screening to confirm menopause. 10. Male participants: 1. Male participants must inform their female sexual partners who are WOCBP of the contraceptive requirements of the protocol and are expected to adhere to using contraception with their partner. 2. Male participants with female sexual partners who are WOCBP must agree to remain abstinent (complete avoidance of heterosexual intercourse) or use adequate contraceptive methods, defined as use of a condom by the male partner combined with use of a highly effective method of contraception by the female partner, during the treatment period and for at least 165 days after the last dose of study intervention. 3. Male participants must not donate sperm for at least 165 days after the last dose of study intervention. 4. Male participants in same-sex relationships or in relationships with WONCBP must agree to remain abstinent (complete avoidance of intercourse) or use a condom to prevent exposure of the partner to study intervention through ejaculate/seminal fluid during the treatment period and for at least 165 days after the last dose of study intervention.	Pregnancy or breastfeeding Severe psychiatric disorders Active substance abuse Unstable medical conditions Inability to comply with study requirements

Inclusion Criteria

Exclusion Criteria

1. Understands the study procedures and can give signed informed consent
2. Male or female between \>18 and \<56 years of age.
3. Willing and able to comply with this protocol and informed consent and be available for the entire duration of the study.
4. Willing to abstain from alcohol and strenuous physical activity (i.e., strenuous or unaccustomed weightlifting, running, bicycling, etc.) from 48 hours prior to study treatment administration until discharge from the clinical unit and prior to each outpatient visit.
5. In good general health, determined by no clinically significant findings in the opinion of the Investigator from medical history, physical examination, 12-lead electrocardiogram (ECG), clinical laboratory findings, and vital signs at Screening and Phase 1 unit Check-in.
6. Has body mass index (BMI) of 18 to 32 kg/m2, inclusive.
7. Women of childbearing potential (WOCBP)
1. WOCBP must have a negative serum or urine pregnancy test within 24 hours prior to the start of study drug.
2. Must not be breastfeeding, lactating, or planning a pregnancy during the study period.
3. WOCBP who are not exclusively in same-sex relationships must agree to remain abstinent (complete avoidance of heterosexual intercourse) or use adequate contraceptive methods, defined as use of a condom by the male partner combined with use of a highly effective method of contraception by the female partner, during the treatment period and for at least 105 days after the last dose of study intervention.
8. Postmenopausal females:
9. Women of non-childbearing potential (WONCBP) and female participants with vasectomized male partners:
10. Male participants:
1. Male participants must inform their female sexual partners who are WOCBP of the contraceptive requirements of the protocol and are expected to adhere to using contraception with their partner.
2. Male participants with female sexual partners who are WOCBP must agree to remain abstinent (complete avoidance of heterosexual intercourse) or use adequate contraceptive methods, defined as use of a condom by the male partner combined with use of a highly effective method of contraception by the female partner, during the treatment period and for at least 165 days after the last dose of study intervention.
3. Male participants must not donate sperm for at least 165 days after the last dose of study intervention.
4. Male participants with potentially postmenopausal partners who are under the age of 55 years must use condoms unless their partner's postmenopausal status has been confirmed by FSH level.
5. Male participants in same-sex relationships or in relationships with WONCBP must agree to remain abstinent (complete avoidance of intercourse) or use a condom to prevent exposure of the partner to study intervention through ejaculate/seminal fluid during the treatment period and for at least 165 days after the last dose of study intervention.
1. Understands the study procedures and can give signed informed consent
2. Male or female ≥18 and ≤80 years of age.
3. Mini Mental Status Exam (MMSE) score \>27 (subjects \>55 years of age only).
4. Has a confirmed diagnosis of AL, ATTR, or other form of systemic amyloidosis, based on any one of the following:
1. A histologic confirmation with a biopsy containing deposits of apple-green birefringent, Congophilic material or other amyloid staining (i.e., thioflavin T or sulfated alcian blue) with confirmatory immunohistochemistry, mass spectrometry or identification of an amyloidogenic genetic variant;
2. Genetic screening with presence of amyloid-related pathology; or
3. Amyloid-specific imaging study (e.g., bone scintigraphy and echocardiogram/CMR consistent with ATTR cardiac amyloid).
5. Subjects with AL systemic amyloidosis must have achieved a hematologic very good partial response (VGPR) or complete response (CR) based on their most recent assessment (e.g., difference in free light chains \<40 mg/L) and within 12 months of Screening and may be receiving maintenance daratumumab.
6. Subjects with ATTR systemic amyloidosis may be receiving a TTR silencer (e.g., inotersen, vutrisiran, or patisiran) or a stabilizer (e.g., tafamadis or diflunisal), but not both.
7. Women of childbearing potential (WOCBP):
1. WOCBP must have a negative serum or urine pregnancy test within 24 hours prior to the start of study treatment.
2. Must not be breastfeeding, lactating, or planning a pregnancy during the study period.
3. WOCBP who are not exclusively in same-sex relationships must agree to remain abstinent (complete avoidance of heterosexual intercourse) or use adequate contraceptive methods, defined as use of a condom by the male partner combined with use of a highly effective method of contraception by the female partner, during the treatment period and for at least 105 days after the last dose of study intervention.
8. Women of non-childbearing potential (WONCBP), and female participants with vasectomized male partners:
1. WONCBP must agree to remain abstinent (complete avoidance of intercourse) or the male partners of WONCBP participants must wear a condom to protect against the transfer of study intervention through bodily fluids during the treatment period and for at least 105 days after the last dose of study intervention.
2. Postmenopausal females must have a documented serum FSH level \>40 mIU/mL at Screening to confirm menopause.
9. Male participants:
1. Male participants must inform their female sexual partners who are WOCBP of the contraceptive requirements of the protocol and are expected to adhere to using contraception with their partner.
2. Male participants with female sexual partners who are WOCBP must agree to remain abstinent (complete avoidance of heterosexual intercourse) or use adequate contraceptive methods, defined as use of a condom by the male partner combined with use of a highly effective method of contraception by the female partner, during the treatment period and for at least 165 days after the last dose of study intervention.
3. Male participants must not donate sperm for at least 165 days after the last dose of study intervention.
4. Male participants in same-sex relationships or in relationships with WONCBP, must agree to remain abstinent (complete avoidance of intercourse) or use a condom to prevent exposure of the partner to study intervention through ejaculate/seminal fluid during the treatment period and for at least 165 days after the last dose of study intervention.
1. Understands the study procedures and can give signed informed consent.
2. Male or female ≥18 and ≤85 years of age.
3. Has a confirmed diagnosis of ATTR cardiomyopathy (ATTR-CM), AL, or other form of systemic amyloidosis
4. Imaging evidence of organ amyloid deposits.
5. For ATTR cardiomyopathy subjects, genetic testing confirming wild type ATTR or identification of an amyloidogenic genetic variant is required. If genetic testing has not been performed prior to screening, then the test may be ordered during screening
6. Subjects with ATTR cardiomyopathy may be receiving a TTR silencer (e.g., inotersen, vutrisiran, or patisiran) or a stabilizer (e.g., tafamadis or diflunisal), but not both.
7. Subjects with AL systemic amyloidosis may be receiving maintenance daratumumab and must have
1. Achieved a hematologic very good partial response (VGPR) or complete response (CR) based on their most recent assessment (e.g., difference in free light chains \<40 mg/L) within 12 months of Screening or
2. Achieved a partial hematologic response, is in stable condition (defined as \>6 months without clonal or amyloidotic organ progression), is not receiving plasma cell directed (PCD) therapy and is not expected to require PCD therapy for the duration of the study.
8. Women of childbearing potential (WOCBP):
1. WOCBP must have a negative serum or urine pregnancy test within 24 hours prior to the start of study treatment.
2. Must not be breastfeeding, lactating, or planning a pregnancy during the study period.
3. WOCBP who are not exclusively in same-sex relationships must agree to remain abstinent (complete avoidance of heterosexual intercourse) or use adequate contraceptive methods, defined as use of a condom by the male partner combined with use of a highly effective method of contraception by the female partner, during the treatment period and for at least 105 days after the last dose of study intervention.
9. Women of non-childbearing potential (WONCBP), and female participants with vasectomized male partners:
1. WONCBP must agree to remain abstinent (complete avoidance of intercourse) or the male partners of WONCBP participants must wear a condom to protect against the transfer of study intervention through bodily fluids during the treatment period and for at least 105 days after the last dose of study intervention.
2. Postmenopausal females must have a documented serum FSH level \>40 mIU/mL at Screening to confirm menopause.
10. Male participants:
1. Male participants must inform their female sexual partners who are WOCBP of the contraceptive requirements of the protocol and are expected to adhere to using contraception with their partner.
2. Male participants with female sexual partners who are WOCBP must agree to remain abstinent (complete avoidance of heterosexual intercourse) or use adequate contraceptive methods, defined as use of a condom by the male partner combined with use of a highly effective method of contraception by the female partner, during the treatment period and for at least 165 days after the last dose of study intervention.
3. Male participants must not donate sperm for at least 165 days after the last dose of study intervention.
4. Male participants in same-sex relationships or in relationships with WONCBP must agree to remain abstinent (complete avoidance of intercourse) or use a condom to prevent exposure of the partner to study intervention through ejaculate/seminal fluid during the treatment period and for at least 165 days after the last dose of study intervention.

Pregnancy or breastfeeding
Severe psychiatric disorders
Active substance abuse
Unstable medical conditions
Inability to comply with study requirements

Contacts and Locations

Study Contact

Scott Stephens, RN

CONTACT

3212287400

Sstephens@attralus.com

Study Locations (Sites)

Midwest Heart and Vascular

Overland Park, Kansas, 66211

United States

Johns Hopkins

Baltimore, Maryland, 21287

United States

St. Luke's Hospital of Kansas City

Kansas City, Missouri, 64111

United States

Cleveland Clinic

Cleveland, Ohio, 44195

United States

OHSU (Oregon Health & Science University)

Portland, Oregon, 97239

United States

Penn Presbyterian Medical Center

Philadelphia, Pennsylvania, 19104

United States

Collaborators and Investigators

Sponsor: Attralus, Inc.

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2022-09-01

Study Completion Date2025-03-01

Study Record Updates

Study Start Date2022-09-01

Study Completion Date2025-03-01

Terms related to this study

Additional Relevant MeSH Terms

Amyloidosis; Systemic