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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05521022




Registration number
NCT05521022
Ethics application status
Date submitted
23/08/2022
Date registered
30/08/2022
Date last updated
3/04/2024

Titles & IDs
Public title
Study of AT-02 in Healthy Volunteers and Subjects With Systemic Amyloidosis
Scientific 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
Secondary ID [1] 0 0
AT02-001
Universal Trial Number (UTN)
Trial acronym
AT02-001
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Amyloidosis; Systemic 0 0
Condition category
Condition code
Metabolic and Endocrine 0 0 0 0
Metabolic disorders
Metabolic and Endocrine 0 0 0 0
Other metabolic disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - AT-02
Other interventions - AT-02 (Placebo)

Experimental: Part 1 AT-02 - Part 1 enrolling Healthy Volunteers (Randomised, Double-blind) Drug: AT-02 Dosage: 30mg to 1000mg Dosage Form \& Route of Admin: Solution for IV Infusion

Placebo comparator: Part 1 Placebo - Part 1 enrolling Healthy Volunteers (Randomised, Double-blind) Dosage Form \& Route of Admin: Normal Saline Solution for IV Infusion

Experimental: Part 2 AT-02 - Part 2 enrolling Systemic Amyloidosis Participants (Single-Arm, Open-label) Drug: AT-02 Dosage: 300mg to 4000mg Frequency: Single Dose Dosage Form \& Route of Admin: Solution for IV Infusion

Experimental: Part 3 AT-02 - Part 3 enrolling Systemic Amyloidosis Participants (Single-Arm, Open-label) Drug: AT-02 Dosage: Dose levels will be determined by the SRC. The starting dose in Part 3 will be determined by the SRC based on all available safety, tolerability, PK, and PD data from all prior cohorts Frequency: Multiple Doses Dosage Form \& Route of Admin: Solution for IV Infusion


Treatment: Drugs: AT-02
AT-02 via IV infusion

Other interventions: AT-02 (Placebo)
Normal saline solution via IV infusion
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence and severity of treatment-emergent adverse events (TEAEs) from Day 1 to end of study (EOS).
Timepoint [1] 0 0
Up to 57+/-7 days
Primary outcome [2] 0 0
Incidence of dose-limiting toxicities (DLTs) in subjects with systemic amyloidosis.
Timepoint [2] 0 0
Up to 85+/-7 Days
Primary outcome [3] 0 0
Incidence and frequency of abnormal and clinically significant abnormal clinical laboratory parameter values.
Timepoint [3] 0 0
Up to 85+/-7 Days
Primary outcome [4] 0 0
Incidence of treatment-emergent anti-drug antibodies (ADA)
Timepoint [4] 0 0
Up to 85+/-7 Days
Secondary outcome [1] 0 0
To determine the plasma pharmacokinetics (PK) profile of AT-02
Timepoint [1] 0 0
Up to 85+/-7 Days
Secondary outcome [2] 0 0
To determine the plasma pharmacokinetics (PK) profile of AT-02
Timepoint [2] 0 0
Up to 85+/-7 Days
Secondary outcome [3] 0 0
To determine the plasma pharmacokinetics (PK) profile of AT-02
Timepoint [3] 0 0
Up to 85+/-7 Days
Secondary outcome [4] 0 0
To determine the plasma pharmacokinetics (PK) profile of AT-02
Timepoint [4] 0 0
Up to 85+/-7 Days
Secondary outcome [5] 0 0
To determine the plasma pharmacokinetics (PK) profile of AT-02
Timepoint [5] 0 0
Up to 85+/-7 Days
Secondary outcome [6] 0 0
To determine the plasma pharmacokinetics (PK) profile of AT-02
Timepoint [6] 0 0
Up to 85+/-7 Days

Eligibility
Key inclusion criteria
Eligibility Criteria for Healthy Volunteers:

Healthy volunteers are eligible to be included in the study only if all the following criteria apply:

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:

a) Postmenopausal females under the age of 55 years must have a documented serum follicle stimulating hormone (FSH) level >40 mIU/mL to confirm menopause
9. Women of non-childbearing potential (WONCBP) and female participants with vasectomized male partners:

a) 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.
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.

Eligibility Criteria for Part 2 Subjects with Systemic Amyloidosis

Subjects with systemic amyloidosis are eligible to be included in the study only if all the following criteria apply:

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.

Eligibility Criteria for Part 3 Subjects with Systemic Amyloidosis

Subjects with systemic amyloidosis are eligible to be included in the study only if all the following criteria apply:

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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/09/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/03/2025
Actual
Sample size
Target
100
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Q-Pharm Pty Ltd - Herston
Recruitment hospital [2] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [3] 0 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [4] 0 0
Box Hill Hospital - Box Hill
Recruitment hospital [5] 0 0
Royal Perth Hospital - Perth
Recruitment postcode(s) [1] 0 0
4006 - Herston
Recruitment postcode(s) [2] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [3] 0 0
5042 - Bedford Park
Recruitment postcode(s) [4] 0 0
3128 - Box Hill
Recruitment postcode(s) [5] 0 0
6000 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Kansas
Country [2] 0 0
United States of America
State/province [2] 0 0
Maryland
Country [3] 0 0
United States of America
State/province [3] 0 0
Missouri
Country [4] 0 0
United States of America
State/province [4] 0 0
Ohio
Country [5] 0 0
United States of America
State/province [5] 0 0
Oregon
Country [6] 0 0
United States of America
State/province [6] 0 0
Pennsylvania

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Attralus, Inc.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Novotech (Australia) Pty Limited
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
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.
Trial website
https://clinicaltrials.gov/study/NCT05521022
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Scott Stephens, RN
Address 0 0
Country 0 0
Phone 0 0
3212287400
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT05521022