AT-02 for Amyloidosis

(AT02-001 Trial)

Recruiting at 11 trial locations

Overseen By Scott Stephens, RN

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Attralus, Inc.

Must be taking: TTR silencers, stabilizers

Disqualifiers: Pregnancy, Breastfeeding, Alcohol, others

Compensation: Varies

Number of Visits: Unknown

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety and tolerability of a new treatment, AT-02, for individuals with systemic amyloidosis, a condition where abnormal proteins accumulate in organs, potentially causing damage. The trial consists of different parts, some involving healthy volunteers and others focusing on those with systemic amyloidosis. Individuals diagnosed with systemic amyloidosis and experiencing ongoing symptoms might be suitable candidates for this study. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop your current medications. However, if you have systemic amyloidosis, you may continue certain treatments like daratumumab for AL amyloidosis or TTR silencers/stabilizers for ATTR amyloidosis. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that AT-02 has potential based on early lab studies. It works by attaching to amyloid, protein clumps that can accumulate in organs, and helps the body remove them. Although specific information on side effects from human studies is not yet available, AT-02 is currently undergoing its first human trials to assess safety.

The trial is in its early stages, focusing on basic safety and treatment tolerance. This phase ensures the treatment does not cause serious harm before further testing. AT-02 is not yet approved for any use, but the FDA has granted it "orphan drug" status for treating a rare condition called amyloidosis. This status is often given to treatments that might help with rare diseases.

So far, there have been no major reports of side effects, but more study results are needed to fully understand how well people handle AT-02. Prospective participants should know that this phase is designed to closely monitor safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for amyloidosis, which often involve chemotherapy or stem cell transplants, AT-02 offers a novel approach by specifically targeting the amyloid deposits directly. Researchers are excited about AT-02 because it is administered as a solution for IV infusion, which allows for precise dosing and could improve patient outcomes. Additionally, the unique mechanism of action of AT-02, which involves breaking down amyloid fibers, represents a potential breakthrough in treating this condition more effectively and with fewer side effects.

What evidence suggests that AT-02 might be an effective treatment for amyloidosis?

Research has shown that AT-02 looks promising for treating systemic amyloidosis. Early studies found that AT-02 can attach to various types of amyloid in major organs. This attachment helps immune cells remove harmful amyloid deposits. In animal studies, AT-02 significantly reduced amyloid build-up in models of systemic amyloidosis. These results suggest that AT-02 could also reduce amyloid in humans. Participants in this trial will receive AT-02 in different parts of the study, including single and multiple doses, to further evaluate its effectiveness and safety. ^{1 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for healthy adults and those with systemic amyloidosis, aged between 18 and 56. Participants must understand the study, not consume alcohol or engage in strenuous activity before visits, have a BMI of 18-32 kg/m2, and women must not be pregnant or planning pregnancy. Contraception is required for sexually active participants.

Inclusion Criteria

Women of childbearing potential must have a negative pregnancy test within 24 hours before starting the study drug.

You agree to follow the study rules and give your consent. You can stay for the whole study.

Your body mass index (BMI) is between 18 and 32.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Part 1: Single-ascending dose escalation

Double-blind, single-center study in healthy volunteers to assess safety, tolerability, and PK of AT-02

Up to 8 weeks

Multiple visits (in-person)

Part 2: Single-ascending dose escalation

Open-label study in subjects with systemic amyloidosis to assess safety, tolerability, and PK of AT-02 and identify maximum tolerated dose

Up to 8 weeks

Multiple visits (in-person)

Part 3: Multiple-ascending dose escalation

Open-label study in subjects with systemic amyloidosis to assess safety, tolerability, PK, PD, and clinical activity of multiple doses of AT-02

Up to 12 weeks

Multiple visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• AT-02
• AT-02 (Placebo)

Trial Overview The study tests AT-02's safety, tolerability, and pharmacokinetics (PK) - how the drug moves through the body. It involves rising single doses in healthy volunteers and multiple doses in systemic amyloidosis patients across international centers.

How Is the Trial Designed?

Group I: Part 3 AT-02 Experimental Treatment 1 Intervention

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

Group II: Part 2 AT-02 Experimental Treatment 1 Intervention

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

Group III: Part 1 AT-02 Experimental Treatment 1 Intervention

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

Group IV: Part 1 Placebo Placebo Group 1 Intervention

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

AT-02 is already approved in European Union, United States for the following indications:

Approved in European Union as AT-02 for:

• Transthyretin-associated amyloidosis (ATTR)
• Immunoglobulin light-chain-associated amyloidosis (AL)

Approved in United States as AT-02 for:

• Transthyretin-associated amyloidosis (ATTR)

Who Is Running the Clinical Trial?

Attralus, Inc.

Lead Sponsor

Trials

8

Recruited

670+

Novotech (Australia) Pty Limited

Industry Sponsor

Trials

76

Recruited

7,800+

Dr. John Moller

Novotech (Australia) Pty Limited

Chief Executive Officer

MD and MBA from the University of Oxford

Dr. Judith Ng-Cashin

Novotech (Australia) Pty Limited

Chief Medical Officer since 2023

MD

Published Research Related to This Trial

In a study involving 12 patients with mild-to-moderate hypertension, both atenolol (100 mg) and enalapril (20 mg) significantly reduced diastolic blood pressure compared to placebo, with atenolol showing a 51% reduction and enalapril a 42.3% reduction.

The study found no significant differences in routine hematochemical parameters among the treatments, indicating that both medications are safe and effective for managing hypertension without adverse effects on blood chemistry.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Duration of the antihypertensive action of atenolol, enalapril and placebo: a randomized within-patient study using ambulatory blood pressure monitoring. Verdecchia, P., Gatteschi, C., Benemio, G., et al.[2013]

In a study of 9 patients with AL amyloidosis, a treatment regimen of pulse dexamethasone followed by maintenance alpha interferon resulted in improvement in organ function for 8 out of 9 patients, indicating its potential efficacy.

This treatment approach, which avoids the leukemogenic risks associated with traditional therapies, showed significant reductions in proteinuria for 6 out of 7 patients with nephrotic syndrome, suggesting it could be a safer alternative for managing AL amyloidosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of AL-amyloidosis with dexamethasone plus alpha interferon. Dhodapkar, MV., Jagannath, S., Vesole, D., et al.[2019]

Systemic amyloidosis, particularly AL and ATTR types, can now be diagnosed quickly using advanced techniques like radioisotope scintigraphy and mass spectrometry, which is crucial for improving patient outcomes.

The prognosis for both AL and ATTR has significantly improved with new treatments such as proteasome inhibitors and tafamidis, leading to better survival rates and symptom relief when the amyloid-forming proteins are effectively managed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The diagnostic challenges of cardiac amyloidosis: A practical approach to the two main types. Varga, C., Dorbala, S., Lousada, I., et al.[2021]

In a study of 86 patients with AA amyloidosis secondary to rheumatoid arthritis, the biologic agent etanercept (ETN) was found to be more effective than the alkylating agent cyclophosphamide (CYC), showing significant improvements in serum CRP, albumin levels, and estimated glomerular filtration rate (eGFR).

The presence of the SAA1.3 allele, which indicates genetic risk, did not influence the treatment response to either ETN or CYC, suggesting that this genetic factor may not be a useful predictor for therapy outcomes in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of etanercept vs cyclophosphamide as treatment for patients with amyloid A amyloidosis secondary to rheumatoid arthritis. Nakamura, T., Higashi, S., Tomoda, K., et al.[2015]

In a Phase 2 study involving 155 women with confirmed endometriosis, elagolix showed a reduction in pain scores compared to placebo, particularly for dysmenorrhea, with significant differences noted at weeks 8 and 12.

Elagolix treatment was associated with minimal changes in bone mineral density, indicating a favorable safety profile for women experiencing endometriosis-associated pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elagolix treatment for endometriosis-associated pain: results from a phase 2, randomized, double-blind, placebo-controlled study. Diamond, MP., Carr, B., Dmowski, WP., et al.[2022]

In a randomized trial with 86 patients, the 5 mg dose of ramipril significantly reduced blood pressure compared to placebo, indicating its efficacy in treating mild to moderate hypertension.

The study found no clinically relevant side effects from ramipril, suggesting it is a safe option for patients, with the minimum effective dosage identified as 5 mg once daily.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A double-blind study to compare the efficacy, tolerance and safety of two doses of the angiotensin converting enzyme inhibitor ramipril with placebo. Villamil, AS., Cairns, V., Witte, PU., et al.[2019]

Atenolol combined with slow-released nifedipine significantly reduced ambulatory blood pressure (ABP) in patients with high blood pressure, showing a clear efficacy of the treatment compared to placebo after one month.

The study highlights the importance of including a placebo group, as analyzing data without it can overestimate the drug's effects, even though the placebo had a slight impact on ABP in patients with initially high blood pressure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Is placebo necessary in a clinical trial on ambulatory blood pressure?]. Chau, NP., Chanudet, X., Mestivier, D., et al.[2013]

In a study involving 31 patients with mild to moderate hypertension, both once-daily and twice-daily doses of the ACE inhibitor trandolapril significantly reduced blood pressure, showing similar efficacy in overall BP control.

The twice-daily regimen of trandolapril was found to be more effective in lowering systolic blood pressure during sleep compared to the once-daily dose, suggesting potential benefits for nighttime blood pressure management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Once-daily trandolapril compared with the twice-daily formulation in the treatment of mild to moderate essential hypertension: assessment by conventional and ambulatory blood pressures. Poirier, L., Bourgeois, J., Lacourcière, Y.[2019]

In a study involving 252 women with endometriosis, both goserelin and nafarelin significantly reduced pain scores and improved symptoms without any statistically significant differences in efficacy or side effects between the two treatments.

Local irritation was reported more frequently in the nafarelin group, while goserelin users experienced injection site symptoms, but overall, both treatments were similarly effective in managing endometriosis symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparative study of the acceptability and effect of goserelin and nafarelin on endometriosis. Bergqvist, A.[2019]

In a study of 308 patients with isolated systolic hypertension, a losartan-based treatment regimen significantly reduced systolic blood pressure (SBP) by an average of 19.2 mm Hg over 12 weeks, compared to a 7.6 mm Hg reduction in the placebo group.

The reduction in SBP with losartan was significantly greater than with placebo, by 11.6 mm Hg, while both treatments had similar tolerability profiles, indicating that losartan is an effective and well-tolerated option for managing isolated systolic hypertension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of a losartan-based treatment regimen on isolated systolic hypertension. Cushman, WC., Brady, WE., Gazdick, LP., et al.[2021]

Therapies for AL amyloidosis, including alkylators and steroids, are effective, but only about 25% of patients can receive high-dose therapy; novel agents like thalidomide and bortezomib have also shown promise in treatment.

Predictors of treatment outcomes include serum brain natriuretic peptide levels, the number of affected organs, and the severity of cardiac involvement, indicating that personalized treatment approaches can be developed for nearly all patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of immunoglobulin light chain amyloidosis. Gertz, MA., Zeldenrust, SR.[2021]

A pooled analysis of 332 women from four clinical trials showed that dienogest 2 mg is well tolerated for up to 65 weeks in treating endometriosis, with a favorable safety profile and low rates of discontinuation due to side effects.

The most common side effects, such as headache and breast discomfort, were mild to moderate, and dienogest maintained estradiol levels within a low-physiological range, indicating effective treatment without causing hormonal deficiency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of dienogest in endometriosis: pooled analysis from the European clinical study program. Strowitzki, T., Faustmann, T., Gerlinger, C., et al.[2022]

In a phase 3 study involving 300 Chinese women with endometriosis, triptorelin pamoate prolonged-release (3-month formulation) was found to be noninferior to the standard 1-month formulation, with over 98% of patients achieving chemical castration after 12 weeks.

Both formulations effectively reduced endometriosis-related pelvic pain and hormone levels, with no new safety concerns, making the 3-month option a convenient alternative that requires fewer injections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of Two Formulations of Triptorelin in Chinese Patients with Endometriosis: A Phase 3, Randomized Controlled Trial. Li, X., Li, H., Shi, H., et al.[2023]

In a 24-week study involving women with confirmed endometriosis, dienogest at doses of 2 mg and 4 mg per day significantly reduced endometriosis severity scores, indicating effective treatment.

Both the 2 mg and 4 mg doses were well tolerated with low discontinuation rates due to side effects, while the 1 mg dose was discontinued due to inadequate bleeding control, suggesting that 2 mg is the optimal dose for future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A dose-ranging study to determine the efficacy and safety of 1, 2, and 4mg of dienogest daily for endometriosis. Köhler, G., Faustmann, TA., Gerlinger, C., et al.[2022]

The combination therapy of daratumumab, cyclophosphamide, bortezomib, and dexamethasone (daratumumab-CyBorD) has become the new standard-of-care for systemic light chain (AL) amyloidosis, showing high rates of hematologic and organ response.

Recent advancements in patient selection and induction regimens have significantly reduced the mortality associated with autologous stem cell transplant (ASCT), while new treatments like venetoclax are proving effective for patients with specific genetic abnormalities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in the treatment of light chain amyloidosis. Palladini, G., Milani, P.[2023]

Citations

1. nature.com nature.com/articles/s44386-025-00015-4

The antibody-peptide fusion protein, AT-02, is an effective ... AT-02 serves as an effective opsonin when bound to amyloid, thereby enhancing phagocytosis of amyloid extracts and fixing complement. These data ...

2. attralus.com attralus.com/press-releases/attralus-presents-new-data-on-its-pan-amyloid-therapeutic-and-diagnostic-candidates-at-the-xix-international-symposium-on-amyloidosis-isa

Attralus Presents New Data on Its Pan-Amyloid ... Preclinical data have shown the ability of AT-02 to bind to multiple amyloid types in major organs, induce macrophage mediated phagocytosis, and ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05521022

NCT05521022 | Study of AT-02 in Healthy Volunteers and ... Systemic amyloidosis is an incurable disease, and about 20% of patients with cardiac or advanced kidney involvement experience early deaths (<1 year). Despite ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2152265025001077

Treatment Patterns and Clinical Outcomes of Patients With ... This study described real-world treatment patterns and outcomes in patients with systemic light chain (AL) amyloidosis in the United States (US).

5. attralus.com attralus.com/press-releases/attralus-presents-in-vivo-preclinical-data-for-at-02-demonstrating-significant-amyloid-reduction-at-18th-international-symposium-on-amyloidosis

Attralus Presents In Vivo Preclinical Data for AT-02 ... In vivo preclinical data for AT-02 demonstrated significant reduction in amyloid in mouse models of human AL amyloidoma and systemic AA amyloidosis.

6. attralus.com attralus.com/press-releases/attralus-therapeutic-at-02-receives-orphan-drug-designation-from-the-u-s-fda-for-the-treatment-of-attr-amyloidosis

Attralus Therapeutic AT-02 Receives Orphan Drug ... Preclinical data have shown the ability of AT-02 to bind to multiple amyloid types in major organs and induce macrophage mediated amyloid ...

7. oneamyloidosisvoice.com oneamyloidosisvoice.com/rarehub/study-02-subjects-systemic-amyloidosis

A Study of AT-02 in Subjects With Systemic Amyloidosis. This is a Phase 2 open-label extension study to evaluate the long-term safety, tolerability, and clinical activity of AT-02.

8. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/4641/529764/Characterization-of-AT02-Bioactivity-and-an

Characterization of AT02 Bioactivity and an Assessment of Its ... Fluorophore labelled AT-02 co-localized with human AL amyloidomas in mice and remained bound to the amyloid for ten days post-injection.