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

Trial Summary

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.

What data supports the idea that AT-02 for Amyloidosis is an effective drug?

The available research does not provide specific data on the effectiveness of AT-02 for Amyloidosis. Instead, it discusses other treatments for different types of amyloidosis, such as AL and ATTR. For AL amyloidosis, treatments like proteasome inhibitors, immunomodulators, and monoclonal antibodies have shown significant improvements in patient outcomes. For ATTR amyloidosis, drugs like tafamidis and RNA-interference agents have improved prognosis. Without specific data on AT-02, it's unclear how it compares to these treatments. ^{1 2 3 4 5}

What safety data is available for AT-02 in treating amyloidosis?

The provided research does not contain any safety data for AT-02 or its placebo in the treatment of amyloidosis. The studies listed focus on treatments for endometriosis, such as dienogest, triptorelin, elagolix, goserelin, and nafarelin, and do not mention AT-02 or amyloidosis. ^{6 7 8 9 10}

Is the drug AT-02 a promising treatment for Amyloidosis?

The information provided does not include any details about the drug AT-02 or its effects on Amyloidosis, so we cannot determine if it is a promising treatment. ^{11 12 13 14 15}

What is the purpose of this trial?

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.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

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 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 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 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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

The diagnostic challenges of cardiac amyloidosis: A practical approach to the two main types. [2021]

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

Advances in the treatment of light chain amyloidosis. [2023]

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

Treatment of AL-amyloidosis with dexamethasone plus alpha interferon. [2019]

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

Treatment of immunoglobulin light chain amyloidosis. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Effectiveness of etanercept vs cyclophosphamide as treatment for patients with amyloid A amyloidosis secondary to rheumatoid arthritis. [2015]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Safety and tolerability of dienogest in endometriosis: pooled analysis from the European clinical study program. [2022]

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

Assessment of Two Formulations of Triptorelin in Chinese Patients with Endometriosis: A Phase 3, Randomized Controlled Trial. [2023]

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

Elagolix treatment for endometriosis-associated pain: results from a phase 2, randomized, double-blind, placebo-controlled study. [2022]

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

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

10. United States 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. [2022]

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

The effect of a losartan-based treatment regimen on isolated systolic hypertension. [2021]

12. United States 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. [2019]

13. Germany 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. [2013]

14. France pubmed.ncbi.nlm.nih.gov

[Is placebo necessary in a clinical trial on ambulatory blood pressure?]. [2013]

15. England 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. [2019]