Andecaliximab for Stone Man Syndrome

(ANDECAL Trial)

Recruiting in Palo Alto (17 mi)

+3 other locations

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2 & 3

Recruiting

Sponsor: Ashibio Inc

Must not be taking: Corticosteroids, NSAIDs, Tetracyclines, Palovarotene

Disqualifiers: Fractures, Surgery, Infections, Malignancy, others

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This study is researching an experimental drug called andecaliximab. The study will include pediatric and adult patients with fibrodysplasia ossificans progressiva (FOP). The study will evaluate how safe and effective andecaliximab is in patients with FOP. The study is looking at several research questions, including: * Safety of andecaliximab in participants with FOP * Whether andecaliximab reduces the number of new heterotopic bone lesions (Heterotopic Ossification; HO) * Whether andecaliximab reduces the number or severity of flare-ups * Pharmacokinetics/pharmacodynamics (PK/PD): How much study drug is in your blood at different times and its impact on blood biomarker(s) * Whether the body makes antibodies against the study drug (which could make the drug less effective or could lead to side effects)

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before participating. Specifically, you must not use systemic corticosteroids above a certain dose, certain NSAIDs, tetracycline drugs, palovarotene, or any unproven therapies for FOP. If you are on these medications, you may need to discuss your eligibility with the study sponsor.

What data supports the effectiveness of the drug Andecaliximab for Stone Man Syndrome?

Andecaliximab has shown promising results in treating advanced gastric and gastroesophageal junction cancers by inhibiting an enzyme involved in tumor growth and spread, suggesting it might help in conditions involving abnormal tissue growth like Stone Man Syndrome. ^{1 2 3 4 5}

Is andecaliximab safe for humans?

Andecaliximab has been tested in humans for various cancers, showing a manageable safety profile with common side effects like nausea and decreased white blood cell counts. Serious side effects were rare, and no unusual toxicity was observed in the studies. ^{1 2 3 4 5}

What makes the drug Andecaliximab unique for treating Stone Man Syndrome?

Andecaliximab is unique because it is a monoclonal antibody that specifically targets matrix metalloproteinase-9 (MMP-9), an enzyme involved in tissue remodeling, which may play a role in Stone Man Syndrome. This targeted approach is different from other treatments that may not specifically address the underlying enzyme activity associated with the condition. ^{6 7 8 9 10}

Research Team

Eligibility Criteria

This trial is for pediatric and adult patients with fibrodysplasia ossificans progressiva (FOP), also known as Stone Man Syndrome. Participants must meet specific health criteria to join, but these details are not provided here.

Inclusion Criteria

My flare-ups include at least two symptoms like pain, swelling, or redness.

I haven't taken any bone-strengthening drugs in the last year.

No open growth plates on bilateral PA hand/wrist or AP knee films at baseline

Exclusion Criteria

Those of childbearing potential unwilling to agree to abstain from sexual activity that could result in pregnancy or unwillingness to use acceptable birth control during the study and for 90 days after the last dose

Significant medical condition or disability or biochemical or hematologic abnormalities that in the opinion of the Investigator would expose the participant to undue risk, prevent the conduct of study procedures, or confound the study results

I have a fracture that has not yet healed.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Part 1a: PET/CT Study

A 13-week double-blind study to assess the impact of two dose levels of andecaliximab administered subcutaneously in participants age ≥ 15 years, focusing on safety, PK/PD, and Na18F uptake in HO lesions

13 weeks

Part 1b: Flare-up Study

A 13-week double-blind study to assess the impact of two dose levels of andecaliximab in participants ≥12 years with frequent flare-ups, focusing on safety, PK/PD, and flare-up incidence

13 weeks

Part 2: Main Study

A 52-week double-blind, placebo-controlled study of andecaliximab in pediatric and adult patients with FOP, assessing safety and efficacy

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

All participants receive study drug in the extension period of the trial

Treatment Details

Interventions

• Andecaliximab (Monoclonal Antibodies)

Trial Overview The study tests the safety and effectiveness of an experimental drug called andecaliximab in reducing new bone lesions and flare-ups in FOP patients. It includes a comparison between the drug and a placebo, monitoring blood levels, effects on biomarkers, and potential antibody development against the drug.

Participant Groups

Group I: Part 1b: Flare-up Study Experimental Treatment 1 Intervention

a 13-week double-blind (Investigator and Participant blinded; Sponsor unblinded) study to assess the impact of two dose levels of andecaliximab administered SC QW in participants ≥12 years of age with a recent history of frequent flare-up episodes on a number of outcomes including safety, PK/PD, and flare-up incidence and symptoms and PROs.

Group II: Part 1a: PET/CT Study Experimental Treatment 1 Intervention

a 13-week double-blind (Investigator and Participant blinded; Sponsor unblinded) Study to assess the impact of two dose levels of andecaliximab administered subcutaneously (SC), once-a-week (QW) in participants age ≥ 15 years, with FOP on a number of outcomes including Safety, Pharmacokinetic (PK) and pharmacodynamic (PD) and the change from baseline of Na18F uptake in HO lesions by PET/CT scan, and Patient Reported Outcomes (PROs).

Group III: Part 2: Main Study Placebo Group 2 Interventions

1-year (52-week) double-blind (Investigator, participant, and sponsor all blinded), placebo-controlled study of andecaliximab Dose level A or B (or age adjusted) SC QW or placebo in pediatric and adult patients with FOP. The Main Study will enroll approximately 80 participants, randomized in a 1:1:1 ratio to andecaliximab Dose level A or B (or age adjusted) SC QW or placebo.

Who Is Running the Clinical Trial?

Ashibio Inc

Lead Sponsor

Trials

1

Recruited

90+

Findings from Research

Andecaliximab (ADX) combined with S-1 and platinum-based chemotherapy showed a promising objective response rate of 73% in patients with advanced gastric or gastroesophageal junction adenocarcinoma, indicating its potential efficacy as a first-line treatment.

The treatment was associated with a manageable safety profile, with common adverse events including peripheral sensory neuropathy and decreased neutrophil counts, suggesting that while there are side effects, they are not severe for most patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1b study of andecaliximab in combination with S-1 plus platinum in Japanese patients with gastric adenocarcinoma. Ooki, A., Satoh, T., Muro, K., et al.[2022]

Andecaliximab, a monoclonal antibody targeting MMP9, was safe and well-tolerated in patients with advanced solid tumors, showing no dose-limiting toxicity and effective target engagement at doses of 800 mg every two weeks or 1,200 mg every three weeks.

In combination with mFOLFOX6, andecaliximab demonstrated promising clinical activity in patients with HER2-negative gastric/gastroesophageal junction adenocarcinoma, achieving a median progression-free survival of 7.8 months and an overall response rate of 48%, without additional toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Andecaliximab/GS-5745 Alone and Combined with mFOLFOX6 in Advanced Gastric and Gastroesophageal Junction Adenocarcinoma: Results from a Phase I Study. Shah, MA., Starodub, A., Sharma, S., et al.[2020]

In a phase I study involving 36 patients with advanced pancreatic adenocarcinoma, the combination of andecaliximab (an MMP9 inhibitor) with gemcitabine and nab-paclitaxel showed a favorable safety profile, with common side effects including fatigue and nausea, but no unusual toxicities reported.

The treatment resulted in a median progression-free survival of 7.8 months and an objective response rate of 44.4%, indicating promising clinical activity in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Andecaliximab (GS-5745) Plus Gemcitabine and Nab-Paclitaxel in Patients with Advanced Pancreatic Adenocarcinoma: Results from a Phase I Study. Bendell, J., Sharma, S., Patel, MR., et al.[2022]

In a phase III study involving 432 patients with untreated gastric or gastroesophageal junction adenocarcinoma, the addition of the monoclonal antibody andecaliximab (ADX) to the chemotherapy regimen mFOLFOX6 did not significantly improve overall survival compared to placebo, with median survival times of 12.5 months for ADX and 11.8 months for placebo.

However, the objective response rate was higher in the ADX group (51%) compared to the placebo group (41%), indicating some potential benefit in tumor response, particularly in patients aged 65 and older.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase III Study to Evaluate Efficacy and Safety of Andecaliximab With mFOLFOX6 as First-Line Treatment in Patients With Advanced Gastric or GEJ Adenocarcinoma (GAMMA-1). Shah, MA., Bodoky, G., Starodub, A., et al.[2022]

The combination of andecaliximab and nivolumab showed a manageable safety profile with no dose-limiting toxicities in Japanese patients with advanced gastric adenocarcinoma, indicating it is a safe treatment option.

In cohort 4, the combination therapy resulted in a promising objective response rate of 50% and a median progression-free survival of 4.6 months, suggesting enhanced antitumor activity compared to andecaliximab monotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of andecaliximab as monotherapy and in combination with an anti-PD-1 antibody in Japanese patients with gastric or gastroesophageal junction adenocarcinoma: a phase 1b study. Yoshikawa, AK., Yamaguchi, K., Muro, K., et al.[2022]

The study identified a specific nanobody (FAF Nb1) that effectively targets and images amyloidogenic gelsolin buildup in a mouse model of gelsolin amyloidosis, demonstrating high specificity and low background signal for potential diagnostic use.

This nanobody, when used with 99mTc-based SPECT/CT imaging, could serve as a non-invasive tool to monitor disease progression and evaluate the effectiveness of new therapies for gelsolin amyloidosis and potentially other amyloid diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-Invasive Imaging of Amyloid Deposits in a Mouse Model of AGel Using 99mTc-Modified Nanobodies and SPECT/CT. Verhelle, A., Van Overbeke, W., Peleman, C., et al.[2019]

In a large phase 2 trial of lecanemab for early Alzheimer's disease, the incidence of amyloid-related imaging abnormalities (ARIA-E) was low (<10%), with less than 3% of cases being symptomatic, indicating a favorable safety profile for the drug.

Lecanemab was associated with mild-to-moderate ARIA-E that typically occurred early in treatment and was more common in individuals who are ApoE4 homozygous, suggesting that monitoring may be particularly important for this group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ARIA in patients treated with lecanemab (BAN2401) in a phase 2 study in early Alzheimer's disease. Honig, LS., Barakos, J., Dhadda, S., et al.[2023]

In an 18-month phase 3 trial with 1795 participants, lecanemab significantly preserved health-related quality of life (HRQoL), showing 49% less decline in EQ-5D-5L scores and 56% less decline in QOL-AD scores compared to placebo.

Lecanemab also reduced caregiver burden by 38%, indicating that its benefits extend beyond the patients to their care partners, highlighting its potential for meaningful impact on both patient and caregiver well-being.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lecanemab Clarity AD: Quality-of-Life Results from a Randomized, Double-Blind Phase 3 Trial in Early Alzheimer's Disease. Cohen, S., van Dyck, CH., Gee, M., et al.[2023]

Lecanemab, a monoclonal antibody targeting specific forms of beta-amyloid, has shown promising efficacy signals in phase 2 trials for Alzheimer's disease, with manageable risks of amyloid-related imaging abnormalities (ARIAs).

The development of lecanemab and other monoclonal antibodies is informed by previous experiences with drugs like aducanumab, emphasizing the importance of targeting specific Aβ conformations (like protofibrils) to effectively slow clinical decline in Alzheimer's patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lecanemab (BAN2401): an anti-beta-amyloid monoclonal antibody for the treatment of Alzheimer disease. Vitek, GE., Decourt, B., Sabbagh, MN.[2023]

Lecanemab, a monoclonal antibody approved for Alzheimer's disease, has been shown to effectively reduce beta-amyloid accumulation and slow cognitive decline in 2729 participants across three clinical trials.

The treatment was well tolerated, with common side effects including headaches and infusion reactions, indicating a favorable safety profile while demonstrating significant improvements in various cognitive assessment scales.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel anti-amyloid-beta (Aβ) monoclonal antibody lecanemab for Alzheimer's disease: A systematic review. Chowdhury, S., Chowdhury, NS.[2023]

References

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

A phase 1b study of andecaliximab in combination with S-1 plus platinum in Japanese patients with gastric adenocarcinoma. [2022]

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

Andecaliximab/GS-5745 Alone and Combined with mFOLFOX6 in Advanced Gastric and Gastroesophageal Junction Adenocarcinoma: Results from a Phase I Study. [2020]

3. England pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Andecaliximab (GS-5745) Plus Gemcitabine and Nab-Paclitaxel in Patients with Advanced Pancreatic Adenocarcinoma: Results from a Phase I Study. [2022]

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

Phase III Study to Evaluate Efficacy and Safety of Andecaliximab With mFOLFOX6 as First-Line Treatment in Patients With Advanced Gastric or GEJ Adenocarcinoma (GAMMA-1). [2022]

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

Safety and tolerability of andecaliximab as monotherapy and in combination with an anti-PD-1 antibody in Japanese patients with gastric or gastroesophageal junction adenocarcinoma: a phase 1b study. [2022]

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

Non-Invasive Imaging of Amyloid Deposits in a Mouse Model of AGel Using 99mTc-Modified Nanobodies and SPECT/CT. [2019]

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

ARIA in patients treated with lecanemab (BAN2401) in a phase 2 study in early Alzheimer's disease. [2023]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Lecanemab Clarity AD: Quality-of-Life Results from a Randomized, Double-Blind Phase 3 Trial in Early Alzheimer's Disease. [2023]

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

Lecanemab (BAN2401): an anti-beta-amyloid monoclonal antibody for the treatment of Alzheimer disease. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Novel anti-amyloid-beta (Aβ) monoclonal antibody lecanemab for Alzheimer's disease: A systematic review. [2023]