Andecaliximab for Stone Man Syndrome

(ANDECAL Trial)

Not currently recruiting at 3 trial locations

Overseen By Ashibio Clinical Study Inquiries

Age: Any Age

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Ashibio Inc

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

Disqualifiers: Fractures, Surgery, Infections, Malignancy, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called andecaliximab (an anti-matrix metalloproteinase-9 monoclonal antibody) to determine its safety and effectiveness for people with fibrodysplasia ossificans progressiva (FOP), a rare condition where muscles and other soft tissues turn into bone. Researchers aim to discover if andecaliximab can reduce new bone growth outside the skeleton, lessen flare-ups, and understand how the drug behaves in the body. Participants must have a confirmed diagnosis of FOP with active symptoms like flare-ups or new bone growth. The trial includes different parts, with some participants receiving the drug and others a placebo (inactive substance) to compare results. As a Phase 2, Phase 3 trial, this research measures the treatment's effectiveness in an initial, smaller group and represents the final step before FDA approval, offering hope for effective treatment.

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.

Is there any evidence suggesting that this trial's treatment is likely to be safe?

Research has shown that andecaliximab was safe in earlier clinical trials, with most participants tolerating the drug well and serious side effects being uncommon. In past studies, researchers tested andecaliximab to prevent extra bone growth in conditions like fibrodysplasia ossificans progressiva (FOP), a rare disease where bone forms in soft tissues. While some side effects might occur, the treatment has generally been safe for patients.

These studies are crucial for ensuring the treatment's safety. However, individual experiences may vary, and what works for one person might not work for another. Participants should discuss any concerns with the study team or their doctor. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for FOP?

Researchers are excited about andecaliximab for treating Stone Man Syndrome, also known as Fibrodysplasia Ossificans Progressiva (FOP), because it offers a new approach compared to typical treatments. Unlike current options that mainly focus on symptom management, andecaliximab targets the specific mechanisms driving the disease. It works by inhibiting a protein involved in the abnormal bone growth characteristic of FOP, potentially slowing or stopping the progression of the condition. Additionally, its subcutaneous weekly administration could provide a convenient treatment schedule compared to more invasive options. This innovative approach could significantly improve patients' quality of life by addressing the root cause of FOP rather than just alleviating its symptoms.

What evidence suggests that andecaliximab might be an effective treatment for fibrodysplasia ossificans progressiva?

Research has shown that andecaliximab targets a specific protein called MMP9, which plays a role in bone formation. In previous studies, patients taking this drug experienced about a 49% decrease in MMP9 levels. This reduction may help prevent new abnormal bone growth in conditions like fibrodysplasia ossificans progressiva (FOP), also known as Stone Man Syndrome. In this trial, participants will be assigned to different treatment arms, including two dose levels of andecaliximab or placebo, to evaluate its impact on outcomes such as safety and bone growth. Earlier trials have generally found andecaliximab to be safe and promising in reducing unwanted bone growth. While more research is needed, these early findings suggest it could effectively manage FOP symptoms. ^{1 2 3 4 5}

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Andecaliximab

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

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]

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]

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]

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Andecaliximab for Stone Man Syndrome (ANDECAL Trial)

This study is researching an experimental drug called andecaliximab. The study will include pediatric and adult patients with fibrodysplasia ossificans ...

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ANDECAL Trial (andecaliximab)

The ANDECAL study will evaluate the safety and efficacy of andecaliximab in participants living with FOP to block excess bone formation (heterotopic bone) and ...

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pubmed.ncbi.nlm.nih.gov/27218676/

Randomised clinical trial: a phase 1, dose-ranging study of ...

Patients with a clinical response to GS-5745 had reductions in matrix metalloproteinase-9 tissue levels (mean 48.9% decrease from baseline ...

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Inhibition of MMP9 as a novel treatment strategy for ...

Andecaliximab, a humanized monoclonal antibody specific to MMP9, has demonstrated a favorable safety profile in prior clinical trials involving ...