A Study of Andecaliximab in Participants With Fibrodysplasia Ossificans Progressiva (FOP)

NCT06508021 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: ASH-FOP-201
• Study Type: interventional
• Target: 92
• Locations: 1 country
• Sites: 3

Brief Summary

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)

Conditions

Fibrodysplasia Ossificans Progressiva

Keywords

Myositis Ossificans; Ossification, Heterotopic; Hallux Valgus; Matrix Metalloproteinase Inhibitors; Matrix Metalloproteinase 9; Inflammation; Activin A receptor, type I protein, human; ALK-2 protein, human; ACVR1 protein, human; Muscle, Skeletal; Myositis; Muscular diseases; Musculoskeletal diseases; Flare; Flare-ups; ANDECAL; Heterotopic bone; Ectopic bone; Munchmeyer's Disease

Outcome Measures

Primary Outcomes (1)

• Number of New HO Lesions as Assessed by WBCT-LH [Whole body, Computerized Tomography (CT), not including the head (less head)]

  Low dose WBCT-LH (whole body CT less head) is used to create detailed images of soft tissues and bones.

  Week 27 and 53

Secondary Outcomes (11)

• Percent change from baseline in Na18F standardized uptake value maximum (SUVmax) of up to 7 individual HO lesion(s) per participant active at baseline as assessed by Na18F PET/CT (Part 1a).

  Week 14

• Change in HO volume over time as assessed by WBCT-LH [Whole body, Computerized Tomography (CT), not including the head (less head)] (Part 1a)

  Week 14

• Change in HO volume over time as assessed by WBCT-LH [Whole body, Computerized Tomography (CT), not including the head (less head)]

  Week 27 and 53

• Number of days during which a flare-up is experienced by the participant as reported by the participant

  Week 14, 27 and 53

• Number of flare-ups as reported by the participant

  Week 14, 27 and 53

Study Arms (3)

Part 1a: PET/CT Study

EXPERIMENTAL

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).

Drug: Andecaliximab

Part 1b: Flare-up Study

EXPERIMENTAL

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.

Drug: Andecaliximab

Part 2: Main Study

PLACEBO COMPARATOR

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.

Drug: Placebo; Drug: Andecaliximab

Interventions

Andecaliximab DRUG

Dose level A or B

Part 1a: PET/CT Study; Part 1b: Flare-up Study

Placebo DRUG

Blinded

Part 2: Main Study

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant and/or guardian able and willing to give informed consent and/or assent as applicable, and willing to adhere to the visits schedule and study procedures.
• Clinical diagnosis of FOP including congenital malformation(s) consistent with FOP (e.g., of the great toes), and either episodic soft tissue swelling consistent with an FOP flare-up and/or progressive HO.
• \. CAJIS score of ≤19. 5. Disease activity within 1 year of screening visit. Disease activity is defined as physician confirmed flare-up like symptoms or clinical progression including newly identified HO or worsening joint function.
• \. Able to understand, undergo, and perform all protocol related procedures, including low-dose WBCT-LH scan without sedation. Assistance from a caregiver is allowed.
• \. Agree to provide access to all relevant current and historical medical records (including radiographs or radiographic records) and growth records.
• Male or female ≥ 15 years of age.
• Serum creatinine ≤ upper limit of normal for age.
• No open growth plates on bilateral PA hand/wrist or AP knee films at baseline
• Able to receive IV radiotracer \[both IV access and no history of a reaction to radiotracer\].
• No use of bisphosphonates or bone active agent within the past year.
• At least 1 active HO lesion at baseline per Na18F PET/CT
• Male or female ≥12 years of age.
• History of multiple flare-up episodes within the past 6 months (to be reviewed and confirmed as qualifying by the PI together with the Sponsor). Qualifying flare-up episodes include any of the following:
• At least 3 qualifying flare-ups in the past 6 months each with continuous symptoms for at least 1 week
• Migratory flare-up swellings across the back

You may not qualify if:

• Body weight \<10kg
• Known non-healed fracture at time of Study Day 1.
• Planned surgery within the timeframe of the study duration or still recovering from recent surgery.
• Respiratory compromise that requires use of supplemental oxygen.
• Participant has
• Known monogenic disorder other than FOP.
• Bone or mineral disorder unrelated to FOP.
• Malignancy (within the past 5 years, except non-melanoma skin cancer, cervical carcinoma in situ, or ductal carcinoma in situ \[DCIS\]).
• Known active infection (including fungal, bacterial, mycobacterial, or viral infection including COVID19)
• Uncontrolled hypoparathyroidism or hyperparathyroidism.
• Per participant report or chart review (no testing required): Uncontrolled hyperthyroidism
• Use of the following medication:
• Systemic corticosteroids with a prednisone equivalent of \>10mg/day within 1 week of Study Day 1. If the participant requires chronic use of \>10mg/day prednisone equivalent of corticosteroids, eligibility will be discussed with the Sponsor.
• NSAIDs of higher than doses recommended by the May 2022 ICCFOP guidelines within 1 week of Study Day 1. If the participant requires chronic use of NSAIDs at doses higher than those recommended by the May 2022 ICCFOP guidelines doses, eligibility will be discussed with the Sponsor.
• Current or chronic use of tetracycline drugs (e.g., tetracycline, demeclocycline, doxycycline, or minocycline).

Sponsors & Collaborators

• Ashibio Inc: lead

Study Sites (3)

University of California San Francisco (UCSF)

San Francisco, California, 94143, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

University of Pennsylvania - Perelman Center for Advanced Medicine

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (2)

• Lounev V, Groppe JC, Brewer N, Wentworth KL, Smith V, Xu M, Schomburg L, Bhargava P, Al Mukaddam M, Hsiao EC, Shore EM, Pignolo RJ, Kaplan FS. Matrix metalloproteinase-9 deficiency confers resilience in fibrodysplasia ossificans progressiva in a man and mice. J Bone Miner Res. 2024 May 2;39(4):382-398. doi: 10.1093/jbmr/zjae029.

  PMID: 38477818 BACKGROUND

• Wein MN, Yang Y. Actionable disease insights from bedside-to-bench investigation in fibrodysplasia ossificans progressiva. J Bone Miner Res. 2024 May 2;39(4):375-376. doi: 10.1093/jbmr/zjae044. No abstract available.

  PMID: 38644656 BACKGROUND

MeSH Terms

Conditions

Myositis Ossificans; Ossification, Heterotopic; Hallux Valgus; Inflammation; Myositis; Muscular Diseases; Musculoskeletal Diseases

Interventions

andecaliximab

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Foot Deformities; Neuromuscular Diseases; Nervous System Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 17, 2024
• First Posted: July 18, 2024
• Study Start: October 25, 2024
• Primary Completion (Estimated): February 4, 2029
• Study Completion (Estimated): February 4, 2029
• Last Updated: October 14, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: After completion of the Biologics License Applications (BLA) and all participants have completed the one year extension.
• Access Criteria: Not decided at this time

Locations

US (3)