A Phase 2, Open-Label, Adaptive, Dose-Ranging Study with Long-Term Extension to Evaluate the Safety, Tolerability, Efficacy, and Pharmacokinetics of Intra-articular AMB-05X Injections in Subjects with Tenosynovial Giant Cell Tumor

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Ammax Bio Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Trial duration

20 Dec 2022 → 9 May 2024

Decision date (initial)

2023-10-06

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2023-507328-22-00

EudraCT number

2022-000101-28

WHO UTN

U1111-1295-7421

ClinicalTrials.gov

NCT05349643

ISRCTN

ISRCTN05349643

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Safety, Efficacy

The objectives of this study are to evaluate the safety, efficacy, pharmacokinetics (PK), and pharmacodynamics of intra-articular (IA) AMB-05X in the treatment of tenosynovial giant cell tumor (TGCT), both after an initial 24 weeks of treatment (Part 1) and after extended treatment and/or observation (Part 2).

Conditions and MedDRA coding

Tenosynovial Giant Cell Tumor

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 15

1. Has never received AMB-05X in another study.
2. Male or female ≥ 18 years of age.
3. Able to understand and willing to adhere to the requirements of this study. Voluntarily signs the informed consent form (ICF) before the conduct of any study-specific procedures.
4. TGCT with only 1 joint involvement that has been diagnosed histologically by a pathologist and documented. If a histological diagnosis has not been made previously, biopsy with histological diagnosis is required before enrollment. a. Individuals with TGCT of the knee joint are eligible. Depending on results in Cohort A and the recommendations of the DMC, individuals with TGCT of the hip and shoulder joint may also be allowed after Cohort A. b. Individuals with TGCT that are amenable or non-amenable to surgery are eligible.
5. Measurable disease of at least 1 cm per RECIST v1.1, assessed from MRI scans by central radiology review.
6. If the subject uses prescription analgesic, the subject must be on a stable prescription analgesic regimen during the 2 weeks before Baseline.
7. Agrees to follow contraception guidelines
8. Adequate hematologic, hepatic, and renal function at Screening
9. Symptomatic TGCT defined as at least 1 of the following: A BPI worst pain score of at least 4 before dosing at Baseline b. A Worst Stiffness NRS score of at least 4 before dosing at Baseline.
10. A subject may be enrolled directly into Part 2 of this study without completing Part 1 if ALL of the following criteria are met:
11. Have measurable disease of at least 1 cm per RECIST v1.1, assessed from MRI scans by central radiology review, and received treatment in Study AMB-051-01.
12. Able to understand and willing to adhere to the requirements of this study. Voluntarily signs the ICF before the conduct of any study-specific procedures.
13. Agrees to follow contraception guidelines
14. Adequate hematologic, hepatic, and renal function at Screening.
15. Symptomatic TGCT

Exclusion criteria 18

1. Use of any investigational drug within 4 weeks or 5 half-lives (whichever is longer) before Study Baseline
2. A female who is pregnant or breastfeeding. For females of childbearing potential, a positive pregnancy test at either Screening or Study Baseline will be exclusionary.
3. A screening QT interval corrected using Fridericia’s formula (QTcF) ≥ 470 ms
4. MRI contraindications (eg, pacemaker, loose metallic implants).
5. History of hypersensitivity to any ingredient in the study drug.
6. History of drug or alcohol abuse within 3 months before Study Baseline.
7. Any other severe acute or chronic medical or psychiatric condition or clinically significant laboratory abnormality that may increase the risk associated with study participation/treatment, interfere with interpretation of study results, or, in the Investigator’s opinion, make the subject inappropriate for this study.
8. Use of any of the following: a. Pexidartinib, any other oral tyrosine kinase inhibitor (eg, imatinib or nilotinib), or any biologic treatment targeting CSF1 or CSF1R (except AMB-05X), within 3 months before the Baseline visit b. Current or recent (within 10 days before starting study treatment) full-dose oral anticoagulants (eg, warfarin), daily treatment with high-dose aspirin (>325 mg/day) or clopidogrel (>75 mg/day).
9. History of extensive or reconstructive surgery on the affected joint (eg, involving plates, screws, or metal implants). A history of prior diagnostic or partial synovectomy is not exclusionary if performed at least 3 months before Study Baseline.
10. Current or prior radiotherapy within 3 months before Study Baseline.
11. Current or prior active cancer within 3 years before Study Baseline that requires/required therapy (eg, surgery, chemotherapy, or radiation therapy), except adequately treated basal or squamous cell carcinoma of the skin, melanoma in situ, carcinoma in situ of the cervix or breast, or prostate carcinoma not requiring treatment apart from active surveillance.
12. Known metastatic TGCT or malignant transformation of TGCT.
13. Hepatitis C virus (HCV) or hepatitis B virus (HBV) or known active or chronic infection with human immunodeficiency virus (HIV).
14. Known active tuberculosis (TB).
15. Significant concomitant arthropathy in the affected joint, serious illness, uncontrolled infection, or a medical or psychiatric history that, in the Investigator’s opinion, would likely interfere with the subject’s study participation or the interpretation of the subject’s results.
16. An individual who is held in detention as the result of a judicial or official decision or who is in a subordinate relationship to the Sponsor or Investigator.
17. An individual who, in the Investigator’s opinion, should not participate in this study for any reason, including instances where the subject’s stability or ability to comply with study requirements is in question.
18. Subjects with TGCT that is only extra-articular by MRI.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Proportion of subjects who achieve an objective response (OR) (objective response rate [ORR]) by central radiology review (which includes both complete response [CR] and partial response [PR]) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) at Week 24 for Part 1
2. Frequency and severity of reported treatment-emergent adverse events (TEAEs)

Secondary endpoints 19

1. Proportion of subjects who achieve an OR (ORR) by central radiology review (which includes both complete response [CR] and partial response [PR]) per RECIST v1.1 (for Part 2 only)
2. Proportion of subjects who were re-treated with AMB-05X (ie, subjects entering the study from Study AMB-051-01) who achieve an OR (ORR) by central radiology review (which includes both CR and PR) per RECIST v1.1 (for Part 2 only)
3. Proportion of subjects who achieve an OR (which includes both CR and PR) per modified RECIST
4. Proportion of subjects who achieve an OR per tumor volume score (TVS), a TGCT-specific method that calculates tumor volume as a percentage of the estimated maximally distended synovial cavity
5. Median duration of response per RECIST v1.1, modified RECIST, and TVS
6. Time to response (TTR) per RECIST v1.1, modified RECIST, and TVS
7. Mean change from Baseline in joint range of motion (ROM) score
8. Mean change from Baseline in the Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function score
9. Mean change from Baseline in Worst Stiffness Numeric Rating Scale (NRS) score
10. Percentage of subjects who respond with a decrease of at least 30% in mean Brief Pain Inventory (BPI) score from Baseline
11. Mean change from Baseline in BPI score
12. Mean change from Baseline in PROMIS Pain Interference score
13. Mean change from Baseline in Patient Global Impression of Change (PGIC) in Physical Functioning for capacity to perform everyday tasks
14. Mean change from Baseline in PGIC in TGCT-related stiffness score
15. Mean change from Baseline in Worst Pain NRS score
16. Mean change from Baseline in EuroQol 5-dimension 5-level (EQ-5D-5L) health assessment
17. Serum and synovial AMB-05X levels
18. Serum and synovial antidrug antibody (ADA) levels against AMB-05X
19. Serum and synovial CSF1 levels

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Ammax Bio Inc.

Sponsor organisation

Ammax Bio Inc.

Address

555 Twin Dolphin Drive Suite 610

City

Redwood City

Postcode

94065-2130

Country

United States

Scientific contact point

Organisation

Ammax Bio Inc.

Contact name

Tiffany Nguyen

Public contact point

Organisation

Ammax Bio Inc.

Contact name

Tiffany

Third parties 3

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 2 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications