A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and Tolerability of INCB000928 in Participants With Fibrodysplasia Ossificans Progressiva (PROGRESS)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Incyte Corp.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

Trial duration

31 Mar 2022 → ongoing

Decision date (initial)

2024-09-25

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Incyte Corporation

External identifiers

EU CT number

2023-504129-38-00

EudraCT number

2021-002286-17

ClinicalTrials.gov

NCT05090891

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Safety, Therapy

To determine the efficacy of INCB000928 for the prevention of new HO lesions in participants with FOP.

Secondary objectives 4

1. To further evaluate the efficacy of INCB000928 on disease activity in participants with FOP.
2. To evaluate the safety and tolerability of INCB000928 in participants with FOP.
3. To confirm the efficacy of INCB000928 between Week 24 and Week 48 in participants who crossover from placebo to INCB000928 at Week 24 versus the same participants between baseline and Week 24.
4. To characterize the PK of INCB000928 in participants with FOP

Conditions and MedDRA coding

Fibrodysplasia Ossificans Progressiva

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-002992-PIP01-21

Plan to share IPD

Yes

IPD plan description

Incyte shares data with qualified external researchers after a research proposal is submitted. These requests are reviewed and approved by a review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Informed consent/assent: a. For adult participants (≥ 18 years of age), ability to comprehend and willingness to sign an ICF. b. For children (2 to < 12 years of age) and adolescent participants (12 to < 18 years of age), written informed consent of the parent(s) or legal guardian and written assent from the underage participant.
2. Female and male participants: a. Cohort 1: ≥ 12 years of age. b. Cohort 2: 6 to < 12 years of age. Cohort 3: 2 to < 6 years of age
3. Clinical diagnosis of FOP (based on findings of congenital malformation of the great toes, episodic soft-tissue swelling, and/or progressive HO).
4. Participant-reported FOP disease activity within 1 year of the screening visit.
5. Ability to swallow and retain orally administered tablets, either whole or crushed and dispersed in foods or liquids, or ability to receive and retain crushed tablets via a feeding tube
6. Willingness to avoid pregnancy or fathering children
7. Willing and able to undergo low-dose WBCT (excluding the head) imaging without requiring intubation.
8. Willing and able to comply with study procedures and requirements and attend all study visits as defined in this Protocol.

Exclusion criteria 18

1. Pregnant or breast-feeding
2. CAJIS score ≥ 24.
3. FOP disease severity that in the investigator's opinion precludes participation
4. History of uncontrolled or unstable cardiovascular, respiratory, renal, gastrointestinal, endocrine, hematopoietic, psychiatric, and/or neurological disease within 6 months of screening.
5. Any clinically significant medical condition other than FOP that would, in the investigator's judgment, interfere with full participation in the study, pose a significant risk to the participant, or interfere with interpretation of study data.
6. Presence of a clinically significant finding on echocardiogram
7. Presence of an abnormal finding on ECG at screening that in the investigator's opinion is clinically significant and/or the following ECG parameters: QTcF interval > 450 milliseconds, ECG evidence of Brugada syndrome, atrial fibrillation or atrial flutter, or Mobitz II or higher grade atrioventricular block.
8. Current treatment with a potent/strong inhibitor or inducer of CYP3A4 within 5 half-lives before the first dose of study treatment or expected to receive such treatment during the study
9. Use of the following medications: a. Imatinib 30 days prior to baseline (Day 1 visit). b. Any medication that might interfere with HO formation in the 30 days or 5 half-lives, whichever is shorter before baseline
10. Participation in an investigational drug study for the treatment of FOP or any other indication within 30 days or 5 half-lives (whichever is longer) before baseline (Day 1 visit).
11. Planning to receive a live vaccine during the course of the study or within 6 weeks after the last dose of study drug.
12. Known or suspected allergy to INCB000928 or any component of the study drug.
13. Known history of clinically significant drug or alcohol abuse as defined by the investigator in the l year before baseline (Day 1 visit).
14. Chronic or current active infectious disease requiring systemic antibiotic, antifungal, or antiviral treatment.
15. HIV, HBV, or HCV infection
16. Participants with laboratory values at screening defined
17. Weight < 30 kg at screening (Cohort 1 only).
18. The following participants are excluded in France: a. Vulnerable populations according to article L.1121-6 of the French Public Health Code. b. Adults under legal protection or who are unable to express their consent per article L.1121-8 of the French Public Health Code. c. Individuals not affiliated with the social security system.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Occurrence of new HO lesions as assessed by low-dose WBCT (excluding the head) from baseline to Week 24.

Secondary endpoints 11

1. • Number of new HO lesions as assessed by low-dose WBCT (excluding the head) from baseline to Week 24.
2. • Total volume of new HO lesions as assessed by low-dose WBCT (excluding the head) from baseline to Week 24.
3. • Change in the total volume of all HO lesions as assessed by low dose WBCT (excluding the head) from baseline to Week 24.
4. • Number of new flares based on FOP PROMPT from baseline to Week 24.
5. • AEs and SAEs, assessed by changes in vital signs, ECGs, echocardiograms, physical examinations, PFTs, BMD, laboratory data, and knee epiphyseal closure (2 to < 21 years of age).
6. • Occurrence of new HO lesions as assessed by low dose WBCT (excluding the head) from Week 24 to Week 48 compared to baseline to Week 24 in participants randomized to placebo during the DB period.
7. • Number of new HO lesions as assessed by low-dose WBCT (excluding the head) from Week 24 to Week 48 compared to baseline to Week 24 in participants randomized to placebo during the DB period.
8. • Total volume of new HO lesions as assessed by low-dose WBCT (excluding the head) from Week 24 to Week 48 compared to baseline to Week 24 in participants randomized to placebo during the DB period.
9. • Change in the total volume of all HO lesions as assessed by low dose WBCT (excluding the head) from Week 24 to Week 48 compared to baseline to Week 24 in participants randomized to placebo during the DB period.
10. INCB000928 PK parameters in plasma and/or saliva: Cmax, tmax, Cmin, and AUCt.
11. • Number of new flares based on FOP PROMPT from Week 24 to Week 48 compared to baseline to Week 24 in participants randomized to placebo during the DB period

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Incyte Corp.

Sponsor organisation

Incyte Corp.

Address

1801 Augustine Cut Off

City

Wilmington

Postcode

19803-4404

Country

United States

Scientific contact point

Organisation

Incyte Corp.

Contact name

Clinical Trial Information

Public contact point

Organisation

Incyte Corp.

Contact name

Clinical Trial Information

Locations

6 EU/EEA countries · 7 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

Documents 66 files

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

Application history

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