A Phase 1/2, Open-Label, Exploratory Clinical Trial to Evaluate the Safety and Efficacy of DT-DEC01 Therapy in Patients with Duchenne Muscular Dystrophy

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Dystrogen Therapeutics Technology Polska Sp. z o.o.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

Decision date (initial)

2024-12-20

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2024-519004-27-00

EudraCT number

2022-003126-42

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

Phase 1 primary objectives include (i) evaluation of safety by clinical observation of the incidence and severity of all adverse events: Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESI) to assess the potential risks (ii) evaluation of efficacy, based on functional assessments of muscle strength and function adjusted to the stage of the disease: (a) for ambulatory patients: Six-Minute Walk Test (6MWT); timed functions of NorthStar Ambulatory Assessment (NSAA): supine to rise and 10-meter walk/run); (b) for non-ambulatory patients: PUL 2.0 and (c) assessments for both ambulatory and non-ambulatory patients: electromyography (EMG) assessment of duration of motor unit potential (MUP) of the selected muscles.

Phase 2 primary objectives include evaluation of safety by clinical observation of the incidence and severity of all adverse events: AEs, SAEs and AESI and to assess the potential risks; and evaluation of the efficacy, based on the functional assessments of muscle strength and function adjusted to the stage of the disease including: (a) for ambulatory patients: 6MWT; timed functions of NSAA: supine to rise and 10-meter walk/run), (b) for non-ambulatory patients: PUL 2.0, (c) for both, the ambulatory and non-ambulatory patients: EMG assessment of duration of the MUP of the selected muscles.

Conditions and MedDRA coding

Duchenne Muscular Dystrophy

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-111111-PIP11-11

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Subject and his legal representative/parent(s)/legal guardian have understood and accepted to participate in the study according to all study procedures by signing the approved informed consent.
2. Boys of age 5 to 18 years old (at the time of screening), diagnosed with DMD confirmed by genetic testing.
3. Subjects must be receiving glucocorticosteroids for a minimum of 6 months prior to the biopsy of muscle tissue.
4. Subjects with progressive, symmetrical proximal muscle weakness of arms and legs.
5. Willingness and ability to comply with scheduled visits, tissue biopsy procedure under anesthesia, drug administration plan, laboratory tests, study restrictions, study procedures, and functional testing adapted to the stage of the disease.
6. Willingness to use acceptable forms of contraception if the subject is sexually active.
7. Patients must be cleared by anesthesiologist for tissue biopsy and DT-DEC01 intraosseous injection procedures which will be performed under anesthesia (local anesthesia / general anesthesia / analgosedation).

Exclusion criteria 14

1. Subject was previously exposed to the IMP, any similar experimental therapy with the use of ATMP or any other cell-based product, gene therapy or translarna / ataluren prior to screening.
2. Subject has known history of immune reaction to the administered therapies or history of GvHD.
3. Subjects with known cognitive impairment or behavioral issues that would impede the ability to follow instructions.
4. Subject is positive for human immunodeficiency virus (HIV) 1 or 2, hepatitis B (HBV) or C (HCV*), cytomegalovirus (CMV*), toxoplasmosis* or syphilis at screening visit (V0a). *In case of positive or doubtful result of anti-CMV IgG and anti-Toxo IgG, anti-HCV total the final qualification decision can be made after confirming the negative Nucleic Acid Test (NAT) results in cell culture.
5. Subject has a history of any autoimmune disease.
6. Ongoing participation in any other therapeutic clinical trial.
7. Presence of pre-existing antibodies in the subject’s serum against the donor lymphocytes.
8. Subject has undergone an organ or bone marrow transplantation.
9. Change in systemic corticosteroid therapy (e.g. initiation of treatment; cessation of treatment; change in dose, schedule, or type of steroid) within 3 months prior to administration of the investigational product.
10. Any injury or procedure which may impact functional testing. Previous injuries must be fully healed prior to consenting. Prior lower limb fractures must be fully healed and at least 3 months should pass from injury date.
11. Presence or history of other musculoskeletal or neurologic disease or somatic disorder not related to DMD including pulmonary and cardiac disease.
12. History of allergic or anaphylactic reaction to a therapeutic or diagnostic protein or additives of the investigational product.
13. Ongoing chronic use of any agents with an immunomodulating (activating or suppressing) effect, such as, but not limited to, immunosuppressants or drugs related to immunotherapy (e.g. based on antibodies), chemotherapy or similar therapy affecting cell proliferation.
14. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for inclusion into this study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 6

1. Phase 1: The frequency of the incidence and severity of all adverse events – AEs, SAEs and AESI.
2. Phase 1: Mean changes from the baseline (V0a) recorded in the functional assessments adjusted to the stage of the disease: for ambulatory patients: 6MWT, timed functions of NSAA: supine to rise and 10-meter walk/run, for non-ambulatory patients: PUL 2.0, at month 1 (V4), 3 (V5), 6 (V6), and 12 (V7).
3. Phase 1: Mean changes from the baseline (V0a) in the EMG assessment of MUP duration of the selected muscles of upper and lower extremity in both ambulatory and non-ambulatory patients, at month 3 (V5), 6 (V6), and 12 (V7).
4. Phase 2: The frequency of the incidence and severity of all adverse events – AEs, SAEs and AESI.
5. Phase 2: Mean changes from the baseline (V0a) recorded in the functional assessments adjusted to the stage of the disease: a. for ambulatory patients: 6MWT, timed functions of NSAA: supine to rise and 10-meter walk/run b. for non-ambulatory patients: PUL 2.0 at month 1 (V4), 3 (V5), 6 (V6), and 12 (V7).
6. Phase 2: Mean changes from the baseline in the EMG assessment of MUP duration of the selected muscles of upper and lower extremity in both ambulatory and non-ambulatory patients at month 3, 6 and 12 .

Secondary endpoints 3

1. Phase 2: Mean changes from the baseline (V0a) recorded by functional assessments (adjusted to the stage of the disease): for ambulatory patients: PUL 2.0, assessment of grip strength by dynamometer; for non-ambulatory patients: assessment of grip strength by dynamometer. At month 1 (V4), 3 (V5), 6 (V6), and 12 (V7).
2. Phase 2: Mean changes from the baseline (V0a) in QoL assessed by PODCI at month 1 (V4), 3 (V5), 6 (V6), and 12 (V7).
3. Phase 2: Evaluation of Overall Treatment Effect at month 1 (V4), 3 (V5), 6 (V6), and 12 (V7).

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Dystrogen Therapeutics Technology Polska Sp. z o.o.

Sponsor organisation

Dystrogen Therapeutics Technology Polska Sp. z o.o.

Address

Ul. Wladyslawa Pytlasinskiego 10/12/14

City

Warsaw

Postcode

00-777

Country

Poland

Scientific contact point

Organisation

Dystrogen Therapeutics Technology Polska Sp. z o.o.

Contact name

Contact Point

Public contact point

Organisation

Dystrogen Therapeutics Technology Polska Sp. z o.o.

Contact name

Contact Point

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

Documents 11 files

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

Application history

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