A phase I/IIa, prospective, mono-center, double-blinded, randomized, controlled study to assess the safety and efficacy of applying PLX-PAD cells for the treatment of mild to moderate knee osteoarthritis - PROTO

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Charite Universitaetsmedizin Berlin KöR

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

Decision date (initial)

2024-03-06

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2023-504212-15-00

WHO UTN

U1111-1290-9812

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To assess the safety and tolerability of local injections of PLX-PAD into the IA space and the periarticular muscle, for the treatment of mild to moderate knee OA.

Secondary objectives 7

1. Primary efficacy Objective: To check the potential clinical improvement in the WOMAC pain score (0-20) at week 26 compared to baseline (BL) at visit 1.
2. To provide an early proof of concept for the reduction of the pro-inflammatory environment, present in the knee joint, and thereby improve cartilage structure, clinical symptoms (e.g. pain, function), and QoL.
3. Exploratory Objective: To further evaluate clinical parameters that mirror the potential treatment efficacy.
4. Exploratory Objective: Individual genetic profiling of trial patients to detect individuals with genetic predispositions for knee OA for further therapy stratification
5. Exploratory Objective: Cellular and molecular biomarker profiling of patients to evaluate the immunomodulatory MOA in knee OA patients and to correlate the efficacy of the treatment with patients´ immune experience.
6. Exploratory Objective: To characterize the effects of PLX-PAD therapy on the morphology of the joint cartilage, the IPFP, and other joint tissues and whether such effects are associated with clinical improvement
7. Exploratory Objective: To characterize the effects of PLX-PAD therapy on the gait pattern

Conditions and MedDRA coding

Osteoarthritis

Regulatory references

Scientific advice from competent authorities

Paul-Ehrlich-Institut

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Signed written informed consent prior to initiation of any trial related measure.
2. Adult patients (f/m), 50 to 80 years old at the time of the screening visit
3. Symptomatic mild to moderate OA of the index knee as defined by the OARSI-Joint Space Narrowing (JSN) Score of 1or 2 (standing Rosenberg AP x-ray)
4. Pain in the index knee of 8-18 on the WOMAC pain score (reporting the last 48 hours, respectively at week 4 and week 1 before inclusion) after washout of at least 5 half-lives of previously taken NASAIDs medication(s)
5. Failed conservative treatment, indicated by Pain in the index knee ≥ 3 months due to OA

Exclusion criteria 5

1. Arthroscopy to the index knee within the last 12 months as well as surgery to other weight-bearing joints, that may interfere with index knee assessments
2. Prior reconstructive cartilage transplantation or resurfacing procedures to the index knee
3. Knee instability of clinical relevance such as lateral, medial or cruciate ligament instabilities that compromise patient during walking at time of screening
4. Patients having received OA knee injection therapy (such as PRP, MSCs, or Hyaluronic Acid) in the last six months before screening
5. Rheumatologic inflammatory arthropathies

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Evaluation of the safety of the (PLX-PAD) cell treatment by assessing all adverse events, with specific consideration to allergic reactions, local site reactions, joint reactions, and immunosuppression. Adverse events shall be assessed for relatedness, seriousness and severity.

Secondary endpoints 16

1. Primary Efficacy Endpoint: The potential change of the WOMAC pain score at week 26 compared to the baseline (BL) (visit 1) (0-20, where 0 is no pain).
2. Assessment of joint synovitis and effusion (MRI) at BL, weeks 26, 52 and 156;
3. Assessment of cartilage score using magnetic resonance imaging (MRI) location-independent analysis for knee articular cartilage at BL and weeks 52 and 156
4. Assessment of WOMAC score at BL, weeks 1, 4, 12, 26, 52, 104, and 156
5. Assessment of the KOOS score at BL, weeks 1, 4, 12, 26, 52, 104, and 156
6. Assessment of PROMIS-29 standardized QoL measure at BL, weeks 1, 4, 12, 26, 52, and 104
7. Exploratory Endpoint: evaluation of the use of pain medication at BL, weeks 1, 4, 12, 26, and 52
8. Exploratory Endpoint: evaluation of the numeric pain rating scale (NPRS) at BL, weeks 1, 4, 12, 26, and 52
9. Exploratory Endpoint: evaluation of the NPRS after 10 Meter Walk Test at BL, weeks 26 and 52
10. Exploratory Endpoint: Genetic profile (Whole-genome sequencing, WGS)
11. Exploratory Endpoint: Biomarker analysis in synovial fluid (SF) specimens at BL and week 52
12. Exploratory Endpoint: Biomarker analysis in blood and urine specimens at BL and weeks 1, 4, 12, 26, and 52
13. Exploratory Endpoint: Semiquantitative analysis of OA related degenerative alterations in the joint: MRI Osteoarthritis Knee Score (MOAKS) at BL, weeks 26, 52, and 156
14. Exploratory Endpoint: Potential change from BL for extension strength for the ipsi- and contralateral knee at weeks 26 and 52
15. Exploratory Endpoint: Functional 3D-gait analysis at BL and weeks 26 and 52
16. Exploratory Endpoint:

Investigational products

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

Test 1

Placebo 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Charite Universitaetsmedizin Berlin KöR

Sponsor organisation

Charite Universitaetsmedizin Berlin KöR

Address

Chariteplatz 1, Mitte Mitte

City

Berlin

Postcode

10117

Country

Germany

Scientific contact point

Organisation

Charite Universitaetsmedizin Berlin KöR

Contact name

Trial centre

Public contact point

Organisation

Charite Universitaetsmedizin Berlin KöR

Contact name

Trial centre

Third parties 9

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Application history

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