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To Evaluate the Safety and Efficacy of TD0015 Pilulae in Patients with Knee Osteoarthritis

Phase 2
Recruiting
Conditions
Knee Osteoarthritis
Interventions
Drug: TD0015 Placebo
Drug: TD0015
Registration Number
NCT06657495
Lead Sponsor
Sao Thai Duong Joint Stock Company
Brief Summary

Preclinical trials in animal models have suggested that the estimated dose of TD0015 in clinical presents no safety concerns.The investigational product is TD0015 pilulae, which is based on the traditional prescription named "Độc hoạt tang ký sinh thang" (Thien Kim Phuong).

The traditional prescription has the effect of circulating blood in the tendons and bones to bring out evil spirits, blood tonic, kidney tonic to prevent recurrence of diseases and against joint degeneration, joint deformation, muscle atrophy, stiffness to recover normal joint function.

Detailed Description

The study objective is to evaluate the safety and efficacy of TD0015 pilulae to determine the optimal dose for investigational product. Phase II analyzes is performed on 90 patients and based on the results of phase II to adjust sample size and study design (if applicable) for phase III.

The trial lasts for \~ 30 months with 6 subject visits (from T0 to T5) and is conducted in National Hospital of Traditional Medicine (Hanoi, Vietnam).

Screening procedure occurs at T0 visit, followed by T1 (15+/-3 days), T2 (30+/-3 days), T3 (45+/-3 days), T4 (60+/-3 days) and T5 (90+/-3 days). The telephone contact visits are performed every 2 weeks by Investigators There are 2 levels of dosages: estimated dose - 5g (arm 1) and 1.5 times (arm 2) of estimated dose - 7.5g. There is also another arm using placebo, thus the trial have 3 arms in total.

As for 3 arms, patients is allowed to use oral NSAIDs (meloxicam 7,5mg x 1-2 tablets/day) when pain is severe.

Treatment time is 60 days. IP is used after a meal, 1 pack/time x 2 times/day.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
90
Inclusion Criteria

Male or female patients ≥ 18 years old must meet ALL or the following criteria clusters 1,2,6 or 1,3,5,6 or 1,4,5,6 to be enrolled:

  1. Knee pain
  2. Bone spurs forming along the edges of the joint, narrowing of joint space in X-ray film (grade I-III) according to Kellgren and Lawrence
  3. Knee joint effusion
  4. Morning stiffness that lasts less than 30 minutes when moving
  5. Knee crepitus when moving
  6. Patient voluntarily agree and and sign in the ICF

According to traditional medicine: The disease type is Wind-Cold-Damp Bi with Kidney and Liver Deficiency. Symptoms are knee joint is pain, cold and heavy. Pain is usually fixed, little movement, mild during the day, severe at night, increased in cold and wet weather. Warm compresses to relieve pain, knee joint may be swollen, limited movement, may have morning stiffness, joint deformity associated with muscle atrophy, back pain, not warm limbs.The tongue is pale, the tongue is white and greasy, and deep-thready-weak pulse.

Exclusion Criteria
  1. Hypersensitivity to any subtances of TD0015 pilulae.
  2. Pregnant or lactating
  3. Currently having surgical indications.
  4. Other conditions asseted by the investigator that are not eligible to be enrolled.
  5. Knee Osteoarthritis grade IV according to classification of Kellgren and Lawrence (specify that large osteophytes, marked narrowing of joint space, severe sclerosis and definite deformity of bone ends)
  6. Self-administration of other anti-inflammatory medicine (except for NSAIDs) during study period as for 3 arms
  7. Patient is treated by NSAIDs within 3 days or has corticosteroid Intra-articular injection within 3 months prior to enrolment
  8. Joint and/or systemic infections
  9. Cardiovascular diseases (arrhythmia, hypertension) without treatment
  10. Cross - hypertensitivity to aspirin or other NSAIDs
  11. History of recent or progressive peptic ulcer/gastrointestinal perforation
  12. Severe liver failure
  13. Severe renal failure without dialysis
  14. Gastrointestinal hemorrhage, recent brain hemorrhage or disorders causing systemic hemorrhage
  15. Uncontrolled heart failure

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboTD0015 PlaceboPlacebo pilulae weighing 5g/pack, after a meal, 1pack/time x 2 times/day
Investigational product 1TD0015estimated dose:TD0015 pilulae weighing 5g/pack , after a meal, 1pack/time x 2 times/day
Investigational product 2TD00151.5 times of estimated dose: TD0015 pilulae weighing 7.5g/pack , after a meal, 1pack/time x 2 times/day
Primary Outcome Measures
NameTimeMethod
Change from baseline on the Western Ontario and McMaster Universities Osteoarthrities Index) WOMAC to evaluate the level of symptomsDay 15th, day 30th, day 45th, day 60th and day 30th after end of study

WOMAC was scored by investigator in visits (T1, T2, T3, T4, T5) and compared with T0

Change from baseline in Pain Scores on the Visual Analog Scaleday 15th, day 30th, day 45th, day 60th and day 30th after end of study

VAS scale: 0 = no pain \| 0--\>2: mild \| 2--\>4: moderate \| 4--\> 6: severe \| 6-\>8: extreme \| 8--\>10: untolerable

Evaluate outcome of treatment according to VAS scale:

* Very Good: 0

* Good: 1 - 4

* Average: 5 - 7

* Weak: \>8

Change in symptoms severity was reported by patient on the Lequesne Indexday 15th, day 30th, day 45th, day 60th and day 30th after end of study

Lequesne Index at prior and after treatment (day 15th, day 30th, day 45th, day 60th and day 30th after end of study).

Percentage of patients taking rescue medication90 days

3 Arms were allowed to use oral NSAIDs (meloxicam 7,5 mg x 1-2 tablets/day) when pain was severe. All NSAIDs in the study need to be documented in detail

The average dose of rescue medication was used90 days
Frequency of AE, SAE90 days

Reference CTCAE 4.03

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (1)

National Hospital of Traditional Medicine

🇻🇳

Hanoi, Vietnam

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