OsteoarthritisPhase 1NCT02424942
First-in-human Study With Ascending Single Intra-articular Doses of GZ389988 in Patients With Painful Osteoarthritis of the Knee
A Phase 1 study testing GZ389988 in people with Osteoarthritis, run by Genzyme, a Sanofi Company at 1 site in Germany.
Trial summary
Primary Objective: To assess the safety and tolerability of ascending single intraarticular doses of GZ389988 in patients with painful osteoarthritis (OA) of the knee. Secondary Objectives: To assess the pharmacokinetic (PK) parameters of ascending single intraarticular doses of GZ389988 in patients with painful OA of… Read more about this study
- Who is it for?
- Ages 40 to 60 years
- Conditions the study is for
- Osteoarthritis
- What is being tested?
- GZ389988
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 28 participants
- Where
- 1 siteGermany
- Study dates
- Apr 2015to Jul 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Men or women 40 to 60 years of age.
- Diagnosis of primary knee osteoarthritis, based upon the following:
- Fulfilling the American College of Rheumatology Clinical and Radiographic criteria for OA (at least knee pain and osteophytes),
- X-ray evidence within the last 6 months for Kellgren and Lawrence classification II to IV.
- Western Ontario and McMaster Universities Arthritis Index (WOMAC) A1 Pain subscore (walking pain) between 50 and 90 using the 100-mm visual analog scale (VAS), corresponding to moderate to severe pain in the index knee, at both screening and baseline assessments at least 48 hours apart.
- Symptomatic for more than 6 months (if both symptomatic knees, at least for the most painful knee that will receive the study drug).
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- Having given written informed consent prior to any procedure related to the study.
- Ambulatory with an active lifestyle and in good general health. (Assistive devices were allowed if used throughout a period of 3 months or more prior to screening, on the condition that they continued to be used throughout the study).
- A male who is sexually active must use a condom as part of a method of highly effective contraception (eg, condom + spermicide, and an additional contraceptive method used by the partner) during sexual intercourse with a women of childbearing potential for the duration of the study period up to the end-of-study visit and should not father a child in this period. Male patients also have to agree not to donate sperm for the duration of the study until the end-of-study visit.
Who cannot join
- Women of childbearing potential.
- Pregnant or breastfeeding women.
- Any uncontrolled, chronic condition or laboratory finding which, in the opinion of the Investigator, could potentially put the patient at increased risk.
- Patients with clinically significant or uncontrolled hepatic, gastrointestinal, cardiovascular, respiratory, neurological (including diabetic neuropathy), psychiatric, hematological, renal, dermatological disease, or any other medical condition that might interfere with the evaluation of the investigational medicinal product (IMP) according to Investigator's medical judgment.
- Chondrocalcinosis.
- Fibromyalgia.
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- Major depression.
- History or presence of drug or alcohol abuse (alcohol consumption >40 grams per day).
- Any patient who, in the judgment of the Investigator, is likely to be noncompliant during the study, or unable to cooperate because of a language problem or poor mental development.
- Abnormal coagulation parameters: outside the range international normalized ratio (INR) 0.85-1.15, activated partial thromboplastin time >33 seconds, platelets <140 x 10^9/L.
- Moderate to severe renal impairment.
- Underlying hepatobiliary disease and/or alanine aminotransferase (ALT) >2 x upper limit of normal (ULN).
- High sensitivity C-reactive protein (hsCRP) >2 x ULN.
- Hemoglobin <10 g/dL, white blood cell count (WBC) <3 x 10^9/L.
- Positive result on any of the following tests: hepatitis B surface (HBsAg) antigen, anti-hepatitis C virus (anti-HCV) antibodies, anti-human immunodeficiency virus 1 and 2 antibodies (anti-HIV1 and anti-HIV2 Ab).
- Secondary OA.
- Ipsilateral hip OA.
- Symptomatic contralateral knee OA with WOMAC A1 pain subscore (walking pain) >30 on 100-mm VAS.
- Prior history of osteonecrosis and/or rapidly progressive OA.
- Intraarticular injection within 3 months prior to inclusion.
- Unable to be maintained for at least 2 weeks prior to entry into study on paracetamol (No non-steroidal non-inflammatory drug [NSAID] use during the 12 weeks of the study; after the end-of-study visit [Day 84 ± 7] patients may be given an NSAID if necessary to provide better control of OA symptoms).
- Any IMP within 3 months prior to the study.
- Any knee MRI contraindication.
- The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Two Part Protocol Using Double Blind Placebo Control to Assess the Safety, Tolerability, and Pharmacokinetics of Single Escalating Intra-articular Doses Followed by Assessment of Efficacy, Safety, Tolerability and Pharmacokinetics of a Single Intra-articular Dose of the TrkA Inhibitor, GZ389988, in Patients With Painful Osteoarthritis of the Knee
Primary Objective:
To assess the safety and tolerability of ascending single intraarticular doses of GZ389988 in patients with painful osteoarthritis (OA) of the knee.
Secondary Objectives:
To assess the pharmacokinetic (PK) parameters of ascending single intraarticular doses of GZ389988 in patients with painful OA of the knee.
To obtain preliminary pharmacodynamic evaluation of ascending single intraarticular doses of GZ389988 in patients with painful OA of the knee.
Read the detailed description
Screening will be performed within 28 days of dosing. Following the single dose of study medication, the study period for each patient will be 84 ± 7 days up to the end-of-study visit.
Total duration for one patient will be up to 17 weeks (up to the end-of-study visit), not including the long term observational safety follow-up by phone call for 12 additional weeks.
- Conditions
- Osteoarthritis
- Being tested
- placebo, GZ389988
- Medical subject headings
- Osteoarthritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
placeboDrug
Pharmaceutical form:solvent for parenteral use
Route of administration: intraarticular
GZ389988Drug
Pharmaceutical form:suspension for injection
Route of administration: intraarticular
| Study group | Role | What they receive |
|---|---|---|
| GZ389988 | Experimental | Single intraarticular injection of GZ389988 in the knee joint Receives: Drug: GZ389988 |
| Placebo | Placebo comparator | Single intraarticular injection of placebo for GZ389988 in the knee joint Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of patients with adverse events
Measured: Up to Day 84 after single intraarticular dose of GZ389988
Proportion of patients with serious adverse events
Measured: 12 additional weeks after day 84 (by phone calls)
Secondary outcomes (13)
Maximum plasma concentration (Cmax) of GZ389988 single dose intraarticular (IA)
Measured: 24 timepoints up to Day 84
Area under the curve from time zero to last quantifiable concentration (AUClast) of single dose GZ389988 IA
Measured: 24 timepoints up to Day 84
Area under the curve (AUC) of single dose GZ389988 IA
Measured: 24 timepoints up to Day 84
Plasma elimination half-life (t1/2z) of single dose GZ389988 IA
Measured: 24 timepoints up to Day 84
Time to peak plasma concentration (tmax) of single dose GZ389988 IA
Measured: 24 timepoints up to Day 84
Time curve from administration to last measurement (tlast) of single dose GZ389988 IA
Measured: 24 timepoints up to Day 84
Apparent volume of distribution (Vz/F) of single dose GZ389988 IA
Measured: 24 timepoints up to Day 84
Apparent total body clearance(CL/F) of single dose GZ389998 IA
Measured: 24 timepoints up to Day 84
Synovial fluid concentrations (if possible) of single dose GZ389988 IA
Measured: 3 timepoints up to Day 84
Change from baseline in WOMAC index (total score)
Measured: Over 1, 2, 3, 4, 6, 8, 10, and 12 weeks following the single intraarticular injection
Change from baseline in WOMAC pain (including WOMAC A1 pain subscores)
Measured: Over 1, 2, 3, 4, 6, 8, 10, and 12 weeks following the single intraarticular injection
Change from baseline in WOMAC stiffness subscore
Measured: Over 1, 2, 3, 4, 6, 8, 10, and 12 weeks following the single intraarticular injection
Change from baseline in WOMAC physical function subscore
Measured: Over 1, 2, 3, 4, 6, 8, 10, and 12 weeks following the single intraarticular injection
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Apr 2015 (estimated)
- Study startApr 2015
- Primary completionJul 2016
- Study completionJul 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for OsteoarthritisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- Genzyme, a Sanofi Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Sciences & Operations, Study director, Sanofi
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02424942
- Sponsor's protocol ID
- TDU13828
- Other IDs
- 2014-004805-34, U1111-1163-0806, 2014
- Status last verified
- Aug 2016
- First submitted
- 10 Apr 2015
- Last updated
- 17 Aug 2016
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Aug 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Two Part Protocol Using Double Blind Placebo Control to Assess the Safety, Tolerability, and Pharmacokinetics of Single Escalating Intra-articular Doses Followed by Assessment of Efficacy, Safety, Tolerability and Pharmacokinetics of a Single Intra-articular Dose of the TrkA Inhibitor, GZ389988, in Patients With Painful Osteoarthritis of the Knee
- ClinicalTrials.gov ID
- NCT02424942
- Acronym / sponsor ID
- TDU13828
- Conditions
- Osteoarthritis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- Genzyme, a Sanofi CompanyIndustry (pharma, biotech, devices)
- Study start
- Apr 2015
- Primary completion
- Jul 2016 (actual)
- Study completion
- Jul 2016 (actual)
- First posted
- 23 Apr 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Primary Objective:
To assess the safety and tolerability of ascending single intraarticular doses of GZ389988 in patients with painful osteoarthritis (OA) of the knee.
Secondary Objectives:
To assess the pharmacokinetic (PK) parameters of ascending single intraarticular doses of GZ389988 in patients with painful OA of the knee.
To obtain preliminary pharmacodynamic evaluation of ascending single intraarticular doses of GZ389988 in patients with painful OA of the knee.
Detailed description
Screening will be performed within 28 days of dosing. Following the single dose of study medication, the study period for each patient will be 84 ± 7 days up to the end-of-study visit.
Total duration for one patient will be up to 17 weeks (up to the end-of-study visit), not including the long term observational safety follow-up by phone call for 12 additional weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| GZ389988 | Experimental | Drug: GZ389988Single intraarticular injection of GZ389988 in the knee joint |
| Placebo | Placebo comparator | Drug: placeboSingle intraarticular injection of placebo for GZ389988 in the knee joint |
Who may qualify
- Ages
- 40 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- Men or women 40 to 60 years of age.
- Diagnosis of primary knee osteoarthritis, based upon the following:
- Symptomatic for more than 6 months (if both symptomatic knees, at least for the most painful knee that will receive the study drug).
- Having given written informed consent prior to any procedure related to the study.
- Ambulatory with an active lifestyle and in good general health. (Assistive devices were allowed if used throughout a period of 3 months or more prior to screening, on the condition that they continued to be used throughout the study).
Key exclusion criteria (24 listed)
- Women of childbearing potential.
- Pregnant or breastfeeding women.
- Any uncontrolled, chronic condition or laboratory finding which, in the opinion of the Investigator, could potentially put the patient at increased risk.
- Patients with clinically significant or uncontrolled hepatic, gastrointestinal, cardiovascular, respiratory, neurological (including diabetic neuropathy), psychiatric, hematological, renal, dermatological disease, or any other medical condition that might interfere with the evaluation of the investigational medicinal product (IMP) according to Investigator's medical judgment.
- Chondrocalcinosis.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| placeboPharmaceutical form:solvent for parenteral use Route of administration: intraarticular | Drug | Placebo |
| GZ389988Pharmaceutical form:suspension for injection Route of administration: intraarticular | Drug | GZ389988 |
Primary outcome
Proportion of patients with adverse events
Time frame: Up to Day 84 after single intraarticular dose of GZ389988
Proportion of patients with serious adverse events
Time frame: 12 additional weeks after day 84 (by phone calls)
13 secondary outcomes
Maximum plasma concentration (Cmax) of GZ389988 single dose intraarticular (IA)
Time frame: 24 timepoints up to Day 84
Area under the curve from time zero to last quantifiable concentration (AUClast) of single dose GZ389988 IA
Time frame: 24 timepoints up to Day 84
Area under the curve (AUC) of single dose GZ389988 IA
Time frame: 24 timepoints up to Day 84
Plasma elimination half-life (t1/2z) of single dose GZ389988 IA
Time frame: 24 timepoints up to Day 84
Time to peak plasma concentration (tmax) of single dose GZ389988 IA
Time frame: 24 timepoints up to Day 84
Time curve from administration to last measurement (tlast) of single dose GZ389988 IA
Time frame: 24 timepoints up to Day 84
Apparent volume of distribution (Vz/F) of single dose GZ389988 IA
Time frame: 24 timepoints up to Day 84
Apparent total body clearance(CL/F) of single dose GZ389998 IA
Time frame: 24 timepoints up to Day 84
Synovial fluid concentrations (if possible) of single dose GZ389988 IA
Time frame: 3 timepoints up to Day 84
Change from baseline in WOMAC index (total score)
Time frame: Over 1, 2, 3, 4, 6, 8, 10, and 12 weeks following the single intraarticular injection
Change from baseline in WOMAC pain (including WOMAC A1 pain subscores)
Time frame: Over 1, 2, 3, 4, 6, 8, 10, and 12 weeks following the single intraarticular injection
Change from baseline in WOMAC stiffness subscore
Time frame: Over 1, 2, 3, 4, 6, 8, 10, and 12 weeks following the single intraarticular injection
Change from baseline in WOMAC physical function subscore
Time frame: Over 1, 2, 3, 4, 6, 8, 10, and 12 weeks following the single intraarticular injection
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Aug 2016.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Sciences & Operations study director
Sanofi
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing GZ389988 in people with Osteoarthritis, run by Genzyme, a Sanofi Company at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Aug 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of patients with adverse events (time frame: Up to Day 84 after single intraarticular dose of GZ389988). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Aug 2016.