A Phase 2, Randomized, Double Blind, Placebo Controlled, Dose Range Finding Study to Access the Efficacy and Safety of Intramuscular Injection of Human Placenta- Derived Cells (PDA-002) in Subjects With Diabetic Peripheral Neuropathy.
Overview
- Phase
- Phase 2
- Intervention
- PDA-002
- Conditions
- Diabetic Nephropathies
- Sponsor
- Celularity Incorporated
- Enrollment
- 26
- Locations
- 7
- Primary Endpoint
- Percent change in the epidermal nerve fiber density (ENFD) at 6 months, compared to baseline
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief Summary
This is a Phase 2, randomized, double-blind, placebo-controlled, dose range finding study in subjects who have diabetic peripheral neuropathy (DPN). The study will enroll approximately 24 subjects. Subjects will be randomized to receive one of 3 treatments: PDA-002 (3 x 10^6 cells), PDA-002 (30 x 10^6 cells), or placebo (vehicle control) in a 1:1:1 randomization approach. Investigational product or placebo will be administered monthly (3 administrations total on Study Days 1, 29, and 57).
Detailed Description
Subjects will undergo a Screening Period (up to 28 days in duration) to determine study eligibility and baseline levels of signs and symptoms of diabetic peripheral neuropathy (DPN) will be established. Subjects will then enter a Treatment Period (6 months in duration). During the Treatment Period, subjects will be evaluated on an ongoing basis (at 8 scheduled study visits). Subjects will receive intramuscular (IM) injections of investigational product (IP) on Study Days 1, 29, and 57 as fifteen 0.30 mL injections (below the knee and above the ankle) in one lower extremity in a blinded manner. After completing the Treatment Period, subjects will enter the Follow-up Period where they will continue to be evaluated at scheduled study visits over the subsequent months. An analysis of all study data will occur after the last subject has completed Visit 9 (Month 6) and after the last scheduled study visit.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Subjects must satisfy the following criteria to be enrolled in the study:
- •Males and females who are at least 18 years of age at the time of signing the informed consent document.
- •Subject must understand and voluntarily sign an informed consent document prior to any study related assessments/procedures are conducted.
- •Subject is willing and able to adhere to the study visit schedule and other protocol requirements
- •Diabetes mellitus (DM) Type 2 as defined by the American Diabetes Association (ADA) or World Health Organization (WHO) criteria.
- •Meet established criteria for diabetic peripheral neuropathy (DPN) due to Type 2 diabetes with the following:
- •Abnormal symptoms 6-item Neuropathy Total Symptom Score (NTSS-6 ≥ 6 points (total score) or ≥ 2.0 points for one or more symptoms) AND
- •Abnormal signs; Utah Early Neuropathy Scale (UENS) score of 2-24 and/or Neurological Impairment Score of the Lower Limb (NIS-LL) score of 2-
- •A female of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test prior to treatment with study therapy. In addition, sexually active Females of Child Bearing Potential (FCBP) must agree to use 2 of the following adequate forms of contraception methods simultaneously such as: oral, inject able, or implantable hormonal contraception, tubal ligation, intrauterine device (IUD), barrier contraceptive with spermicide or vasectomized partner for the duration of the study.
- •Males (including those who have had a vasectomy) must agree to use barrier contraception (latex condoms) when engaging in sexual activity with FCBP for the duration of the study
Exclusion Criteria
- •The presence of any of the following will exclude a subject from enrollment:
- •Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
- •Other causes of neuropathy in diabetic subjects: chronic inflammatory demyelinating polyneuropathy; neuropathy due to vitamin B12 deficiency, hypothyroidism, and uremia syndrome; and neuropathy due to entrapment or trauma.
- •A reversible course of acute painful diabetic neuropathy syndrome: treatment-induced diabetic neuropathy that presents in the setting of rapid glycemic control; diabetic neuropathic cachexia; and diabetic anorexia, a diabetic neuropathy that is seen with intentional weight loss.
- •History of a prior diagnosis of severe peripheral arterial disease (PAD).
- •Thrombocytopenia and coagulopathy, to avoid severe bruising or bleeding due to multiple intramuscular (IM) injections.
- •Any condition including the presence of laboratory abnormalities that places the subject at unacceptable risk if he or she were to participate in the study.
- •Any condition that confounds the ability to interpret data from the study.
- •Subjects who are taking opioids for the treatment of DPN.
- •Pregnant or lactating females.
Arms & Interventions
PDA-002 Dose Level 1: 3 x 10^6 cells
3 x 10\^6 PDA-002 cells administered intramuscular (IM) on study Days 1, 29, and 57.
Intervention: PDA-002
PDA-002 Dose Level 2: 30 x 10^6 cells
30 x 10\^6 PDA-002 cells administered IM on study Days 1, 29, and 57.
Intervention: PDA-002
Placebo
Subjects will receive placebo administered IM on study days 1, 29, and 57.
Intervention: Placebo
Outcomes
Primary Outcomes
Percent change in the epidermal nerve fiber density (ENFD) at 6 months, compared to baseline
Time Frame: Baseline up to 6 months
Epidermal nerve fiber density is a measurement used to assess the extent of peripheral diabetic neuropathy. The number of nerve fibers in a skin biopsy will be counted and quantified. A reduction in the number of nerves fibers (EPND)is indicative of worsening neuropathy.
Secondary Outcomes
- Adverse Events (AEs)(Up to approximately 2 years)