Study of PIPE-791 for Subjects With Chronic Osteoarthritis Pain or Chronic Low Back Pain

This is a double-blind, randomized, placebo-controlled, 2-period crossover study designed to evaluate the safety and tolerability of PIPE-791 in approximately 20 adults with COAP and 20 adults with CLBP (with or without painful lumbosacral radiculopathy). Subjects will be randomized to receive either PIPE-791 or placebo daily for 4 weeks, followed by a crossover to the alternate treatment assignment for an additional 4 weeks.

A washout period of all chronic pain medications is required prior to randomization. Rescue medications, including acetaminophen and naproxen, will be permitted during the study.

Subjects will complete regular clinic visits for safety assessments, laboratory testing, and physical evaluations. Daily pain scores and dosing information will be reported by subjects using an electronic diary (e-diary).

All subjects who complete dosing will have a post-treatment safety follow-up/end of study (EOS) phone visit approximately 28 days after the last dose of study drug. Subjects who prematurely discontinue dosing and all assessments from the study will have an early termination (ET) visit as soon as possible on or after their last dose of study drug.

The total duration of participation, including screening, treatment, and follow-up, is approximately 16 weeks.

Key Inclusion Criteria

• Male or female 18 to 70 years of age, inclusive, at the first Screening visit.
• Only one of the following chronic pain diagnoses at least 6 months prior to Screening:
• Osteoarthritis of the knee OR low back pain (with or without painful lumbosacral radiculopathy)
• Plain radiographs of the knee or lumbar spine consistent with diagnosis within 9 months prior to or during Screening.
• History of related daily pain for at least 6 months prior to Screening.
• Have a body mass index <40 (inclusive) at Screening.
• Willing to maintain a consistent regimen of any ongoing (stable format and frequency for the duration of study participation) non-pharmacologic pain-relieving therapies.
• Willing to discontinue medications taken for chronic pain conditions and usage of transcutaneous electrical nerve stimulation for the duration of the study.
• Male or female subjects with reproductive potential agree to comply with a highly effective contraceptive method as per protocol through 90 days after last study drug administration.
• Subjects taking systemic hormone-replacement therapy must be on a stable dose and regimen for at least 1 month prior to Screening.
• General good medical health with no clinically significant or relevant abnormalities except those attributed to the underlying chronic pain condition, including medical history, physical exam, vital signs, ECG, and laboratory evaluations (hematology, chemistry, and urinalysis) as assessed by the Investigator.
• Ability to use an eDiary to record daily pain scores.

Key Exclusion Criteria

• History of refractory chronic pain after multiple failed treatments as determined by the Investigator (e.g., no response to all of the following: surgery and/or nerve blocks, a regimen of at least two non-opioid pharmacotherapies, and physical rehabilitation, and weak opioids).
• Concurrent diagnosis of fibromyalgia or evidence of chronic widespread pain, or other pain that may interfere with the assessment of CLBP or COAP.
• Demonstrated noncompliance recording daily Numerical Rating Scale (NRS) scores during Screening.
• Have had a procedure within the past 6 months intended to produce permanent sensory loss in the target area of interest, e.g., an ablation procedure.
• Received capsaicin treatment (e.g., Qutenza) within the past 3 months prior to screening.
• Have surgery planned during the study for any reason, related or not, to the disease state under evaluation.
• Are non-ambulatory (use of assistive devices is allowed).
• History of Reiter's syndrome, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, arthritis associated with inflammatory bowel disease, sarcoidosis, or amyloidosis.
• Diagnosed with OA during childhood or adolescence, including post-traumatic OA or OA due to genetic (e.g., hip dysplasia) or congenital (e.g., metabolic disorders) conditions.
• History of or clinical signs or symptoms of active joint infection, crystal disease of the knee, or a history of arthritis due to crystals (e.g., gout, pseudo gout).
• History of prior lumbar or thoracic spine surgery (e.g., discectomies, laminectomies, foraminotomies, or fusion).